NICHOLAS J. PETRELLI, MD, Medical Director, Helen F. Graham Cancer Center, Newark, Delaware; and Professor of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania

WESLEY L. HICKS, JR, DDS, MD, FACS, Attending Surgeon, Department of Head and Neck Surgery, Roswell Park Cancer Institute; Associate Professor of Otolaryngology, Head and Neck Surgery, and Neurosurgery, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York; and Director, Head and Neck Surgical Fellowship Program, Roswell Park Cancer Institute

RONALD A. ALBERICO, MD, Associate Professor of Radiology, Assistant Clinical Professor of Neurosurgery, School of Medicine and Biomedical Sciences, State University of New York at Buffalo; Director of Neuroradiology/Head and Neck Imaging, Department of Radiology, Roswell Park Cancer Institute, Buffalo, New York; and Acting Director of Pediatric Neuroradiology, Buffalo Children’s Hospital, Buffalo, New York GARTH R. ANDERSON, PhD, Professor of Cellular and Molecular Biology, Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York JIMMY J. BROWN, DDS, MD, FACS, Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, California AMOS O. DARE, MD, Clinical Instructor, Department of Neurological Surgery, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York WADE DOUGLAS, MD, Fellow, Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, New York KEVIN J. GIBBONS, MD, Program Director and Director of Skull Base Surgery, Department of Neurological Surgery, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York WILLIAM GIESE, MD, JD, Associate Professor, Department of Radiation Oncology, Roswell Park Cancer Institute, Buffalo, New York iii

RALPH W. GILBERT, MD, FRCSC, Associate Professor, Head and Neck Surgical Oncology; Reconstructive Microsurgery, University Health Network; Princess Margaret Hospital; and Department of Otolaryngology, University of Toronto, Toronto, Canada CHRISTINE G. GOURIN, MD, FACS, Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, Augusta, Georgia PATRICK J. GULLANE, MB, FRCSC, FACS, Otolaryngologist-in-Chief, University Health Network; Wharton Chair in Head and Neck Surgery, Princess Margaret Hospital; and Professor and Chairman, Department of Otolaryngology, University of Toronto, Toronto, Canada SYED HAMED S. HUSAIN, DO, Radiology Resident, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York DOMINICK LAMONICA, MD, Director of Nuclear Medicine, Division of Diagnostic Imaging, Roswell Park Cancer Institute; and Assistant Professor of Radiology and Clinical Nuclear Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York PABLO MOJICA-MANOSA, MD, Fellow, Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, New York JEFFREY N. MYERS, MD, PhD, Associate Professor of Head and Neck Surgery, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas LARRY L. MYERS, MD, Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, Texas RYAN F. OSBORNE, MD, Director, Head and Neck Oncology, Cedars-Sinai Medical Center; and Assistant Professor, Department of Otolarynology–Head and Neck Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, California LANCE E. OXFORD, MD, Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, Texas CARSTEN E. PALME, MB BS, FRACS, Clinical Fellow, Oncologic Head and Neck Surgery, Department of Otolaryngology, University of Toronto, Toronto, Canada JAMES REIDY, DO, Fellow, Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, New York NESTOR R. RIGUAL, MD, FACS, Associate Professor of Clinical Otolaryngology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo; and Attending Surgeon, Section of Plastic and Reconstructive Surgery, Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, New York JAMES K. SCHWARZ, MD, Assistant Professor, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York



IGOR SIROTKIN, MD, Radiology Resident, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York DANIEL L. STOLER, PhD, Assistant Professor, Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York MAUREEN SULLIVAN, DDS, Chief, Department of Dentistry and Maxillofacial Prosthetics, Roswell Park Cancer Institute, Buffalo, New York DAVID J. TERRIS, MD, FACS, Porubsky Professor and Chairman, Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, Augusta, Georgia KEITH WILSON, MD, Associate Professor, ENT/Head and Neck Surgery, University of Cincinnati, Cincinnati, Ohio SAM M. WISEMAN, MD, FRCS(C), Assistant Professor of Surgery, University of British Columbia School of Medicine; and Attending Surgeon, Department of Surgery, St. Paul’s Hospital, Vancouver, British Columbia, Canada ROBERT L. WITT, MD, Chief, Section of Otolaryngology, Department of Surgery, Christiana Care Health System, Newark, Delaware; and Assistant Professor, Department of Otolaryngology, Jefferson Medical College, Philadelphia, Pennsylvania MAHER N. YOUNES, MD, Postdoctoral Fellow, Department of Head and Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas



Guest Editor October 2004 Adjuvant Therapy of Pancreatic Adenocarcinoma John P. Jr. Guest Editors July 2003 Management of Peritoneal Surface Malignancy Paul H. PhD Guest Editor VISIT THESE RELATED WEB SITES Access your subscription at: http://www. . MD. Thomas. Jr. Guest Editors July 2004 Palliative Care Lawrence D. Thomas. and Charles R. MD. MD. Hoffman. Wagman. MD. FACS. Guest Editor RECENT ISSUES October 2003 Intraoperative Radiotherapy Hollis W. Merrick. MD. MD.FORTHCOMING ISSUES April 2004 Multidisciplinary Approach to Anal Cancer Morton S. MD. Guest Editor April 2003 Emerging Perspectives in Soft Tissue Sarcoma Raphael E. Pollack. Sugarbaker. MD. FRCS. and Charles R.

pipe smoking. over 17 million new cancer cases have been diagnosed. Cancers of the oral cavity and pharynx were diagnosed in an estimated 27. and an Associate Professor of Surgery at the State University of New York at Buffalo. In 2003.500 Americans died of cancer. these new cancer cases do not include carcinoma in situ of any site except urinary bladder and do not include basal and squamous skin cancers. Nevertheless. These incidence rates are more than twice as high in men as in women and are greatest in men who are over age 50. The known risk factors for these cancers are cigarettes.1016/j. In this issue of the Surgical Oncology Clinics of North America. New York. and the use of smokeless tobacco. All rights reserved.334. Hicks is a member of the Department of Head and Neck Surgery at the Roswell Park Cancer Institute in Buffalo. cigars. under the direction of Wesley Hicks. MD. There were an estimated 7200 deaths in 2003 from oral cavity and pharyngeal cancer.100 new cancer cases were diagnosed in 2003.see front matter Ó 2004 Elsevier Inc. MD Consulting Editor Approximately 1.010 . which is equivalent to more than 1500 people a day.soc.700 new cases in 2003. Jr. Since 1990. Excessive consumption of alcohol is also a risk factor. incidence rates for cancers of the oral cavity and pharynx continued to decline in the 1990s in both African American and white males and females. According to the American Cancer Society.2003.. DDS. Dr. doi:10. an outstanding array of authors has been assembled to discuss many clinical and scientific issues regarding cancers of the head and neck.12. 1055-3207/04/$ . approximately 556.Surg Oncol Clin N Am 13 (2004) xiii–xiv Foreword Current diagnosis and therapy for head and neck malignancies Nicholas J. Petrelli.

These researchers are from the Departments of Surgical Oncology.xiv N. On the clinical side. Nicholas J. Hicks and his colleagues on an outstanding issue of the Surgical Oncology Clinics of North America. this issue is a must-read for trainees in the three major disciplines of surgery. USA Jefferson Medical College Philadelphia. and Cancer Genetics. Cancer predisposition genes and the genetic heterogeneity of head and neck tumors are discussed in detail. MD Consulting Editor Helen F. and Anderson on the role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck is especially interesting. and medical oncology. I congratulate Dr. This article provides a clear discussion of the clinical treatment modalities in relationship to histopathologic characteristics. As I have stated in previous forewords for the Surgical Oncology Clinics of North America. Experimental Pathology. the article by Osborne and Brown from the Division of Otolaryngology/Head and Neck Surgery at the University of California– Los Angeles Medical Center deals with carcinoma of the oral pharynx with an analysis of subsite treatment heterogeneity. radiation oncology. Graham Cancer Center 4701 Ogletown-Stanton Road Suite 1212 Newark. respectively. Petrelli / Surg Oncol Clin N Am 13 (2004) xiii–xiv The article by Wiseman. Stoler. Pennsylvania .J. Trainees in pathology and radiology should also make this issue a part of their educational matriculation. Petrelli. Delaware 19713.

see front matter Ó 2004 Elsevier Inc. This issue is not intended to be an exhaustive explanation regarding the armamentarium or clinical paradigms for the treatment of head and neck cancer. there are a plethora of treatment options and clinical outcomes based on both the site and stage of the primary tumor. We anticipate that this issue will give readers a general overview of head and neck cancer and the common surgical/medical approaches to this disease. that it will serve as a solid foundation for those who wish to pursue a personal clinical interest in head and neck surgical oncology. Each article is a self-contained clinical caveat with a complete explanation of how specific subsites within the head and neck region can be 1055-3207/04/$ . The recent movement to combined modality therapy has been driven by the clinical need to improve disease-free survival while minimizing functional and cosmetic morbidity. doi:10. however. MD Guest Editor Squamous cell carcinoma is the most common histologic malignancy of the head and neck region. Jr.12. This issue of the Surgical Oncology Clinics of North America presents what we believe is a rational organ-specific approach to malignancies of this region. All rights reserved.2003. in our opinion. Here much more work can and should be done.009 . Oncologic head and neck surgery is one of the most clinically challenging and complex areas of surgical oncology. requires further translational research efforts melding clinical expertise with bench scientific discovery.soc. Despite this monotonous pathologic presentation.Surg Oncol Clin N Am 13 (2004) xv–xvi Preface Current diagnosis and therapy for head and neck malignancies Wesley L. Hicks. We anticipate.1016/j. Advancement in treatment and survival in head and neck surgery.

hicks@roswellpark.xvi . Hicks / Surg Oncol Clin N Am 13 (2004) xv–xvi evaluated and treated.L. whose diligent and exacting work made this issue possible. NY 14263. FACS Department of Head and Neck Surgery Roswell Park Cancer Institute School of Medicine and Biomedical Sciences State University of New York at Buffalo Elm & Carlton Streets Buffalo. DDS. USA E-mail address: wesley. MD. my belief was affirmed that an understanding of the clinical nuances pertinent to each head and neck subsite must be mastered to obtain effective and improved clinical outcomes. Wesley L. After reviewing the articles in aggregate. I wish to express my sincere gratitude and thanks to the contributing authors. Hicks Jr.

Canada.3] and Jackson and Loeb [4] determined that the normal rate of mutation is insufficient to allow for the observed genetic change in neoplasms to take 1 Current address: Department of Surgery.anderson@roswellpark. Vancouver. Anderson. Roswell Park Cancer Institute. Paul’s Hospital. NY 14263. FRCS(C)a.c. Roswell Park Cancer Institute. MD. Anderson). Daniel L.R. Garth R. results in the natural selection of a genomically heterogeneous cellular mass. USA a Human beings are composed of a highly complex community of cells. British Columbia. or when bathed in an environment of genotoxic compounds. NY 14263.* Department of Surgical Oncology. or instability. PhDa. All rights reserved. The information carried by the genetic code must be accurately replicated and efficiently repaired to ensure the survival of cells. St. or cancer. 1081 Burrard (G.1016/S1055-3207(03)00118-2 . and species. Loeb [2. this genomic destabilization. In humans. Buffalo. the importance of maintaining the integrity of their genetic blueprint can be appreciated by the approximately 130 genes involved in DNA repair alone [1]. that threatens the survival of the organism as a whole. doi:10. Elm and Carlton Streets. E-mail address: garth. and each cell type has its own role that is defined by the genetic instructions it expresses. When these cellular self-repair mechanisms break down. * Corresponding author. Wiseman. NY 14263. The importance of genomic instability in tumorigenesis and tumor evolution may be seen in the work of numerous investigators who have demonstrated that cells must undergo multiple genetic alterations to become neoplastic. cells become genomically unstable. Elm and Carlton Streets. organisms. Buffalo. V6Z 1Y6. Buffalo.see front matter Ó 2004 Elsevier Inc. USA c Department of Cancer Genetics. PhDb.1.Surg Oncol Clin N Am 13 (2004) 1–11 The role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck Sam M. Roswell Park Cancer Institute. USA b Department of Experimental Pathology. 1055-3207/04/$ . Ultimately. their genetic instructions must be accurately transmitted from one generation to the next. For cells to function normally. Stoler. Elm and Carlton Streets.

head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer worldwide [6]. This article provides an overview of the clinical and experimental evidence. Many patients with head and neck cancer are cancer predisposed HNSCC arises from a complex interaction between the host (genetic factors) and the environment. Despite advancements in medicine. supports this concept. In addition. certain individuals demonstrate a predisposition to developing head and neck tumors. and certain nutritional deficiencies [17–19]. Genomic instability is now seen as an essential enabling component that allows tumors to evolve [5]. nondrinking patients with HNSCC treated at Roswell Park Cancer Institute.M. other environmental factors that are currently believed to play a role in HNSCC development include viruses. In addition to tobacco and alcohol exposure. The current authors recently described a cohort of 40 nonsmoking. of genomic instability as a major force driving HNSCC tumorigenesis and evolution. radiation exposure. and white. The American Cancer Society estimates that there will be 28. Furthermore. and implications.100 deaths from cancer at these head and neck sites in 2002 [8]. The occurrence of this malignancy.2 S.and 20-fold [12]. Epidemiologic and experimental evidence suggests that. the concurrent consumption of alcohol with tobacco may have a multiplicative effect on the risk of developing HNSCC [14–16]. Despite a lack of exposure to tobacco and alcohol. 60 y). With a yearly global incidence of 500. Mortality from this disease correlates with tumor size and the presence of local nodal or distant metastatic disease [9–11]. and radiation therapy.900 new cases of oral cavity and pharynx cancers diagnosed and 8900 new cases of larynx cancer diagnosed in 2002 [7]. because of an inherent inability to maintain their genomic integrity in the presence of specific environmental stressors. surgery. These patients tended to be elderly (median age. the long-term survival of individuals diagnosed with HNSCC has not increased significantly over the past 20 years. More than 50 years ago. 10 patients (25% of study population) eventually developed a second primary tumor. It is estimated there will be 11. Slaughter et al [13] recognized the ‘‘field cancerization’’ that occurs in patients with HNSCC as a consequence of prolonged carcinogenic exposure of the upper aerodigestive tract. they had oral cavity primary tumors and were predisposed to second primary tumor development. female. It is this ‘‘field cancerization’’ that is believed to be responsible for the 2% yearly incidence of second primary tumors that develop in this patient population.000 cases. with the 5-year survival rate remaining at 52% in the United States [8]. even in the absence of environmental carcinogen exposure. Tobacco exposure has long been recognized as increasing the risk of developing HNSCC between 2. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 place. The occurrence of second primary tumors in this patient population suggests a possible genetic pre11disposition of these individuals to HNSCC .

these individuals are vulnerable to DNA damage and subsequent cancer development [26. Copper et al [22] found that first-degree relatives of patients with HNSCC had an increased risk of developing upper aerodigestive tract tumors (relative risk [RR]. Information concerning whether nonsmoking patients with HNSCC have a prognosis different from smoking patients with HNSCC is limited. Of the 46 nonsmokers in this study. Foulkes et al [23] performed a similar study in southern Brazil and found first-degree relatives of patients with HNSCC to have a relative risk of 3.6 for developing the disease. epidemiologic studies suggest the families of patients with HNSCC are themselves genetically predisposed to developing HNSCC.53.S. In a study examining 26 individuals with multiple primary upper aerodigestive tract tumors. immunodeficiency.7. RR. Homozygous individuals age prematurely and are cancer predisposed [26]. and consequently. although the magnitude of this predisposition is limited.5). There are several rare ‘‘cancer predisposition’’ syndromes that arise from genes that maintain genomic integrity. 14. .5 times the general population for developing HNSCC. siblings had a relative risk of 8. respectively). 1. 1. oral. Foulkes et al [25] demonstrated that the relative risk of developing HNSCC was significantly higher in relatives of individuals who developed multiple versus single primary tumors (RR. Koch and McQuone [21] described a cohort of 46 nonsmokers (individuals who never used tobacco on a regular basis) who developed HNSCC. Goldstein et al [24] found only a slight increase in the relative risk of first-degree relatives of patients with HNSCC for developing these tumors themselves (RR. The overall length of survival of the patients in this study did not vary significantly with either smoking history or drinking history. 7.27]. Werner’s syndrome is an autosomal recessive disorder that has been linked to the WRN locus on chromosome 8p. including HNSCC. which encodes a DNA helicase that interacts with topoisomerase III and plays an important role in DNA repair.27]. Genomic instability arises in these individuals from impaired DNA repair. 3. pharynx. dwarfism. In this study. Fanconi’s anemia. Bloom syndrome. with an especially high risk amongst siblings (RR. Bloom syndrome is an autosomal recessive disorder that arises from an alteration of the Bloom syndrome gene. and are cancer predisposed [27]. Patients who have Bloom syndrome or Werner’s syndrome have deficient RecQ-like DNA helicases [26. and ataxia telangectasia. Werner’s syndrome.M. Family members of patients with HNSCC also are predisposed to upper aerodigestive tract tumor development.89 versus 3. and matching was performed according to racial group. and compared them to a large cohort of smokers who developed HNSCC. 37 patients (84%) were also nondrinkers. Only the study by Goldstein et al [24] collected smoking details for relatives. Thus.2). In a study performed in the United States. Affected individuals have impaired fertility. however. These syndromes have a constellation of associated malignancies. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 3 development [20].6). In a study performed in The Netherlands. These cancer predisposition syndromes include the genomic instability syndromes.

Mismatches of nucleotides may occur during DNA replication when DNA polymerase inserts the wrong bases into newly synthesized DNA. Normally. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 Fanconi’s anemia is a rare genetic disorder in which affected individuals are predisposed to developing squamous cell carcinoma (SCC) of the gingiva. The integrity of the mismatch repair enzyme systems is measured by microsatellite instability. The highest rates of chromosomal breakage are observed in individuals with a family history of HNSCC and in those with multiple primary tumors [33.34]. In addition. Genomic instability and head and neck cancer Genomic instability may be broadly considered either chromosomal or intrachromosomal.M. This disorder is also characterized by developmental abnormalities and a propensity to develop hematologic disorders and bone marrow failure.34]. Intrachromosomal genomic instability. and individuals with germ-line mutations in the genes that encode these mismatch repair enzymes have impaired DNA replication fidelity. It is currently believed that the protein defects that arise in affected individuals may result in loss of regulation of DNA repair [28]. Hereditary nonpolyposis colorectal cancer is associated with a high frequency of microsatellite instability. tongue. The DNA repair capacity after exposure to the carcinogen benzo(a)pyrene diol epoxide also is impaired in patients with HNSCC [35]. Hsu et al [32] developed the bleomycin mutagen sensitivity test as a method of assessing cellular DNA repair capacity. The ATM gene functions in surveying for DNA damage and is responsible for activating DNA repair and apoptosis genes. This test is performed by exposing lymphocytes in culture to the drug bleomycin and quantifying the number of chromosome breaks per lymphocyte in culture. tandemly repeated DNA sequences (microsatellites) distributed throughout the human genome [30]. Individuals diagnosed with hereditary nonpolyposis colorectal cancer have been reported to be at increased risk of developing HNSCC [31]. Ataxia telangiectasia is a rare genetic disorder that arises from a defect in the ataxia telangiectasia gene (ATM gene). and have facial or conjunctival telangiectasias. and are predisposed to cancer development. Individuals homozygous for the defective gene develop progressive neuromuscular degeneration. Heterozygous individuals also have a cancer predisposition [29]. an unsteady gait. or a measure of the integrity of short. these DNA mismatches are repaired by mismatch repair enzymes. Further evidence suggesting patients with HNSCC are cancer predisposed may be appreciated on experimental studies applying mutagen sensitivity testing to the HNSCC patient population.4 S. investigators have found that certain polymorphisms of the DNA repair gene XRCC1 are associated with an increased risk for HNSCC development [36]. and mandible. the form most . This test has been successfully able to identify individuals at high risk for developing head and neck tumors [33.

and chromosomal translocations can be visualized by cytogenetic analytic techniques. Although clustering aberrations have been described. CGH analyses performed on HNSCCs have demonstrated multiple chromosomal aberrations found in these tumors [38–40]. Using CGH methodology.M. levels were twice as high in the cancers as in the dysplastic tissue (30% versus 15%. has demonstrated how measurements of genomic instability in patients with HNSCC may be of clinical value. dysplastic tissue. however. Cancer predisposition genes Cancer predisposition genes may play an important role in the increased genetic susceptibility observed in patients who have HNSCC. deletions. Thus. Piccinin et al [41] demonstrated low rates of microsatellite instability in patients who had HNSCC with a single primary or multiple primary tumors. neck nodal status.18. changes in ploidy status. Although not all chromosomes are affected in each tumor. Although microsatellite instability was absent in the blood. or the fractional allelic loss rate (FAL). Independent measures of intrachromosomal instability can be assessed by cytogenetic techniques and CGH on ordered Bac clone arrays. and overall patient prognosis.37]. inversions. Important .37]. By studying 80 HNSCCs. or alcohol consumption) in patients. Both groups had similarly low rates of microsatellite instability. and SCCs.18. and oligobase or point mutations. The study of the fraction of chromosomal arms on which allele loss is observed. were unable to demonstrate any correlation between microsatellite instability and clinicopathologic features (tumor site. Hashimoto et al [40] were able to demonstrate a correlation between specific chromosomal aberrations and pathologic tumor stage in 32 patients with HNSCC. nodal metastasis. Field et al [44] were able to demonstrate a positive correlation between FAL and tumor grade. This finding led these authors to conclude that microsatellite instability played an important role in HNSCC progression. all autosomal chromosome arms have been described as being affected in head and neck tumors [17. consists of amplifications. consistent cyogenetic abnormalities common to all HNSCCs have not been demonstrated [17. These alterations can be readily assessed by comparative genomic hybridization (CGH) and microsatellite instability measurements.S. Chromosomal instability. they have been of limited clinical applicability. respectively). The literature has been conflicting regarding the role of microsatellite instability in head and neck tumor progression. tumor grade. Using makers for 11 chromosomal loci. whereas measurements of microsatellite instability in HNSCC suggest genomic instability is driving tumor progression. history of prior treatment. El-Naggar et al [42] examined microsatellite instability in peripheral blood. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 5 frequently observed in sporadic disease. Field et al [43]. disease stage.

The affected individual develops a sarcoma before age 45. and in 28 of 48 (58%) HNSCCs. Recently. The TP53 gene is frequently mutated in several human cancers. and has another first. including lung cancer. In sporadic head and neck tumors. also suggesting both substances may be linked to aberrant P53 expression in HNSCC. In a group of 232 patients with HNSCC. Somatic homozygous deletions and mutations of the 9p21 region are commonly observed in patients with sporadic HNSCC [45]. is believed to have a dual role in protecting the cell from cancer development. in 7 of 24 (29%) hyperplastic lesions. it helps prevent DNA damage from being passed on to the next cell generation by causing damaged cells to undergo apoptosis before division. colon cancer. Koch et al [56] described a much higher incidence of TP53 mutations in smokers (44%) than in nonsmokers (18%). Yu et al [46] performed molecular analyses of a family with a high incidence of HNSCC and melanoma. This inhibition of D1-cdk 4/6 complex activity does not allow for retinoblastoma phosphorylation. allowing damaged DNA to be repaired. and identified a germ-line p16 tumor-suppressor gene mutation. along with this group’s earlier description of a separate. The p16 tumor-suppressor gene is located on chromosome 9p21 and encodes a 16kDa protein that binds to the cyclin-dependent kinases (cdk) 4 and 6 and prevents them from complexing with cyclin D1. which is located on chromosome 17. alternatively. has a first-degree relative with cancer before age 45. Patients who have Li-Fraumeni syndrome are at increased risk of developing laryngeal cancer [47]. Therefore.M. the P53 protein. The TP53 gene is a well-known tumor-suppressor gene and represents one of the most common sites for genetic abnormalities to be found in human tumors [48]. Field et al [57] correlated tumor TP53 status and the patient’s history of smoking and alcohol consumption. The TP53 gene product. . The incidence of TP53 mutation in premalignant head and neck lesions has been reported to be much lower (19%) than in invasive lesions (43%) [54]. in 12 of 26 (46%) dysplastic lesions. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 cancer predisposition genes that have been found to be mutated in patients with HNSCC include p16 and TP53 tumor-suppressor genes. Li-Fraumeni syndrome arises as a consequence of germ-line mutations in the TP53 gene. cells that lack or only produce abnormal P53 protein are more susceptible to malignant transformation [48]. suggest a familial HNSCC syndrome may exist [46]. Shin et al [55] reported P53 immunohistologic expression by the adjacent normal epithelium in 6 of 31 (19%) normal epithelium specimens adjacent to squamous cell carcinomas. Multiple investigators have demonstrated that 40% or more of sporadic HNSCC contain TP53 mutations [52–54].or second-degree relative with a history of sarcoma at any age or a cancer diagnosed before age 45. and thus blocks the cell cycle G1/S transition. The P53 protein causes cell cycle arrest. These results. and breast cancer [49– 51].6 S. TP53 mutation is currently believed to represent a relatively late step in head and neck tumor evolution. unrelated family harboring a p16 germ-line mutation and exhibiting a HNSCC predisposition.

These observed differences in genes and gene expression. The genetic heterogeneity of head and neck tumors is not surprising when the genomic instability exhibited by these tumors is considered. . at different head and neck disease sites. for quantitative DNA content. however. Furthermore. provide early evidence suggesting that HNSCC may actually represent a genetically heterogeneous group of diseases. and 37 hypopharyngeal cancers for the following: amplification of oncogenes at the 11q13 region (CCND1. bcl-2. oncogenes MYC and ERBB1. desmoplakin 1.S. loss of heterozygosity at P53 and NAT2. and nonmetastatic protein 23 [nm23]) in 33 laryngeal cancers. E-cadherin. investigators have provided evidence that suggests.006 and P = 0. myc. Jacob et al [60] evaluated five tumor regions in 12 patients who underwent surgery for oropharyngeal carcinoma. despite often being separated by only a very small anatomic distance. epidermal growth factor receptor (EGFR). FGF4. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 7 Genetic heterogeneity of head and neck tumors Despite considerable histologic homogeneity. Takes et al [58] studied expression of several proteins (P53. 31 pharyngeal cancers. as separate and distinct disease entities [59]. these results suggest that HNSCCs are genetically heterogeneous tumors. respectively).0002. EMS1). and cellular DNA content. Recently. retinoblastoma (Rb). As has been suggested. HNSCCs are actually a heterogeneous group of disease entities. Specimens were each evaluated by immunohistochemical assessment for proliferation markers (Ki67 and proliferating cell nuclear antigen). but they may also exhibit considerable intratumoral heterogeneity.03). These authors found that cyclin D1 had a very high level of expression in the pharynx cancer (P = 0. Aneuploid tumors were found in a significantly lower proportion of larynx tumors than in other sites (P = 0. Tumors from different head and neck sites display a wide range of biologic behaviors. cyclin D1.M. Not only are these tumors genetically heterogeneous from one tissue site to the next.0001). there may be different pathways of tumorigenesis and tumor progression that are responsible for the observed clinical differences in biologic behavior of disease originating from different sites. Consistent with the genomic instability exhibited by head and neck malignancies. and they are not treated in a uniform manner. epithelial cellular adhesion molecule (Ep-CAM).0004) and EGFR had a very low level of expression in the larynx cancer (P\0. 29 oropharyngeal cancers. This group found that FGF3 and FGF4 had a significantly higher degree of amplification in the hypopharyngeal tumors (P = 0. Rodrigo et al [59] examined 38 laryngeal cancers. Their results demonstrated a considerable variation of proliferation and differentiation both intratumorally (within the same tumor) and extratumorally (between different tumors). for integration of the human papilloma virus types 6b and 16. FGF3. neuroglioblastoma derived oncogene (neu). perhaps head and neck tumors should be studied in a manner similar to how they are viewed and treated clinically. and morphologic tumor-front grading. and 36 oral cancers. at the genetic level. HNSCCs do not all exhibit uniform biologic behavior.

genomic instability may be viewed as a fundamental force driving head and neck tumorigenesis and evolution. and sputum have already been described [61.148(4):1483–90. Head and neck cancers are highly heterogeneous tumors and exhibit a wide variety of forms of genomic instability. . Laser-capture microdissection represents a powerful tool for isolating very specific cell populations from tumors [64]. It is only through study of this fundamental force that drives the development of these tumors that clinicians may gain the insight required to develop new diagnostic and therapeutic modalities to benefit the HNSCC patient population as a whole. Sequencing of 96 clones from each of the six libraries constructed suggested the existence of 132 novel genes. [3] Loeb LA. or genes. Mutator phenotype may be required for multistage carcinogenesis. Methodologies for detection of genetic mutations in saliva. Lindahl T. The recognition that HNSCC is a genetically heterogeneous disease represents a major step toward developing an understanding of its underlying genetic basis. Other possible applications include use of genomic instability measurements. Brennan et al [63] have described a molecular technique for analyzing histopathologically negative margins and lymph nodes for the presence of p53 gene mutation. Mitchell M. [5] Anderson GR.M. References [1] Wood RD. blood. Thus. as tools to screen for primary or recurrent disease.23(11):1037–46. Stoler DL. Leethanakul et al [65] performed laser-capture microdissection on oral cavity SCC to construct stage-specific cDNA libraries. Loeb LA. Science 2001. 291(5507):1284–9.62].8 S.51(12):3075–9. Cancer Res 2001. To develop an insight into this genetically heterogeneous disease. Wiseman et al / Surg Oncol Clin N Am 13 (2004) 1–11 Summary Measurements of genomic instability. which may play a role in the pathogenesis of HNSCC. Brenner BM. Bioessays 2001. The current literature suggests that many individuals diagnosed with HNSCC are genetically predisposed to developing malignancy because of some inherent deficiency of their capacity to maintain their genome in the presence of environmental stressors. investigators must not only focus their efforts on specific head and neck disease sites. Future study of the specific genetic mechanisms that underlie genomic instability in the HNSCC patient population is needed. Cancer: the evolved consequence of a destabilized genome. Sgouros J. may potentially be used as molecular markers to predict disease course and response to therapy. This study showed that a positive molecular margin significantly predicted disease recurrence.61(8):3230–9. [4] Jackson AL. The mutation rate and cancer. A mutator phenotype in cancer. Human DNA repair genes. Genetics 1998. Cancer Res 1991. or identification of genes responsible for instability. [2] Loeb LA.

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Surg Oncol Clin N Am 13 (2004) 13–35

Imaging in head and neck oncology
Ronald A. Alberico, MDa,b,* Syed Hamed S. Husain, DOb, Igor Sirotkin, MDb
Department of Radiology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA b State University of Buffalo School of Medicine and Biomedical Sciences, Buffalo VA Medical Center 3495 Bailey Avenue, Buffalo, NY 14215, USA

Since the initial description of the pathologic distribution and patterns of spread of tumors in the head and neck, the pretreatment assessment of the size, extent, and pattern of spread has been necessary for optimal treatment planning. It has subsequently become apparent that decisions, including the operative approach, possibility of organ preservation or functional preservation of tissue, and the appropriateness of an operative role in patient care, hinge on these important pieces of information. Clinical examination alone, however, is limited in its ability to properly assess the extent and size of head and neck tumors, especially for submucosal extension of disease and extent of nodal metastasis. Modern radiologic imaging has provided the means to maximize information available to clinicians during the treatment-planning process. The combination of CT, MRI, ultrasound, and positron emission tomography (PET) has enabled clinicians to obtain a great deal of information about the patient before planning the surgical approach. Both CT and MRI have been shown to be superior to clinical examination in evaluating the size and extent of head and neck tumors and in detailing the extent of nodal metastases [1–4]. Imaging also has added to the cost and, in some cases, the controversy of the preoperative assessment and posttreatment follow-up period. The choice of which imaging modality is preferred remains controversial and remains part of an ongoing discussion [5]. This article describes a strategy for imaging head and neck neoplasia in an effort to simplify the process and emphasizes the strengths and weaknesses of the available imaging modalities. In addition, the article emphasizes techniques for imaging and reporting on patients who have head
* Corresponding author. E-mail address: (R.A. Alberico). 1055-3207/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/S1055-3207(03)00124-8


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and neck cancer in a manner that maximizes the clinician’s ability to make appropriate treatment plans and avoid unnecessary complications. The primary goal in imaging of head and neck oncology is to answer the pertinent clinical questions. Too often, the radiologist can get caught up in the collateral findings and provide information that is confusing or superfluous while omitting key points needed for the treatment plan. Although the clinician may feel comfortable filling in the blanks, the scan may not be optimally designed to answer the clinical question, particularly in postoperative patients. Frequently, the radiology requests provide insufficient clinical information to adequately plan the scan, possibly resulting in exclusion of anatomy crucial to the diagnosis. The solution to these problems is knowledge and communication. The radiologist must be familiar with the surgical procedures available and the anatomic criteria that exclude various procedures from consideration. In addition, the radiologist must be made aware of the clinical findings and concerns to select the appropriate imaging modality and optimize the imaging technique. The radiologist’s goal should be not only to answer the questions of size and extent of tumor but to point out potential surgical complications resulting from vascular relationships to the tumor, and individual anatomic variants that may complicate the procedure. The formation of a differential diagnosis based on lesion location and imaging characteristics plays an important, but secondary, role in this process. Even with the best modern imaging available, the radiologist is still relegated to the role of gross pathologist, with some limited physiologic data, and, as always, the final answer is in the histology. Imaging techniques The radiology and head/neck surgery literature over the last decade has supported either CT or MRI as the primary technique for evaluating patients who have head and neck cancer. This situation has divided the radiology community into two groups, each of which feels passionately about their respective choices. CT has been shown to be superior to MRI in evaluating necrosis in nodal metastases [6], whereas MRI is better for detecting perineural extent of disease and disease at the skull base [5,7,8]. Other authors have shown improved lymph node detection with MRI [3]. Both modalities have advantages and disadvantages in the evaluation of head and neck cancer. CT has the advantage of increased speed and availability and better patient tolerance. The bony framework is better evaluated with CT and small calcifications are more apparent. CT has the disadvantage of requiring ionizing radiation and iodinated contrast agents. MRI is more sensitive for subtle spread of disease along nerves and into the skull base. In addition, MRI has higher soft tissue contrast resolution and direct multiplanar imaging capability. Disadvantages of MRI include lower patient tolerance and dangers associated with metallic implants, pacemakers

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and other hardware, and increased expense. MRI is also subject to many artifacts that can make interpretation more difficult. Patient motion is always a concern in MRI, particularly in patients who have difficulty suspending swallowing and lying flat. PET scanning and ultrasound take a definite back seat to CT and MRI in evaluating the head and neck. Ultrasound is useful for image-guided biopsy and can provide the fastest, easiest means to guide the needle to the appropriate target. Doppler sonography has shown some ability to improve the specificity and sensitivity of nodal staging in clinically N0 neck disease, as has PET imaging, but the clinical criteria for exploring N0 neck disease frequently obviates the need to use PET or ultrasound for this purpose [9]. The current authors have found that, for most patients, CT, when properly performed, provides a readily available and easily tolerated assessment of head and neck neoplasia. It is easier to interpret for nodal staging and successfully completed more often than MRI. Multidetector CT obtained with thin images (2.5 mm) and contrast is able to detect perineural disease and is readily reformatted into multiple imaging planes. The current authors typically assess patients initially with CT and will obtain MRI only if perineural spread of disease is suspected or ambiguous on CT, or to better evaluate cartilage or marrow invasion. MRI is also useful in patients who have tumors that are typically lower in attenuation on CT, such as liposarcomas, and may provide additional information in patients with this type of tumor. The current authors also use MRI for thyroid tumors that may potentially be treated with radio-iodine therapy to avoid the iodine load inherent in CT contrast media. Gadolinium contrast agents, which are usually used in MRI, can be used as an alternative for specific patients in CT who are allergic to iodinated contrast and who have contraindications to MRI evaluation. When necessary, the current authors use gadolinium as an alternative contrast agent in CT. All scans are not equal, and to answer the pertinent clinical questions, properly performed scans are needed. The current authors begin all CT imaging for head and neck cancer above the orbit to include the skull base foramina and pterygopalatine foramen. The authors previously used single detector helical scanners with 5-mm thick sections at 5 mm intervals with 3 mm sections through the larynx. Currently, with multidetector scanners, it is possible to scan with 2.5 mm section thickness and 2.5 mm section interval through the entire neck without significant time constraints. Multiplanar and three-dimensional models can be readily obtained from these data, including CT angiography as needed to assess vessel–tumor relationships. Artifacts on CT at the oral cavity can limit the evaluation of the intrinsic tongue and hard palate; sections angled through the oral pharynx using a coronal oblique orientation can result in improved visualization of these areas with a minimum of effort (Fig. 1). It is important to find an imaging center that uses techniques such as these, with an effort to guide the treatment plan of the individual patient in the proper direction.


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Fig. 1. (A) Scout image from a CT scan of the neck and skull base for SCC shows dental hardware and the usual scan section orientation. (B) The axial section from the angle scanned in A at the level of the oral pharynx has extensive artifact from dental hardware, which obscures the pharyngeal and parapharyngeal structures (arrow). (C) Scout image with coronal oblique sections planned to avoid dental artifact through the oral pharynx. (D) The oral pharyngeal walls and tonsils are now visible with associated left-sided mass (arrow).

Imaging the primary tumor The most important role of imaging in head and neck cancer is to evaluate the primary tumor and its extent. Although T1 lesions are much more conspicuous on clinical examination than in images (Fig. 2), submucosal disease and the extent of tumor across tissue planes and along

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nerves is best seen with imaging [10,11]. The findings may affect the choice of radiation field needed to cover a lesion and can affect the surgical options offered to the patient. The extent of tumors can frequently be observed through the submucosal spaces on the images, resulting in higher tumor staging than is suspected on clinical grounds, whereas in other cases the clinical staging is confirmed. The images are key in defining the final extent of the tumor (Figs. 3 and 4). Invasion of tumor into adjacent structures, such as the mandible, or along perineural pathways may be clinically inconspicuous. The sensitivity and specificity of imaging in detecting these patterns of disease is well described in the literature; MRI is the preferred method for detecting perineural disease and mandibular invasion [10–19]. Most reports to date have not accounted for recent advances in CT technology, including multidetector scanning. The current authors have found that perineural spread, although more obvious on a high-quality, motion-free MRI, is detectable on CT, in most cases, by loss of the normal fat signal at the foramen [10,18–19]. Perineural spread of tumor is usually the result of squamous cell carcinoma (SCC), although this finding is likely caused by the prevalence of this tumor in the population. Perineural spread is also commonly seen in adenoid cystic carcinoma, followed by mucoepidermoid carcinoma [10,18]. Because perineural spread is present in a higher percentage of cases in these relatively rare tumors, MRI may provide a more sensitive assessment of the extent of disease for salivary

Fig. 2. Axial section from a contrast-enhanced CT scan with a subtle high-attenuation lesion (arrow) that represents a T1 SCC. This finding was much more apparent on clinical examination.


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Fig. 3. (A) This axial contrast-enhanced CT section reveals a typical-appearing highattenuation mass of the right floor of mouth and tongue (arrows). (B) The coronal reformatted image from the scan in A demonstrates the superior inferior extent of the mass (arrows) and confirms the lack of extension across the midline.

malignancy. MRI offers advantages in detecting marrow invasion in the mandible and the cartilage of the larynx (Figs. 5–9). SCC, which originates in the mucosa, comprises most head and neck cancer. Imaging can play a roll in the preoperative diagnosis of different histologic subtypes by placing tumors in different spaces in the neck. The suprahyoid neck is typically divided into muscosal, parapharyngeal, parotid, and masticator spaces, with the parapharyngeal space further divided into pre- and poststyloid components. The mucosal space is composed of the mucosal surfaces of the nasal and oral pharynx. Lesions in this space are most likely SCC with minor salivary tumors, including benign, mixed tumors; mucoepidermoid carcinoma; and possibly adenoid cystic carcinoma. The mucosal spaces of the oral pharynx, specifically the soft palate, may provide perineural pathways of tumor spread along the greater palatine or lesser palatine nerves (Fig. 10). The parotid space includes superficial and deep lobes of the parotid and involves the space between the styloid process and posterior mandibular ramus (stylomandibular tunnel). Tumors of the parotid include the primary salivary tumors listed previously and metastatic disease and lymphoma involving intraparotid nodes. The parotid space provides a pathway of perineural spread along cranial nerve VII to the stylomastoid foramen (see Fig. 9). The poststyloid parapharyngeal space (carotid space) is defined by the styloid process and fascia anteriorly, paraspinal musculature posteriorly and medially, and the sternocleidomastoid (SCM) muscle laterally. Tumors of this space include schwannomas, glomus tumors, metastatic adenopathy or lymphoma, and lipomas or liposarcomas. Perineural spread along the vagus nerve or direct spread along the carotid artery or jugular vein can lead into the skull base. A mass within this space can also result in vocal cord paralysis by means of its effect

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Fig. 4. (A) Axial contrast-enhanced CT of the neck reveals a high-attenuation mass in the right pharyngeal tonsil (arrow). (B) A section lower in patient shown in A demonstrates involvement of the tongue as the tumor spreads anteriorly along the palatoglossus muscle (arrows). (C) A section higher than that shown in A reveals some early spread to the soft palate as well (between arrows).

on the vagus nerve. The prestyloid parapharyngeal space borders the masticator space anteriorly, the mucosal space medially, and the styloid process posteriorly. It contains fat and lymphatics and is rarely directly involved as a primary tumor site. Displacement of this fat by large masses can give insight as to which space a large mass is originating from, thus affecting the differential diagnosis. This space communicates with the pterygopalatine fossa (see Fig. 8) and has access to all perineural routes associated with the fossa, including spread along the vidian and rotundum canals and into the inferior orbital fissure. The masticator space is defined by the muscles of mastication and is affected primarily by sarcomas and nerve sheath tumors, including rhabdomyosarcoma, liposarcoma, and schwannomas. Metastatic disease and lymphoma can affect this space as


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Fig. 5. (A) Sagittal T2-weighted MRI image reveals a large intracranial component to this esthesioneuroblastoma (arrows). Note the cystic and solid components of the mass, which is a characteristic of these tumors. (B) The coronal T1 fat-saturated gadolinium-enhanced image reveals the heterogeneous enhancement of this lesion and its sharp demarcation from the brain, which is not yet invaded (arrows).

well. Perineural spread from the masticator space usually involves cranial nerve V and specifically its third division (see Figs. 6 and 7). Imaging of the infrahyoid neck is less complex overall but requires knowledge of laryngeal anatomy and operative approaches. Most infrahyoid head and neck tumors are SCC or metastatic disease to the lymph nodes. Three-dimensional and multiplanar modeling of the CT data can provide the surgeon with a better appreciation of the anatomy preoperatively, providing a more surgically oriented perspective of the pathology and, in some cases, allowing for production of synthetic prostheses to be prepared preoperatively to fit the patient’s anticipated surgical defect [20–22]. The normal distribution of adipose tissue in the larynx allows clinicians to differentiate the false from the true vocal cords on CT and to see the paraglottic space (see Fig. 10; Fig. 11). The various surgical approaches to laryngeal cancer include supraglottic and supracricoid laryngectomy and vertical hemilaryngectomy and total laryngectomy. Diagrams of these procedures can be modeled from modern CT images (see Fig. 11; Figs. 12 and 13). For patients with laryngeal tumors, the images can define extension of a primary neoplasm in the paraglottic space across the laryngeal ventricle or across the midline that would render supraglottic or vertical hemilaryngectomy unlikely to provide tumor-free margins. This finding would affect the potential for operative cure in these patients. With this information, the head and neck surgeon can have a more informed discussion with the patient regarding potential operative options and prognosis. CT provides the best, most rapid, and consistently motion-free images in this population. MRI is more sensitive for invasion of the thyroid

and patterns of tumor spread to the pyriform sinus and retropharyngeal tissues typically can be defined by high attenuation on contrast-enhanced CT and enhancement on MRI. D) The invasion of the mandibular marrow space is clearly seen in these coronal and axial contrast-enhanced T1-weighted MR images from the same patient (arrows). (B) Contrast-enhanced axial CT section in the same patient shows the lack of fat signal typical of perineural spread in the same mandibular foramen imaged 3 weeks earlier (curved arrow). and the perivertebral muscles. These must include all primary and metastatic bone . Note the normal fat signal in the foramen of the contralateral side (straight arrow). Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 21 Fig. The hypopharynx is readily seen on MRI and CT.A. cartilage and may be useful in certain patients for evaluation of direct cartilage invasion.R. Less common tumors in the infrahyoid neck also include tumors of the perivertebral space. which includes the cervical spine and cord. There is currently no well-defined role for PET or ultrasound in evaluating the primary tumor site in the infrahyoid neck. (A) Axial contrast-enhanced fat-saturated T1 image of the suprahyoid neck reveals a nodule of enhancing tissue (arrow) in the mandibular foramen of this patient who has a retromolar trigone SCC. 6. Direct invasion of the cervical spine or perivertebral space is best evaluated with MRI because it is more sensitive for bony invasion than CT. (C.

and other central nervous system tumors. however. Tumors of the thyroid gland include adenomas and thyroid malignancies of all subtypes.23].4. The poststyloid parapharyngeal space continues into the infrahyoid neck as the carotid space and is a site for metastatic disease and lymphoma. tumors.A. so care must be taken to avoid unnecessary iodine loads before diagnosis. Compare this to the normal contralateral side (short arrow). the iodine load from contrast material can decrease uptake for potential nuclear medicine scanning and result in delayed therapy. uses a threshold size to determine if a node is abnormal. Morphology of the node is also considered in determining the likelihood of metastasis. A detailed discussion of thyroid neoplasm is beyond the scope of this article. (A) An axial contrast-enhanced T1-weighted image from an MRI of the neck reveals an enhancing mass at the top of the right masticator space just below foramen ovale (between arrows). (B) A coronal contrast-enhanced T1-weighted image reveals the perineural spread of the tumor into foramen ovale along cranial nerve V3 to involve Meckel’s cave (long arrow). Glomus tumors and schwannomas also can be found in this space. imaging of the thyroid is best obtained with a combination of nuclear medicine thyroid scanning. however. and MRI. ultrasound. leading to an unacceptably low negative predictive value [3. however. 7. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig. Improved negative predictive value is important in defining a population that would benefit from surgery without the need for neck dissection and radiation. including CT and MRI. limitations in the clinical examination result in relatively low sensitivity and specificity (60%–70%). schwannomas. Imaging.5 cm. this size varies between 1 and 1. Nodal staging Staging of nodal disease in the neck traditionally has been based on clinical examination. including the transverse-to-longitudinal ratio and the . Depending on the reference. CT is excellent as well.22 R. and neurofibromas.

R. 8. An axial section from a contrast-enhanced CT of the neck in a patient with mucoepidermoid carcinoma of the left parotid gland reveals loss of the normal fat attenuation in the left stylomastoid foramen (thick arrow). This finding was confirmed to be perineural spread from the patient’s left tonsillar fossa SCC. Note the normal low attenuation of the contralateral side (thin arrow). 9. . Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 23 Fig.A. Fig. An axial section from a contrast-enhanced CT of the neck reveals loss of the normal fat attenuation within the left pterygopalatine fossa (arrow).

The false cords are above the ventricle with the muscular true cords below. (B) Axial CT section at the level of the paraglottic space shows the fat within the space to better advantage (arrows). (D) Offmidline sagittal reformat from the same patient clearly shows the air within the laryngeal ventricle (long arrow). with sensitivity varying from 40% to 80% and specificity from 90% to 95%. (A) Axial CT section of the larynx a t the level of the false cords (arrows). attenuation of the node [24. which decreased positive predictive value to 44%. In a large-scale study by Curtin et al [3]. MRI did not achieve a 90% negative predictive criterion in that study. Although CT could achieve this 90% negative predictive value. regardless of size threshold used. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig.25]. Note the low attenuation of the paraglottic fat. Attempts at increasing sensitivity with PET scanning or Doppler sonography to detect malignancy in normal-size . attempts were made to obtain a negative predictive value of 90% with CT and MRI using size criteria alone or size criteria in combination with internal morphology. it required a size threshold of 5 mm.24 R. (C) Coronal reformation from the same scan shows the fatty attenuation in the paraglottic space (long arrow) and false cords (short arrow) compared with the muscle attenuation of the true vocal cords (curved arrow). Even with a combined approach. 10.A. the literature varies widely on the specificity and sensitivity of nodal staging with MRI and CT.

however. Given the increased sensitivity of image-based nodal staging compared with clinical staging. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 25 Fig. Because the cricoid cartilage is preserved by the surgery. the surgeon. exclusion of patients from treatment of the neck with radiation or neck dissection based on imaging is not appropriate. The thyroid cartilage is blue. the cricoid cartilage is light blue. The line delineates the surgical resection for a vertical hemilaryngectomy. including those of the American Academy of .26]. limiting their ability to treat patients. regardless of imaging technique. Combined MRI and CT have approached 90% sensitivity for metastatic node detection in one study [1]. Until negative and positive predictive values of nodal disease are improved. 10. Various classification systems for nodal disease in the neck therefore have been used in the past. and the hyoid bone is white. The description of nodal locations in the neck requires precise language to facilitate communication between the head and neck radiologist. (B) A color three-dimensional diagram of the larynx. It would seem that. and the pathologist. nodes have had some success. the epiglottis is red.A. but the sensitivity is only marginally improved over that of MRI or CT [25. Without such a system. negative predictive value has not achieved a level that would be clinically useful in excluding clinically N0 neck disease without unacceptably low positive predictive values. extension of tumor into the cricoid or arytenoid would contraindicate this type of voice-sparing procedure. this is sufficient to warrant nodal evaluation with imaging. The location of nonpalpable adenopathy in the neck in patients who have disease of any nodal stage can affect the size and extent of radiation fields and the side and extent of neck dissection. there are other uses for nodal assessment with imaging that can affect patient care and prognosis.R. again showing the surgical plan for a supracricoid laryngectomy. (A) An axial contrast-enhanced CT scan at the level of the true vocal cords (arrow). 11. Note the high attenuation (muscle) of the true vocal cords compared with the false cords seen in Fig. patterns of nodal disease and their relationships to tumor prognosis and location would lack precision and result in inaccuracies in clinicians’ knowledge of disease prognosis and patterns of spread.

26 R. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig. They defined level I as submental (IA) and submandibular (IB). with both levels anterior to the posterior margin of the submandibular gland. 12. the hyoid bone is white. and the epiglottis is red. . a modern classification system should refer to anatomic landmarks that are reliably identified in the axial plane and at the time of surgery. The thyroid cartilage is blue. and did not account for retropharyngeal nodes described in the original anatomic system proposed by Rouviere [27]. Because modern nodal assessment almost always includes imaging. Otolaryngology–Head and Neck Surgery and the American Joint Committee on Cancer. (C) Color volume– rendered model of the larynx again reveals the surgical margin. however. (A) Sagittal CT reformatted image of the neck reveals the resection plan for a supraglottic laryngectomy. The previous nodal classification systems also have been based on anatomic landmarks that are not necessarily conspicuous in the axial plane. the cricoid cartilage light blue. Som et al [27] undertook this considerable task. (B) Coronal section reformatted from the same scan shows the surgical plan through the laryngeal ventricle between the true and false vocal cords. In 1999.A. above the hyoid bone. Note the line goes through the laryngeal ventricle and spares the vocal cords. These classification systems did not always precisely define nodal locations.

pathologists. The supraclavicular nodes are at the level of the clavicles lateral to the common carotid arteries. Note the cricoid cartilage is spared and only one arytenoid cartilage is resected. This system provides the precise framework needed to facilitate communication among and between surgeons. with level VII nodes located between the carotid arteries below the top edge of the manubrium to the level of the brachiocephalic vein.R. and lateral to the common carotid arteries. posterior to the back of the submandibular gland. with and without preservation of the epiglottis. Retropharyngeal nodes are defined as medial to the internal carotid arteries. The level of the clavicles is defined as the first axial section in which the clavicles are visible. Although all nodal levels may not be commonly used by surgeons in all . with level IB lateral to the digastric muscle anterior belly. and below the mylohyoid muscle. Level IA is between the anterior bellies of the digastric muscles. and radiologists. 14).A. with level IIB nodes posterior to the vein and separable from it by a fat plane. Level IIA consists of nodes in the level II region that are inseparable from the jugular vein by a fat plane. (A) An axial CT reformatted image at the level of the true vocal cords demonstrates the surgical plan for a supracricoid laryngectomy. Level VI nodes are between the common carotid arteries from the bottom of the hyoid bone to the top edge of the manubrium. 15). Level V nodes are posterior to the back of the SCM muscle from the skull base to the bottom of the cricoid arch (level VA) and continue posteriorly to the line connecting the back of the SCM muscle and the posterolateral margin of the anterior scalene muscle to the level of the clavicle (level VB). within 2 cm of the skull base. (B) A sagittal section of the same scan shows the two possible plans for the supracricoid laryngectomy. Level III nodes are anterior to the back of the SCM muscle and between the bottom of the hyoid bone and the bottom of the cricoid arch (Fig. Level IV nodes are located below the bottom of the cricoid arch but above the clavicles. and anterior to the back of the SCM muscle (Fig. Level II extends from the skull base to the bottom of the hyoid bone. They are anterior to the line joining the back of the SCM muscle with the posterolateral margin of the anterior scalene muscle. 13. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 27 Fig.

allowing . and assessment of anatomic variants that may impact the surgical approach.29]. an effort to adhere to this classification system should improve the quality of surgical–pathologic correlation and result in research in head and neck cancer. and other deep or difficult-to-palpate regions of the neck [28. posterior to the back of the submandibular gland. Note that the nodes are enlarged. inseparable from the jugular vein. 14. With proper techniques. and anterior to the back of the SCM muscle. The current authors’ preferred CT technique is to access the face through the buccal space using a short guide needle to the posterior edge of the pterygoid muscle. The application of this technology to head and neck cancer can result in safe and efficacious tissue sampling of retropharyngeal. CT-guided percutaneous biopsy has been widely studied in the literature for virtually all potential targets. Other applications of head and neck imaging in malignant disease Other applications of head and neck imaging include CT or ultrasoundguided biopsy of suspected recurrent or primary disease. nodal biopsy with ultrasound or CT guidance can be performed with minimal risk to the patient [23]. evaluation of the neck post treatment. including the brain. which has historically been difficult to study because of low numbers of patients and inconsistencies in language used in the literature and pathology and radiology reports.A.28 R. parapharyngeal. An axial contrast-enhanced CT section reveals metastatic adenopathy at level IIA on the right and the left (arrows). Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig. locations. abnormal in shape (rounded). and abnormally low in attenuation. Nodes are above the bottom of the hyoid bone.

for multiple passes with a 22-guage needle into the substance of the mass. The use of imaging in postoperative patients is perhaps the most difficult part of head and neck imaging interpretation for the radiologist. lateral to the carotid artery.31]. the guide needle can be angled slightly at the skin surface to obtain samples at different locations within the tumor mass. An axial contrast-enhanced CT section reveals an enlarged. rounded hypoattenuating node at level III on the right (arrow). 16). which increases over time to as high as 58%. and anterior to the back of the SCM muscle. MRI in the postoperative setting frequently proves difficult for patients. 15. The node is between the bottom of the hyoid bone and the bottom of the cricoid cartilage. without additional percutaneous passes and with good maintenance of an entry point close to the tumor margin (Fig.R. This again emphasizes the need for communication between surgeons and radiologists to obtain accurate evaluation of the patient and the optimal imaging technique [32]. MRI has been shown to have a high false-positive rate after radiation. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 29 Fig. Knowledge of the surgical procedure performed and the type or location of any operative flap reconstruction. because motion and suspension of swallowing can be difficult to control. with minimal additional risk. Recognition of the post-treatment appearance of head and neck cancer on CT is an acquired skill that requires practice and readily available follow-up information for the radiologist to become proficient. Sufficient tissue for diagnosis was obtained in 98% of patients who underwent biopsy. will decrease the false-positive rate in MRI.A. From this approach. CT has a specificity and sensitivity of 80% to 90% [30. . The current authors have performed biopsies in 38 patients using this technique over the last 4 years without complication. and history of radiation treatment.

16. The operative flaps typically contain fat and muscle. (B) This section shows the biopsy needle piercing the lateral pharyngeal node. with identifiable vascular pedicles. A lack of metabolic change with initiation of therapy implies therapy may not be effective [31].A. This finding could potentially provide an early indicator that a new therapeutic regimen should be considered. perineural. or tracheal invasion is crucial. The section includes part of the biopsy guide needle in the buccal space. The postradiation density of tumor is intermediate between muscle and fat but may maintain the shape of the original neoplasm (Fig. Note the initial scan was obtained with contrast to locate the carotid artery. (A) An axial CT section of the neck without contrast reveals a lateral pharyngeal node on the left (arrow). but the welltrained eye. spinal. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig. Controversy still exists as to whether CT or MRI performs these perspective tasks with higher sensitivity. with some articles stating improved sensitivity of PET over MRI and CT for evaluation of recurrent disease. 18 and 19). This communication is particularly important with head and neck malignancies. Overall patient numbers have been low in these studies. The initial evaluation of PET scanning in recurrent disease and for tumor response to chemotherapy has been promising [33–35]. The role of any radiologist is to provide the clinician with important anatomic details about the patient that may affect the difficulty or feasibility of the planned therapeutic approach.30 R. . 17). and the clinician who is informed of the planned clinical procedure and is aware of the surgical approach and risks. however. which was clearly lateral to the node before biopsy. Other studies have implied PET has a role during initiation of chemotherapy to evaluate initial tumor response using glucose metabolism as an indicator of tumor response. The use of three-dimensional and multiplanar reformatted images in CT or MRI to help define tumor relationships to vessels and the likelihood of vascular. is the best tool for alerting the surgeon to potential pitfalls related to anatomic variants in a specific patient (Figs.

(B) The coronal reformatted image from A confirms the paraglottic spread of the tumor (arrow).R. 17. This tumor also extended across the midline anteriorly. (C) A follow-up CT scan after radiation therapy in the same patient reveals the typical low attenuation of treated tumor. excluding the patient from voice-preservation surgery.A. Important anatomic variants must be pointed out so the surgeon can avoid potential intraoperative complications. This process includes evaluation of the size. Summary Evaluation of head and neck cancer with imaging is a topic that is far more extensive than can be covered in this article. (D) A coronal reformation of C confirms that the paraglottic space also shows evidence of radiation effect (arrow). Note that the mass effect from the tumor has not yet subsided and continues to indent the supraglottic airway. The main reason for head and neck imaging is to evaluate the true extent of disease to best determine surgical and therapeutic options. location. (A) An axial contrast-enhanced CT section through the larynx at the level of the paraglottic space reveals a high-attenuation mass crossing the laryngeal ventricle through that space (arrow). which is between muscle and fat density (arrow). Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 31 Fig. These variants can be evaluated with the appropriate multiplanar and three-dimensional images to provide as much information as possible to the surgeon . and extent of tumor infiltration into surrounding vascular and visceral structures.

Compare this to the normal side (open arrow) in which the attenuation is normal and the foramen is comparatively small. (C) Sagittal reformatted image of the mass demonstrates the lack of fatty attenuation at the opening of the palatine foramen on the left (arrow). and pathologist. This finding is consistent with perineural spread on the CT and changed the surgical plan from intraoral resection to a split mandible procedure with partial resection of the maxilla. imaging frequently enables a limitation of the diagnostic and histologic possibilities based on lesion location and signal-attenuation characteristics. 18. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 Fig. surgeon.32 R. preoperatively. (B) A bone window of the same section demonstrates the size asymmetry to better advantage (arrows). Although secondary to the previously described tasks.A. (D) Sagittal reformatted image of the normal side reveals the expected normal fatty attenuation. (A) An axial contrast-enhanced CT section at the level of the hard palate in a patient with a superficial palatal carcinoma on clinical examination reveals an asymmetry in attenuation and size of the greater palatine foramen (solid arrow). Perineural tumor in the greater palatine foramen was found pathologically. which may lead the clinical . to precisely define their location by a standard classification system that can be understood and consistently applied by the radiologist. radiation oncologist. nodal staging should be assessed in an effort to increase the number of abnormal nodes detected by physical examination and. more important. Second.

A. 19. (C) An axial contrast-enhanced CT section reveals the mass to be secondary to a tortuous carotid artery. and artifacts related to multiple causes. each has some limitations. and other modalities. and readily available but has . well tolerated. and high sensitivity for perineural and intracranial disease. not the least of which is motion. The disadvantages of MRI include lower patient tolerance. MRI. (B) The cutaway view of the same image reveals a densely enhancing structure in the submucosa of the retropharyngeal space (arrow).R. (A) A volume-rendered CT laryngoscopy view reveals a posterior bulge in the wall of the upper hypopharynx (arrows). which resulted in a retropharyngeal position of the carotid bifurcation on the right (arrows). and has emphasized the constant evolution of this controversy because of the evolving imaging technology. CT is fast. investigation along a different path. This finding was brought to the attention of the head and neck surgeon. Alberico et al / Surg Oncol Clin N Am 13 (2004) 13–35 33 Fig. saving the patient unnecessary risk and shortening the time to diagnosis and ultimate treatment. Although CT and MRI are both well suited to evaluation of the deep spaces and submucosal spaces of the head and neck. This article has attempted to detail the current state of the controversy between CT. MRI has the advantages of higher soft tissue contrast resolution. contraindications in pacemakers and certain other implanted metallic devices. the lack of iodine-based contrast agents.

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E-mail address: maureen. There are three treatment modalities involved in eradicating head and neck cancer: (1) surgery. (2) radiation therapy. doi:10. With a complete understanding of the role of the dental oncology team involved in the pretreatment. the goal of cure with an acceptable quality of life can be obtained. and rehabilitation phases of treating patients with head and neck cancer. Elm and Carlton Streets.see front matter Ó 2004 Elsevier Inc. with or without chemotherapy. however. and oral pathology. Historically. Because all of these treatments dramatically affect the oral environment.1016/S1055-3207(03)00121-2 . oral medicine.sullivan@roswellpark. and (3) combined treatment. dental oncologist. Close communication between the head and neck surgeon. Buffalo. and limit the possibility of complications that can lead to significant morbidity. treatment. The oral complications secondary to the management of head and neck malignancies have been well described [1–3]. maxillofacial prosthetics. USA Dental oncology is the discipline within dentistry that combines general dentistry. All rights reserved. whether surgical or nonsurgical. Roswell Park Cancer Institute. the dental oncologist must play an integral role in all facets of 1055-3207/04/$ . To maximize the possibility of optimal function and cosmesis. it became apparent that early intervention by a dentist familiar with the complications associated with head and neck malignancies was required. radiation oncologist. NY 14263.Surg Oncol Clin N Am 13 (2004) 37–46 The expanding role of dental oncology in head and neck surgery Maureen Sullivan. a comprehensive dental screening must be performed during the pretreatment phase. and maxillofacial prosthodontist is paramount in achieving function and cure. DDS Department of Dentistry and Maxillofacial Prosthetics. To provide state-of-the-art care for patients who have head and neck cancer. close scrutiny of the dental condition is crucial. the maxillofacial prosthodontist was the only dental specialist involved in the treatment and rehabilitation of patients with head and neck cancer.

soft tissue necrosis. The immediate effects of radiation include mucositis. All teeth deemed unrestorable. Comprehensive evaluation of the dental patient includes Panorex (Orthopantomograph OP 100. These assessment procedures also provide the dental oncologist an opportunity to perform necessary dental procedures in the operating room setting. If third molars are completely impacted without evidence of pathology. and hypoguesia. depending on the type of radiation used.38 M. including periodontal probing. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 Dental oncologic assessment Because radiation therapy is used frequently in the treatment of head and neck malignancies. rampant dental caries. these effects can be minimized with close attention to the dental condition. which is generally preferred by the patient and. The dental hygienist must be familiar with the secondary . a full-mouth series of intraoral radiographs. if oral surgery is addressed during the head and neck surgeons’ initial treatment-planning phase. Furthermore. and the field of involvement. the need for existing restorative dental work is evaluated and any necessary restorative dentistry is completed. trismus. and therefore the type of restoration is not as critical as removing a potential source of mechanical irritation during treatment. This procedure has received much attention in the literature in an attempt to find a formula for dental extraction requirements before radiation [4. The specific type of restorative material used in patients that will become xerostomic has been a consideration [7]. Finland) radiograph. with or without pulpal involvement. and advanced periodontal disease are generally extracted. there should be adequate time for healing if radiation therapy is required. trismus. these procedures should be completed. and. potentially the most devastating effect. prompt attention to the dental condition at the time of diagnosis can allow time for adequate healing before the onset of radiation. The time required for adequate healing should be between 2 to 3 weeks [6]. especially those in the field of radiation should be extracted. the patient will require procedures under general anesthesia performed by the head and neck surgeon to formulate an appropriate plan for tumor removal. These effects are variable. The long-term effects may include xerostomia. After all obvious sources of infection have been eliminated. Instrumentarium Corp. The oral cavity undergoes monumental insult as a direct result of radiation therapy to the head and neck. If the patient has not had a thorough periodontal scaling and prophylaxis within the 3 previous months to diagnosis. pain. Again. All teeth with advanced dental decay. There have been a few studies evaluating the efficacy of fluoride-releasing materials. if oral surgery is required. the dose. Partially impacted third molars with evidence of pericoronitis and any teeth with periapical pathology should be extracted. and intraoral examination. Tuusala. Frequently. they are left and simply monitored.5]. osteoradionecrosis (ORN). allows for longer healing time if radiation treatment is required. more important.

Those patients who require partial maxillectomy that includes the tuberosity. an evaluation for xerostomia is rendered based on the location of the tumor and the type of subsequent radiation required. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 39 complications associated with head and neck radiation. NA. in which the muscles of mastication and the temporomandibular joint are within the field of radiation. to be effective without significant side effects. pilocarpine administered during and after radiation therapy was found to offer no benefit [14]. United Kingdom).4% stannous fluoride product. Duraphat. hamular notch region and the pterygoid fossa area are at risk.M. Also at this time. Maryland) has been investigated for its use as a chemoprotectant. containing a 0. the importance of impeccable oral hygiene can be emphasized. Gaithersburg. such as pilocarpine (Salogen.1% fluoride paste is prescribed. chemotherapy can be used before surgery to decrease the possibility of distant metastases. Corona. If this process is perceived to be arduous by the patient. Instructing patients on the use of tongue blades to use as a lever and monitoring the range of opening can be useful as well [19]. further controlled clinical studies must be performed. which reduces the severity of radiation-induced mucositis and maintains salivary function in patients with head and neck cancer undergoing radiation therapy [15–18]. Daily opening exercises can be a worthwhile task for minimizing this debilitating complication. A daily fluoride delivery system is also recommended. California) is a parasympathomimetic agent that stimulates exocrine gland tissue. Amherst. For tumors located within the nasopharynx. This action promotes salivation and is believed to be most effective if administered at the onset of radiation. Patients who are at high risk for developing trismus should be given instruction for its prevention rather than treatment once it occurs. New York) have been shown to be effective in preventing decay in the xerostomic population [8]. The topical fluoride varnish is applied on the surfaces of all teeth. Many different means of fluoride delivery have been explored in the literature [9.. in an attempt to maintain salivary function [11–13]. In a recent study. with profound hydration. the radiation oncologist is consulted regarding the use of a salivary stimulant. Although amifostine shows promise. especially if postoperative radiation is required.10]. these include the fabrication of custom fluoride carriers. Patients requiring resection of part of the mandible without reconstruction are at considerable risk. The use of chemotherapeutic agents in the treatment of head and neck cancer historically has not been as widely used as surgery or radiation. the use of topical fluoride varnishes containing 5% sodium fluoride (eg. Ivoclan. This agent must be administered daily throughout radiation therapy. Inc. especially if postoperative radiation is required. trismus therapy must not be overlooked. Amifostine (Ethyol. the use of a 1. Recently. MGI Pharma. Inc. Historically. For head and neck malignancies.. Medimmune. . Chemotherapy was reserved for advanced-stage disease or as an adjunct when front-line treatment failed. or it can be used concurrently with radiation therapy. Pilocarpine (Watson Laboratories. At this juncture. which are worn nightly for 5 to 10 minutes.

prosthetic reconstruction is frequently required. Because the retention of facial prostheses is of great concern.21]. to ensure appropriate intercuspation of the remaining mandible. and therefore presurgical impressions and radiographs are required. maxillofacial prosthodontist. prosthetic rehabilitation is generally preferred. Because large facial defects are challenging to reconstruct surgically. Presurgical facial impressions are crucial if tumor eradication involves total auriculectomy or rhinectomy. and the head and neck surgeon is important and should be initiated at the pretreatment phase to allow for a more predictable reconstructive outcome. At the time of tumor removal. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 When chemotherapy is suggested as a course of treatment for head and neck cancer. The risk of infection is great because of a depressed peripheral white blood cell count. if prosthetic rehabilitation is required. The use of split-thickness skin grafts to line the surgical closure of the maxillary defect generally allows for adequate scar band formation. with or without occlusal splinting. a maxillofacial prosthodontist should evaluate the area to be treated. The skin overlaying facial implants must be extremely thin and ideally free of hair follicles. In addition. which can occur approximately 1 week after infusion. It is critical that the patient is made aware of oral hygiene measures to limit the possibility of bacteremia during cycles of chemotherapy. In the . When large palatal defects are anticipated. At this stage. Dental considerations during treatment Head and neck surgery that entails mandibulectomy with immediate reconstruction involving free-tissue grafting is challenging for not only the head and neck surgical team but the dental team as well. the dental oncologist may be required to implement intermaxillary fixation. In conjunction with the pretreatment dental assessment. Communication between the dental oncologist. which provides an optimal surface for engaging the eventual prosthesis [20. the timing of the dental assessment is important. The quality of the remaining teeth and alveolar bone adjacent to the surgical defect is important when predicting the support for prosthesis. this determination includes CT imaging to evaluate quality and quantity of available bone. This procedure ensures that the remaining mandible is able to function within the confines of the temporomandibular joint and provides a template for positioning of the grafted bone. the possibility of using implants should always be discussed at the pretreatment phase [22]. The head and neck surgeon should consult with the maxillofacial prosthodontist before surgery to establish a design for immediate surgical obturation if resection of the hard palate is unable to be reconstructed by local or regional flap surgery.40 M. all possible sources of oral infection should be eliminated before the onset of chemotherapy. osseointegrated implants should be considered.

The use of partial and complete dentures should be avoided until the acute effects of therapy have improved. There is currently no means of preventing oral mucositis. coating agents. only a means of palliation once it occurs. and chemotherapy used. Evaluation for pain. The use of keratinized skin grafts to line the surgical defect can be beneficial in providing a supportive surface for a maxillary obturator. It is during the treatment phase that trismus therapy should be closely monitored if radiation involves the muscles of mastication. After the surgical packing has been removed.M. and evaluating the quality of the patient’s oral-care regimen should be performed weekly following the immediate post-treatment phase. therefore. the immediate obturator can be modified and worn by the patient until complete healing has been achieved. close observation and meticulous hygiene are required [23]. type of radiation. This condition is first observed within 1 to 2 weeks of therapy and continues until therapy is completed. Osseointegrated implants in free-bone grafts have been used with greater success in recent years. tongue. infection is the greatest risk to the graft. Close scrutiny during radiation therapy of patients who have head and neck cancer is required to monitor toxicity. Patients are at risk of many types of infection when tissue breakdown occurs. Long-term dental oncologic considerations Following treatment. The placement of implants at the time of free-flap surgery can be achieved. and swallowing. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 41 immediate postsurgical period. . in addition to the patient’s ability to maintain oral hygiene [28. or saliva substitutes can be recommended in addition to systemic pain management. Mucositis is the thinning and eventual breakdown of the oral mucosa caused by chemotheraputic agents or head and neck radiation. Evaluating the healing of oral tissues before the placement of removable prosthetics is recommended to decrease the possibility of unnecessary tissue trauma. infection.29]. Rinsing with topical analgesics. Because the treatment for tumors of the mandible. hard and soft palate. The severity of radiation-induced mucositis depends on the tumor location. the dental oncology team must closely monitor patients who have head and neck cancer to minimize the complications of treatment. speech. Immediate placement of a surgical obturator for defects of the hard palate can allow the patient to speak and eat. rehabilitation requires immediate attention to assessing the patient’s post-treatment status. and should be treated for evidence of bacterial or fungal infections locally to avoid the possibility of lapse in treatment. and facial structures can significantly compromise a patient’s ability to function. or at a second-stage surgery once graft viability has been confirmed [24–27]. This step is most significant when surgery is combined with radiation therapy.

xerostomia induced by head and neck radiation is well described in the literature [34. If prosthetic rehabilitation is required. thereby enabling separation of the nasal and oral cavities. however. If the mandible is reconstructed with a microvascular free flap. the retention of a maxillary speech aid can be difficult.42 M. osseointegrated implants can provide a more reliable means of rehabilitation. Surgical reconstruction of the hard palate is possible. a palatal augmentation prosthesis may provide better tongue contact to the palate. The success of the prosthesis varies significantly with the amount of hard and soft tissue affected [30. This may be delayed even further if radiation therapy is required. Periodontal management is a challenge. Patients’ progress can be monitored at follow-up examination with the dental hygienist. or mandible itself. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 For defects of the mandible caused by resections of the floor of mouth. and maintain posterior teeth becomes difficult. For example. and the nature of the residual dentition. tongue. For patients with significant tongue morbidity. the ability to wear prostheses.31]. it is important to continue monitoring patients with head and neck cancer who are at continued risk of complications secondary to radiation therapy. The management of the surgical removal of some or all of the soft palate is challenging. especially for the teeth left in the field of radiation therapy. either because of surgery or radiation. osseointegrated implants may be considered. If there is a lapse in a regular trismus therapy. if significant tissue bulk remains. rehabilitation with an intraoral prosthesis is impossible [32]. If the patient is edentulous. Fabrication of a speech-aid appliance attempts to provide closure of the oral pharyngeal resection. It has been suggested that radiation increases the periodontal attachment loss because of disruption in cellularity and vascularity. eat. Trismus therapy must be maintained not only during radiation therapy but throughout the life of the patient. a palatal lift prosthesis may elevate an incompetent soft palate [33]. It is generally agreed that 3-month recalls are required with . Rampant tooth decay in patients who have undergone radiation of the head and neck can lead to significant morbidity. therefore. which occurs between 3 to 6 months following surgery. With initiation of prosthetic rehabilitation. fabrication of a definitive prosthesis can take place following complete the healing of the surgical defect. Because there is currently no means of preventing xerostomia when the salivary glands are in the field of radiation. Tongue depressors or custom trismus screws can be used to monitor patients’ compliance with daily opening exercises. access to the defect. attention to patient compliance with oral hygiene protocol cannot be understated. fabrication of a mandibular resection prosthesis retained by osseointegrated implants may be required to restore continuity.35]. If the soft palate is present but not functioning. The reconstruction of a palatal defect can be extremely challenging depending on the size of the defect.

In cases of advanced necrotic lesions. Summary A comprehensive dental oncologic screening should be part of the pretreatment workup of patients who have head and neck cancer.48]. hyperbaric oxygen therapy can be of benefit in conjunction with surgical resection of the affected area [47. radiation oncologist. however. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 43 minimal soft tissue trauma. This screening should be performed by a dentist who is familiar with the pathologic process of disease and type of treatment being rendered. or rampant decay can necessitate the extraction of teeth in the field of radiation. The mandibular molar region is generally the most affected area in most clinical studies. Clearly. isolated area of exposed bone or. This situation has received considerable attention in the literature as a predisposing factor in the development of ORN.44]. from denture trauma. conservative treatment involving local wound care is preferred if the area involved is small and isolated. Hyperbaric oxygen therapy is extremely costly. The dental oncologist must provide the timeline for the surgeon and radiation oncologist in which all necessary dental treatment will be completed. in addition. Most clinicians agree that in high-risk patients where all attempts at maintaining the dental condition have failed. There is a significant amount of controversy surrounding dental extractions following radiation therapy.M. It is generally agreed that the mandible is at greater risk than the maxilla. and may be contraindicated in the patient with compromised respiratory function. and it rarely occurs when the total radiation dose is less than 6000 cGy. or most often from trauma caused by dental extraction. periodontal disease. in advanced cases. followed by a short duration of chlorhexidine rinsing [36–38]. close communication between the dental oncologist. soft tissue breakdown. ORN can present as a small. It is important at this juncture . Recent studies suggest that the risk of postradiation ORN can be dramatically reduced if hyperbaric oxygen treatments are used before dental extractions. Some authors suggest that safe oral surgery can be performed with nontraumatic techniques on patients following radiation therapy [43. In cases where ORN develops after head and neck radiation. progress to pathologic fracture with profound pain [40–42]. he or she should comprehend the various morbidities associated with eradicating head and neck malignancy. ORN can occur spontaneously.46]. Hyperbaric oxygen is believed to promote the revascularization of hypoxic tissues [45. Despite efforts to maintain adequate oral health following head and neck radiation. all oral-surgical attempts should be made with extreme caution. and head and neck surgeon is required to determine the best course of treatment. ORN is defined as a radiation-induced nonhealing wound rather than an osteomyelitis of irradiated bone [39].

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Cancer 1976. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1987. [48] Beumer J. et al. Johnson R. Kline S. J Am Dent Assoc 1985. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. The treatment of radiation necrosis with hyperbaric oxygen. [47] Hart GB.3:49–54.46 M. Sanders B. Johnson R. Mainous EG. Studies in the radiobiology of osteoradionecrosis and their clinical significance.64:379–90. . Harrison R. Sullivan / Surg Oncol Clin N Am 13 (2004) 37–46 [45] Marx R. Osteoradionecrosis: predisposing factors and outcomes of therapy.37:2580–5.6:819. [46] Marx R. Head Neck 1984.

including radiologists. Palme.on. It accounts for 14% of head and neck cancers reported to the National Cancer Data Base each year [1]. * Corresponding author. with mortality in approximately 12 per 100. It is imperative that physicians adopt a multidisciplinary approach that encompasses both surgical and medical expertise. E-mail address: patrick.000 individuals. This approach necessitates not only oncologically sound ablation of the tumor but also timely and state-of-the-art reconstructive techniques. oral rehabilitation is not complete without the expert assistance from speech pathologists. Patrick J. Gilbert. All rights reserved. France and Hungary have an annual incidence of 40 per 100. are integral in the multidisciplinary approach. Canada Squamous cell carcinoma (SCC) of the oral cavity is a significant public health issue. dentists. adjuvant therapy used by both radiation and medical oncologists is vital to improve disease-specific outcome. and the mortality rate was approximately 25% [2]. University of Toronto. anesthesiologists.J. FRACS. Toronto. doi:10.000 individuals [3]. MD. The incidence of this disease is even higher in developing nations where it is the third most common malignancy after both cervical and gastric carcinoma [4].Surg Oncol Clin N Am 13 (2004) 47–70 Current treatment options in squamous cell carcinoma of the oral cavity Carsten E. In addition. In comparison. The anatomic and functional complexity of the oral cavity and because SCC is locally invasive and can involve adjacent sites make the diagnosis and management of this disease entity extremely challenging.gullane@uhn. nurses. 610 University Avenue.1016/S1055-3207(03)00123-6 . FRCSC Department of Otolaryngology.000 new cases were diagnosed in the United States in 2002. ON M5G 2M9. Finally. which uses a wide range of resources. FACS*. and nutritionists experienced in head and neck oncology. Approximately 29. FRCSC. (P. MB BS.see front matter Ó 2004 Elsevier Inc. Ancillary medical specialists. Gullane). and prothodontists. MB. 1055-3207/04/$ . Ralph W.

also have been proposed as potential causative factors. lymphoma. minor salivary gland carcinomas. A constant and prolonged exposure to these two known causative factors results in ‘‘field cancerization’’ of the oral mucosa [9].8]. Most patients are men with a median age of 60 years [5]. such as osteosarcoma. however. Submucosal malignancies arising at the junction of the hard and soft palate often originate in the minor salivary gland and may include adenoid cystic. erythroplakia. significant periodontal disease.11]. and this results in a chain of events that ends in the development of malignancy with the potential for local destruction and distant spread [10. The mechanisms are multifactorial and include activation of proto-oncogenes and deactivation of tumor suppressor genes.E. and chronic trauma from ill-fitting dentures or jagged teeth. In the differential diagnosis. it is important to recognize that it may be caused by excessive exposure to ultraviolet radiation and therefore should be classified more appropriately as a skin carcinoma [14]. The dominant causative environmental factor in the development of oral SCC is smoking. . Other factors.48 C. who now account for approximately 30% of all cases [6]. In addition there are several other oral pathologic conditions that are potential precursors in the development of malignancy. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Etiology Predisposing factors in the development of oral cavity SCC can be divided into those that are specific to the patient and those of environmental origin. In addition. however. mesenchymal tumors. Although lip carcinoma is included within the oral cavity. There is an increasing trend of this disease in women. Pathology SCC accounts for approximately 90% of all oral cavity malignancies [5]. and possibly chronic hypertrophic candidiasis [2]. oral submucous fibrosis. Genomic instability develops. An association with Epstein-Barr virus and the human papilloma virus has been suggested. leukoplakia.13]. The culturally specific habits of chewing betel nuts and tobacco and reverse smoking are also implicated in the cause of oral cavity SCC [12. A recent Canadian report showed that the incidence of oral SCC in women increased by 84% over the period from 1983 to 1997 [7]. but clear causation has not yet been established [15–17]. This factor combined with the chronic consumption of alcohol constitutes a 35-fold greater risk for developing an oral cavity malignancy [2. which include erosive lichen planus. such as poor oral hygiene. the incidence of oral cavity SCC is approximately 4% in patients younger than 35 years [6]. melanoma. Mucosal melanoma needs to be considered in the differential diagnosis of a bluish mass on the alveolus. Other mesenchymal tumors. mucoepidermoid. or acinic cell carcinoma. and tumorlike conditions must be considered.

Malignant neoplasms of the oral cavity. Otolaryngology–head and neck surgery.) . 1. Staging of these tumors is classified according to the Union Internationale Contre le Cancer and the American Joint Committee on Cancer tumor-node-metastasis (TNM) system (Box 1) [18].C. which accounts for approximately 30% of all oral cavity SCC [5]. 3rd edition. such as necrotizing sialometaplasia. (Modified from Sharma PK. The floor of the mouth is second in frequency. Tumorlike conditions. The most common site involved is the mobile tongue (ie. each with its unique diagnostic and management challenges (Fig. retromolar trigone. In: Cummings CW. buccal mucosa. and the lips. et al. Louis. anterior two thirds of the tongue).E. Baker SR. 1). Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 49 can occur in younger patients. Patients who have these lesions present with discomfort on swallowing. can involve the hard palate and present a diagnostic and management dilemma. Vol. Schuller DE. with approximately 28% of oral cavity SCC. SCC of the oral cavity involves several distinct subsites. with permission. 3. MO: Mosby. followed by SCC involving the upper (including the hard palate) and lower alveolar ridge. Oral cavity subsites. Tumors of the mobile tongue occur most commonly on its lateral and ventral surface and tend to spread in both a radial and vertical fashion. St. editors. Fig. 1998.

through cortical bone. these lesions are therefore usually diagnosed at an early stage (ie.E. larger than 3 cm and not more than 6 cm N2b Multiple ipsilateral nodes. These tumors spread early to involve adjacent sites such as the mandible.cancerstaging. The retromolar trigone is a less common site for oral cavity SCC but deserves special Illinois. TNM staging of oral carcinoma Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor is 2 cm or less in greatest dimension T2 Tumor is larger than 2 cm but no larger than 4 cm in greatest dimension T3 Tumor is larger than 4 cm in greatest dimension T4 Tumor invades adjacent structures (eg. Neoplasms that originate in the floor of the mouth and along the lower alveolar ridge tend to invade the mandible early. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Box 1. visit www. or deep muscle of tongue) Nodal involvement (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Single ipsilateral node. T1 or T2). 6th edition (2002) published by Springer-Verlag New York (For more information. 3 cm or less in greatest dimension N2a Single ipsilateral node. skin. Any citation or quotation of this material must be credited to the AJCC as its primary source. into maxillary sinus. 6 cm or smaller N2c Bilateral or contralateral nodes. tongue . pterygoid muscle. 6 cm or smaller N3 Metastasis in a lymph node more than 6 cm in greatest dimension Distant metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis) Used with the permission of the American Joint Committee on Cancer (AJCC). and patients may present with loosening of teeth and ill-fitting dentures. Chicago. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York. The original and primary source for this information is the AJCC Cancer Staging Manual. on behalf of the AJCC. Inc.50 C.

orbit. SCC of the lip commonly occurs in white individuals who have a life-long outdoor occupation [2]. Once these lesions have extended beyond their site of origin. The selection of appropriate therapy depends on certain patient. and soft palate. pattern of invasion. Management The management of patients who have oral cavity SCC begins with a comprehensive history and complete head and neck examination. degree of functionality. growth pattern. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 51 base. chemotherapy.13].C. treatment becomes more complex. depth of invasion. Patient factors have been outlined previously. and tend to invade in small groups of tumor cells have been associated with a significant rate of occult nodal metastases [23]. and lymphovascular and perineural invasion) [19– 22]. stage. and those pertaining to individual tumor sites are discussed later. Nonsurgical management includes the use of radiotherapy. Oral cavity SCC presents with regional cervical lymph node involvement in a significant proportion of patients. The buccal mucosa is a common site of origin in India and the southeastern parts of the United States because of the high incidence of betel nut chewing in the former and the use of snuff in the latter [12. tumor suppressor genes and protooncogenes) have been proposed as indicators for regional involvement. Surgery is further subdivided into ablative and reconstructive approaches. malignancy grading of the tumor front. Potential molecular markers (ie. This site includes all the intraoral lining of the inner surface of the cheeks and lips from the line of contact anteriorly to the pterygomandibular raphe posteriorly and attaches to the superior and inferior alveolus. tumor. Treatment modalities are divided into surgical and nonsurgical options or a combination of both. . Institutional factors relate to the expertise. For example. Aggressive local invasion frequently occurs with extension to involve the paranasal sinuses. and treatment philosophy established by the multidisciplinary team. and/or the cranial cavity. The hard palate and maxillary alveolus are involved in approximately 10% of cases [5]. and understanding and personal wishes of the patient before embarking on any therapeutic path. infratemporal fossa. and various histopathologic features (eg. with significant ablative and reconstructive challenges. have depth of invasion greater then 3 mm. 2). family support. SCC of buccal mucosa may occur de novo or become involved by way of direct extension from other oral cavity subsites. and these need to be considered in the management of each individual patient. In addition. but their routine application has yet to be proved [11. Various therapeutic philosophies exist. pterygopalatine fossa. neoplasms that are larger than 2 cm. tonsil. The incidence of regional metastases is associated with subsite. it is vital to confirm any comorbidities. and ancillary services aimed at functional rehabilitation (Fig.24].E. resources. and institutional factors. which includes an office-based fiberoptic-endoscopic evaluation of the upper aerodigestive tract.

modified radical neck dissection. Abbreviations: MRND. radial forearm free flap. ECG. and a chest radiograph. Investigations Investigations can be divided into those that are general and specific and include a complete blood film. RFFF. biochemistry. 2. Specific investigations should include imaging of the primary tumor site and .E.52 C. Management algorithm for oral cavity carcinoma. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Fig.

Adjuvant radiotherapy improves locoregional control and disease-specific survival rates in patients with advanced-stage lesions [30]. Before embarking on surgery. which helps in the planning of the most appropriate therapeutic approach. however. as an additional benefit. however.28]. and detect any bony invasion. Recent literature has focused on single photon emission CT (SPECT) scanning in evaluating the mandible. axial and coronal planes) [25]. In addition. anesthetic fitness needs to be confirmed by the anesthesiologist and other members of the medical team (eg. demands that further prospective studies be performed before its universally acceptance. MRI is superior in the delineation of soft tissue lesions within the tongue and in the floor of the mouth. They can assist. the patient’s management should be discussed within the setting of a multidisciplinary tumor board. Lack of availability. in the planning of tumor resection and in evaluating the remaining dentition [27. or Panorex radiographs [27. Pulmonary imaging in the form of a chest radiograph or CT scan for more advanced tumors is imperative in the evaluation of any underlying lung disease and in the exclusion of possible metastatic involvement. however. including the hard palate. Invasion of the facial skeleton. if available. The goal of imaging is to assist in the staging of the primary tumor. cardiologist.C. is best visualized using thin slices with bone algorithm (ie. neural involvement and intracranial extension can be accurately evaluated with this modality. cost. Finally. and mandible. respiratory specialist).28]. stages I or II) [29]. CT scanning is widely used in the management of head and neck malignancy. Panoramic X-ray or occlusal view radiographs of the mandible are simple and cost-effective firstline investigations that have a high specificity but low sensitivity for excluding mandibular invasion and are therefore useful with gross tumor involvement only. avoids the distortion seen in patients with heavily restored dentition [28]. Its sensitivity in excluding invasion (95%) was far superior to CT or dental CT scans. MRI allows direct multiplanar evaluation of the pathology and. and histopathologic verification of the tumor type. Dental CT scans have been developed and.E. evaluate cervical lymphatics. Chemotherapy in a neoadjuvant setting has been investigated and shows promise. examination of the upper aerodigestive tract under general anesthesia. offer more choice in the assessment of mandibular invasion [26]. its use is presently limited to institutional trials . paranasal sinuses. and limited application of this modality. Its many advantages include the clear delineation of the bone–soft tissue interface in the evaluation of the neck and its universal availability. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 53 regional lymphatics. Specific sites Tongue Surgery is the mainstay of treatment for early-stage disease of the oral tongue (ie.

In expert hands. or lateral osteotomies). Both the mandibulotomy and lingual release afford good access. These include the peroral. particularly those that have deep tongue involvement and extent across the midline require a more radical approach. Palliative chemotherapy useful and can be offered to patients for whom definitive curative management is no longer an option. (A) Right T2 lateral tongue SCC.33].54 C. (B) transoral resection of lesion. need for reconstruction. Prior radiotherapy can increase the rate of complications that occur with a mandibular swing. which include size of the primary tumor. however. The approach selected depends on several factors. by means of midline. mandibular swing (ie. both for tumor ablation and subsequent reconstruction [32. paramedian. There are several surgical approaches to disease of the oral tongue. and the expertise and preference of the individual surgeon. however. . Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 [31]. Patients treated with a mandibulotomy did report superior ability of speech. mandibular invasion. and (C) primary closure with absorbable suture. or cheek flap approach [32. and a recent comparison of these two approaches showed no significant difference in outcome [35]. The advantage of the tongue drop is the avoidance of an osteotomy with its associated complications of malunion and/or nonunion [34]. 3. degloving.E. More advanced lesions. Neoplasms staged T1 or T2 that do not invade the mandible are best managed using a peroral approach (Fig. complication rates are low. Fig.33]. lingual release. swallowing. dentition. and chewing when compared with the lingual release group. 3). extent of cervical lymph node involvement.

care needs to be taken in placing the osteotomy site between the tooth roots. a thin titanium (eg. In patients with teeth. however. however. (A) Lip-split and midline mandibulotomy approach to the oral cavity.C. It is important to reduce the prominence of the symphyseal region of the mandible using a high-power burr to compensate for the thickness of the reconstruction plate. 2.E. The potential negative impact of a facial scar was not borne out in this analysis [35]. 4). if there is dental crowding. (B) Repair with radial forearm flap and plate. Commercially available plating systems have improved reconstruction and have diminished morbidity.3-mm) plate is used to stabilize the . Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 55 Fig. Once this has been achieved. 4. extraction of one tooth is preferred. Mandibular swing with either a midline or paramedian osteotomy is the current authors’ preferred approach to the oral cavity (Fig.

one or two lag screws can be used to achieve a similar result (Fig. . Surgery is the primary mode of therapy with the need for complex reconstruction. These neoplasms frequently involve adjacent sites. Floor of the mouth Tumors in the floor of the mouth are located either anteriorly or laterally along the oral tongue. This combined therapy frequently results in significant functional disability. lack of speech. adjuvant radiotherapy is recommended when resection margins are close or involved [38]. In addition. 5) [36]. Lag screws for repair of midline mandibular osteotomy. Alternatively. direct tumor invasion through the lingual cortex and tooth roots will eventually occur [37]. Once invasion of the neurovascular canal occurs. Retromolar trigone and lower alveolus Patients who have tumors located on or near the lower alveolus tend to present with mandibular invasion and advanced-stage disease. osteotomy and a tension band splint or circumdental wire help minimize excess movement. however.56 C. with direct invasion of the pterygopalatine and infratemporal fossa. including the oropharynx.E. and trismus. xerostomia. which tends to invade the mandible along its occlusal surface at the site of tooth sockets. with resultant dysphagia. The management of these lesions is challenging because of their proximity to the mandible. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Fig. dentition does offer some resistance. The state of dentition therefore plays a significant role in the selection of appropriate surgical treatment. which often necessitates composite free-tissue transfer. Edentulous patients seem to have less resistance to the advancing tumor front. the tumor tends to spread to the skull base along the inferior alveolar nerve. 5. In contrast.

which is used in a select number of patients where orbital support and/or repair are necessary. such as cerebrospinal fluid leak. (C) flap advancement and closure. orbit.C. 6) [40]. and the Abbe and Karapandzic flaps are the reconstructive options of choice (Fig. . on occasion. usually requires free-tissue transfer. (A) Lower lip SCC. paranasal sinuses. Reconstruction is challenging. meningitis. which provide adequate function and acceptable cosmesis.E. and a combination of the radial forearm free Fig. In addition. resection that transgresses the cranial base mandates the use of free-tissue transfer to minimize potential postoperative complications. Total lip replacement. and (D) Postoperative result. Alternate options include free-tissue transfer. or intracranial abscess [39]. orbital exenteration. however. Management frequently requires partial or total maxillectomy with. The lip Most lip cancers occur on the sun-exposed lower lip. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 57 Upper alveolus and hard palate Tumors arising from the upper alveolus and hard palate tend to involve important adjacent structures at the time of presentation (ie. approximately 7% arise from the upper lip and 4% involve the commissure. however. or brain). 6. (B) excision and outline of bilateral Karapandzic advancement flaps. Some form of advancement flap is necessary if the defect exceeds 30% of the lip. Simple excision and primary closure is advocated in defects that involve less than one third of the lip. most defects are repaired using a combination of a skin graft and maxillary prosthesis.

The dilemma arises in lesions that are close to or abut the mandible. In certain situations. SPECT and MRI also show promise. there is no one diagnostic modality that provides accurate preoperative assessment of bone invasion. with Panorex/occlusal views.58 C. Results support using a marginal mandibulectomy in most patients in whom no gross clinical and radiologic evidence of mandibular invasion exists. or in those with advanced (ie. a plate is applied to reduce the incidence of fracture. where the bony defect is situated posterolaterally in elderly and edentulous patients. 7). the oral commissure. The goal of resection is to provide a clear margin of more than 1 cm with removal of all microscopic disease. however. Primary radiotherapy is an alternative form of treatment. excessive resection of normal. including those in which lesions are close to and abutting the inferior alveolar ridge. In addition. CT scans. Currently. This procedure involves a resection of either the superior half of the mandible or the lingual cortex (Fig. Ultimate locoregional control and survival rates compare well with those for segmental mandibulectomy [44.45]. uninvolved tissue. Careful clinical examination is paramount. The reconstructive menu in the current authors’ institution includes a vascularized osseous free-tissue transfer. Where the resection includes more than 60% of the height of the mandible. but in select cases. 8). neck levels I to III) should be considered in patients with neoplasms that involve either the upper lip. [T2) or recurrent lesions. tumor stage. The management of the mandible requires a balanced approach. adjuvant radiotherapy is recommended in most patients with mandibular invasion. The current authors’ approach to the evaluation of the mandible includes a thorough clinical examination. and a high index of suspicion. especially in elderly patients and in those who are medically unfit for prolonged anesthesia and hospitalization. but their limited availability curtails their routine use [28]. A combination of Panorex/occlusal views and CT scanning has a high sensitivity (81%) and specificity (88%) [27]. it may be left unreconstructed. because these lesions have a significant incidence of occult metastases [42]. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 flap and the palmaris longus sling has become a popular option [41]. with avoidance of unnecessary. A marginal mandibulectomy is a widely accepted approach where there is no clear evidence of bone invasion [43]. the standard of care is usually segmental mandibulectomy (Fig. The mandible Mandibular involvement has significant implications for both prognosis and postoperative rehabilitation. . Where the mandible is involved clinically and radiologically. with reported sensitivities of more than 90%. and studies have shown it to be highly sensitive ([94%) but lacking in specificity (25%) [27]. immobile lesions of the floor of the mouth and/or in edentulous patients are highly suggestive of bone invasion. Treatment of the cervical lymphatics (ie.E.

(C) Repair with free vascularized fibular bone and overlying skin. 7. Andersen et al [46] in a recent review reported on 106 patients with clinically positive neck disease. . however. with most clinically involved cervical lymph nodes requiring a neck dissection. single lymph node disease involving the upper neck. (A) T4 right lower alveolar SCC. The neck The management of the neck in patients who have SCC of the oral cavity is determined by the treatment approach to the primary neoplasm. The primary sites were varied with approximately half involving the oral cavity. including lateral segmental mandibulectomy and radical neck dissection. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 59 Fig. (B) Composite resection.E. Recent studies. The standard is a modified radical neck dissection encompassing levels I to V. have questioned this approach for small.C.

(B) Exposure of the lateral oral cavity. 8. Gooris et al [47] evaluated the therapeutic use of performing a supraomohyoid neck dissection followed by radiotherapy in patients with primary lip SCC and concomitant neck disease (ie. or radiotherapy [48. Adjuvant radiotherapy was used in 72% of patients. a selective neck dissection as part of a combination approach may be adequate treatment of clinically positive neck disease. stage N1 or N2) involving only level I.49].60 C. There are three accepted treatment approaches: close observation. MRI and positron emission tomography are used in the evaluation of clinically negative neck disease in head and neck carcinoma [50–52]. Ionna et al [54] recently reported the use of sentinel node biopsy in patients with oral cavity SCC staged T1 or T2. The technique of sentinel node biopsy as used in the management of melanoma has been proposed in an effort to identify those patients with occult disease [53]. Locoregional control exceeded 90%. with an overall locoregional control rate of 94% [46].E. >90%) [50]. A significant number of patients have occult disease. The management of clinically negative neck disease provides further controversy. (C) Posterior marginal mandibulectomy. however. CT scanning. (A) Cheek flap approach. elective neck surgery. Although these studies were retrospective and relied heavily on adjuvant radiotherapy. All patients were treated with an appropriate selective neck dissection. The combination of clinical examination and CT compares well with the ‘‘ gold standard ‘‘ of elective neck dissection (sensitivity. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Fig. The sentinel node . and the goal is to detect those patients who have occult or positive disease to avoid any unnecessary morbidity associated with elective neck surgery. Physical examination.

trismus. anterior floor of mouth) usually require bilateral neck treatment. nasolabial) are alternate options. floor of the mouth. there exists a significant rate of fistula formation.C. It is thin. The simplest approach is to permit the defect to heal by secondary intention. The current authors’ approach in the management of clinically N0 neck disease is to perform either unilateral or bilateral selective neck dissections encompassing levels I to IV. Splitthickness skin grafting is an alternative. however. In addition. and graft failure [58]. tongue. pliable. The gold standard in soft tissue reconstruction of the oral cavity is the radial forearm free flap [60]. The first option is to leave posterolateral defects unreconstructed (eg. especially in edentulous patients [59]. or skin flaps (eg. and this is certainly appropriate for small lesions of the tongue. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 61 was identified in 95% of patients. Treatment of early-stage disease is adequate with single-modality therapy. Although results of this approach are promising. in . however.E. or buccal mucosa. Reconstruction A wide variety of reconstructive options are currently available to repair surgical defects of the oral cavity [57]. Byers et al [56] reported that ‘‘skip metastases’’ involving only levels III or IV exist in up to 15% of patients with oral tongue SCC. It provides significant flexibility to the surgeon because of the size of the potential skin paddle and adequate length of its vascular pedicle. In addition. 9) [61]. with minimal failure rates (Fig. Even T2 lesions have a known incidence of occult disease of more than 15%. however. adjuvant radiotherapy is recommended if occult disease is identified. and the overall sensitivity of this approach was 100%. in large defects. The importance of including the neck in the treatment regime rests on the fact that oral cavity SCC has a significant rate of occult metastases. and these are best suited for defects that involve the anterior floor of the mouth. necessitating treatment of the N0 neck. The sensitivity dropped significantly in centers performing fewer than 10 sentinel node biopsies per year. Neck dissections encompassing levels I to III are generally adequate. and the selection of treatment modality generally depends on the approach to the primary tumor. The management of clinical negative neck disease therefore continues to be controversial. midline lesions (eg. and potentially sensate and therefore well suited for intraoral reconstruction. Three options are available for managing segmental mandibular defects. Ross et al [55] recently presented the results of a multicenter trial on the feasibility of this technique in the management of patients with head and neck SCC and concluded that sentinel node biopsy identified 95% of sentinel nodes with an overall sensitivity of 90%. further multi-institutional trials need to be performed to evaluate and test this modality before it can become part of the routine workup in patients who have clinically N0 neck disease. Local mucosal.

this modality is associated with high extrusion rates despite adequate soft tissue cover (eg. (A) Cosmetic result of the lip-split approach. and/or extracapsular spread [70]. multiple nodal involvement. significant perineural/perivascular invasion. . Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 Fig.62 C. pedicled mycocutaneous or free soft tissue flap) and therefore is usually not recommended as a primary reconstructive approach (Fig. locoregional control and survival rates for early-stage oral cavity SCC with surgery alone are comparable to radiotherapy. In addition. however. (B) Postoperative appearance of the radial forearm free flap for the repair of lateral oral tongue defects. studies have demonstrated that a return to normal oral function is achieved more often with primary surgery when compared with radiotherapy alone [68]. 10) [62–64]. 9. In select patients. including xerostomia and dysphagia [66. These features may include positive or close margins. Simple plate reconstruction is another alternative. because of significant morbidity. and therefore the current authors advocate primary surgery in these patients [29]. it may form the primary therapeutic option if comorbidities and patients’ wishes preclude the use of surgical excision. or scapular free flap) [65]. Many patients require postoperative radiotherapy if certain adverse features exist.E. and survival rates have been improved in those for whom complete surgical resection is possible [30. Radiotherapy and chemotherapy Radiotherapy is an integral part of the management of oral cavity SCC. elderly and edentulous patients) and manage these defects with only soft tissue replacement (eg.67]. bone involvement. Furthermore. iliac crest.38]. A significant number of patients will develop a metachronous neoplasm and therefore it is important to reserve radiotherapy for the treatment of tumor sites that are less amenable to function-preserving surgery [69]. Primary radiotherapy is not the treatment of choice for early-stage oral cavity SCC. The gold standard approach today is the use of an osseocutaneous free-tissue transfer (eg. patients with advanced malignancies staged III or IV are best treated with a combined approach. In addition. however. pedicled mycocutaneous or free soft tissue flap). fibula.

iridium-192 wires). soft tissue involvement. Chemotherapy for the treatment of oral cavity SCC is presently reserved either for palliation or within the setting of institutional trials. Significant local complications. however. multiple nodal disease. Licitra et al [31] examined the use of cisplatin and 5-fluorouracil in a neoadjuvant setting. Reconstruction plate extrusion 3 years following therapy. T1 or T2) treated with primary brachytherapy (ie. The survival rates were 88% and 74%. respectively.C.E. comparing favorably to results obtained with surgery and/or external beam radiotherapy. including soft tissue and bone necrosis occur with this modality. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 63 Fig. or extracapsular spread). 10. Adjuvant radiotherapy was given in those patients with adverse factors (eg. The results . and have resulted in limited application of this form of management. positive margins. Marsiglia et al [72] recently published a series of 160 patients with floor of mouth and tongue SCC (ie. They compared toxicity and outcome in two treatment arms: chemotherapy and surgery versus surgery alone. Brachytherapy is an alternative for both primary and recurrent lesions [71].

chemotherapy is not part of the first-line management of patients who have oral cavity SCC. Overexpression of this receptor is associated with a poorer prognosis in patients with head and neck cancer. Certain transgenic mouse models have been developed to test the role of COX-2 in tumorigenesis [11].64 C. This finding probably reflects the action of various oncogenes and growth promoters that induce the expression of COX-2. Input from a dentist and prosthodontist. providing hope for the possible use of this technique in the future. and its application is reserved for palliative purposes only. is also vital for successful and expedient rehabilitation in these patients. swallowing. The results showed that this combined treatment is well tolerated and may form part of a future treatment regime for patients with advanced and resectable oral cavity carcinoma. These findings suggest that this agent may someday assist in the prevention and treatment of oral cavity cancer [75]. Chemoprevention is a strategy that aims at preventing the development of invasive carcinoma. At present. The future may rest on the development of novel treatment strategies that seek to exploit the molecular characteristics of the tumor. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 revealed no survival advantage with neoadjuvant chemotherapy. and it was postulated that blocking this receptor would control the malignant potential and form the basis of targeted molecular therapy. It may be possible in the future to adopt a less aggressive and organ-sparing approach if further studies support the findings by these authors. a cyclooxygenase inhibitor. The authors reported a decreased need for adjuvant radiotherapy. Myers et al [74] recently targeted epidermal growth factor receptor in an experimental xenograft animal model. Among the possible targets is cyclooxygenase-2 (COX-2). and/or mastication. It has potent antiangiogenic properties and has been shown to reduce oral cavity SCC tumor volume in vivo. The results have been promising in blocking the growth of human oral cavity SCC.E.and postoperative cisplatin concurrently with slightly accelerated hyperfractionated radiotherapy in an attempt to reduce treatment toxicity and improve disease control. which is expressed in premalignant tissue and certain cancers. and less need for mandibular resection in those patients who received chemotherapy. Celecoxib. Rehabilitation Post-treatment rehabilitation is vital in patients with oral cavity SCC because significant functional morbidity is encountered that affects speech. has been shown to be effective in the prevention and treatment of colon cancer. however. Schuller et al [73] reported the use of pre. Oral rehabilitation commences at the time of initial consultation and is coordinated by a speech pathologist. however. however. Certain agents have been isolated that curtail the development of lower gastrointestinal carcinoma. Extensive human trials are required before this agent becomes part of the routine management. .

80]. recent analysis has not substantiated this. Factors other than those included within the TNM staging system have been found to be significant for prognosis. Bova et al [24] found that these factors were present in 55% to 68% of oral tongue SCC and predicted advanced neck disease. In addition to these tumor factors. and the presence of perineural/perivascular invasion [19. This finding was not mirrored in the African American population. the most important predictive factor for occult nodal disease in oral tumors staged T1 or T2 was depth of invasion in excess of 3 mm [23]. This finding compares well with a previous report by Spiro et al [21]. Patients aged 40 years or younger had a superior outcome when compared with those aged 66 years or older [5. increased tumor grade. such as cyclin D1 and p16. The most important factor for prognosis is the state of the cervical lymphatics. The answer may lie with molecular markers. type of tumor front. who found that depth of invasion of greater then 2 mm was associated with increased regional failure and reduced survival. poor prognostic factors in a group of 102 patients with oral cavity SCC [22]. Patients with early-stage tumors (T1 or T2) have survival rates of 70% to 90% [29. Presentation with advanced-stage disease was associated with low socioeconomic status in white patients. The addition of radiotherapy has significantly improved disease-specific outcome in these patients. African Americans have a significantly greater risk of presenting with advanced-stage disease and therefore have a worse overall survival rate when compared with whites (35% versus 51%. Those with more advanced stage (ie.76.C.38. Certain ethnicities seem to have more aggressive disease. with survival rates halved in the presence of pathologic nodal involvement [79]. however [78]. suggesting features other than environment may be responsible for the poor outcome in this group [5].70]. such as grade of tumor. respectively). extracapsular spread. These nuclear proteins are important in controlling the cell cycle and overexpression of cyclin D1 and loss of p16 have been found to be common genetic events in head and neck cancer. however.E. stage III or IV) of disease have survival rates of less than 25%. In a recent analysis.77]. however. incomplete surgical resection is significantly associated with an adverse outcome [22]. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 65 Prognostic factors and outcome The overall disease-specific survival rate for patients who have oral cavity SCC is approximately 50% [5]. The presence of overexpression of cyclin D1 and loss of p16 were complementary in predicting for a greater relapse rate and reduced disease-specific survival rate. These factors include histopathologic features. depth of invasion. and reduced disease-specific survival on multivariate regression analysis [24]. These results show promise that routine evaluation of these parameters . Young age also has been postulated to affect prognosis. A recent multivariate analysis found that a high combined Byrne’s invasive front grading score and tumor invasion characterized by small groups of dissociated cells were independent.

25:236–9.5:267–79. and the rehabilitation of patients who have oral cavity SCC. [12] Janakarajah N.E. van der Waal I. Winn DM. Karnell LH. Smejkal W. [11] Sudbø J. Muir CS. treatment and outcome of oral cavity cancer: a National Cancer Data Base report. CA Cancer J Clin 2002.52(4): 195–215. The future may lie in the development of treatment regimes that combine early detection with organ preservation and result in improved cure rates and quality of life. Smoking and drinking in relation to oral and pharyngeal cancer. Singapore Med J 1984. Arch Otolaryngol Head Neck Surg 1998. reconstructive options. Leemans R. Presentation. [8] Blot WJ. Fraumeni JF. [5] Funk GF. Wright BA. [4] Parken DM. et al. Day TA. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003. Int J Cancer 1988. J Oral Pathol Med 2003. 124:951–62. Franceschi S.48:3282–7. Eur J Cancer Prev 1996. Soong SJ. Dewar R.32: 63–70.24(2):165–80. Summary Oral cavity SCC remains a significant health problem and requires a multidisciplinary approach. Oral cancer and precancerous lesions. References [1] Hoffman HT. [2] Neville BW. Levi F. Hoffman HT. Laara E. Comparative descriptive epidemiology of oral and oesophageal cancers in Europe. Squamous cell carcinoma of the buccal mucosa: analysis of prognostic factors. Head Neck 2002.41:184.6:963–8. Cancer Res 1988. Southwick HW. Boyle P. Trask DK. Cancer 1953. 1996. Funk GF. Trends in the incidence of oral cancer in Nova Scotia from 1983 to 1997. Major advances have been made in surgical approaches. Which putatively pre-malignant oral lesions become oral cancers? Clinical relevance of early targeting of high-risk individuals. Mc Laughlin JK. Estimates of the worldwide frequency of sixteen major cancers in 1980. Clinical presentation of buccal carcinoma in a review of twenty nine patients. et al. Tabor MP. Field cancerization in oral stratified squamous epithelium. The National Cancer Data Base report on cancer of the head and neck. [6] Negri E. These advances have significantly improved disease-specific outcome and quality of life. Zhen WK. Treatment with surgery alone or in combination with adjuvant radiotherapy for more advanced lesions is the standard of care. Head Neck 2002. Zain R. Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Cancer epidemiology and prevention 2nd edition. [7] Howell RE. Robinson RA. Karnell LH.154:411–4. New York: Oxford University Press.24:198–206. .95(2): 205–12. [13] Urist MM. Am J Surg 1987. Brakenhoff RH. Menck HR. [9] Slaughter DP. [3] Schottenfeld D. O’Brien CJ. Serra-Majem L. [10] Braakhuis BJM. La Vecchia C. Snow GB.66 C. Reith A. Palme et al / Surg Oncol Clin N Am 13 (2004) 47–70 may become useful in the management of patients who have oral cavity SCC. Robinson RA.

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and selection of the various treatment modalities is largely center driven. 1055-3207/04/$ . A small contribution comes from the lateral extensions of the posterior pharyngeal (J. (3) the tonsil complex (ie.see front matter Ó 2004 Elsevier Inc. Jimmy J. CA 90048. Drew University of Science and Medicine. MDa. and (4) the base of tongue. The limits of the oropharynx as a whole can usually be easily appreciated during clinical * Corresponding author.Surg Oncol Clin N Am 13 (2004) 71–80 Carcinoma of the oral pharynx: an analysis of subsite treatment heterogeneity Ryan F. Los Angeles. The oropharynx can be divided into four subsites: (1) the posterior pharyngeal wall. The circumvallate papillae and palatoglossal muscle mark the anterior limits.1016/S1055-3207(03)00117-0 . CA 90059-3051. MD. 8700 Beverly Boulevard. All rights reserved.J. (2) the soft palate. USA a The treatment of malignant tumors of the oropharynx is far from straightforward. E-mail address: jimbrown@cdrewu. 12021 South Wilmington Avenue. There seems to be no consensus as to the best mode of primary treatment. USA b Department of Otolaryngology–Head and Neck Surgery. The muscular pharyngeal wall between these two planes defines the posterior limits. Brown). Los Angeles. tonsillar fossa. tonsil. and pillars). DDS.* Head and Neck Oncology. doi:10. Room 5004. FACSb. and is compounded by the wide variability in treatment to the different subsites of the oropharynx as shown by reports from the major centers that treat this disease. Charles R. Relevant anatomy The superior and inferior boundaries of the oropharynx are marked by horizontal planes at the levels of the hard palate and vallecula or hyoid bone. respectively.b. Brown. Most of the lateral wall of the oropharynx is primarily composed of the tonsil and the tonsillar fossa. Osborne. Cedars-Sinai Medical Center.

Assigning tumor to subsite of origin Determining the subsite of origin in oropharyngeal carcinomas can be a daunting task and frequently comes down to an educated guess based on subjective and objective information. It is therefore not unusual for a clinician to be incapable of making a definitive subsite designation. J.J. and otalgia are common complaints of oropharyngeal disease in general. Lesions located at transition zones. neurovascular and fibromuscular structures. The second factor rests with the size and position of a given lesion. Patient symptoms are perhaps the least helpful markers of subsite origin. especially in the presence of gross disease. such as between the soft palate and anterior tonsillar pillar. Therefore. imaging studies. The first factor relates to mucosal continuity between subsites. 20% poorly differentiated.F.72 R. This distribution is fairly uniform throughout the other subsites of the oropharynx. or patient symptoms to discern lesion subsite of origin. MRI with gadolinium provides the highest soft tissue resolution but rarely does much better than the examination of an experienced clinician in positively identifying the subsite of origin. the histopathologic entities seen in the oropharynx represent a derivation of tissue normally present there. making it difficult to strictly demarcate one subsite from another. the lateral extension of the postpharyngeal wall merges almost imperceptibly with the posterior tonsillar pillar. Similarly. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 examination. Osborne. Histopathology In general. Some authorities have attempted to use histologic differentiation. and 20% well differentiated [1]. or large lesions involving contiguous subsites may present a diagnostic dilemma. The reason for the great difficulty is twofold. clearly visualizing the limits of the subsites of the oropharynx can be more of a challenge. Approximately 60% of soft palate lesions have been found to be moderately differentiated. the remainder of the article pertains to the management of squamous cell carcinomas (SCCs) at the various subsites of the oropharynx. . and lymphoid aggregates in the Waldeyer’s ring opens the possibility to a wide variety of mesemchymally derived sarcomas and carcinomas. because dysphagia. the soft palate. Because the oropharynx is lined with stratified squamous epithelium. 85% to 90% of carcinomas seen are squamous cell in origin. For example. In comparison. odynophagia. The presence of minor salivary glands. A discussion of the management of all malignancies found in the oropharynx is beyond the scope of this article. which includes the uvula is continous with the anterior tonsillar pillar. which may encompass more than one subsite.

Soft palate The soft palate functions to prevent air escape during phonation and nasal regurgitation during deglutition. They tend to be asymptomatic unless they become bulky. The overall 5-year survival rate for patients presenting with unilateral lesions is 70. Approximately 25% of patients treated for a soft palate tumor will present with a second primary tumor. they are usually identified early and referred for definitive management. As such. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 73 Posterior pharyngeal wall Tumors that are isolated to the posterior pharyngeal wall are very uncommon. however. yet there are well-recognized lymphatic drainage patterns that permit contralateral spread. the treatment of a small lesion often results in a large defect. Although early-stage soft palate lesions readily lend themselves to primary surgical treatment. The effect of location on prognosis is well documented. these . They are known for their early metastases to bilateral jugular and retropharyngeal nodes because of their posterior and relatively midline location.8% and drops to 51% for patients with midline or bilateral lesions [2]. Modern palatal obturators and surgical reconstructive efforts have reduced the degree of functional deficits. Osborne. these lesions give the impression that they can be readily encompassed by a surgical procedure without compromise of function. it may provide the least challenge to routine examination. They rarely extend laterally to other subsites of the oropharynx but rather infiltrate deeply into the retropharyngeal and prevertebral tissues. The biologic characteristics of these tumors are the same as those of tumors of the hypopharynx. many clinicians have limited experience in their management. Thus. even the smallest lesions have the capability of seeding both sides of the neck with metastatic disease. SCC of the soft palate is a relatively uncommon malignancy and remains virtually asymptomatic because of its location.R. with the floor of the mouth being the most common secondary site [3–8]. the submucosal nature of the disease demands that adequate margins be taken to minimize recurrences. Because of the relative infrequency of these lesions. which results in functional difficulties. despite the relatively asymptomatic presentation of carcinomas in this region. J. Therefore. At first glance. There exists no true barrier to lateral tumor spread.J. The soft palate forms a mucosa-covered muscular bridge from one side of the oropharynx to the other. until a lesion reaches a substantial size. the treatment philosophies and approaches are the same as those used for tumors of the hypopharynx. The lymphatic drainage is weighted in an ipsilateral direction. however.F. Thus. This possibility becomes more of a reality as lesions approach or cross the midline. Of all the subsites of the oropharynx. and the aponeurosis of the underlying musculature provides a transient barrier at best.

with comparable locoregional control and overall 5-year survival results [10. 5th edition. it ranks second only to laryngeal cancer. These lesions spread rapidly across broad muscosal surfaces and frequently involve adjacent subsites of the oropharynx. As with palatal primary tumors. tumors involving the posterior pillar or tonsil proper tend to be far more exophytic and invasive but are less likely to spread to adjacent subsites until an advanced stage of disease. its relatively ‘‘out of the way’’ lateral location permits normal speech and swallowing functions to carry on in the presence of early-stage lesions (T1 and T2). Osborne. Furthermore.J. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 deficits are not reduced to an appreciable level such that the resultant functional status matches that of patients treated with primary irradiation [4]. early-stage tonsillar carcinomas (T1 and T2) that remain confined to that subsite can be treated with either radiotherapy or surgical modalities. This is one reason the source of many unknown primary tumors is ultimately found to originate in the tonsil.3].). In comparison. Manual for Staging Cancer.74 R. . respectively. Philadelphia: LippincottRaven. Trismus or the restriction of tongue mobility usually indicates advanced disease (T4). The 5-year disease-free survival rates for T3 and T4 lesions are 39% to 56% and 32% to 39%. In general. Because the local control rates for T1 and T2 lesions remains the same at 91% to 100% and 70% to 75%. Studies that have attempted to analyze the modality which offers the best control rates are limited by small numbers and many patient selection biases [9]. dysphagia. J. Despite these limitations. the asymptomatic nature of this disease causes many patients to present with more advanced lesions (T3 and T4) after the presence of pain. there is strong support that surgery combined with radiotherapy probably offers the best chance for obtaining locoregional control. Unlike the soft palate. primary radiotherapy is considered the treatment of choice for early-stage soft palate lesions [3–6]. pp. such as the soft palate or tongue base. the more cryptic locations of the tonsillar complex places this region at high risk for being poorly visualized or overlooked by the casual examiner. Importantly. for either surgery or radiotherapy [2. respectively. Among carcinomas of the aerodigestive tract. This symptom is likely caused by disease extension into the musculature of the pterygoids or base of tongue. 1997. 37. the surgeon must not be conservative with surgical margins out of fear of the functional and reconstructive challenges that may present postoperatively. lesions involving the anterior tonsillar pillars tend to be less invasive and rarely bulky. to achieve similar control rates as radiotherapy. Tonsillar complex Tonsillar carcinoma represents approximately 75% of all carcinomas presenting in the oropharynx. for any treatment modality.11].F. Advanced soft palate lesions portend a poor prognosis. or dysarthria may prompt them to seek help. respectively (American Joint Committee on Cancer. 29. Thus.

Debate continues to revolve around whether surgery should be used up front or for the purposes of salvage. which improves disease-free 5-year survival rates to 85% to 100% for T1 tumors and 80% to 92% for T2 tumors.D. All T3 lesions are not the same. thus minimizing the morbidity associated with treatment of these tumors and maximizing the locoregional control [12]. radiotherapy controlled 89% of T3N0 lesions. and only half of patients with salvaged tumors survive more than 48 months [13. however. Less than 25% of patients who fail radiotherapy have tumors that are considered surgically salvageable. The overall disease-free 5-year survival rates remain acceptable and similar at 75% to 85% for T1 and 55% to 80% for T2 lesions using either surgery or radiation for treatment [10. Patient selection is paramount when considering primary radiotherapy for advanced cancers of the tonsil. Despite the single-modality treatment chosen.F. J. The enthusiasm for this treatment approach must be tempered with the reality that many of these patients’ tumors may not be surgically salvageable after failure of primary radiotherapy. The treatment option for advanced (T3 and T4) tonsillar tumors that provides the greatest chance of disease control involves both surgery and radiotherapy. irradiation largely has become the first-line treatment for early-stage tonsillar carcinomas. This situation therefore can decrease the early detection rate of persistent or recurrent disease. treatment decisions are based on multiple factors: patient health profile. The recurrence rate of tonsil-confined lesions approximated 10% . Osborne. Local extension to other oropharyngeal subsites. and the presence or absence of nodal disease. the control rate dropped to 63%. For instance. availability of adequate radiation or surgical services. When lesions were limited to the tonsillar fossa. patient compliance. especially with large primary tumors. In an effort to spare patients the significant morbidity associated with surgical resection.R. Anderson Cancer Center attempted to identify patient or tumor factors that may predict patients’ responsiveness to radiotherapy [15].14]. When base of tongue involvement was noted. however. a study from the University of Texas M. decreased the curative effects of radiotherapy. radiotherapy with surgical salvage has been advocated. leading to recurrences that have extended beyond the scope of surgical resection. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 75 In these cases. patient preferences. such as the base of tongue in particular. Treatment in this manner allows the reservation of surgery for salvage. control rates at the primary site for T1 lesions approximate 83% to 90% and 70% to 78% for T2 lesions.J. The effects of radiation on the soft tissues can alter the sensitivity of the clinical examination to such an extent that a partial response to therapy can easily be mistaken for a complete response. The degree of histologic differentiation had no influence on locoregional control. Because surgical resection of these lesions offers no curative advantage.11].

costly. Perez et al [20] found a 52% recurrence rate when patients with advanced tonsillar lesions were treated with single-modality radiotherapy. may have a role in patients with residual tongue disease who have completed a course of EBRT and are not candidates for surgical salvage. The classic composite resection with postoperative radiation offers improved locoregional control and survival over any single-modality treatment. J. which further supports the concept of combined-modality therapy for advanced tonsillar carcinomas. the approach to these early-stage lesions are primarily based on the wishes of the patient. centers that approach T1 and T2 tongue base tumors with surgery as a first-line therapy report essentially the same control rates. and the morbidities associated with each treatment the patient is willing to accept. There seem to be no studies . Therefore. Brachytherapy combined with external beam radiotherapy (EBRT) was initially believed to be a superior treatment option to EBRT alone for base of tongue lesions. others use primary radiotherapy and reserve surgery for salvage [29–31]. EBRT is time-consuming.32.F. such as the University of Florida. most centers favor the use of radiotherapy to both the base of tongue and neck. Strong arguments have been made from both sides about which approach is less functionally disabling. Therefore. are achieving local control rates for T1 and T2 tumors of 75% to 100% [21.33]. and increases the risk of soft tissue necrosis. It has since fallen out of favor because of the lack of data that supported its independent use [15–18]. In general.22. The current authors prefer this approach as well. Centers using primary radiotherapy. The role of brachytherapy remains controversial. In addition to unacceptable local control rates. Some centers primarily use surgery with or without radiotherapy [21–28]. Analysis of the literature to objectively compare the efficacy of surgery with or without postoperative radiotherapy versus primary radiotherapy is extremely difficult.14. followed by planned interval neck dissection for N1 or greater neck disease. Tongue base Treatment selection for base of tongue carcinomas is institutionally driven. A review of the literature showed that combination therapy can decrease the rate of local recurrence by 25% to 50% when compared with radiotherapy or surgery alone [10. health status. Greater controversy exists in the management of advanced (T3 and T4) tongue base tumors. the mainstay of treatment for T4 and T3 lesions that demonstrate ulceroinfiltrative features and involve adjacent subsites of the oropharynx has been combination therapy. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 versus a 47% recurrence rate when there was tongue base invasion. Osborne. however. This rate of recurrence was 33% when combination therapy was instituted.76 R. Interstitial implants. institutional resources. Similarly.J. These findings have been mirrored in other studies in the literature [16–18].18–20]. requires additional personnel.

When treating patients with large T3 and T4 tumors. although there seems to be a small improvement in locoregional control when a combined modality is used [33]. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 77 without significant inherent patient selection bias. have ulcerative features. Analysis of the 5-year survival rates for patients with T3 and T4 tumors treated with single-modality radiotherapy shows that these rates equal those seen in patients treated with surgery alone. patients with large lesions are believed to be unlikely to achieve satisfactory local control with radiotherapy alone and are treated with a combined approach. Osborne. At other centers. patients who have significant comorbidities or have tumors that are deemed unresectable are referred for radiotherapy. At some institutions. the clinician must use cruder indications of response. Foote et al [34] showed that. 16% of patients are upstaged at the time of surgery and 31% are down-staged.F. these biases vary from one treatment center to another. in which 46% were up-staged. clinicians have yet to truly achieve this goal. or infiltrate into the deep musculature of the tongue. less infiltrative lesions. Approach to management of the neck Management of the regional lymphatic spread of disease is virtually the same for all subsites of the oropharynx. radiotherapy alone offers local control rates of 59% to 73% and 35% to 44%. the greatest errors in judgment were made in the T1 lesions. Despite sophisticated scientific efforts to identify which tumors are likely to be more radiosensitive. Weber et al [35] showed that T3 and T4 tumor response to radiotherapy could be predicted from morphologic growth patterns of the tumor. the best chance for obtaining local control seems to be a combination of radical surgery with postoperative radiotherapy. J. and the T3 lesions. Those patients with ulceroinfiltrative tumors had a 5-year local control rate of 58% and a 5-year survival rate of 33%. are treated with radiotherapy with or without chemotherapy. Another reason the literature reveals such disparities in treatment protocols lies in the inaccurate and varied pretreatment clinical staging of these lesions. patients with exophytic lesions.J. such as subtotal or total glossectomies. such as gross tumor appearance. overall. reserving surgery for salvage. In general. respectively [33. Patients with exophytic tumors had a 5-year local control rate of 84% and a 5-year survival rate of 67%. Those patients with lesions amenable to resection and who are otherwise relatively healthy are offered surgery with or without postoperative radiotherapy. reserving primary radiotherapy for smaller.R. The range of these control rates reflects tumor differences in radiosensitivity. To further compound the problem. in which 58% were down-staged. significant comorbid states. When patients present with tumors that cross the midline. Thus. The risk of occult cervical . Significantly. or those who will not accept the functional deficits of large resections.35].

There exists no way to ascertain from the literature the true independent effects of chemotherapy on oropharyngeal carcinomas. treatment of N0 neck lesions is justified for all T stages of disease. the use of postoperative radiotherapy is recommended. In the treatment of very advanced oropharyngeal lesions. The medical oncologist has a justified role in the team approach to the treatment of advanced oropharyngeal carcinomas. Most patients being treated with chemotherapy were either enrolled in a study or were receiving treatment at a research-based institution. the role of chemotherapy has changed from experimental to standard of care. Osborne. Very little is known about its role as an adjuvant therapy. Treatment success data for late-stage disease (T3 and T4) are less . Clinically positive (N+) neck disease can be managed in several ways. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 metastases ranges from 15% to 30%. Most studies of merit used chemotherapy for induction or concomitant therapy. the cervical adenopathy can be addressed with surgery as well. They have been shown to improve locoregional control and survival statistics when given with concomitant radiotherapy [36. Summary The data indicate that SCC of the various subsites of the oropharynx can be treated successfully with acceptable locoregional control and survival rates by using either surgery or primary radiotherapy for T1 or T2 primary lesions. therefore. Most early-stage primary lesions are treated with definitive radiotherapy. a planned interval neck dissection approximately 6 to 8 weeks following radiotherapy is common practice. it is recommended that the nodal disease is concurrently irradiated. There are now many promising cytotoxic agents currently under investigation. When the primary site is treated with radiation. Elective neck dissections also can be used in this setting and produce equal control rates with the added advantage of providing a histologic specimen for diagnostic and prognostic information. If the pretreatment nodal tumor burden is significant. Chemotherapy In the past.F. the role of chemotherapy in the treatment of oropharyngeal carcinoma was generally considered experimental and used for palliation. which is also used to address clinically negative neck lesions. Cisplastin and 5-fluorouracil continue to be the most commonly used agents in the treatment of oropharyngeal carcinomas. however. J.37]. When surgery is used as definitive therapy for the primary lesion.J. In the presence of extracapsular spread or multiple positive nodes. because there are no studies in which chemotherapy was used as the sole treatment modality with curative intent.78 R. however.

[16] Tong D. Pfaizgraf K. Stevens G. Results of irradiation in squamous cell carcinoma of the soft palate and uvula. Parker R. Maisel R. Carcinoma of the oropharynx: soft palate. Tran L.63:2442–5. Byers R.7:206–11. [14] Shrewsbury D. . Selch M. Otolaryngol Head Neck Surg 1988. [2] Weber R. Radiother Oncol 1988. Bahadur S. J. [19] O’Brien C. et al. Wolf P. Medina J. Definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa. One problem is that the diversity of approaches to these lesions hinders any meaningful comparisons between series from different treatment centers. Aron BS. Carcinoma of the tonsil: results of combined therapy. J Otolaryngol 1984. Carcinoma of the tonsillar regions: a comparison of radiation therapy with combined radiation and surgery.F. Castle G. Million R. Laramore G. Cassisi N.62: 709–13. Carcinoma of the tonsillar region. Haselow R. Primary radiation therapy in the treatment of squamous cell carcinoma of the soft palate. and anterior faucial pillar. Otolaryngol Head Neck Surg 1981. [6] Horton D. Tiwae R.99:16–24.106: 130–2. References [1] Horton D.99:16–23. Fu K. Spiro R. Primary radiation therapy in the treatment of squamous cell carcinoma of the soft palate. Aust N Z J Surg 1992. Laryngoscope 1986. Carcinoma of the tonsillar fossa. [15] Remmlec D.104:1477–81. Isaacs J. Treatment of choice for squamous carcinoma of the tonsillar fossa. Boles R. J Otolaryngol 1985. et al. uvula.13:165–8. Long term treatment results of post-operative radiation therapy for advance stage oropharyngeal carcinoma. Carcinoma of the soft palate treated with irradiation: analysis of results and complications. Int J Radiat Oncol Biol Phys 1989. uvula. Osborne. This situation has ensured the same heterogeneity in treatment philosophy. Peters L. Rath G. Parsons J. Cancer 1992. Diaz R. Greenberg P.49: 2009–14. Laryngoscope 1994.89:979–85. [12] Wong C. [3] Amdur R.15:619–25. Otolaryngol Head Neck Surg 1988. J Laryngol Otol 1992.63:2442–5.R. [5] Keus R. [10] Mizono G. Arch Otolaryngol Head Neck Surg 1989. 96:240–4.84:2172–80. [17] Maltz R. Griffin T. Doyle J. Adams G. [13] O’Grady M. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 79 encouraging. Mendenhall W. Greenberg P. Carcinoma of the soft palate and anterior tonsillar pillar. Meoz R. Peters L. Ang K. et al. Wolf P. regardless of which modality is used or which treatment center is administering treatment. et al. Cancer 1989. Pontvert D. [4] Garett P. Limitations of radiotherapy in the definitive treatment of squamous cell. Duvall A. Carcioma of the soft palate. Harrison L. Brunin F. [18] Zelefsky M.115:1186–9. Fletcher G. et al. Carcinoma of the tonsillar fossa: an update. This finding may suggest an intrinsic property of these lesions or the patient that may be going unnoticed. Armstrong J. Head Neck Surg 1985. [7] Tandon D. [11] Spire J.70:2388–95. and anterior faucial pillar. Beale F. [9] Leemans C. Carcinoma of the tonsillar region. Squamous cell carcinoma of the soft palate. Engelbrecht W. There exists heterogeneity in patient populations and approaches to staging and characterization of these diseases. [8] Weber R.14:221–5. Guillamondegui O. Cancer 1982.9: 185–94.16:657–62.J. Cancer of the tonsil. Cancer 1989. Flores A. which is largely institutionally based. Tran L. Squamous cell carcinoma of the soft palate. et al. Shumrick D. Laryngoscope 1974. Radiat Oncol 1987.

J.91:143–50. Fee W. Laryngoscope 1972.6:1645–52. Million R. dose. Earle A. O’Fallon W.47:333–42. DeSanto S.F. [29] Foote R. [21] Barrs D. Stringer S. Gidley P. Time. et al.82:1446–54. A reevaluation of split-course technique for squamous cell carcinoma of the head and neck. et al.J. [32] Spanos W. [35] Weber R.104:1466–70. Time-dose relationships for local tumor control and complications following irradation of squamous cell carcinoma of the base of tongue. Rozenbom C. Head Neck 1993. Sharan V.160:415–9. Wollin M. Kagan A. Carcinoma of the tongue. Cancer 1981. DeSanto L. Carcinoma of the tonsillar fossa: a nonrandomized comparison of irradiation alone or cominded with surgery: long term results. Cassisi N.12:107–14. Olsen K. J Surg Oncol 1989. Squamous cell carcinoma of the tonsil and tongue-base region. External beam irradiation alone or combined with neck dissection for base of tongue carcinoma: an alternative to primary surgery. Mendenhall W. [28] Whicker J. Million R. Devineni V. [22] Hintz B. Surgical treatment of squamous cell carcinoma of the base of the tongue. Am J Clin Oncol 1990. Is interstitial implantation essential for successful radiotherapeutic treatment of base of tongue carcinoma? Int J Radiat Oncol Biol Phys 1989. Goffinet D. Peters L.21:349–58.105:479–85. Combined modality therapy of head neck cancer.80 R. Brown / Surg Oncol Clin N Am 13 (2004) 71–80 [20] Perez C.41:165–71. Otolaryngol Clin North Am 1979. Head Neck 1991. [30] Gardner K. [34] Foote R. [27] Strong E. [24] Riley R. Treatment selection for base tongue carcinoma. Cancer of the tongue based treated by a transpharyngeal approach. et al. Parsons J. Fletcher G. Carcinoma of the tongue: review of 20 cases. and tumor volume relationships in irradiation of squamous cell carcinomas of the base of the tongue. Treatment selection for carcinoma of the base of tongue.82:1853–60.17:1191–7. Long term results after chemoradiation for locally confined squamous cell head and neck cancer. Int J Radiat Oncol Biol Phys 1980. [36] Stupp R. Calcaterra T. Vokes E. Hankins P. Laryngoscope 1994. Otolaryngol Head Neck Surg 1983. Bova F. Osborne. Shukovsky L.15:300–7. . Am J Surg 1990. [33] Hinerman R. Squamous cell carcinoma of the base of the tongue: a clinicopathologic study of 81 cases. Devine K. Squamous cell carcinoma of the base of the tongue. Mendenhall W. et al. Wolf P. Laryngoscope 1972. Carmichael T.99:300–3. Parsons J. Int J Radiat Oncol Biol Phys 1987. Summers G. et al. Mendenhall W. [25] Rollo J.13:282–90. et al. Parsons J. Ann Otol Rhinol Laryngol 1990. Morrison W. [26] Schleuning A. et al. Thawley S. Base of tongue carcinorna: patterns of failure and predictors of recurrence after surgery alone. Semin Oncol 1994.37:2591–9.13:440–7. [23] Moore D. Davis D. Cancer 1976. et al.13:507–10. [31] Parsons J. [37] Adelstein D. Weichselbaum R. Arch Otolaryngol 1979.

Gourin). Hypopharyngeal carcinoma is associated with the highest mortality of all cancers of the head and neck. Hypopharyngeal carcinoma is associated with a high incidence of submucosal spread. doi:10. Squamous cell carcinoma (SCC) accounts for 95% of hypopharyngeal pathology. Recent advances in reconstructive techniques and perioperative care have allowed resection of advanced disease with single-stage reconstruction of a functional alimentary tract. because of a shift in the pattern of failure from local to distant disease and the development of second primary tumors. In addition. Augusta. * Corresponding author. FACS*. Poor survival rates are attributed to a preponderance of late presentations and to the unique behavior of tumors occurring in this location. FACS Department of Otolaryngology–Head and Neck (C. Therefore.Surg Oncol Clin N Am 13 (2004) 81–98 Carcinoma of the hypopharynx Christine G. which can be difficult to detect clinically and can result in underestimating the extent of disease. 1120 15th Street. Gourin. USA Carcinoma of the hypopharynx is uncommon.see front matter Ó 2004 Elsevier Inc. Overall survival rates remain poor and largely unaffected.2]. More than 75% of patients who have hypopharyngeal tumors have stage III or IV disease at presentation [1]. Tumors of this region typically remain silent until the disease has reached an advanced stage and causes symptoms from airway or digestive tract obstruction or pain from neural invasion. MD. Cervical metastases are present in 60% to 80% of patients and signify more advanced disease and a poorer prognosis [3–7].1016/S1055-3207(03)00122-4 . while causing the least morbidity and the most effective palliation of symptoms. treatment goals are aimed at eradicating disease and restoration of function. MD. All rights reserved.G. The overall 5-year disease-specific survival rate is approximately 30% to 35% [1.2]. David J. GA 30912. accounting for 4% of all malignancies of the head and neck reported by the National Cancer Data Base and 7% of all malignancies of the upper aerodigestive tract [1. E-mail address: cgourin@mcg. 1055-3207/04/$ . improved locoregional control has been demonstrated with the use of combined-modality therapy. Terris. Medical College of Georgia. however.

In patients with N+ disease. lateral pharyngeal and retropharyngeal nodes. Isolated early-stage lesions of the pharyngeal wall or pyriform sinus have the best prognosis and long-term survival but comprise fewer than 20% of hypopharyngeal carcinomas [3.7–10]. accounting for fewer than 5% of cases [2]. zones II (72%–75%). pp. the postcricoid area. These data provide useful guidelines for treatment planning. Tumor staging based on the American Joint Committee on Cancer classification system (AJCC Cancer Staging Manual. and the posterior hypopharyngeal wall. Springer-Verlag: New York. serial sectioning studies. Tumors that involve the posterior hypopharyngeal wall and the medial wall of the pyriform sinus have bilateral nodal drainage and have a high incidence of involvement of the contralateral neck.G. The proximity of the hypopharynx to the larynx and cervical esophagus mandates that the extent of disease be accurately determined before embarking on treatment. Hypopharyngeal carcinoma is unique in demonstrating a high propensity for extensive submucosal spread. and more than one third of patients without clinical evidence of nodal disease will harbor occult metastases [3–8]. representing more than 60% of all cases. Ho et al [11] found that submucosal tumor extension was present in 60% of specimens. The hypopharynx is served by an extensive lymphatic network. In . 20 mm laterally. and IV (21%–45%) are most often affected. The pyriform sinus is the most commonly involved site. Between 60% and 75% of patients will have clinically involved neck nodes (node-positive [N+]) at presentation. 33–45. 25 mm medially.82 C. submucosal spread was not detectable on gross examination. The incidence and extent of submucosal spread were higher in patients who had undergone previous radiation therapy. The limits of submucosal extension in this series were 10 mm superiorly to the oropharynx. and 20 mm inferiorly toward the esophagus. III (55%–72%). 2003. D. Lymphatic drainage proceeds first to the jugular lymphatics and then to the tracheoesophageal nodes.J. zones I (1%– 10%) and V (11%–15%) are less commonly affected [12. 6th edition. Gourin. Within the hypopharynx are three anatomic subsites: the paired pyriform sinuses. Using whole organ.) shows that contiguous involvement of adjacent sites portends more advanced disease (Box 1). In one third of patients. and the parapharyngeal space.13]. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 Clinical behavior The hypopharynx is described as the region of the pharynx that begins at the level of the hyoid bone and extends to the inferior border of the cricoid cartilage. appearing histologically as tongues and islands of tumor infiltration beneath an intact mucosa. Contralateral occult metastases are present in 37% of patients with N+ disease [14]. The true extent of disease may be initially underestimated because of submucosal extension and the presence of skip lesions [3]. and the postcricoid region is least commonly involved. with macroscopically undetectable submucosal spread present in 82% of patients [11].

N0. M0 Stage II: T2. on behalf of the AJCC. N0. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York. thyroid gland. Chicago. Note: central compartment soft tissues includes prelaryngeal strap muscles and subcutaneous fat T4b: Tumor involves prevertebral fascia. more than 3 cm but not more than 6 cm in greatest dimension. Illinois. any N. N0. or in multiple ipsilateral lymph nodes or bilateral or contralateral lymph nodes. . M1 Used with the permission of the American Joint Committee on Cancer (AJCC). visit www. N1. without fixation of hemi-larynx T3: Tumor [4 cm in greatest diameter or with fixation of hemi-larynx T4a: Tumor invades thyroid/cricoid cartilage. esophagus. none greater than 6 cm N2a: Metastasis in single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension N2b: Metastasis in multiple ipsilateral lymph nodes. 3 cm or less in greatest dimension N2: Metastasis in a single ipsilateral lymph node. M0. none more than 6 cm in greatest dimension N3: Metastasis in a lymph node more than 6 cm in greatest dimension Distant metastasis M0: No distant metastasis M1: Distant metastasis present TNM stage Stage I: T1. any T..cancerstaging. M0 Stage IV: T4. N0 or N1. M0. any T. or involves mediastinal structures Nodal stage N0: No regional lymph node metastases N1: Metastasis in a single ipsilateral lymph node. M0 Stage III: T3.Box 1. Staging of hypopharyngeal cancer Tumor stage Tis: Carcinoma in situ T1: Tumor limited to one subsite of the hypopharynx and 2 cm or less in greatest dimension T2: Tumor invades more than one subsite of hypopharynx or an adjacent 6th edition (2002) published by Springer-Verlag New York (For more information. or measures [2 cm but not more than 4 cm in greatest diameter. hyoid bone. none more than 6 cm in greatest dimension N2c: Metastasis in bilateral or contralateral lymph nodes. Inc. encases carotid artery. M0. The original and primary source for this information is the AJCC Cancer Staging Manual. N2 or N3. Any citation or quotation of this material must be credited to the AJCC as its primary source. T1 or T2 or T3. or central compartment soft tissue.

Metastatic disease involves the retropharyngeal lymph nodes in at least 20% of patients who have hypopharyngeal cancer [15]. taken together. have shown no correlation between the incidence of distant metastases and locoregional disease control [20. These data.J. bone.8.5 cm) of nodes in this location and will miss occult metastases [17].26]. after 2 years. A 20% incidence of occult nodal metastases to ipsilateral paratracheal lymph nodes has been reported in patients with postcricoid lesions and tumors that involve the pyriform fossa apex staged N0 [14]. Locoregional recurrence may eclipse the appearance of distant metastatic disease.19]. The highest incidence of retropharyngeal node metastases was seen in patients with disease involvement of the posterior wall of the hypopharynx (57%) or the cervical esophagus (50%). 36% harbor occult nodal metastases in the ipsilateral neck. The true incidence of retropharyngeal nodal involvement is probably not known because dissection of this level is not routinely performed. Gourin. Imaging studies may underestimate retropharyngeal nodal disease based on the small size (\1. and 27% have occult disease in the contralateral neck [14]. advanced-stage neck disease (N2 or N3).23–25]. and with improved locoregional control.G. distant metastatic disease is responsible for a greater proportion of treatment failures [3. extracapsular spread. and parapharyngeal nodes be included in treatment planning. The incidence of clinically involved retropharyngeal nodes by imaging criteria in patients with hypopharyngeal cancer is 5% [16]. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 patients who have clinically N0 tumors.11. Retropharyngeal nodes were positive for occult metastases in 15% of patients with stage N0 disease [15]. Disease control above the clavicles has been associated with a higher incidence of distant metastases in studies that reported results of radiation therapy.22.6–8.10]. Others. A histologic study of routinely dissected retropharyngeal nodes showed metastases in 20% of patients with hypopharyngeal carcinoma [15].8]. and more than 90% of . D. The incidence of distant metastases is increased in patients who have stage IV disease. distant metastatic disease may subsequently become apparent.19. Distant metastases are present in 6% of patients at initial presentation [2. and liver. Between 12% and 32% of patients develop clinically apparent distant metastases during the course of treatment [3. which has been described as a site of recurrent disease in 5% of patients when untreated [8]. Occult metastases may involve lymph nodes in the parapharyngeal space. The most common sites of involvement are the lungs. Metastases to the thyroid gland and paratracheal lymph nodes occur in 30% of patients who have hypopharyngeal tumors [18]. however. require that both sides of the neck and the retropharyngeal.19–23].84 C. with or without surgery [7. tracheoesophageal. and lymphovascular invasion [7. Salvage of distant metastatic disease is possible in only 6% of patients. involvement of retropharyngeal nodes. Most mortality in the first 2 years following diagnosis is caused by locoregional recurrence.17.25.

A nationwide review of 2939 cases of hypopharyngeal cancer from 1980 to 1992 showed that 9% of patients had stage I disease. such as radiation therapy. several treatment options exist for patients who have hypopharyngeal cancer. Finally. Second primary tumors are present in 7% of patients at the time of initial diagnosis [2]. The 5-year disease-specific survival rates by stage was 63% for stage I. Radiation therapy alone also may be used and seems to be most useful for small (T1 or T2) lesions. Early-stage cancer is considered to be any T1 or T2 lesion with N0 neck disease. may significantly limit treatment options available to the patient [2. Hyperfractionated radiation therapy seems to confer some advantages over conventional radiation therapy in improved locoregional control.7].C. and prior treatment. and 22% for stage IV disease. Table 1 American Joint Committee on Cancer TNM staging classification N0 T1 T2 T3 T4 I II III IV N1 III III III IV N2 IV IV IV IV N3 IV IV IV IV . are considered to be advanced cancers (Table 1).J. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 85 patients die within 2 years of detection of distant metastases [20]. Most patients who have hypopharyngeal cancers present with advancedstage disease. organ preservation therapy using chemoradiation is being increasingly studied and may result in larynx preservation in one third of patients. and most (56%) had stage IV disease at presentation [2]. D. 58% for stage II. or any primary lesion associated with N+ neck disease. Surgery combined with radiation therapy is the standard treatment for most patients who have hypopharyngeal carcinoma. 42% for stage III. Gourin. 22% had stage III disease. 11% had stage II disease. The incidence of distant metastases may be significantly decreased by the addition of chemotherapy to radiation therapy according to several reports and a European Organization for Research and Treatment of Cancer (EORTC) trial specifically evaluating pyriform sinus cancer [27–30]. Between 10% and 17% of patients will subsequently develop a second primary tumor. A history of previous head and neck cancer is present in 16% to 23% of patients.G. Treatment Currently. whereas T3 or T4 lesions.7]. which is a significant cause of mortality in patients who survive for more than 2 years after the initial diagnosis of hypopharyngeal cancer [3.

D. and 20 mm laterally. Gourin. Wei [18] suggested that. The lesion is excised down to the prevertebral fascia. More commonly. The resulting defect may be left to granulate secondarily. an adequate resection margin in patients who have not received previous radiation therapy is 15 mm superiorly. Posterior hypopharyngeal wall Posterior hypopharyngeal wall lesions may be treated with wide local excision. local or regional flaps. usually a combination of both approaches is required for adequate exposure and resection. Subsequently. Patients who have undergone previous radiation therapy require resection margins of 20 mm superiorly. to encourage development of a blood supply to its most distal tip.86 C. The deltopectoral flap is an axialpattern skin flap that is based on perforators of the internal mammary artery. Will total laryngectomy be required. Larger defects can be reconstructed using the deltopectoral skin flap or the pectoralis major myocutaneous flap. or free-skin or visceral flaps. Its use requires a staged procedure. Before modern methods of soft tissue reconstruction. the flap is inset into the defect and divided at yet a later stage. The deep margin in either situation should be greater than 1 mm to ensure complete removal of the tumor without leaving residual disease in the prevertebral musculature [18]. Accurate staging is necessary to answer the following questions: Will excision leave a partial or circumferential hypopharyngeal defect. The location and extent of disease determine the extent of resection required. the deltopectoral flap was widely used. and What is the extent of neck dissection that is required? The predilection of hypopharyngeal carcinoma for submucosal spread must be kept in mind when planning resection of the primary tumor. It has been largely . particularly for midline disease. keeping in mind the extent of resection required to address the possibility of submucosal extension of disease. and 30 mm laterally. based on measurements of submucosal extension in whole organ studies. Prevertebral involvement dooms this approach to failure. The flap is a medially based skin paddle from the upper chest and is initially elevated and reset several weeks in advance of its use when possible. the hypopharynx may be approached through either a suprahyoid pharyngotomy or lateral pharyngotomy. Endoscopic resection has been described for carefully selected small lesions that are widely accessible endoscopically [31].J. The resulting partial posterior hypopharyngeal wall defect usually requires coverage with a split-thickness skin graft. Split-thickness skin grafts should be used whenever possible because of their ease of harvest and minimal morbidity to the patient.G. 30 mm inferiorly. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 Surgical treatment Preoperative evaluation is critical in determining the appropriate surgical approach for treatment of hypopharyngeal carcinoma. 40 mm inferiorly. The graft is sewn to the prevertebral fascia and musculature and bolstered for 5 days.

Pulmonary function tests may provide some objective measure of pulmonary function. or extension of the tumor to within 1. Pyriform sinus Lesions of the pyriform sinus. which results in a significant partial pharyngeal defect.5 cm of the pyriform apex. Similarly. The proximity of the apex of the pyriform to the postcricoid mucosa requires total laryngectomy and cervical esophagectomy in addition to partial pharyngectomy for removal of the tumor and results in a circumferential pharyngeal defect [3]. require at least a partial resection of the larynx for adequate excision. but it requires a laparotomy for harvest with intestinal anastomosis and thus increased morbidity. aspiration is expected in the postoperative period. is significant. The bulk of the pectoralis flap may interfere with swallowing but undergoes atrophy with time. previous pulmonary resection. Transoral CO2 laser excision of pyriform sinus tumors recently has been reported by one group to be effective. The radial forearm and lateral thigh flaps may be harvested as free-skin flaps for use in hypopharyngeal reconstruction. and candidates for partial laryngopharyngectomy must have adequate pulmonary reserve and be in otherwise good medical condition. which provides an extremely reliable and predictable blood supply. by virtue of their proximity to the larynx. These require microvascular anastomosis and result in some donor site morbidity but are thin and pliable and well suited for use in the hypopharynx. The pectoralis flap may be harvested with or without an associated skin paddle: harvest of the overlying skin adds to the bulk of the flap. The jejunal free flap may be used as a patch graft and has an advantage of providing lubrication to this area. larger tumors require total laryngectomy with partial pharyngectomy. Earlystage lesions. Free flaps are a third option for reconstruction.C. Gourin. The use of any free flap requires suitable recipient vessels. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 87 replaced by the pectoralis major myocutaneous flap.J. which.G. even when used as a muscle-only flap. Arytenoidectomy is usually required for adequate excision of the pyriform fossa. an inactive or bed-ridden patient. such as T1 lesions or T2 lesions of less than 2 cm. The pectoralis flap is based on the thoracoacromial artery. with results comparable to transcervical approaches [32]. Regardless of the approach used. D. partial laryngopharyngectomy is unsafe for cancer that involves the apex of the pyriform sinus. can be treated by partial laryngopharyngectomy or extended supraglottic partial laryngectomy. Contraindications to partial laryngopharyngectomy are severe chronic obstructive pulmonary disease. Partial pharyngeal defects may be closed primarily if sufficient mucosa remains to give a tension-free closure over a #36 Maloney esophageal . but far more physiologically useful is a determination of an active lifestyle and good exercise tolerance. This procedure is unsafe for any tumor that is larger than 2 cm. The ability to climb two flights of stairs (the ‘‘Ogura stair test’’) is a reliable test of adequate pulmonary reserve [33].

by elevating and transposing the flap and. The length of hospitalization and the time to oral alimentation is measured in week to months. regional flaps. If insufficient mucosa remains. and jejunal flaps all have been used successfully. Staged reconstruction of pharyngoesophageal defects has been supplanted by newer methods of reconstruction but may be useful when multiple reconstructive efforts fail. Circumferential pharyngeal defects require more involved reconstructive efforts. At a second staged procedure several months later. fistula formation. similar to attempting to roll up a telephone book. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 dilator. such as the deltopectoral flap and pectoralis major flap. Postoperative complications. The radial forearm. The bulk of the pectoralis major flap makes tubing the flap difficult. The pectoralis major flap is the preferred method of reconstruction to patch partial pharyngeal defects because of its ease of harvest. lateral thigh. The incidence of complications has been reported to be 56% with the deltopectoral flap. Because laterally based cervical skin flaps tend to have marginal circulation at the tip. Cervical skin-flap reconstruction is a foreign concept to most recently trained head and neck surgeons. because these are staged procedures. and stenosis have been reported to occur in 90% of patients who have undergone surgical reconstruction with cervical skin flaps [35]. likely because of better blood supply compared with cervical skin flaps [35]. subsequently dividing the pedicle and closing the defect. D. medially based cervical skin flaps were used extensively to reconstruct pharyngoesophageal defects. the thickness of the pectoralis flap and its . partial flap loss occurs frequently. or free-skin or visceral flaps. Gourin. with a greater potential for stricture formation and anastomotic failure. including stenosis. and free-radial forearm. have been reported in 41% of patients [36]. Both the Wookey procedure and the deltopectoral flap are associated with a significant incidence of flap complications and. The pectoralis major myocutaneous flap allows single-stage reconstruction of circumferential defects and is widely used for this purpose today. and jejunal free flaps may be used to fill the defect but carry significantly higher donor site and surgical morbidity. but this seems to be less of a problem with lateral defects after resection of the pyriform fossa. and reliability. In addition. stricture. but before the development of the deltopectoral and pectoralis major flap. For posterior defects.J. The deltopectoral flap is used in a similar fashion. Cervical skin flaps. Flap necrosis. the bulk of the pectoralis major flap may interfere with swallowing. there are an average of three procedures before successful reconstruction is accomplished.88 C. Wookey popularized this technique in the 1940s when he developed a method of pharyngoesophageal reconstruction (the so-called ‘‘Wookey procedure’’) by elevating a laterally based skin flap to form the new posterior wall of the pharyngoesophageal defect.G. at a second staged procedure. medially based flaps from the original flap were elevated and closed longitudinally in the midline to create a new pharyngoesophageal segment [34]. closure may be achieved with the use of the pectoralis major myocutaneous flap. and fistula formation. low morbidity. lateral thigh.

such as the radial forearm. The first-line reconstructive technique for the resulting pharyngoesophageal defect is gastric transposition. Functional outcome seems to be better when the pectoralis major is used to reconstruct a partial defect as opposed to a circumferential defect: patients with circumferential defects have greater difficulty swallowing after pectoralis major reconstruction [37. however. The radial forearm fasciocutaneous flap is based on the radial artery. in addition.G. Free-flap reconstruction of circumferential defects can be accomplished using jejunal free flaps or free-skin flaps. excessive mucus production often results and interferes with tracheoesophageal voice restoration. and scapular flaps. like the pectoralis flap. Because the radial artery in most patients is the dominant vessel to the deep palmar arch. must be tubed to reconstruct a circumferential defect. The secretory properties of the jejunum have been believed to be beneficial. it must be determined that there is a patent anastomosis across the palmar arch between the radial and ulnar arteries before harvest. The main disadvantage of the jejunal flap is the requirement for laparotomy. with a longer suture line resulting and greater potential for anastomotic complications. insetting is relatively straightforward. total esophagectomy is required. Postcricoid lesions Postcricoid tumors are usually advanced at the time of presentation and require total laryngopharyngectomy and cervical esophagectomy. presumably because the suture line is longer in a tubed flap. The primary advantage of the gastric pull-up is that it allows for reliable singlestage reconstruction with a single anastomosis. D. but in the current authors’ experience. or the gastric pull-up. The use of the radial forearm free flap. Jejunal free flaps have the advantage of being tubular and match the defect closely in caliber. the donor site defect is smaller and associated with less morbidity. Abdominal complications related to laparotomy occur in 6% of patients. Donor site morbidity can be significant. Free-skin flaps.38]. is associated with a shorter hospitalization time and decreased time to oral alimentation. Gourin. unlike the radial forearm flap. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 89 adynamic properties may impair swallowing function.41]. and fistula development and swallowing difficulty occur in 18% of patients [39]. The lateral cutaneous thigh flap has gained in popularity as an alternative method of reconstruction and. If disease extends below the lower border of the cricoid.C. most patients are able to successfully achieve full oral alimentation without the need for supplemental enteral feedings [40. but laparotomy and its attendant risks and longer recovery time are avoided. lateral thigh. particularly in patients treated with radiation therapy. compared with the jejunal flap. This flap is associated with a somewhat higher incidence of stricture and fistula formation compared with the jejunal flap. with three enteric anastomoses resulting from harvest. Jejunal harvesting is contraindicated in patients who have Crohn’s disease or ascites. Stricture formation is .J.

reflux. Neck dissection Because of the high incidence of nodal metastases.90 C. Ipsilateral paratracheal node dissection (zone VI) should be included as part of selective neck dissection for all patients who have postcricoid tumors and tumors that involve the pyriform fossa apex [14]. D. and an overall perioperative mortality rate of 20% [35. because the only anastomosis is high in the neck where stricture rarely occurs. Patients who have laterally situated tumors are usually treated with . Terris / Surg Oncol Clin N Am 13 (2004) 81–98 uncommon. which occurs in 20% of patients. The scarcity of metastases to zones I and V supports sparing these zones in this scenario [12. with colon interposition reserved for patients with contraindications to gastric surgery or as a salvage technique. and dumping syndrome. The entire esophagus is removed and the stomach is transposed through the superior mediastinum into the neck.J. Only 30% of patients develop good speech with available techniques of voice restoration [42]. pulmonary complications can occur from thoracic dissection. a 25% incidence of reconstructive complications. Organ necrosis occurs in 3% of patients [38]. including necrosis. Colon interposition has been associated with a high incidence of postoperative infection. respectively.43]. The right or left colon may be used. Gastric transposition entails a complete vagotomy and pyloroplasty. and swallowing after a gastric pull-up can be complicated by early satiety. The weight of the stomach and gravitational pull can cause anastomotic tension and suture line disruption. Contralateral neck dissection is indicated in patients who have midline lesions of the posterior hypopharyngeal wall and postcricoid tumors because of the increased incidence of occult contralateral metastases. The most common long-term complication is reflux. Gourin. The main disadvantage of the gastric pull-up is a significant morbidity and mortality from the procedure. Selective neck dissection of zones II through IV is recommended for all patients with clinically N0 neck disease. and therefore the colon is usually placed in a subcutaneous pocket anterior to the sternum to avoid mediastinal complications if necrosis occurs.G. Patients with clinical evidence of neck disease (N+) require modified radical neck dissection or radical neck dissection of zones I through VI. fistula and stricture. Colon interposition has fallen out of favor because of a 45% incidence of major medical complications. The distal anastomosis is made between the distal colon and stomach. based on the superior mesenteric artery or middle colic artery. ipsilateral neck dissection is warranted in all patients who have hypopharyngeal cancer. Colon transposition is a second-line method of pharyngoesophageal reconstruction when total esophagectomy is required. Gastric transposition is considered the reconstructive technique of choice for total esophageal defects. and the operative mortality is approximately 10% [34]. In addition.44]. Gastric pull-up is not warranted when disease is limited to the cervical esophagus. The rate of major perioperative complications is 50%.

D.7.46]. Bilateral zone VI dissections are rarely performed because of the risk of postoperative hypocalcemia [7].C. with the exception that T4 lesions of the posterior wall seem to have a higher incidence of local recurrence when compared with lateral lesions. probably because of prevertebral muscle involvement [23]. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 91 ipsilateral neck dissection alone. lymphovascular invasion. with better locoregional control and fewer surgical complications.J. Surgery with postoperative radiation therapy is associated with local recurrence rates of 4% to 18% and regional recurrence rates of 17% to 47% [3. N2 or N3 neck disease is associated with 5-year disease-specific survival rates of 0% to 20% compared with 28% to 57% in patients with N0 or N1 disease [3.6. Tumors that involve the medial wall of the pyriform sinus have a higher incidence of regional failure in the contralateral neck compared with lateral wall lesions. and require bilateral neck dissection [6]. Results Limited data exist regarding the results of surgical treatment alone. and avoids the loss of important prognostic information obtained from a nonirradiated surgical specimen [45]. or close or positive margins. No significant difference has been shown in local or regional control rates between pyriform lesions and posterior wall lesions. extracapsular spread.7]. Retrospective reviews comparing surgical treatment alone with surgery plus postoperative radiation therapy have shown decreased locoregional recurrence rates (11%–14% versus 39%– 57%. such as perineural invasion. Gourin. more than two lymph nodes with metastatic disease.46].G. Locoregional recurrence has been reported to be higher in patients with postcricoid lesions compared with those who have lesions in other sites [2]. Advanced-stage neck disease is significantly associated with increased locoregional recurrence rates and poorer 5-year disease-specific survival rates.11. but T4 lesions may require bilateral neck dissection when involvement of the medial wall of the pyriform sinus or postcricoid mucosa is suspected. For most patients. because the combination of surgery and postoperative radiation therapy has become the standard of care for all but very small primary lesions with negative margins and no histologic evidence of nodal metastases [7]. Most patients who have hypopharyngeal cancer have histologic indications for adjuvant postoperative radiation therapy. The presence of extracapsular spread is associated with . respectively) with the addition of postoperative radiation therapy [8. Postoperative radiation therapy is superior to preoperative radiation therapy. Within subsites. surgery alone does not provide sufficient disease control. respectively) and improved 5-year disease-specific survival rates (40%–48% versus 18%–25%. medial wall pyriform sinus lesions have a higher incidence of failure in the contralateral neck when compared with lateral pyriform lesions but have equivalent local and regional recurrence rates [6].

51]. Because of the prevalence of nodal disease and the poor results of surgical salvage.21–23.27. and larynx preservation is rarely possible [50. Early-stage T1 or T2 lesions have the best prognosis for locoregional control with radiation therapy alone.47]. In patients who have clinically staged N0 disease. however. the presence of occult metastatic disease results in poorer 5-year disease-specific survival rates compared with patients who have N0 disease without occult nodal disease (32% versus 50%. Advanced-stage primary disease (T3 and T4) and advanced-stage nodal disease (N2 or N3) are associated with dismal rates of laryngeal preservation and 5-year disease-specific survival rates of 0% to 12%. Gourin.92 C. suffer from an inherent selection bias by including patients referred for radiation therapy because of inoperable disease or poor patient condition. thus contraindicating surgery or chemotherapy [21]. Surgical resection results in loss of the larynx in 56% to 79% of patients and pharyngoesophagectomy in 27% to 44% of patients [2.7–10]. respectively) [7].7]. These numbers have driven the search for effective organ-sparing methods of treatment. Primary radiation therapy The results of treatment with primary radiation therapy for curing patients who have hypopharyngeal cancer are not as favorable as they are for those who have tumors in other sites. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 poorer survival rates among patients with nodal disease [8]. because residual disease may be more likely to recur locally [56].52–56].27.G. Some of these studies. In patients with indications for elective treatment of the neck. Neck dissection following radiation therapy may provide prognostic information.49]. Locoregional control has been reported to occur in 35% to 40% of patients in several nonrandomized single-institution trials [8.J.48]. with rates comparable to those obtained with combined surgery and radiation therapy [9. D. with 5-year disease-specific survival rates as high as 69% [2. Fewer than one third of patients are alive at 5 years with a functional larynx [48].7. primary radiation therapy is not considered a first-line treatment for most patients with advanced-stage hypopharyngeal cancer. Most surgeons believe postradiation neck dissection is . More than 30% of patients who have N2 or N3 disease harbor residual occult microscopic disease in cervical lymph nodes after definitive radiation therapy. the combination of surgery and radiation therapy seems to result in better regional control rates compared with reliance on postoperative radiation therapy alone to sterilize N0 neck disease [6. Surgical salvage after failure of radiation therapy is successful in less than 10% of patients. Local control rates for early-stage disease have been reported to range from 77% to 89%. The addition of a neck dissection following radiation therapy for patients who have N2 or N3 disease improves regional control rates and may cure a subset of patients with residual microscopic regional disease [

J. prospective phase 3 trial to date investigating chemoradiation in patients who have hypopharyngeal cancer was conducted by the EORTC Head and Neck Cancer Cooperative Group [29].23]. to distinguish between responders who are likely to benefit from radiation therapy and nonresponders who are more likely to fail and require surgery. has resulted in more widespread interest in chemotherapy as adjunctive treatment. Patients . resulted in larynx preservation in two thirds of patients who otherwise would have required total laryngectomy. These findings resulted in the acceptance of organ preservation therapy in the treatment of laryngeal cancer and have led to interest in determining whether these findings hold true for other sites in the head and neck.27]. Several nonrandomized studies have reported that hyperfractionated radiation therapy provides a 15% to 25% improvement in local control rates for larger tumors [9. The only randomized. Multiple chemotherapeutic agents have been tried in combination with surgical therapy or radiation therapy. without compromising survival. There is an increased incidence of treatment-related complications on this schedule when compared with conventional radiation therapy and these seem to be dose related [9. In 1990. Chemoradiation therapy Chemotherapy sometimes yields impressive initial tumor responses.23]. Hyperfractionated radiation therapy seems to improve local control rates but incurs socioeconomic and time constraints and does not seem to result in improved survival when compared with conventional radiation therapy [9. Induction chemotherapy with cisplatin and 5-FU. particularly in combination with 5-fluorouracil (5-FU). D.G. Prospective randomized studies are needed to separate out selection bias to determine the efficacy of radiation therapy alone in patients who have hypopharyngeal cancer compared with other modalities of therapy. but it is not a curative modality and does not improve survival rates in patients who have head and neck cancer.C. It has been suggested that doses of 7680 to 7920 cGy administered by twice-daily fractionation are required to demonstrate benefit: the larynx must be shielded at doses greater than 7440 cGy to prevent laryngeal complications from treatment [23]. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 93 indicated for residual neck disease and for patients with N2 and N3 neck disease who seem to have had a complete response to treatment [57]. followed by definitive full-course radiation therapy in responders. the use of chemoradiation for organ preservation was established by the Department of Veterans Affairs Laryngeal Cancer Study Group in a landmark prospective randomized trial [58]. suggesting that tumors that are sensitive to chemotherapy are radiosensitive. The response of SCC to cisplatin.23. Gourin. Patients who respond to chemotherapy show a subsequent response to definitive radiation therapy. Induction chemotherapy consists of the administration of two or three cycles of chemotherapy initially.

respectively). When surgical salvage is required after treatment with organ-preserving techniques. the . The administration of chemotherapy and radiation therapy concurrently may result in a synergistic effect.94 C. 60% of patients treated with this modality have moderate to severe impairment in swallowing ability and a restricted diet caused by pharyngeal dysfunction [64–66]. seem to be more severe with concurrent regimes compared with induction chemotherapy and subsequent radiation therapy. Patients who present with a fixed vocal cord should be counseled accordingly as to expectations about treatment and results. Neck dissection after chemoradiation is associated with a complication rate of 38% [70]. The 5-year estimate of retaining a functional larynx for the chemoradiation group was 35% [29]. the postoperative complication rate is significant. including wound breakdown and fistulas [71]. or to surgery with postoperative radiation therapy. A similar incidence of laryngeal preservation with the use of platinum-based chemotherapy and radiation therapy has been reported by other institutions [27. Significant laryngeal and pharyngeal dysfunction has been reported following chemoradiation [64–68]. however. More recently. the simultaneous administration of chemotherapy with radiation therapy. Acute side effects of treatment. Concurrent treatment with chemotherapy potentially treats distant disease and locoregional disease and may improve survival rates [63].59–61]. Pretreatment vocal cord fixation seems to be the strongest predictor of a poor functional outcome. A decreased incidence of distant metastases was identified in the organ preservation group compared with the surgery group (25% versus 36%. This trial found no significant difference between the chemoradiation arm and the surgery arm in local (12% and 17%. Gourin. Primary resection without free-flap reconstruction is associated with a 77% incidence of postoperative complications. When free flaps are used for reconstruction.G. which is suggested by impressive initial complete response rates [62]. respectively) or regional (19% and 23%) recurrence rates and 5-year disease-free survival rates. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 with T2 to T4 lesions who required total laryngectomy as part of definitive surgical treatment were randomized to receive either induction chemotherapy with cisplatin and 5-FU followed by definitive radiation therapy. These data suggest that larynx preservation with chemoradiation is far less likely for hypopharyngeal cancer than for laryngeal cancer but can be attempted without compromising survival. there seems to be no difference in long-term side effects between either modality of chemotherapy delivery [30]. Prospective randomized trials to test this hypothesis are in progress.28. the preserved organ is not always functional.J. particularly mucositis. concurrent chemoradiation. Dysphagia may have a slow onset during treatment and a prolonged recovery period: at 1 year after chemoradiation. Although larynx preservation is possible with chemoradiation. with more than 50% of patients requiring a feeding tube or tracheostomy 6 months after the completion of therapy compared with patients without vocal cord fixation [69]. has been used to take advantage of the effects of simultaneously administered chemotherapy as a radiation enhancer. D.

Herson J.18:317–22. Damm M. Robinson RA. Karnell LH. Laryngoscope 1982.92:357–64. Huo J. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 95 incidence of wound complications following chemoradiation has been reported to be 20%.124:951–62. [7] Kraus DH. Junghuelsing M. et al. Vankemmel B. Staar S. Squamous cell carcinoma of the pyriform sinus. Hypopharyngeal patient care evaluation. overall survival rates for patients who have hypopharyngeal carcinoma have not improved. The best results are obtained with multimodality therapy.132:439–43. Chemoradiation is an effective alternative method of aggressive treatment but may be associated with significant dysfunction of the end organ when preservation is possible. [10] Eckel HE. . Gourin. Brown GS. Harrison LB. [9] Garden AS. Head Neck 1994. Laryngoscope 1997.C.J. Karnell LH. Shah JP. Medial vs. [2] Hoffman HT. Menck HR. Ariyan S. Otolaryngol Head Neck Surg 2001. Volling P. Myers EN. Because of poor long-term survival rates. [4] Shah JP. Goepfert H. Otolaryngol Head Neck Surg 1997. DeLaTorre JC. Yuen PW. Am J Surg 1976. Fee WE. D. Head Neck Surg 1987. Delobelle-Deroide A. Lam LK.124:561–9. Spiro RH. Sittel C. Fletcher GH. Squamous cell carcinoma of the hypopharynx—analysis of treatment results.107:1005–17.15:405–12. and results.G. Shah AR. Combined surgery and radiation therapy for squamous cell carcinoma of the hypopharynx. Ang KK. Shah JP. These data suggest that free-flap reconstruction should be performed when salvage surgery of the primary site is required. Head Neck 1996. [3] Ho CM. Wagner RL. Radical surgery with postoperative radiation therapy remains the standard of care. Peters LJ. Oswald MJ. Funk GF. Wei WI. mortality. Brock HA. The National Cancer Data Base Report on cancer of the head and neck. two thirds of patients are palliated rather than cured of disease. but at best. Morrison WH. Surgical treatment for hypopharynx carcinoma: feasibility. Carcinoma of the hypopharynx. Early squamous cell carcinoma of the hypopharynx: outcomes of treatment with radiation alone to the primary disease. [5] Lefebvre JL. Castelain B. [6] Johnson JT.16: 401–5. and less severe with an average hospital stay of 8 days [72]. Summary Despite advances in surgical and nonsurgical treatment. Lymph node invasion in hypopharynx and lateral epilarynx: a prognostic factor. and this disease still has a poor prognosis. lateral wall pyriform sinus carcinoma: implications for management of regional lymphatics. Zelefsky MJ. local control remains the most important factor in planning treatment. Bacon GW.116:637–41. Lam KH. References [1] Hoffman HT. Arch Otolaryngol Head Neck Surg 1998. Clayman GL.10:14–8. Organ preservation strategies have not been as successful in hypopharyngeal cancer as for cancers of other head and neck sites. to provide meaningful palliation and best possible quality of life. Head Neck 1993. Strong EW. [8] El Badawi SA.

12:197–203.19:567–75. Arch Otolaryngol Head Neck Surg 2002.111: 1099–103. D. Davis LW. Patterns of cervical node metastases from squamous carcinoma of the oropharynx and hypopharynx. Wei WI. Shah AR. The dilemma of treating hypopharyngeal carcinoma: more or less. [28] Adelstein DJ. [22] Horwitz SD. Caldarelli DD. Gourin. Treatment of carcinoma of the hypopharynx. Tuason L. ORL J Otorhinolaryngol Relat Spec 2001. Incidence and sites of distant metastases from head and neck cancer. Saxton JP.10:4–13. Int J Radiat Oncol Biol Phys 1991. Hendrickson FR. [18] Wei WI. Int J Radiat Oncol Biol Phys 1993. [25] Alvi A. [20] Spector G. Parsons JT.96 C. Cervical node metastases in squamous cell carcinoma of the head and neck: what to expect. Mendenhall WM. Combined chemotherapy and radiotherapy versus surgery and postoperative radiotherapy for advanced hypopharyngeal cancer. Head Neck 1997. [14] Buckley JG. [13] Mukherji SK.17:293–7.26:751–7. et al. Arch Otolaryngol Head Neck Surg 1997. Johnson JT. Ridant AM. J Natl Cancer Inst 1996. Development of distant metastasis after treatment of advanced-stage head and neck cancer. .22: 380–5. Mendenhall WM. [30] Fu KK. Laryngoscope 2001. Luboinski B. Andersen PE. Mendenhall WM. Cassisi NJ. Lam KH. Kirkpatrick A. Does node location affect the incidence of distant metastases in head and neck squamous cell carcinoma? Int J Radiat Oncol Biol Phys 1989. [23] Fein DA.21:549–56. [16] McLaughlin MP. [26] Leibel SA. [12] Candela FC. A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. [24] Ferlito A.128:229–32. Mamelle G. Kinishi M. et al. Head Neck 1996. Cassisi NJ. Kothari K. Chevalier D. Armao D. Squamous cell carcinoma of the pyriform sinus: a retrospective study of 351 cases treated at the Institute Gustav-Roussy. The effect of local-regional control on distant metastatic dissemination in carcinoma of the head and neck: results of an analysis from the RTOG head and neck database. Raben A.G. Combined-modality therapy for head and neck cancer. Marcial VA. McCarty PJ. Head Neck 1987. ORL J Otorhinolaryngol Relat Spec 2001. Arch Otolaryngol Head Neck Surg 2000.11:1781–90. Rao PV.2:107–11. Head Neck 2001. Shah JP. Collette L.19:500–5.123:959–65. et al. Head Neck 1995. Coia LR. Submucosal tumor extension in hypopharyngeal cancer. Oncology 1997. Accuracy of computed tomography in determining the presence or absence of metastatic retropharyngeal adenopathy.23:995–1005. Distant metastases from laryngeal and hypopharyngeal cancer. Silver CE.126:1478–81. Talbot M. Wanamaker JR. Strong EW. Head Neck 1997.88:890–9. [21] Vandenbrouck C. Head Neck Surg 1979. De La Rochefordiere A. Significance of retropharyngeal node dissection at radical surgery for carcinoma of the hypopharynx and cervical esophagus. [27] Zelefsky MJ. et al. Eschwege F. et al. Cohen JI. [29] Lefebvre JL.J. Kraus DH. Mondin V. Scott CB. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 [11] Ho CM. Mancuso AA. [17] Morrissey DD. Lavertu P. Wood BG. Parsons JT. Mohri M. Sahmoud T. Spangler AE.63:224–8. Rinaldo A. Parsons JT. Cervical node metastases in laryngeal and hypopharyngeal cancer: a prospective analysis of prevalence and distribution.18:405–11. Ng WF. Head Neck 2000. Retropharyngeal adenopathy as a predictor of outcome in squamous cell carcinoma of the head and neck.63:202–7.17:190–8. Wax MK. Joshi VM. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. Million RR. Million RR. [15] Amatsu M. Stringer SP. Head Neck 1990. Pharyngeal wall carcinoma treated with radiotherapy: impact of treatment technique and fractionation. Mohiuddin M. Yuen AP. MacLennan K. Pfister DG. [19] Ellis ER. Sicot H. Shah JP. EORTC Head and Neck Cancer Cooperative Group.

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Hughes PG.324:1685–90. Harrison LB. Factors predictive of poor functional outcome after chemoradiation for advanced laryngeal cancer. Kies MS. Chauvel P. Newman L. Sebelik M. Terris / Surg Oncol Clin N Am 13 (2004) 81–98 [54] Parsons JT. Arch Otolaryngol Head Neck Surg 1995. Bradford CR. posttreatment neck dissections. Haines IE. Shah JP. Cassisi NJ.125:401–5. Crane CH. Chepeha DB. [58] Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group. Peters LJ. Arch Otolaryngol Head Neck Surg 1999.J. et al. Esclamado RM. Otolaryngol Head Neck Surg 2002. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. [61] Demard F. Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Cummings CW. Response to chemotherapy as a justification for modification of the therapeutic strategy for pharyngolaryngeal carcinomas.12:225–31. Strong E.13:699–718. Hematol Oncol Clin N Am 1999. [70] Davidson BJ. [60] Kraus DH. Lee DJ. Picken CA.111:31–7. Laryngoscope 2001. [68] Kotz T. Gourin. Cohen JI. Vallicioni J. Bradford CR. Haraf DJ. et al. Sessions RB. Robbins KT. Miller AE. Pellitteri P. Harrison LB. [69] Staton J. Arkinson JL. Shaha AR. Planned neck dissection as an adjunct to the management of patients with advanced neck disease treated with definitive radiotherapy: for some or for all? Head Neck 1999. Stringer SP.21:606–13. N Engl J Med 1991.126:384–9. Arch Otolaryngol Head Neck Surg 1999. Sessions RB.98 C. Cullen KJ. Arch Otolaryngol Head Neck Surg 2000. . Head Neck 2001. Analysis of wound complications.6:749–68. et al.111:1192–6. Myers LL. Abraham S. et al. Cullen KJ. Million RR. Forastiere AA. Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.121:974–80. Chemoradiotherapy for organ preservation in oral and pharyngeal carcinoma. Planned neck dissection for advanced primary head and neck malignancy treated with organ preservation therapy: disease control and survival outcomes. List M. Sessions R. Viera F. Beitler JJ. [56] Newkirk KA. [64] Koch WM. J Am Coll Surg 2001. Santini J. The use and misuse of neck dissection for head and neck cancer. Beitler JJ. Kleid S. Samant S.9:850–9. Stenson K. The role of chemotherapy in the curative treatment of head and neck cancer. Picken CA. [63] Gillison ML.125: 410–3.18:1652–61. [57] Robbins KT. Larynx preservation in head and neck cancers.121:162–5. Eisele DW. Mendenhall WM. [67] Smith RV. Lyden T.11:400–4. [59] Pfister DG. Smith RV. Davidson BJ. Neck dissection after twice-a-day radiotherapy: morbidity and recurrence rates. Surg Oncol Clin N Am 1997. Newkirk KA. Byers RM. Int J Radiat Oncol Biol Phys 2002. Kotz T. A discussion of the National Comprehensive Cancer Network practice guidelines. Harrison L. Humerickhouse R. Otolaryngol Head Neck Surg 1994. Dawson LA.193:91–102. Wolf GT. J Clin Oncol 1991. Head Neck 1990. [55] Narayan K. Armstrong JG. Haxer MJ. [65] Vokes EE. Free tissue reconstruction of the hypopharynx after organ preservation therapy: analysis of wound complications. Spiro RH. Arch Otolaryngol Head Neck Surg 1995.127:43–7. Wadler S. Wadler S. Pfister DA. Lavertu P. [71] Sassler AM. Thyss A. [62] Pfister DG.53:23–8. [66] Eisbruch A. Larynx preservation with combined chemotherapy and radiation therapy in advanced hypopharynx cancer. Complications from planned. et al. Pharyngeal transport dysfunction consequent to an organ-sparing protocol. Surgery after organ preservation therapy. Schneider M. Miller D. Harter KW. Long-term swallowing problems after organ preservation therapy with concomitant radiation therapy and intravenous hydroxyurea.23:73–9. Poole M. Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer. J Clin Oncol 2000. Pfister DG. Head Neck 1989. Harter KW. D.G. [72] Teknos TN.

such as: painters. doi:10. and is often a disease of the elderly. tobacco being the single most important risk factor. All rights reserved. NY 14263. Mojica-Manosa). but most studies show that it has a synergistic effect with tobacco use [6.*. MDb. Italy. Cessation of smoking for more than 15 years decreases the risk to nearly that of nonsmokers [4. Spain has one of the highest rates in the world—some regions reach a rate of 20 cases per 100. Men are affected four times more frequently than women [1]. Elm and Carlton Streets. The relationship to alcohol and larynx carcinoma is unclear. and Poland.000 persons. Roswell Park Cancer Institute. Wade Douglas. E-mail address: pablo.Surg Oncol Clin N Am 13 (2004) 99–112 Larynx squamous cell carcinoma: concepts and future directions Pablo Mojica-Manosa. The male/female ratio is greater in glottic carcinoma than supraglottic carcinoma. MDa. Buffalo. In addition. Keith Wilson. and those * Corresponding author. P. There are more than 30 known carcinogens in tobacco. 1055-3207/04/$ .O. Less than 1% of the cases developed in patients under 30 years of age [2]. multiple factors contribute to the development of this (P. Medical Science Building. metal-working and plastic-working machine operators. USA b University of Cincinnati. Functional impairment of the larynx is a burden to patients who suffer from laryngeal carcinoma.7]. Box 670528. James Reidy. The American Cancer Society estimated that there would be 8900 cases of laryngeal carcinoma in 2002. The peak incidence is in the sixth and seventh decade of life. MDa Department of Head and Neck Surgery. DOa.see front matter Ó 2004 Elsevier Inc. certain occupations and exposures increase the risk of developing carcinoma of the larynx. with 3700 deaths. Cincinnati. Another risk factor for developing larynx carcinoma is alcohol use.1016/S1055-3207(03)00130-3 . the second most common cancer of the head and neck region after the oral cavity. As with most tumors. Other countries with high incidence are France. The most well-known are polycystic aromatic hydrocarbons and nitrosamines [3]. construction workers.mojica@roswellpark. USA a The larynx is a sphincter and is therefore one of the most important structures in the upper aerodigestive tract. OH 45267.5].

and the thyroepiglottic ligament inferiorly. pre-epiglottic space. glottic. The supraglottis is derived from midline wedge-shape structures and ultimately has bilateral blood supply and lymphatic drainage. The most inferior aspect is the petiole. Treatment options are often based on the anatomic site of laryngeal cancer. This space is continuous laterally with the para-epiglottic space. and nerves. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 exposed to diesel and gasoline fumes. It provides a formidable barrier for carcinoma invasion to the base of the tongue [9]. wood dust. or asbestos [8]. Anatomy The larynx is divided anatomically and clinically into three areas: supraglottic. Larynx The supraglottic larynx extends from the epiglottis down to the lateral angle of the ventricles. The infrahyoid portion is covered by mucosa posteriorly and abuts the fat of the preepiglottic space anteriorly. The pre-epiglottic space is surrounded by the hyoepiglottic membrane superiorly. and the lymphatic drainage tends to be ipsilateral. which is attached to the thyroid cartilage by way of the thyroepiglottic ligament. the thyrohyoid membrane anteriorly. these perforations provide a route of spread for supraglottic carcinoma from the mucosa to the pre-epiglottic space [9]. It is a fenestrated structure that provides a pathway for the extension of normal structures like lymphatics. It is the point of attachment of numerous muscles and ligaments. Dietary factors that predispose an individual to laryngeal carcinoma include intake of salt-preserved meat and high dietary fats and chronic gastric reflux disease. The suprahyoid portion is covered by mucosa in both sides. It is composed of the greater cornu laterally and lesser cornu medially. It is widest at the top and tapers down to the petiole. infrahyoid. The glottic larynx extends from the lateral angle of the ventricle down to one centimeter below the apex of the ventricles. The epiglottis is composed of elastic cartilage. It contains the true vocal cords. In addition. therapeutic radiation. It arises from lateral cell masses that come together. submucosal glands. the hyoid bone and arytenoids cartilage mucosa. The hyoepiglottic ligament is the roof of both the paraepiglottic and preepiglottic spaces. blood vessels. There is a suprahyoid.100 P. the posterior and anterior commissure. This includes the epiglottis. The hyoid bone is the most superior structure of the supraglottic larynx. . and petiole portion. This section describes how the anatomy relates to cancer origin and spread. These spaces are important because they provide the route for superior and inferior spread in the larynx [9]. and subglottic. the epliglottis posteriorly. This space is bounded anterolaterally with the thyroid cartilage and thyrohyoid membrane and medially with the quadrangular membrane.

The overall metastatic rate to cervical lymph nodes for larynx squamous cell carcinoma in general for all subsites is: T1. respectively. and 25% to 40% for T4 tumors [12]. The lymphatic spread has also been studied by site. 65% to 80% [10–12]. which is a pathway of less resistance to tumor progression. The lymph nodes that are more commonly involved are levels II. lymphatics have a higher propensity for extralaryngeal extension. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 101 The lamina propia of the true vocal cords has a superficial layer composed of loose fibrous tissues that makes up Reinke’s space. It is a rare site for primary tumor origin. This area contains the paraglottic space. the rate of bilaterally disease in the neck is higher in centrally located and large tumors [16]. However.P. An intermediate and deep layer consisting of elastic and collagenous fibers forms the vocal ligament. which is a pathway for tumor progression through the larynx [9]. which is attached to the thyroid cartilage. 30% to 70%. Blood vessels and lymphatics are almost absent in this space. In the supraglottic larynx. the rate of node metastasis differs from that of the supraglottic. The occult metastasis ranges from 20% to 50% base on the T stage. Lymphatic and distant spread Lymphatic spread from the primary tumor of the larynx is of great importance because of its impact on treatment options and survival. The rate of lymph nodes metastasis is also influence by the subsite in the supraglottis. 10% to 20% for T3. The incidence of clinical or occult node metastasis in tumors presenting at the marginal zone or large size tumors is greater when compared with centrally located or transglottic tumors. with most of the patients also presenting nodal involvement at levels II to IV [15]. 6% to 25%. but is more commonly associated with subglottic extension from the glottis. Because of the proximity of the cricothyroid membrane and the rich postcricoid. In glottic tumors. For T1/T2 the rate for clinical or occult metastasis is 30% to 70%. This area is devoid of perichondrium. and IV [13. T3 and T4. This commisure extends superiorly from the thyroepliglottic ligament.14]. having 50% of those with contralateral disease. The most anterior aspect is the cricothyroid membrane. the rate of nodal involment depends on the T stage. Another structure that makes tumor invasion more resistant is the conus elasticus. 5% to 10% for T2. Past studies have shown that levels I and V have been involved in 6% and 1%. This membrane extends from the true vocal cord down to the upper border of the cricoid cartilage. The rate of neck metastasis overall is less than 5% for T1. III. which creates resistance to tumor invasion [9]. T2. Bilateral and contralateral neck metastasis is rare except in subglottis and . The subglottic larynx extends from the bottom of the glottic to the inferior aspect of the cricoid cartilage. The true vocal cords meet anteriorly in the anterior commissure tendon.

after a follow-up of 2 years [18]. and the so-called ‘‘hot potato’’ voice. With an increased understanding of the molecular biology of cancer. Factors that portend a poor prognosis include: increasing T stage. airway compromise. bone. stridor. Accurate examination by way of indirect or direct laryngoscopy is of most importance to staging and treatment planning [30]. larynx tumors are classified using the American Joint Committee for Cancer guidelines. and presence of distant metastasis [21–24]. Overexpression of the c-myc oncogene has been correlated with a resistance to radiation and chemotherapy and increased metastatic potential [27]. much research has been directed in characterizing this tumor type. Diagnosis The diagnosis of laryngeal cancer should be suspected when hoarseness is present for more than 2 to 3 weeks.102 P. The most common affected organ is the lung. and presence of distant metastasis (M stage) (Table 1) [20]. Other symptoms associated with laryngeal tumors are hemoptysis. Little is known about primary subglottis tumors. In addition.26]. halitosis. because their incidence is less than 1% of all larynx tumors. The clinical development of distant metastasis for larynx tumors of the supraglottis and glottis are 15% and 3%. Mediastinal node involvement has also been described [17]. followed by the mediastinum. Second primary malignancies develop in 11% to 19% of patients. Dysphagia. extracapsular spread of the cancer. One important aspect to consider with this type of tumor is the high rate of paratracheal node involvement (65%) and low rate of cervical node involvement (20%) [17]. Mutations in p53 and ras genes have been associated with high-grade tumors and increased metastatic potential [29]. They are staged according to the tumor size (T stage). and liver. respectively. presence of cervical lymph node metastasis (N stage). The incidence of distant metastasis without local recurrence is greater for supraglottis tumors than for glottis tumors. with this type of extension delphian node involvement and thyroid invasion are evident [12]. There have been studies pointing to DNA aneuploidy as a factor for increased recurrence when compared with diploidy tumors [25. usually within the first 5 years after treatment [19]. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 supraglottis extension of the tumor. airway insufficiency upon exertion. Tumors in the glottic usually present early because of vocal cord involvement. and neck mass are more common in advance disease. tumors of the supraglottis usually present later because of a lack of symptoms in the early stages. presence of cervical nodal metastasis. Expression of int-2 has been associated with decreased survival [28]. A critical . Staging and prognosis In the United States.

or invades mediastinal structures Subglottis T1 Tumor limited to the subglottis T2 Tumor extends to vocal cords with normal or impaired mobility T3 Tumor limited to larynx with vocal cord fixation T4a Tumor invades through the thyroid cartilage or invades tissues beyond the larynx (eg. strap muscles. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 Table 1 TNM staging of larynx carcinoma 103 Primary tumor (T) Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ Supraglottis T1 Tumor limited to one subsite of supraglottis with normal vocal cord mobility T2 Tumor invades mucosa of more than one adjacent subsite of supraglottis. thyroid. 3 cm or less in greatest dimension N2a Single ipsilateral node. or minor thyroid cartilage erosion (eg. soft tissues of neck including deep extrinsic muscle of the tongue. paraglottic space. or minor thyroid cartilage erosion (eg. soft tissues of neck including deep extrinsic muscle of the tongue. medial wall of pyriform sinus) without fixation of the larynx T3 Tumor limited to larynx with vocal cord fixation or invades any of the following: postcricoid area. thyroid. glottis. or invades mediastinal sturctures Glottis T1 Tumor limited to the vocal cords (may involve anterior or posterior commissure) with normal vocal cord mobility T1a Tumor limited to one vocal cord T1b Tumor involves both vocal cords T2 Tumor extends to supraglottis or subglottis. or region outside the supraglottis (eg. or esophagus) T4b Tumor invades prevertebral space. or there is impaired vocal cord mobility T3 Tumor limited to the larynx with vocal cord fixation or invades paraglottic space. pre-epiglottic tissues. encases carotid artery. encases carotid artery. mucosa of base of tongue. thyroid. strap muscle. or esophagus) T4b Tumor invades prevertebral space. encases carotid artery. inner cortex) T4a Tumor invades through the thyroid cartilage or invades tissues beyond the larynx (eg. strap muscles. soft tissues of neck including deep extrinsic muscle of the tongue. or invades mediastinal structures Regional lymph nodes (N) Nx Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Single ipsilateral node. trachea. or esophagus) T4b Tumor invades prevertebral space. greater than 3 cm and less than 6 cm N2b Multiple ipsilateral nodes less than 6 cm N2c Bilateral or contralateral nodes less than 6 cm N3 Metastasis in a lymph node more than 6 cm in greatest dimensions (continued on next page) . trachea. inner cortex) T4a Tumor invades through the thyroid cartilage or invades tissues beyond the larynx (eg trachea.P. valleculla.

. . patients must be warned of this possibility when conservation surgery is contemplated. With a suction catheter tip. while invasion of bony or cervical lymph nodes is better evaluated with CT [31. visit www. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 Table 1 (continued ) Distant metastasis (M) Mx Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Data from the American Joint Committee on Cancer (AJCC). and mucosal extent of the tumor. especially with bulky tumors. on behalf of the AJCC. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York. A chest X ray and liver function test is sufficient for a metastatic survey in the absence of systemic complaints [35]. A biopsy of the lesion should be performed in this case.34]. Direct visualization can assess the size. trachea.cancerstaging. Involvement of the soft tissue. and early cartilaginous invasion is better evaluated with MRI.104 P. Both CT and MRI provide adequate assessment. PET imaging can be used to differentiate postchemotherapy and radiation changes of sterilized tumor and fibrosis from recurrence in comparison with CT and MRI in those nonsurgical or organ-preserving patients. Inc. Operative endoscopy is the gold standard for pretreatment staging. and regional lymph node in the neck. which could reveal the need for a total laryngectomy. vocal cord involvement. extralaryngeal spread. cartilage involvement. The true extent of the tumor is fully evaluated during surgical exploration. subglottis extension. The original and primary source for this information is the AJCC Cancer Staging Manual. paraglottic space extension. Adjunct to the history and physical examination is the use of radiologic studies to ascertain the depth of the tumor involvement. location. The status of laryngeal ventricles and the subglottic extend of the tumor are the two most challenging aspects of direct laryngoscopy. Under general anesthesia. areas of friable mucosa and submucosal firmness—which may represent submucosal extension—may be identified.32]. These studies help evaluate the presence of pre-epiglottic space extension. Chicago. Illinois. digital palpation of the base of the tongue and vallecula may reveal areas of extensive submucosal spread. Any citation or quotation of this material must be credited to the AJCC as its primary source. and bronchial tree should be evaluated to rule out any synchronous tumors in the upper aerodigestive tracts. and extralaryngeal involvement. component of evaluation is an assessment of the size and location of the tumor. 6th edition (2002) published by Springer-Verlag New York (For more information. It is also helpful for surveillance for second primary malignancies [33. The

extension. supraglottic laryngectomy. respectively. leiomyosarcoma. The mainstay of treatment for advanced supraglottic carcinoma is combination modality therapy that includes surgery and radiation. The vast majority of laryngeal tumors are squamous cell carcinomas. liposarcoma. fibrous histiocytoma. synovial sarcoma.P. with stage III at 40% and stage IV at 20% [8]. T4). radiation. exophytic tumors tend to respond better to radiation than endophytic tumors. This article concentrates on the management of this type of tumor. Important secondary goals of treatment include a serviceable voice and the ability to swallow without aspiration. T2) tumors. surgery and radiation treatment are equivalent in terms of locoregional control and survival. neuroendocrine. and total laryngectomy. cure rates. The most common tumor types include cystic adenoid (adenocarcinoma). Other tumor types include pseudosarcoma. The type of procedure is influenced by the site of the 5-year survival rates for surgery. Chemotherapy and radiation is an alternative that is under . of which chondrosarcomas predominate. Cure rates are lower for advanced tumors (T3. It is important to consider the patient’s age and general medical condition. and carcinoid. in T2 tumors. respectively [37–40]. and 2. For example. nodal status. Several factors may affect treatment. Tumor location and extent and the patient’s general medical condition may also dictate the treatment option. Surgical salvage for radiation failure equalizes locoregional control for both modalities. For early (T1. they are 80% to 90% and 70% to 80%. depending on the stage. Treatment Treatment of this type of tumor should focus on providing an adequate oncologic chance of cure while attempting to minimize morbidity. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 105 Pathology Only 1% of all laryngeal tumors are of the nonsquamous type. or combination therapy. Supraglottic carcinoma Treatment options for carcinoma of the supraglottis varies widely for local control. is important to inform the patient that it may ultimately change to a total laryngectomy if the tumor extension goes beyond the previous examination studies. Sarcomas have been reported. and giant cell tumors. The control rates for surgery and radiation in T1 tumors are 90% to 95% and 80% to 90%. and poorly differentiated tumors tend to metastasize more readily than well-differentiated ones [36]. Although conservation surgery may be planned. supracricoid subtotal laryngectomy. The most common approaches to stage I and II are vertical partial laryngectomy. and surgeon’s expertise.

Radiation therapy is recommended for advance cases. thyroidectomy. subglottic extension. anterior commissure involvement. Glottic caricinoma Locoregional control in glottic carcinoma differs from the supraglottic carcinoma because of its embryology. and the 2-year disease-free survival is 79% for T3 and 58% for T4 [8]. Anterior commissure invasion may change the T stage from T1 to T4 in a few millimeters. ranging from 84% to 96%. T4). Locoregional control after surgery or radiation for T1 is 98% and 85% to 95%. Local control rates for surgery are greater. For cases in which nonsurgical treatment yields a response of less than 50%. Radiation therapy is less effective with vocal cord mobility impairment [42]. For advanced glottic cancer (T3. presence of cervical node metastasis. In rare cases. especially if both cords are diseased. salvage with surgery may be indicated [41]. . the local control rates for radiation therapy range from 40% to 60%. Laryngeal preservation can be achieved with the combination of chemotherapy and radiation 60% of the time [41]. conservation surgery may be attempted. Treatment usually involves the combination of surgery and radiation therapy. Most cases are a subglottic extension from glottic carcinoma. Combined modality therapy is considered superior to either surgery or radiation alone. and involvement of the airway. and paratracheal node dissection. The most common surgical treatment is total laryngectomy. and total size of the tumor.106 P. If a nonsurgical approach is chosen. It is recommended that surgery include laryngectomy. Subglottic carcinoma Primary subglottic carcinoma is rare. Subglottic extension may increase recurrence from 12% to 32% if extension is greater than 5 mm posteriorly or 10 mm anteriorly [43]. respectively. Total laryngectomy is usually performed. Many factors can influence the decision regarding optimal treatment. Clinical consideradtions include endophytic versus exophytic. involvement of soft tissue in the neck. the combination of chemotherapy with radiation is an effective treatment and will conserve the larynx 60% of the time. Treatment options will be affected by decreased vocal cord mobility. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 evaluation. extensive cartilage invasion. for T2 it is 82% and 65% to 75%. Elective neck dissection is recommended when the risk of cervical nodal metastases is greater than 25%. The ultimate decision to treat advanced glottic carcinoma depends on the tumor specifics and the patient’s desires and general medical condition. Vocal cord impairment will decrease local control from 77% to 50% in 3 years. while near total laryngectomy or supracricoid laryngectomy may be used in certain cases. Involvement of the subglottic space increases the risk of extralaryngeal spread. respectively [8].

the risk of pathological or clinically involved nodes is between 30% and 70%. adjuvant. the location of the tumor influences the incidence of nodal metastasis. Elective neck treatment in the form of surgery or radiation is recommended for T3 or T4 glottic lesions. the rate is higher when compared with more centrally located tumors. and IV in the clinically negative neck. so does the risk of bilateral neck spread. These nodal patterns support the removal of levels II. The goal of this approach is to preserve the larynx in those patients who would otherwise need a total laryngectomy. The experimental arm consisted of two initial cycles . with contralateral disease occurring 50% of the time. The rate of occult disease is approximately 15% for T3 and approximately 30% for T4 [46]. Bilateral or contralateral disease will be seen with subglottic and supraglottic extension of the tumor. selective node dissection can be adequate treatment. The most significant of these protocols comes from the multi-institutional trail performed by the Department of Veterans Affairs Laryngeal Cancer Study Group [41]. In the last decade. One important aspect of supraglottic carcinoma is the fact that as the tumor size increases. Radiation can be used as primary. III. In this study. Because the rate of occult metastases for T1 and T2 lesions is between 1% to 8%. Radiation can be considered for definitive treatment of cervical nodal metastases in patients presenting with N0 or N1 disease [50]. Because of the embryology of glottic carcinoma. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 107 For the supraglottis. A comprehensive neck dissection should be performed for the clinically positive neck. the risk of pathologic metastatic node involvement ranges from 15% to 48% depending on the site and size of the tumor [8]. the incidence of nodal spread differs and the rate of contralateral disease is lower.P. followed by radiation. induction chemotherapy was administered with cisplatin and 5-FU. it is recommended that both sides of the neck be included in the treatment planning for tumors T2 or higher. Postoperative radiation to the neck should be considered for patients who present with multinodal disease or extracapsular spread [51]. If there is extension beyond the subglottis. For cases in which there is pathologic node involvement of only one node. For lesions in the marginal zone. With this in mind. whether with surgery or radiation. Radiotherapy and chemotherapy in the treatment of laryngeal cancer Radiation therapy may be used in the treatment of laryngeal cancer in a variety of ways. chemotherapy has played a more important role as neoadjuvant therapy in combination with radiation to treat advanced laryngeal carcinoma. Many study protocols using chemotherapy and radiation to preserve laryngeal function have demonstrated that the larynx can be preserved without compromising survival.45]. In the clinically negative neck. or neoadjuvant modality. there is little role for elective neck treatment [44. For T2 tumors. level IV should be included in the dissection [47–49].

seroma.59]. In those cases where PCF persists despite conservative therapy. pneumonia. outcomes. Some studies suggest that concomitant chemotherapy and radiation therapy may provide better locoregional control when compared with sequential chemotherapy/radiation therapy [55]. Complications. or free flaps may be used to correct the defect [63–65]. .57]. Mojica-Manosa et al / Surg Oncol Clin N Am 13 (2004) 99–112 of chemotherapy. renal failure. reduced laryngeal elevation. In addition. and reduced posterior tongue base movement [60]. diarrhea. Toxicities include mucositis. and 64% of the patients retained their larynx in the chemotherapy/radiation therapy arm. and conventional fractionation versus accelerated fraction radiotherapy. such as reduced laryngeal closure. The major drawback for the induction concurrent chemotherapy/ radiation therapy is the substantial morbidity. The survival and locoregional control was equivalent between both arms. the most troublesome is PCF. and pharyngocutaneous fistula (PCF) formation (5% to 15%) [61. Nevertheless.108 P. and cessation of oral intake will promote fistula closure most of the time. if the tumor responded with more than 50% reduction. If the tumor had less than 50% reduction or progression of the disease. Protocols have decreased total radiation dosages in an attempt to minimize this. and myelosuppression. hematoma. local. There have been studies investigating the differences between sequential and concomitant chemotherapy/radiation therapy. mortality has been reported with chemotherapy and radiation in the range of 0. Problems in function after chemotherapy and radiation have been reported. Acute complications include wound infection. it should be mentioned that preservation does not translate into function automatically. Conservation management with appropriate wound care.62].6% to 6% [58. with incidence rates increasing to 20% to 30%. More recent studies show that complete clinical response has been seen 59% to 68% of the time [52–54]. the patient completed a third cycle of chemotherapy followed by radiation. Complications increase when radiation therapy is used preoperatively. Studies that followed that of the Department of Veterans Affairs Laryngeal Cancer Study Group have tried to identify the combination and sequence schedule that will yield the best responses for organ preservation and morbidity without compromising survival. At present. and future directions Complications after surgery can be classified as acute or chronic. a total laryngectomy was performed with adjuvant radiation. This approach has prevented 7% to 18% of patients from completing a full course of neoadjuvant therapy [56. regional. no study has demonstrated conclusively that either concomitant chemotherapy/radiation therapy or accelerated fractionation is better than standard sequential chemotherapy followed with conventional fractionation radiation therapy in demonstrating a difference in overall survival. different chemotherapy combinations (most cisplatin-based). particularly if radiation is administered in the therapeutic range. early detection. dermatitis.

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which is associated with a poor prognosis. A heightened risk after radiation exposure [2] is not uniformly reported [3]. Newark. The overall detection rate for salivary gland malignancy based on clinical features is approximately 30%. Patients who have deep-lobe parotid tumors may present with distortion of the lateral pharyngeal wall on intraoral examination. Both benign and malignant tumors can present with pain in a small percentage of patients. Parotid gland tumors constitute 70% to 80% of tumors of the salivary gland. including allelic loss. Parotid pleomorphic adenoma is the most common parotid neoplasm.Surg Oncol Clin N Am 13 (2004) 113–127 Major salivary gland cancer Robert L. Four fifths of the parenchyma of the gland lies lateral to the facial nerve. Malignant parotid tumors are slightly more common in women.000 individuals. USA b Department of Otolaryngology. Jefferson Medical College. Department of Surgery. Wilmington. All rights reserved. facial nerve palsy. Philadelphia. slowgrowing tumors that are indistinguishable from benign tumors. accounting for 60% to 70% of parotid tumors. Approximately 80% of parotid tumors occur in the lower part of the gland. MDa. Malignant salivary gland tumors generally present as painless. Trismus may represent infratemporal fossa involvement. Witt. may be factors in some cases. and 90% of parotid neoplasms present in the superficial lobe. DE. with a peak incidence in the fifth through seventh decades of life. and absence or addition of a chromosome.* a Section of Otolaryngology.1016/S1055-3207(03)00126-1 . Most malignant salivary gland tumors arise from the excretory or intercalated duct reserve cells [1]. Suite 112. in the superficial lobe. Genetic alterations. palpable cervical lymph nodes. and 20% of parotid gland tumors are malignant.b. PA. and deep fixation and rapid enlargement of the tumor are significant parameters for parotid gland tumors [4].com 1055-3207/04/$ . USA Salivary gland tumors represent 3% of head and neck tumors and 0. Their origin is largely unknown. chromosomal translocations. Malignant salivary gland tumors have an incidence of less than 1 per 100. DE 19806. E-mail address: robertlwitt@aol. Approximately 10% of patients who have parotid gland malignancies present with facial paralysis. * 2401 Pennsylvania Avenue. Christiana Health Care Systems.see front matter Ó 2004 Elsevier Inc. doi:10.6% of all tumors in the body.

Imaging and fine-needle aspiration Preoperative CT.) (Box 1). however. MRI may indicate an inferior tail of parotid mass. Infiltration of the tumor into muscle or bone on MRI is predictive of malignant disease. and they can be mistaken for mucoepidermoid carcinoma or adenoid cystic carcinoma [7. Imaging is helpful for submandibular and sublingual gland tumors. Weakness or numbness of the tongue indicates perineural involvement of the hypoglossal or lingual nerve. and survival rates are similar to those in patients who have submandibular gland tumors of the same histologic type. American Joint Committee on Cancer. The American Joint Commission on Cancer 2002 classification of major malignant salivary gland tumors follows the tumor-node-metastasis (TNM) system of staging (AJCC Cancer Staging Manual. There is difficulty in distinguishing a benign oncocytic tumor from an acinic cell carcinoma.8]. mobile mass of the tail of the parotid gland is not mandatory. Fine-needle aspiration (FNA) for a small. MRI. The 5-year survival rate has recently been reported to be as high as 50% [5]. facial nerve dysfunction and cervical lymph node metastasis. Most parotid cancers are high-grade tumors. Sublingual gland tumors are very rare. Management of parotid tumors with fixation. histologic patterns of pleomorphic adenoma are variable. MRI provides superior resolution of soft tissue structures and is the preferred modality for evaluating a parotid tumor and neck metastasis. The accuracy of FNA in broadly distinguishing benign and malignant tumors. is more than 90% in most series [7]. Furthermore. They present as a submucosal mass on the anterior floor of the mouth. Springer-Verlag: New York. Highresolution MRI may detect perineural involvement. submandibular gland cancers are regarded as more aggressive and are associated with a lower survival rate compared with parotid gland tumors of the same histologic type. Positron emission tomography categorizes only 69% of parotid tumors correctly when attempting to distinguish benign from malignant parotid masses [6]. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 Cervical lymph node metastasis is observed in 10% to 20% of malignant cases. 6th edition.L. The breadth of histologic subtypes in parotid tumors makes cytologic diagnosis a formidable goal. and a Warthin’s tumor (adenolymphoma) from a low-grade mucoepidermoid carcinoma [8].114 R. Submandibular gland tumors are malignant in 50% of cases. debilitated patients with a parotid neoplasm. such as . In elderly. 2002. and deep-lobe tumors with parapharyngeal extension is enhanced with imaging. constituting 10% of all salivary gland malignancies. or ultrasonography rarely alters the clinical course for small tumors of the superficial parotid lobe. but generally. approximately 80% are malignant. with a global 5-year survival rate of 45% to 50%. when clinical presentation would suggest an upper cervical nonparotid neck mass. Fixation to the mandible or skin infiltration suggest extraparenchymal extension.

tuberculosis. The original and primary source for this information is the AJCC Cancer Staging Manual. any T N3. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York. M0 M0. Chicago. It also is helpful in patients who have . any N Stage IVc any T any N M0 M0 M0. T1/T2/T3 N0. visit www. Inc. a Warthin’s tumor. Any citation or quotation of this material must be credited to the AJCC as its primary source. T1/T2/T3 N0/N1/N2 N2 Stage IVb T4b. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 115 Box 1. M0 M1 Data from the American Joint Committee on Cancer (AJCC).R. on behalf of the FNA can distinguish an upper cervical neck mass from a low tail of parotid tumor. FNA may obviate the need for surgery. ear canal. the use of FNA may avoid parotid gland surgery in sarcoidosis. M0 M0. mandible. histoplasmosis. 6th edition (2002) published by Springer-Verlag New York (For more information.L. and benign cervical adenopathy in patients with HIV and in children. Illinois. TNM staging system for salivary gland tumors T: tumor T1 tumor smaller than 2 cm T2 tumor 2 to 4 cm T3 tumor 4 to 6 cm or tumor with extraparenchymal extension T4a tumor invading skin.cancerstaging. In addition. lymphoma. or facial nerve T4b tumor invading skull base or pterygoid plates or encasing carotid artery N: regional lymph nodes N1 single ipsilateral node smaller than 3 cm N2a single ipsilateral node 3 to 6 cm N2b multiple ipsilateral nodes smaller than 6 cm N2c bilateral or contralateral node smaller than 6 cm N3 node larger than 6 cm M: distant metastases M0 no distant metastases M1 distant metastases present Staging Stage I Stage II Stage III T1 N0 T2 N0 T3. N1 Stage IVa T4a.

More rigorous attention to the operative margin may be required when results of preoperative cytologic tests reveal malignancy. a World Health Organization. and pathologists in 6 countries. 2nd edition. Histologic typing of malignant salivary gland tumorsa Acinic cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Polymorphous low-grade adenocarcinoma Epithelial-myoepithelial carcinoma Basal cell adenocarcinoma Sebaceous carcinoma Papillary cystadenocarcinoma Mucinous adenocarcinoma Oncocytic carcinoma Salivary duct carcinoma Adenocarcinoma Myoepithelial carcinoma Carcinoma ex pleomorphic adenoma Squamous cell carcinoma Small cell carcinoma Other carcinomas Data from: Seifert G in collaboration with Sobin LH. Springer-Verlag: Berlin. The type of malignant tumor is much more difficult to classify correctly by FNA. and molecular biology In 2002. Histology. . 1991.116 R. Mucoepidermoid carcinoma Mucoepidermoid carcinoma is the most common malignant tumor of the parotid gland and the second most common malignant tumor of the Box 2. Preoperative diagnosis is helpful to advise patients about the extent of surgery that may be required or that operative findings may dictate sacrifice of the facial nerve. 2002. immunohistochemistry. and can distinguish a salivary gland neoplasm from a metastatic occult upper respiratory tract primary tumor in a patient who has a painless mass that does not enlarge with oral intake. Finally. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 submandibular neoplasms. the World Health Organization suggested the histologic typing of malignant salivary gland tumors listed in Box 2. Histological typing of salivary gland tumors.L. World Health Organization international histological classification of tumors. there have been no reports of seeding of tumor along the needle tract.

164. Washington. (From Ellis GL. 1). In: Rosai J.L. Subclassification includes low-grade. Wide excision without radiation therapy results in 5-year survival rates for low-grade tumors that approach 75%. editor. There is a slight female predilection. whereas high-grade tumors are dominated by poorly differentiated squamous cells with poorly defined margins. Photomicrograph of low-grade mucoepidermoid carcinoma (magnification 40Â with H&E stain). and high-grade tumors. neural invasion. and tumor necrosis. with less than 10% of patients presenting with facial nerve dysfunction. intermediate-grade. Low-grade tumors are circumscribed but not encapsulated and have a predominance of mucin cells (Fig.R. High-grade mucoepidermoid carcinoma presents with facial nerve Fig. with permission. Mucoepidermoid carcinoma is located in the parotid gland in 80% to 90% of patients. Differentiation between high-grade mucoepidermoid carcinoma and poorly differentiated squamous cell carcinoma (SCC) may require special staining with periodic acid–Schiff stain for the presence of glycogen in the mucin or positive staining for mucicarmine in the mucous cells. Atlas of tumor pathology. 1. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 117 submandibular and sublingual glands. 1996.) . DC: Armed Forces Institute of Pathology. p. Auclair PL. Tumors of the salivary gland. comprising approximately one third of parotid malignancies. high mitotic activity. Most mucoepidermoid carcinomas are low grade. Mucoepidermoid carcinomas contain mucin-producing cells and epithelial cells.

Recommended treatment is surgery and radiation therapy. The tubular subtype. with the classification depending on the predominant subtype. 206. Lymphatic spread is less common than distant metastasis to bone and lung. In: Rosai J. Atlas of tumor pathology. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 dysfunction in 25% of patients and has a propensity for locoregional and distant recurrence. The incidence of facial nerve dysfunction in adenoid cystic carcinoma is 20%. Grading is not as successful in predicting clinical outcome in submandibular mucoepidermoid carcinoma. surgical Fig. DC: Armed Forces Institute of Pathology. including the skull base in 42% of patients [8]. 1996. Recurrences generally develop within 5 years. has the best prognosis. Photomicrograph of the cribriform type of adenoid cystic carcinoma demonstrating the ‘‘Swiss cheese’’ appearance (magnification 100Â with H&E stain).118 R. allowing distant spread. with a more glandular histology.) . Adenoid cystic carcinoma Adenoid cystic carcinoma is the second most common salivary gland malignancy. which yields a 5-year survival rate of 50%. representing 10% to 20% of major salivary gland cancers. although most of these tumors present as an asymptomatic mass. Arrows show pseudolumens that are in continuity with the stroma of the tumor. Invasion into salivary gland parenchyma and soft tissues is common. Tumors of the salivary gland. Women are more commonly affected. but late recurrences develop 10 to 20 years later. The solid subtype has sheets of cells and is associated with a grim prognosis. Auclair PL. 2). other significant factors include the site of origin. The factors with the greatest impact on survival are the stage of the disease and histologic grade. Perineural involvement by direct invasion is the hallmark of adenoid cystic carcinoma. p. (From Ellis GL. Most tumors display more than one histologic subtype. Washington. Histologic subtypes include the most common ‘‘Swiss cheese–appearing’’ cribriform pattern (Fig. with permission. editor. It is the most common malignancy of the submandibular gland and sublingual glands: half of all sublingual tumors are adenoid cystic carcinomas.L. 2.

L. Atlas of tumor pathology. Regional lymph nodes are the most likely site of metastasis. This low-grade tumor occurs primarily in the parotid gland and rarely presents with facial nerve dysfunction (Fig. with permission. making this tumor second only to Warthin’s tumor for bilateral presentation [10]. Many patients survive for several years after recurrence. In: Rosai J. Washington. respectively [9]. (From Ellis GL. 1996. DC: Armed Forces Institute of Pathology. Acinic cell carcinoma Acinic cell carcinoma constitutes 10% to 15% of malignant salivary gland tumors. including solid. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 119 margin. follicular. Two thirds of the patients are female.R. Photomicrograph of acinic cell carcinoma (magnification 200Â with H&E stain). but up to 80% ultimately succumb to this malignancy. The 10-year survival rates for the solid and cribriform subtypes have been reported as 0% and 62%. and microcystic. which do not correlate with Fig. 3). Approximately 3% of acinic cell carcinomas occur bilaterally. p. medullary. papillary cystic. There are numerous subtypes. editor.) . Tumors of the salivary gland. 186. Auclair PL. and previous radiation therapy. 3.

but the invasive subtype is associated with regional and distant metastasis [13]. with both epithelial and mesenchymal metastasizing components. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 prognosis. the degree of invasion and histologic grade have an impact on survival. In addition. These tumors have been reclassified into subtypes with similar histopathology .L. Surgery without radiation is recommended for this well-circumscribed tumor. The most common of the three types of malignant mixed tumors. A noninvasive subtype with either complete encapsulation or only limited microscopic invasion has an excellent prognosis. with most occurring in the parotid gland. a lethal tumor with few survivors. large tumor size. these tumors are associated with a mortality rate of 22% [15]. Sudden enlargement may represent malignant transformation. Finally under this category is the rare histologic curiosity known as benign metastasizing pleomorphic adenoma. Cervical neck node metastasis occurs in 25% of patients. The malignant mixed tumor also can present as a true carcinosarcoma from the beginning. Clinical findings and histologic features at the initial diagnosis that indicate a greater likelihood of malignant transformation are as follows: older patient age. Malignant mixed tumors Malignant mixed tumors comprise 5% to 10% of salivary gland malignancies. Adenocarcinoma and related classifications Adenocarcinoma is a shrinking category (as is undifferentiated carcinoma). Gender is not a factor in presentation. Surgery and postoperative radiation therapy are recommended and lead to an overall 5-year survival rate of 40%. carcinoma ex pleomorphic adenoma (CEPA). typically presenting as an adenocarcinoma. Five-year survival rates of 75% are achieved but these rates decrease with longer follow-up periods. Local recurrences are treated with further surgery. arises from a pleomorphic adenoma that has been untreated for many years or from a previously treated pleomorphic adenoma that has recurred. and they are histologically indistinguishable from pleomorphic adenoma. Ploidy results do not predict tumor behavior in CEPA. These tumors have an absence of cytologic atypia. submandibular gland location. The most common epithelial types are SCC and adenocarcinoma. and prominent zones of hyalinization or at least moderate mitotic activity [11]. Immunohistochemistry has demonstrated that activation of c-myc and ras p21 protooncogenes and the involvement of the p53 mutation may play an important role in the malignant transformation of pleomorphic adenoma [14]. The rate of malignant transformation approaches 10% in tumors that have been present for 15 years [12]. and the most common mesenchymal tumor is chondrosarcoma.120 R. Acinic cell carcinoma is the second most common pediatric salivary gland malignancy after mucoepidermoid carcinoma. Only the epithelial component metastasizes. however.

Metastatic disease to an intraparotid lymph node from a skin primary tumor.R. and this tumor is associated with low recurrence rates and a high rate of expected survival. contiguous spread of SCC from an adjacent skin primary tumor. which originates from the excretory duct reserve cell and resembles intraductal carcinoma of the breast. poorly differentiated mucoepidermoid carcinoma (mucin stains must be negative to exclude mucoepidermoid carcinoma). PLGA has a varied histologic (polymorphic) appearance of papillae. and squamous metaplasia must be excluded. representing 1% of cases. Carcinomas with ductal features without other distinguishing characteristics are termed ‘‘adenocarcinoma. The prognosis is generally poor. With advanced-stage disease. Melanoma Most malignant melanomas arise from cutaneous primary sites. and solid aggregates. Salivary duct carcinoma. Squamous cell carcinoma Primary SCC of the parotid gland is rare. Approximately 20% of patients present with facial nerve dysfunction. widely infiltrating the parotid gland. survival rates are less than 50%. Invasion helps distinguish PLGA from the benign pleomorphic adenoma. is an extremely aggressive tumor with low survival rates [16]. for which it can also be mistaken. Differentiating salivary duct carcinoma from the more indolent polymorphous low-grade adenocarcinoma (PLGA) is important. Before histologic refinements. Mucosal and ocular primary sites also must be considered. Up to 60% of patients who have this SCC present with cervical lymph node metastasis and facial nerve dysfunction. The immunoreactivity of smooth muscle–specific proteins also helps differentiate adenoid cystic carcinoma from PLGA [16]. Perineural involvement can make distinction from the more aggressive adenoid cystic carcinoma difficult. Immunoreactivity of smooth muscle–specific proteins helps differentiate adenocarcinoma from the high-grade salivary duct carcinoma. Treatment consists of wide excision and postoperative radiation therapy. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 121 and biologic behavior based on electron microscopy and immunohistochemistry. A 5-year survival rate of less than 50% is generally predicted. not otherwise specified. PLGA has a female predominance (2:1) and arises primarily from intraoral minor salivary glands. with the parotid gland being a frequent metastatic location. Primary SCC arises from metaplastic parotid duct epithelium. Local and regional spread is limited. glandular structures. These tumors often act in an aggressive fashion. with frequent regional and distant metastasis. salivary duct carcinoma and PLGA were classified as adenocarcinoma. There is a 2-to-1 male preponderance.’’ Adenocarcinoma is generally an aggressive tumor.L. Radical surgery and postoperative radiation therapy are required for this highly malignant tumor. .

and primary melanomas may be near or overlap the nodal basin in the head and neck. nonHodgkin’s lymphomas.6% rate of facial nerve dysfunction (and one case of temporary facial nerve paresis) [17]. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 Identifying the primary tumor of a parotid metastasis can be exceptionally difficult when the rare spontaneous regression of the primary tumor occurs. Preoperative lymphoscintigraphy using intradermal injections of technetium Tc 99m antimony trisulfide colloid. Sentinel node biopsy in the parotid gland has been performed without facial nerve dissection. Undifferentiated carcinoma Undifferentiated carcinomas include large cell undifferentiated carcinoma. Immunohistochemical analysis can help differentiate the low-grade mucosa-associated lymphoid tissue lymphoma from myoepithelial sialadenitis. Molecular biology DNA flow cytometry can assist in the characterization and diagnosis of salivary gland malignancies. followed within 4 hours by intraoperative handheld gamma-probe localization. even intermediateand high-grade lymphomas of the parotid gland can have a satisfactory prognosis with chemotherapy and radiation therapy. Lymphoma Lymphoma of the parotid gland represents 1% to 2% of parotid malignancy presenting either primarily or as part of disseminated disease. however. This procedure can be coupled with intraoperative injection of 1% isosulfan blue dye. Bang et al [20] reported that 43% of salivary gland tumors were reclassified after DNA . The complex lymphatic drainage of the head and neck has slowed the use of sentinel node biopsy. In many cases. with a 2. Technical success rates have risen to 95%. with 80% of patients presenting in stage I or II disease [18]. small cell undifferentiated carcinoma. and face has been questioned. Primary lymphoepithelial carcinoma may arise from a benign epithelial lesion. Many patients have multiple positive nodes. Most are B-cell. Primary lymphomas are usually low grade. has been used to improve sentinel node biopsy. The incidence is equal in men and women.122 R. with an associated Epstein-Barr virus infection [19]. and lymphoepithelial carcinoma. and this tumor rarely occurs before the age of 50. which can be difficult to diagnose. lymphoma can be diagnosed with FNA using immunohistochemistry.L. The routine elective use of superficial parotidectomy for patients who have primary melanoma of the scalp. auricle. Patients with Sjogren’s syndrome have a 40-fold greater risk for ¨ a parotid lymphoma than the general population. It has been reported in Asians and Greenland Eskimos. Further study to define the role of sentinel neck nodes in the parotid gland and the surgical procedures to address them is required.

and nodal metastasis are indications for nerve monitoring. superficial tumors that extend to the deep lobe. Deep-lobe tumors. such as mucoepidermoid.L. Facial nerve dissection can be performed atraumatically with a fine hemostat. and its oncoprotein expression is an independent indicator of clinical aggressiveness in parotid cancer [22]. facial nerve dysfunction. The p53 tumor-suppressor gene may be involved in salivary gland carcinogenesis. The development and progression of cancer are regulated by various oncogenes and tumor-suppressor genes. Facial nerve monitoring for a mobile tumor of the superficial lobe will not decrease the rate of facial nerve dysfunction [24]. Electrosurgical dissection is eschewed. CEPA. Tenascin immunoreactivity is intimately associated with c-erbB-2 positivity and weak staining of collagen IV [23]. The facial nerve trunk emanating from the stylomastoid foramen is superior to the cephalic margin of the digastric muscle. and salivary duct carcinoma [21]. the facial nerve branches are elevated from surrounding parotid tissue or tumor. recurrent tumors. tumors larger than 4 cm. Bipolar scissors. Collagen IV and tenascin are extracellular matrix constituents. the harmonic scalpel. Genetic alterations. play an important role in the progression of malignant salivary gland tumors. The pes anserinus of the facial nerve is invariably located 2 mm to 4 mm inferior to this most important anatomic landmark. The cartilaginous tragal pointer leads to the tympanomastoid suture. specifically adenocarcinoma. and plastic scissors. The sternocleidomastoid muscle is separated from the parotid gland. The minimal operation for a parotid mass is superficial parotidectomy with facial nerve dissection. Low-grade parotid tumors may be treated with superficial parotidectomy.R. such as those involving p53 and c-erbB-2. and hemostat/stimulator probes with a dedicated nerve monitor have been advocated. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 123 flow cytometry. fixed tumors. After completion of the superficial parotidectomy. Weak immunoreactivity for collagen and intense staining of tenascin are determinants of recurrent disease. DNA aneuploidy noted in undifferentiated adenocarcinoma or squamous carcinomas is associated with reduced survival times compared with those of predominantly diploid tumors. and the deep lobe is separated from the . bipolar coagulation. The incision in the preauricular skin curves gently 2 mm below the ear lobule to prevent distortion of the ear lobule. and tumors involving the parapharyngeal space. Enucleation will result in higher rates of recurrence and facial nerve dysfunction. Treatment Salivary gland surgery Surgery is the primary treatment for salivary gland malignancy. acinic cell. Deep-lobe dissection or total parotidectomy is indicated for deep-lobe tumors. and adenoid cystic carcinomas [20]. high-grade tumors. and subsequently 3 cm below the mandible so as not to traumatize the marginal mandibular branch of the facial nerve.

A facial nerve surrounded by tumor is best treated with resection. Parapharyngeal parotid tumors can present as an oropharyngeal submucosal mass and can pass posteroinferiorly or posterosuperiorly to the stylomandibular ligament. Infrequently. ear numbness. Complications of submandibular and sublingual gland surgery revolve around the cranial nerves dissected. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 masseter and other muscles. Neck dissection Neck metastases are present in 10% to 20% of parotid gland malignancies. hematoma. the mucosa of the floor of the mouth. and the hypoglossal nerve deep to the posterior belly of the digastric muscle. retrograde identification of peripheral nerve branches is required for large. high rates of survival confirm the efficacy of postoperative radiation therapy in eradicating microscopic remnants of tumor after surgery. Facial skin involvement requires reconstruction with local or regional flaps or free-tissue transfer. Preoperative facial nerve weakness suggests a very high likelihood of facial nerve sacrifice intraoperatively. Sublingual gland resection should proceed with cannulation of Wharton’s duct using a lacrimal probe and identification of the lingual nerve. If direct neurorrhaphy is not possible. In cases in which the tumor extends close to the nerve. the lingual nerve.L. Involvement of the middle cranial fossa and medial neurovascular structures of the jugular foramen may require subtotal petrosectomy. Although this procedure transgresses the classic oncologic principle that malignant tumors should be resected with a wide margin. The cervical-parotid approach is successful for most cases. A balance between eradicating the tumor and preserving the facial nerve is warranted.124 R. and salivary fistula. Complications include facial nerve dysfunction. En bloc excision may require resection of the floor of the mouth or marginal or segmental mandibulectomy. Frey’s syndrome. most commonly with the greater auricular or sural nerve. Cortical mastoidectomy can be used to identify the intratemporal course of the facial nerve and to follow it to the stylomastoid foramen. Facial nerve branches should be spared unless they are involved with tumor. cable nerve graft reconstruction is performed. These structures. identified by its looping course along the hyoglossus muscle. bulky tumors or for surgical procedures for recurrent tumors. the tumor potentially can be peeled off the nerve and treated with postoperative radiation therapy. and the associated alveolar mandible may require resection if sublingual gland cancer is present. The survival rate . These generally occur in levels II and III. Submandibular gland tumor resection calls attention to the following anatomic sites: the marginal mandibular branch of the facial nerve deep to the platysma (ligation of the facial vein and upward traction protects this branch). Suction drainage will minimize the risk of hematoma and allow the wound to be readily observed without a dressing. Anterior or lateral mandibulotomy is required more commonly for malignant tumors approaching the skull base.

The risk of neck recurrence is higher in patients with node-positive disease [25]. . positive margins. high-grade tumors (excluding adenoid cystic carcinoma.L. CEPA. II. SCC. Neck dissection for N0 neck disease remains a debated topic. In N0 neck disease. although chemotherapy has been used in palliative settings. and serial sectioning of lymph nodes have increased the rate of reported micrometastasis. Significant factors for survival are as follows: advanced age. facial nerve involvement. preoperative facial nerve dysfunction. Nodal metastasis reduces the survival rate by 50%. high-grade mucoepidermoid carcinoma. and positive margins. with few sequelae from radiation [27]. in order of frequency. Immunohistochemistry. the risk of subsequent nodal metastasis was only 4% (7 of 164 cases) [26]. Selective neck dissection at levels IB. and distant metastasis [26].R. In a reported series of N0 parotid gland malignancies treated with parotidectomy and radiation therapy without neck dissection. Radiation therapy as the primary treatment may be appropriate for patients with unresectable tumors or those with overwhelming comorbidities. and the upper part of level V should be considered in patients who have high-risk N0 disease. Recurrence The pattern of recurrence for most parotid gland malignancies. positive nodal disease. facial nerve involvement. and high-grade tumors are candidates for postoperative radiation therapy. and T3 and T4 tumors have a 27% risk of nodal metastasis [25]. the odds of neck micrometastasis being present are increased in adenocarcinoma. Combined therapy with surgery followed by radiation therapy has resulted in improved 5-year disease-free survival rates as high as 77%. is local recurrence. Chemotherapy or combined radiation therapy and chemotherapy have not improved survival (excluding lymphoma). Witt / Surg Oncol Clin N Am 13 (2004) 113–127 125 for parotid gland malignancies without metastasis is 75%. Postoperative radiation therapy for patients with positive surgical margins was reported to be effective for T1 and T2 disease but not for advanced-stage disease [28]. T1 and T2 tumors have a reported 12% risk of metastasis. Radiation therapy Patients who have advanced-stage disease. and extraglandular tumor extension. high-grade tumors. Selective neck dissection may assist in determining the need for postoperative radiation therapy. in which lymph node metastasis is rare). Clinically positive neck metastases are treated with neck dissection. cell culture techniques. and treatment has ranged from 50 to 70 Gy. molecular analysis. nodal metastasis. cervical neck metastasis. III. Retrospective reviews have not defined a radiation dose–response relationship. extraparenchymal spread. tumor stage.

Summary Major salivary gland cancers are rare. Suen J.160(4):373–6. facial nerve dysfunction. Sobin LH. Influence of local surgery and radiotherapy on the natural history of pleomorphic adenomas. Cancer 1992.9(6):652–7. Vol. 1255–302. . All salivary gland malignancies require follow-up periods of 20 years for true measures of clinical outcomes. McLean NR. Atypical features in salivary gland mixed tumors: their relationship to malignant transformation. Needle aspiration biopsy in salivary gland lesions. [7] Shaha AR. et al. and perineural growth. St Louis. [9] Eneroth CM. Arch Surg 1975. Takahara O. Robinson DW. Moberger G. Hobsley M. [2] Land CE. Am J Surg 1990. Acta Otolaryngol 1968. 2. Watson NE Jr. perineural involvement. and facial nerve monitoring. Tokuoka S. References [1] Hanna E. Incidence of salivary gland tumors among atomic bomb survivors. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 Recurrence in submandibular gland cancer is most significantly related to the initial stage at presentation. Matsuura H. J R Coll Surg [Edinb] 2001. Hayashi Y. Neoplasms of the salivary glands. Otolaryngology–head and neck surgery. p. Greven KM. Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography. Ellis GL.66(3):248–60. extraparenchymal spread. The World Health Organization’s classification of salivary gland tumors.L. A clinicopathologic study of 242 cases. The tumor stage at presentation will dictate the need for imaging. surgical margin. [12] Seifert G.110(1):64–8. Hjertman L. A commentary on the second edition. Cappellari JO. tumor grade.126 R. Adenoid cystic carcinoma of salivary origin. Acinic cell carcinoma: collective review.51(3):181–5. including bilateral cases. Keyes JW Jr. Signs and symptoms of malignant parotid tumours: an objective assessment. MO: Mosby. Malata CM. Survival rates for sublingual gland cancer are similar to those for submandibular gland malignancy. with many histologic types and subtypes. postoperative radiation therapy.128(4):512–20. Malignant tumours of the submandibular salivary gland: a 15-year review. 1950–1987. [8] Spiro RH.70(2):379–85. Immunohistochemistry has enhanced diagnosis. [10] Levin JM. In: Cummings CW. FNA. lymph node metastasis. Strong EW. and survival rate.146(1):28–36. Lower recurrence rates with positive margins can be achieved with postoperative radiation therapy.105(6):579–84. 3rd edition. Williams DW III. Lin F. Tumor stage. [5] Camilleri IG. Br J Surg 1986. and nodal metastasis are factors influencing the indication for neck dissection. Saku T. editor. [11] Auclair PL. Mod Pathol 1996. Evaluation of radiationrelated risk.73(1):74–6. [3] Watkin GT. precise attention to surgical landmarks and technique will reduce complications. Radiat Res 1996. [6] McGuirt WF. with most deaths caused by metastatic disease. Kelly CG. Huvos AG. Laryngoscope 1995. 1998. Webber C. Jaffe BM. Other factors include clinical skin or soft tissue invasion. [4] Wong DS. In addition. histologic type. Br J Plast Surg 1998. DiMaio T.46(2):91–5. Adenoid cystic carcinoma of the palate. Am J Surg 1974.

Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma. Zarbo RJ. Prokopakis EP. et al. c-myc. Clausen OP. [21] Kamio N. Morton DL.71(9):2699–705. Payne D. Primary malignant lymphoma of the parotid gland. Foshag LJ. Baena L.30(5): 271–9. Witt / Surg Oncol Clin N Am 13 (2004) 113–127 127 [13] Brandwein M. The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma. Ear Nose Throat J 2001.80(11):803–6. Am J Surg Pathol 1992. Virchows Arch 1996. tumour stage. Theise ND. [26] Kirkbride P. Hitchcock CL. Labastida S.R. Bianchi S. Ellis GL. 115(4):569–75.6(2):150–4. Metastasizing mixed tumor of salivary glands. [17] Ollila DW. J Oral Pathol Med 1994. Syrjanen S. Collagen IV and tenascin immunoreactivity as prognostic determinant in benign and malignant salivary gland tumours. Facial nerve monitoring in parotid surgery: the standard of care? Otolaryngol Head Neck Surg 1998. Thomas MJ. [22] Gallo O. Aoki Y. [15] Wenig BM. Montgomery WW. [14] Deguchi H. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996.252(3):139–42. [19] Wu DL. Gullane P. Thoresen S. Gallegos F. Acta Pathol Jpn 1993. Warde P. Arch Pathol Lab Med 1999.119(5):468–70. Essner R. Boddi V. [20] Bang G.L. [23] Karja V. [28] Sakata K. Myers EN. Malignant lymphoepithelial lesion of the parotid gland: a case report and review of the literature. p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome. Huvos AG. Eur Arch Otorhinolaryngol 1995. Coexpression of p53 and c-erbB-2 proteins is associated with histological type.170(6):342–6. [16] Prasad AR. Gown AM. Dardick I. Cancer 1995. et al. [27] Spiro IJ. DNA flow cytometry of reclassified subtypes of malignant salivary gland tumors. Shemen L. Muta N. Stern SL. Franchi A. Karasawa K. 43(7–8):413–22. ras p21 and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands. Donath K.23(7):291–7.16(9): 845–58. Wang CC. Gnepp DR. Outcome of curative management of malignant tumours of the parotid gland. Cancer 1993. Hasezawa K. Strahlenther Onkol 1994. Savera AT. Ann Surg Oncol 1999. [25] Rodriguez-Cuevas S. Liu FF. Giannelli E. Carcinoma of the parotid gland. Hayashi Y. Brady T. Syrjanen K. Noninvasive and minimally invasive carcinoma ex mixed tumor: a clinicopathologic and ploidy study of 12 patients with major salivary tumors of low (or no?) malignant potential. Alajmo E.123(9):801–6. Hamano H. J Otolaryngol 2001.124(5):573–7. O’Sullivan B. Arch Otolaryngol Head Neck Surg 1998. [18] Barnes L. A clinicopathologic and flow cytometric analysis. Nakagawa K. Acta Otolaryngol 1995. Saw D.81(6):655–64. .428(2):75–83. Radiation therapy for patients of malignant salivary gland tumors with positive surgical margins. [24] Witt RL. Analysis of treatment results and patterns of failure after combined surgery and radiation therapy. Risk of nodal metastases from malignant salivary gland tumors related to tumor size and grade of malignancy. and cell proliferation in malignant salivary gland tumours. 75(8):2037–44.

1016/S1055-3207(03)00129-7 . Buffalo. Buffalo.000 new cases and 1400 deaths projected for 2003 [1]. Fig. All rights reserved. E-mail address: dominick. DTC typically has a low incidence and a good prognosis.see front matter Ó 2004 Elsevier Inc. For unclear reasons. Nevertheless. Metastases.Surg Oncol Clin N Am 13 (2004) 129–149 Iodine 131 (131I) as adjuvant therapy of differentiated thyroid cancer Dominick Lamonica. Approximately 75% to 80% of these carcinomas can be categorized as papillary and 15% to 20% as follicular [3]. Elm and Carlton Streets. Building 10. USA b Department of Nuclear Medicine. some factors separate patients into low and high risk for recurrence and adverse outcome. NY 14263. State University of New York at Buffalo. School of Medicine and Biomedical Sciences. 1055-3207/04/$ . 3435 Main Street. Extent and Size [7. Roswell Park Cancer Institute. AGES a staging system with origins at the Mayo Clinic that stands for Age. In the management of patients who have thyroid cancer. 1 summarizes cumulative mortality rates over a 20-year period for Mayo Clinic patients with papillary carcinoma that is judged to be high (25%–40%) or low risk (1%–ÿ2%) using four of these scoring systems: European Organization of Research and Treatment of Cancer (EORTC) [4]. Parker Hall. with 22.lamonica@roswellpark. The discovery and use of radioactive iodine are major reasons that nuclear medicine originally achieved its specialty standing and central role in the management of thyroid disease. nuclear medicine and surgical oncology often interface. Division of Diagnostic Imaging. Extent and Size [6]. and AMES a staging system originating in the Lahey Clinic which is an acronym for Age. Union Internationale Contre le Cancer (UICC) [5].* Department of Nuclear Medicine. Elm and Carlton Streets. Nearly 90% of malignant tumors involving the thyroid are differentiated thyroid carcinomas (DTCs).b. and numerous classification systems have been proposed to assess overall risk. doi:10. Room 105. Cumulative survival rates at 20 years are even more impressive for Mayo Clinic patients at low (survival * Roswell Park Cancer Institute.8]. NY 14214-3007. the annual incidence of thyroid carcinoma has risen over the last quarter century [2]. USA a Thyroid carcinoma is the most common endocrine malignancy in the United States. NY 14263. MDa. Buffalo.

Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 Fig. UICC (upper right).\10%) risk from follicular tumors in a system incorporating age and the presence of vascular invasion and distant metastases at diagnosis [9]. to a lesser degree. In addition to age at diagnosis and. . Although follicular carcinomas are typically smaller when discovered. J Endocrinol Metab Clin North Am 1990. Mayo Clinic patients with papillary carcinoma judged to be at high (25%–40%) or low (1%–2%) risk for mortality using EORTC (upper left). tumor features. Papillary thyroid carcinoma. multifocality. AGES (lower left). 1.) rate. tumor variables alone were used in a system for the clinical staging of thyroid malignancies. such as size. extrathyroidal extension. Patient-specific prognostic factors For reasons that are poorly understood. both the age and gender of the patient at diagnosis influence disease behavior and outcome to initial therapies. 88%–90%) versus high (survival rate. A recent large-scale retrospective analysis comprising patients from the Ohio State University (OSU) and US Air Force (USAF) who had both papillary and follicular cancers focused principally on tumor-specific factors associated with disease recurrence and cancer-specific mortality [10]. with a propensity for hematogenous dissemination and distant metastasis. patient gender. From a nuclear medicine perspective. they are usually found later in life and are more advanced. and the presence of distant metastases were all shown to affect outcomes. From a clinical standpoint. all of the previously mentioned factors warrant review at the time of initial consultation. As a part of this study.19:561. we believe that it is most important to base decisions regarding adjuvant 131I therapy on anatomic staging at the time of diagnosis. (From Hay ID. Survival statistics for equally staged papillary tumors are also poor.130 D. and AMES (lower right) classification systems. with permission.

Long-term impact of initial surgical and medical therapy on papillary and follicular cancer. Recurrence and cancer death based on age at diagnosis. Although the incidence of tumor recurrence from midlife on is high. Thyroid carcinoma is more often a fatal illness in patients older than 40 years when first diagnosed. 2. Most physicians therefore agree that these patients warrant careful attention. emphasizing the need for adequate early treatment and careful follow-up examinations.D. Mortality further increases when it is diagnosed over subsequent decades [11. it is even more frequent among children (Fig. Some risk of recurrence and cancer-specific mortality remains well beyond 20 years from initial diagnosis for all patients (Fig. although children more often present with advanced-stage tumors. Fig. Jhiang SM. which typically recur [13–15]. Long-term survival statistics for the pediatric population are usually good. Am J Med 1994. A second patient-specific factor that is believed to affect outcome is gender. Two largescale studies have reported that male gender has an overall negative effect on survival [4. despite the more favorable outcomes in this age group.) .12]. A different overall pattern emerges when disease recurrence is examined relative to age. 3).10]. (From Mazzaferri EL. particularly when lesions are diagnosed in midlife and beyond. there is evidence throughout the literature that the prognosis from thyroid carcinoma is less favorable among male patients.97:422. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 131 Age at diagnosis is included in nearly all series as a factor influencing mortality in DTC. 2). Although gender holds variable statistical weight in different study populations.

4% compared with 7.0 cm).5 cm to be one third that of larger tumors. Long-term impact of initial surgical and medical therapy on papillary and follicular cancer. Gross or microscopic . Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 Fig. with a cancer-specific mortality rate of 0.97:421. They are usually multifocal tumors at presentation. more aggressive forms of microcarcinoma do exist [19].001) [10].5 cm (P > 0.132 D. It is included in seven of the nine scoring systems compiled in Table 1. Although they are less common. These microcarcinomas can be a source of locoregional and distant metastatic tumor [20]. This finding is particularly true for lesions located below the limits of palpation (\1. Most small carcinomas contained within the thyroid gland rarely recur. and it is most often the spread of disease that first brings them to clinical attention [21]. 3. The size of the primary tumor is a major factor affecting disease control in both papillary and follicular tumors.0% for tumors larger than 1. Papillary microcarcinomas are often uncovered as a result of surgery for benign conditions. The invasion of perithyroidal tissues by tumor also has a clear statistical bearing on recurrence and mortality from DTC. (From Mazzaferri EL. and these almost never recur. however. Jhiang SM. The OSU/USAF series described the 30-year recurrence rate for lesions smaller than 1.) Tumor-specific prognostic factors The size and extent of the tumor at diagnosis have been shown repeatedly in series both in the United States and abroad to have statistical bearing on outcome in DTC. Am J Med 1994. Recurrence and cancer death based on time from initial diagnosis.

23]. More controversy exists concerning the relevance of locoregional lymph node metastases in DTC. One large-scale review of 13 series comprising 1231 Table 1 Risk stratification systems for differentiated thyroid carcinoma Recognized risk factors Scoring system United States AMES [7] (Lahey Clinic) AGES [6] (Mayo Clinic) MACIS [23] (Mayo Clinic) University of Chicago [16] OSU/USA [10] MSKCC [17] AJCC [18] Europe EORTC [4] UICC [5] Patient-specific Age Age Age. brain). Some investigators claim that regional lymph node metastases have little impact on overall outcome [7. size Metastases. histologic grade of primary tumor.22. size of primary tumor. . b Extent invasion. A major clinical and pathologic feature of DTC in children is spread to regional lymph nodes [13]. Age. extent. tumor-positive cervical lymph nodes. sizec Graded. extent. lung. size Metastases. Metastases. extent Metastases. Finally. size Metastases. MACIS. The spread of metastatic tumor beyond the lymph node capsule is an especially worrisome finding. American Joint Committee on Cancer. anaplastic. Invasion. Size.25]. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 133 evidence of direct extension to local tissues signals an increased risk for recurrence. distant tumor in sites outside of neck (ie. size Abbreviations: AJCC. bone. lymph node statuse. medullary. f Cell type. extentb. d Grade. size Metastases. c Size. extent. consider this finding a risk factor for both disease recurrence and cancer-specific mortality [10. Completeness of resection. poorly differentiated follicular. extent Metastases.24. and a lower percentage (13%) of patients with follicular tumors [3]. extent. Others. This pattern of spread is considered even more worrisome when disease has extended to contralateral or bilateral neck nodes.D. More than one third of patients (35%) who have papillary carcinoma present with locoregional lymph node metastases. All recognized scoring systems list direct tumor invasion beyond the gland capsule as a major risk factor for cancer-related death (see Table 1). or to mediastinal nodes [10]. however. extent. all other. size Metastases. sex Age Tumor-specific Metastasesa. extent (invasion beyond gland). lymph node status. as is extension of the primary tumor to tissues outside of the thyroid gland [26]. extension of tumor to extrathyroidal soft tissues. e Lymph node status. completeness of resection — — Age Age Age. lymph node status. a Metastases. cell typef. there is little debate over the impact of distant metastatic tumor on overall survival rates. Some series have reported the incidence of cervical metastases in children with DTC to be as high as 90% [15].

131 Postsurgical I remnant ablation When the surgical team intends to perform total or near-total thyroidectomy. The term ‘‘radioiodine ablation’’ refers to the use of 131INa to destroy what is presumed to be normal thyroid tissue remaining within the neck following operation. and the presence of distant metastases.’’ macroscopic tumor within the lung. and the central nervous system (CNS) or other tissues (10%). skeleton. close to 50% of these patients die of their disease within 5 years [27]. Emphasis is given to tumor size. It clearly increases the sensitivity of diagnostic 131I scans and the efficacy of further 131I treatments. It has been shown to reduce the risk of tumor recurrence and thereby lessen the chances of adverse outcome relating to treatment failure [10. which was followed in order of frequency by metastases in bone (25%). In summary. Overall. 2. the current author does not include it in treatment decisions for the individual patient. and attention to critical structures within the neck usually interferes with complete surgical removal of glandular tissues. Although young patients often demonstrate more favorable outcomes to treatment.30].29]. Although age is weighted by many physicians.134 D. patients are typically referred for a postoperative 131I scan for assessment for remnant thyroid tissue and adjuvant administration of radioactive iodine. these same factors can be used to tailor therapy to individual disease risk both in the operating room and in the clinic following surgery. Improved mortality figures are not sufficient cause to ignore data that clearly point to an increased incidence of tumor recurrence and associated morbidity. the reasons are not well understood. or brain is typically difficult to treat and often fatal [28. these are outweighed by similarities. Furthermore. DTC is typically less iodine-avid than is the . local soft tissue invasion. although differences exist in the various staging and prognostic scoring systems used at clinics in the United States and in Europe. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 patients estimated that 5% of papillary carcinomas and 13% of follicular carcinomas have extended beyond the neck at diagnosis. The current author does not believe that age alone should override the red flags of anatomic staging. All of these characteristics have a clear bearing on the risk of tumor recurrence and cancer-specific mortality. This distant spread of tumor was most common within the lung (49%). Total resection of the thyroid is a difficult proposition. Although some forms of pulmonary spread may be compatible with long-term survival and even ‘‘cure. lung and bone (15%). The current author has found that more than 90% of patients referred for radioiodine scan in the weeks following surgery show uptake within the neck indicative of some thyroid remnant. Radioiodine ablation of residual thyroid tissue in the setting of intermediate-stage tumor is advised for the following reasons: 1.

The radioiodine localization that enables both tumor detection and effective therapy is enhanced by thyroidstimulating hormone (TSH) release. a low-iodine diet is initiated. To postpone and alleviate the effects of a T4 deficit. 131 I therapy of differentiated thyroid carcinoma The approach to radioiodine therapy of metastases from DTC varies in many clinics within the United States. 5550 MBq (150 mCi). Fixed ‘‘high-dose’’ ablation.) 2. T3 has a much shorter half-life and may be discontinued 10 to 14 days before 131I dosing. prominent vascular invasion. or extension of tumor to extrathyroidal soft tissue. provided there has been surgical removal of all gross and microscopic evidence of tumor. 1850 to 4625 MBq (50–125 mCi). (Dosing is based on age. patient size. postoperative 131I ablation greatly improves disease monitoring by facilitating the use of serum thyroglobulin (Tg) as a tumor marker and eliminating the variable ‘‘background’’ Tg levels that persist with normal thyroid remnant and often confound accurate interpretation of laboratory results. tumor characteristics. Fixed ‘‘low-dose’’ ablation.0 cm or with any of the following in the operative specimen: multifocal tumor. 1. liothyronine sodium (T3) is given for 3 to 4 weeks. The current author’s initial postoperative ablation doses of radioactive iodine for papillary or follicular tumors usually follow a regimen comprising two levels. Finally. which can be difficult to stimulate with significant postsurgical remnant in place.0 cm in diameter without pre. levothyroxine sodium (T4) is withheld in preparation for 131I scanning and ablation.or postsurgical findings that suggest persistent tumor (local or distant) have clear therapeutic relevance and such patients warrant safe augmentation of the 131I dose. spread to locoregional lymph nodes.or postsurgical evidence of spread to locoregional lymph nodes or extension to extrathyroidal soft tissue. Persistent or recurrent tumor seen on . and uptake within thyroid remnant. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 135 normal glandular epithelium. Pre. Radioiodine ablation is ordinarily performed following a 131I diagnostic survey demonstrating persistent radioiodine concentration within the surgical bed 6 to 8 weeks after the operation. 3. is performed following surgery for solitary tumors smaller than 4. which is intended to further enhance uptake of the radioisotope.D. The demonstration of iodineconcentrating tumor outside the operative bed on preablation 131I imaging often calls for an increase in the 131I doses typically used for the ablation of normal postsurgical thyroid remnant. Following surgery. is reserved for patients with lesions larger than 4. At the same time.

Fixed-dose augmentation does not involve measurement of radiation dose to thyroid remnant or to functioning metastatic lesions but instead focuses on the empiric dosing of radioiodine based on knowledge of the extent and location of tumor. Dose reduction may be warranted for unusually large remnants or extensive diffuse lung tumor that strongly retains 131I to avoid prolonged count reductions or possible lung injury. the current author has found that many of the lymph nodes first detected on a postoperative radioiodine scan are at or below the radiographic size criterion (1 cm) for characterization as abnormal. There is evidence to suggest that a radioiodine dose that is not sufficient to deliver at least 35 Gy will be ineffective and that such lesions should be addressed surgically or by external beam radiotherapy [33. 2. 3. if not impossible. Tumor invading soft tissues within the neck that may have been incompletely excised is most often addressed with 131I doses in the range of 5500 to 7400 MBq (175–200 mCi). Type I (remnant/tumor) dosimetry: Investigators who have looked at some of the issues surrounding effective radioiodine therapy of DTC have determined that normal glandular remnant requires a radiationabsorbed dose of at least 300 Gy for likely ablation (80%) and that iodine-concentrating tumor limited to lymph nodes within the neck should receive at least 80 to 100 Gy for similar efficacy [32]. Type II (blood-based) dosimetry: It is frequently difficult. a calculation of the radiation dose delivered to a glandular remnant or metastatic lesion requires serial measurement of the uptake of 131I at 2 or optimally 3 times over a 1-week period.136 D. . Finally. This is a fact that increases the likelihood of effective treatment with radioiodine. Although it is necessary to measure the volume of larger lesions treated with 131I to accurately estimate the absorbed dose from systemic radiotherapy. Dose augmentation for treatment can take one of three forms: 1.34]. A documented tumor that is limited to lymph nodes within the neck that are not obviously involved by disease or that are beyond the reach of the surgeon’s knife is usually treated with 5500 to 6475 MBq (150–175 mCi) of 131I. patients who have clear evidence of distant metastatic disease are usually safely administered doses in the 7400 to 9250 MBq (200–250 mCi) range. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 postablation imaging may also be most effectively addressed with additional 131 I. to estimate radiation delivery to sites of metastatic tumor. A sliding scale is used in accordance with the operative report and visualization of disease on diagnostic scans within limits determined to be safe for most adult patients. Fixed dosing: This is an approach that was first introduced and effectively applied to the management of patients with DTC by a team of physicians at the University of Michigan. In addition to some anatomic estimate of lesion dimension. and it may be the treatment system most commonly used in clinics throughout the United States today [31].

acute radiation symptoms have been described in the immediate post-treatment period in close to two thirds of patients receiving 131I therapy [39. Serious complications from dose maximization were avoided by using this approach and limiting blood exposure to 200 cGy while keeping whole body retention under 4440 MBq (120 mCi) at 48 hours or under 2960 MBq (80 mCi) in patients with diffuse lung disease. Post-therapy imaging is included for all patients undergoing ‘‘high-dose’’ remnant ablation or therapy for locoregional or distant metastases. The patient is then reimaged in 6 to 12 months with formal blood-based dosimetry. the bone marrow [35]. These symptoms are usually reported for doses in excess of 5550 MBq (150 mCi). Prior knowledge of distant metastases or of persistent tumor within the neck will prompt the physician to include dosimetry in the initial postoperative evaluation. 131 Acute and long-term effects of Early effects I therapy Although 131I is lethal to the cells most able to concentrate it. Enhanced radioiodine uptake outside the confines of the surgical bed on postoperative examination often indicates metastases from DTC. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 137 Iodine-avid metastatic disease may be distributed in such a way that volume cannot be measured. To increase the likelihood of effective delivery of 131I. it is not without immediate and long-term effects on background tissues free of disease. If this pattern is first evident on the initial postoperative survey. It has been estimated that as many as 20% to 25% of patients will demonstrate lesions not evident on pretreatment studies [37]. which will allow safe administration of a maximum permissible dose of 131INa for therapy of metastatic tumor. There are probably few situations where the results will significantly alter treatment plans [38]. the current author’s approach is to maximize the ablative dose within the previously noted fixed-dose guidelines for 131I therapy. and this post-treatment period is often marked by fatigue.D. The system was originally proposed and validated by Benua et al [35] and Leeper and Shimoaka [36] of the Memorial Sloan-Kettering Cancer Center (MSKCC). Imaging is done not only to document effective uptake within thyroid remnant and tumor but to gain added information about the extent of disease. This finding is more frequent in cases where patients with negative pretreatment imaging are treated empirically with 131I based on rising serum Tg levels. systems have been developed for maximum delivery of targeted systemic radiotherapy within limits that will protect what has been determined to be the dose-limiting organ for most patients.40]. Mild. loss of . This system requires serial blood sampling and measurement of retained activity over a 1-week period.

and submandibular salivary glands following 131I administration. can result when high doses of radiation are delivered to large gland remnants [41]. local swelling may be sufficient to precipitate vocal cord dysfunction [44]. headache. Count reductions can be expected to resolve by 1 12-week period is advocated.138 D. and occasional vomiting. A University of Michigan study reported anemia (35%). Long-term hematologic effects are not likely if the red marrow dose is kept within the aforementioned 200 cGy exposure limit. the salivary effects from 131I treatment can sometimes be prominent. leucopenia (10%). Such effects are usually limited to patients who have an invasive tumor involving the vocal cords or who have large thyroid remnants adjacent to the recurrent laryngeal nerves. because this situation requires prompt attention [43]. Weekly monitoring of counts over an 8. It is important to appreciate that large gland remnants will compete for finite doses of administered 131I. The gastrointestinal component that is often described also may reflect the direct effect of physiologic localization of radioiodine within normal salivary tissues and gastric mucosa. effective delivery of 131I. particularly in patients with documented coronary artery disease or compromised cardiovascular function. cervical swelling. These are situations that call for careful monitoring. All such patients should be made euthyroid before treatment and should be observed carefully for signs of thyroid storm within 10 days of 131I therapy. The current author therefore recommends re-operation for patients known to have large gland remnants and residual tumor that requires the upfront. Such competition is believed to interfere with the detection and effective treatment of a tumor that may have been incompletely excised [45. These effects have been reported to occur in up to one third of individuals treated with 131I doses. Tenderness and swelling may result from radiation effect on the lingual. Symptoms usually become evident over a 24. parotid. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 appetite. and thrombocytopenia (3%) in 157 patients treated with an average dose of 207 mCi. Finally. and difficulty swallowing. Rarely. Radiation thyroiditis. nausea. Patients also may experience symptoms of transient hyperthyroidism caused by release of stored hormone from large remnants or from extensive functioning follicular tumor [42]. A reduction in platelet and white blood cell counts may be witnessed over the weeks following 131I therapy based largely on the dose administered and on the effective half-life of radioiodine in the individual patient. and treatment will likely involve the systemic administration of . Cytopenias are frequently observed following high-dose radioiodine therapies for DTC. with red cell declines persisting slightly longer than white cell and platelet effects [47].46]. with a direct correlation to the radiation dose received [48]. This symptom constellation usually resolves over a 48-hour period. characterized by throat discomfort. Physicians should be wary of this effect. particularly for patients receiving doses in excess of 9250 MBq (250 mCi) for treatment of widespread disease.

100 MBq (300 mCi) of 131I. The latter symptom complex is often precipitated by eating and may persist for some months. altered taste and conjunctival irritation. it has been reported in nearly 60% of women receiving 131I doses in excess of 29. Patients should be aware of this finding. This same study of women and pregnancy before and after 131 I therapy for thyroid carcinoma revealed no evidence for increased risk of congenital malformation. The testicular effects described from 131I therapy in men are proportional to . A different situation exists for men undergoing 131I therapy for thyroid cancer. Emphasizing hydration and encouraging salivary flow through use of lemon drops or chewing gum over the early post-treatment period may reduce these symptoms. stillbirth. or prematurity following treatment of this disease. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 139 48-hour period following administration of therapy and have been described as reflecting the radiation effect of large 131I doses in patients with minimal thyroid remnant. It seems that there is no increase in risk of birth defects from treatment of children or women of childbearing age. The reasons for this finding are not entirely clear. A single 131I treatment involving only moderate doses of radioiodine (1850– 3700 MBq [50–100 mCi]) is sufficient to cause reduction in sperm count [53]. Female reproductive function is usually unaffected by single administrations of 131I. however. because the testes are especially vulnerable to the effects of radiation. Such statistics are usually directly correlated to cumulative radiation dose.600 MBq (800 mCi) [10. Although permanent sterility has not been recorded for premenopausal women receiving less than 11. particularly in patients receiving repeated high-dose 131I treatments for refractory tumor.D. Women treated in the current author’s clinic are advised to avoid pregnancy during the 12 months following 131I therapy.52]. although this observation suggests a possible relation to irradiation of the ovaries. the chances of long-term organ or tissue injury increase with the cumulative dose of radioactivity required for treatment. however. One study noted that the miscarriage rate after 131I ablation that used doses in excess of 100 mCi was nearly double the increase observed following thyroidectomy alone [50]. Late effects of 131 I treatment Although most of the immediate effects described previously resolve during the weeks following 131I therapy. These effects include dry mouth. Despite these 12-week period. and ear and jaw pain caused by intermittent salivary obstruction from desquamation of glandular epithelium [49]. most often resolving spontaneously over an 8. Transient alteration or loss of taste sensation can result. longstanding adverse effects are possible. Long-term studies suggest that fertility is unaffected for women younger than 30 years at the time of therapy [51]. Permanent reproductive organ impairment may result from repeated therapies for this disease.

Permanent count reductions and white cell and platelet abnormalities are sometimes seen in patients receiving more than 37 GBq of 131I for treatment of thyroid cancers. a fact that only enhances the mutagenic properties of ionizing radiation for both normal and diseased tissues. An approach that uses dosimetry would safely permit the upfront augmentation of therapy. on average. Placed in perspective. It would also be recommended in therapies for those patients who have compromised renal function. Again. even with the added radiation exposure from 131I treatment. 131I treatments are normally spaced at 12month intervals and are usually not repeated any sooner than 6 months for the more aggressive tumor variants. this risk does not exceed the risk of dying from metastatic thyroid cancer [2]. the current author recommends . it is uncommon. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 the total dose of radioactivity received over the course of treatment [54]. 30% to 50% of the administered 131I dose is excreted within 24 hours in athyrotic patients who have normal renal function. which is particularly needed for disease outside the neck. the lifetime risk of leukemia is small enough so that.140 D. functioning tumor.600 MBq (800 mCi) [55]. It is the current author’s experience that. Sperm banking should be considered for young men who have extensive disease. The standard fixed-schedule dose of 7400 MBq (200 mCi) usually advocated for treatment of lung metastases is therefore safe for treatment of pulmonary disease in the overwhelming majority of patients. A small increase in deaths from bladder cancer and leukemia has been reported with cumulative 131I doses in excess of 37 GBq [51]. Many of the patients received high doses of radioiodine over short time intervals. In view of these effects. Permanent sterility has been described in men receiving cumulative doses greater than 29. 131 I imaging and follow-up Following radioiodine ablation of thyroid remnant or treatment of iodine-concentrating thyroid tumor. Exceptions to this are patients with large thyroid remnants or those with an overwhelming mass of persistent. Radiation-induced malignancy is probably the most serious among the potential late effects of 131I treatment. however. Based on five events in 59 patients. the risk is proportional to cumulative dose of radioactivity and underscores the need for attention to bowel and bladder function in the days following therapy. A large-scale metaanalysis comprising 13 series and 2753 patients reported a slight increase in prevalence of acute myelogenous leukemia (AML) for patients who had received 131I therapy for thyroid cancer [57]. dosimetry guidelines were adjusted to ensure retained activities were kept under 4440 MBq (120 mCi) at 48 hours in all patients and under 2960 MBq (80 mCi) at 48 hours in those who had diffuse lung metastases [56]. Lung fibrosis was originally reported in the early experience of the MSKCC group [32]. Lung fibrosis is often a concern for physicians treating patients who have diffuse pulmonary spread of iodine-avid thyroid tumor.

Uptake in the neck is likely in this setting. then annually. The initial postoperative radioiodine survey is done to assess the presence of normal thyroid remnant following total or near-total thyroidectomy. Once two negative 131I surveys have been documented. highlighting a need for further workup to determine the most effective and appropriate therapy [60].62]. with clinic visits every 6 to 12 months and further diagnostic studies based on the results of serial examination and laboratory testing. Serum Tg is usually undetectable (\0. once normal thyroid remnant has been eliminated. The current author has also seen benefit from the empiric administration of 131 I. this paradigm has recently changed. Diagnostic scans for this application are acquired with 74-MBq (2-mCi) doses of 131INa. This imaging schedule is accompanied by regular follow-up examinations within the clinic. Although in the past eligibility for 131 I therapy was principally determined by uptake on radioiodine scans alone. the current author believes it is appropriate for patients to enter long-term follow-up. A lowering of serum Tg levels also has been recorded in 30% to 50% of such patients in response to treatment [62]. Several investigators have demonstrated post-treatment evidence of tumor uptake in more than one half of patients with negative diagnostic 131I studies when they were treated empirically with 3700 MBq to 5550 MBq (100–150 mCi) of 131I based only on elevated serum Tg [61. and serum Tg assay at 6 and 12 months and annually thereafter. The tracer dose is doubled but is kept below 111 MBq (3 mCi) because of a concern that the diagnostic dose of 131I might interfere with radioiodine concentration for subsequent 5-year intervals used in the past for disease monitoring. thyroid function testing at 3 months and 6 months. patients are re-imaged to detect any persistent or recurrent tumor. and this study is therefore performed using only a small 37-MBq (1-mCi) dose of 131 I. with a physical examination every 3 to 6 months for the first 2 to 3 years. allowing serial comparison of this tumor marker in the assessment of a patient’s disease as well. the current author ordinarily advocates obtaining at least two negative 131I scans over the first 5 years following initial 131I administration to increase the chances of early detection and prompt treatment of recurrent tumor at a time when it is most likely to be discovered. 131I studies in the current author’s clinic are accompanied by stimulated serum Tg assays. unrecognized areas of disease may become apparent on whole body survey. In patients who are at increased risk for recurrence.59]. In place of serial 131I scans at 3. both in terms of lowering of tumor marker and resolution of . it has been suggested that regularly repeating the 131I whole body scan adds little to the DTC workup in this setting. For reasons described previously. Once remnant ablation is achieved.5 ng/mL) in patients free of disease following successful postsurgical 131I remnant ablation. a concept termed ‘‘stunning’’ [58.D. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 141 a minimum of one follow-up 131I study to assess the efficacy of the radioiodine dose. recombinant human thyroid-stimulating hormone (rhTSH) -stimulated Tg testing has been suggested as an even more sensitive indicator of disease recurrence. Recently.

patients are begun on T4 replacement and enter a regular schedule of clinical follow-up based largely on surgical findings and results of post-therapy imaging. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 anatomic findings on CT without clear evidence of uptake on pretreatment images. An rhTSH-stimulated Tg level of more than 2 ng/ mL recently has been described as having a sensitivity of 100% for the detection of recurrent disease [60. and bone metastases represent an even greater challenge. Macronodular lung tumor is considerably more difficult to treat with 131I. In this situation. The 10-year survival rate for patients treated with 131I for lung metastases evident only on post-treatment whole body survey has been reported to be 100%. A similar application for 131I is anticipated for rare individuals with isolated CNS lesions [66].63]. Patients who have disease outside the neck who respond to 131I therapy have significantly longer survival times than those who do not [11]. Serum Tg levels of more than 10 ng/mL in patients who are off thyroid hormone replacement or levels greater than 5 ng/mL in patients undergoing T4 treatment are currently used by some clinicians to determine the need for additional 131I therapy [37]. Further management L-thyroxine therapy Following surgery and initial radioiodine therapy for DTC.30]. The numbers are lower but still impressive for disease seen either on pretherapy 131I imaging alone (91%) and/or with an accompanying micronodular pattern on radiographic study (63%) [64]. This is an approach further strengthened by concerns over lesion stunning. Dominant or solitary skeletal sites optimally require a multidisciplinary team approach centering on surgery or external beam radiotherapy [65]. 131 I therapy of differentiated thyroid carcinoma: outcomes A beneficial effect has been demonstrated from the use of 131I for the postoperative ablation of thyroid remnant in patients at intermediate risk for disease recurrence [10. . There can be considerable impact for the 131I treatment of distant metastases within the lung. CT. Here as well. one might still consider moving ahead with additional empiric 131I therapy based on a rising tumor marker alone. If a surgically treatable lesion cannot be identified on diagnostic studies (eg. 4).142 D. the post-treatment surveys acquired 7 to 10 days following 131I therapy often provide the image evidence of DTC missing from the interim diagnostic studies. MRI. 131I can have a role for the treatment of residual disease (Fig. however. The Tg thresholds for consideration of additional 131I therapy of DTC are in evolution. or ultrasound) that are done for rising Tg levels.

D. (B) Positive post-treatment images 1 week after 131I therapy. 4. . (A) Skeletal metastases (arrowheads) from papillary thyroid carcinoma on initial postoperative 131I scan. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 143 Fig. (C) Negative follow-up 131I images 1 year post therapy.

144 D. reported that.4 micro-International Units per mililiter (uIU/mL) [69].1–0. The degree of TSH suppression required remains controversial. If there is documentation of residual neck disease or distant metastatic . Despite ongoing debate. the degree of TSH suppression taken alone did not predict those individuals at greater risk for recurrent disease [68]. however. A retrospective European investigation showed degree of TSH suppression as an independent predictor of disease recurrence [67]. it is recommended that intermediate-stage patients be started on a dose of T4 sufficient to maintain serum TSH levels just below the lower limit of the normal range 0. however. A more recent prospective study in the United States. when it was measured against other variables. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 Fig. 4 (continued) Studies have suggested that the recurrence rate of DTC is reduced by the augmented administration of T4.

it is important to stress that patient management must be individualized. Using these results. Serum Tg should be undetectable when persistent thyroid tissue or thyroid carcinoma is not present. Moreover. because this approach has not been proved equally effective. From these results. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 145 tumor following initial therapy. the current author does not use rhTSH stimulation for patients who are expected to receive therapeutic doses of 131I. the T4 dose is further adjusted. Here. The more important point of this study was that the addition of a stimulated Tg level to rhTSH-simulated imaging allowed detection of all patients who had recurrent tumor without the negative effects of hormone withdrawal. provided greater attention was paid to scanning technique [63].D. and that there may be patients who cannot tolerate such dose augmentation. Serum Tg testing and rhTSH It is the current author’s practice to perform a stimulated Tg assay at the time of the initial postoperative 131I scans. Thus. there are other factors that need consideration in the decision to substitute rhTSH for the standard imaging preparation. . The proposed technical modification involved a doubling of the tracer dose of 131I from 74 MBq to 148 MBq (2 mCi to 4 mCi) to account for the increased renal clearance of free iodide in the rhTSH-stimulated patient. both on and off supplementation at the usual time of the first follow-up 131I imaging.02 uIU/mL) from serum samples on second-generation assays. the choice of scan preparation is based largely on risk and on the probability that a patient will require additional treatment with 131I. the current author believes that using this combined method for the follow-up of DTC is worthwhile to reduce morbidity for patients at relatively low risk for tumor recurrence requiring therapy. A more recent investigation showed the difference between the two techniques to be less marked. At present. he still cannot downplay the morbidity associated with the cessation of thyroid hormone.71]. Although the current author attempts to lessen the ill effects of hormone withdrawal by routinely using T3 during T4 withdrawal for imaging and therapy. the replacement dose of T4 is usually further augmented to limit or remove evidence of circulating TSH (\0. These are both done in the TSH-stimulated state either following hormone withdrawal or rhTSH administration. Laboratory testing and 131I scans are obtained to determine the efficacy of the ablative or therapeutic dose. This assay is repeated at 6 months on hormone replacement and again at 12 months. This is a change that some clinicians are reluctant to make because of considerations regarding possible stunning of iodine-concentrating tumor and a potential for reduction in efficacy of subsequent radioiodine therapy. Two large-scale studies of rhTSH show that less disease may be detected on 131I scans following rhTSH injection versus with T4/T3 withdrawal [70. as elsewhere. An initial TSH assay is usually obtained at 12 weeks or on the first follow-up visit following postoperative 131I ablation and initiation of hormone replacement.

Thyroid Cancer Cooperative Group. and a benefit in advanced disease has not been established. The role of chemotherapy in noniodine responsive DTC is still in question. An aggressive approach is advocated. 1987. A prognostic index for thyroid carcinoma: a study of the E. the administration of 131I is not entirely without risk. Thomas A. CNS critical lesions. Summary The importance of the optimization of the upfront management of DTC cannot be underestimated. A situation that would not allow use of this dual approach using rhTSH imaging and Tg would be the patient with autoantibodies to Tg. 4th edition. Loree TR.0 cm confined to the gland). Hicks WL. female patients \40 y. TNM classification of malignant tumor: International Union against Cancer. except in situations widely accepted to be low risk (ie. Any distant lesion demonstrating the capacity for radioiodine uptake also should be addressed with 131I. New York: Springer Verlag. Sobin LH. CA Cancer J Clin 2002. [2] Mazzaferri EL. although as yet unproven. Kloos RT.C. 131I has demonstrated efficacy for the postsurgical management of DTC. [4] Byar DP. Thun M. [3] Fuchshuber P.12(1):99–106. Although its acute and long-term side-effect profile is not especially worrisome relative to other forms of systemic cancer therapy. both within the neck and for dominant foci of distant metastatic tumor (ie. functioning tumor. . Murray T.15:1033–41.T. Current approaches to primary therapy for papillary and follicular thyroid cancer. For non–iodine-concentrating tumor that cannot be approached surgically. Taking into account many of the issues described in this article. In conclusion. with tumors \1. Lamonica / Surg Oncol Clin N Am 13 (2004) 129–149 Moreover.R. cardiac insufficiency).86:1447–63.52: 23–47. the administration of 131 I should in every case be optimized. because this will potentially treat tumor not evident on diagnostic survey. alternative for treatment of patients unable to tolerate the prolonged effects of profound hypothyroidism (ie.146 D. Oncology 1998. because these would likely invalidate the added information obtained with this laboratory assay. [5] Hermanek P. J Clin Endocrinol Metabol 2001. external beam therapy remains an option. DeLacure MD. Distant tumor greatly reduces the chances for survival in all patients. Eur J Cancer 1979. Differentiated thyroid carcinoma: risk group assignment and management controversies.O. brain and bone). rhTSH is a welcome and necessary option for those who cannot mount a TSH response to hormone withdrawal (ie. Dor P. The loss of iodine-concentrating ability removes systemic radioiodine from the therapeutic equation and thereby virtually eliminates chances for cure. References [1] Jemal A. Green SB. et al. It also should be applied carefully and judiciously to patients expected to derive benefit. pituitary insufficiency) and a needed. Cancer statistics 2002.

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and spinal accessory nerve. All rights reserved. St.*. NY 14263. In this article. Radical neck dissection (RND). Roswell Park Cancer Institute. including shoulder dysfunction. The presence of lymphatic metastases is associated with a decrease in the survival rate of up to 50% of patients [1. Buffalo. Elm and Carlton Streets. E-mail address: nestor. This operative procedure has significant long-term morbidity. Canada. USA b Section of Plastic and Reconstructive Surgery. Department of Head and Neck Surgery. cutaneous paresthesia. Buffalo. Most head and neck cancers arise from the squamous epithelium of the upper aerodigestive tract.see front matter Ó 2004 Elsevier Inc. first described by Crile [3] in 1906. internal jugular vein. (N. MD. and future directions pertaining to neck dissections in the management of cancers of the head and neck.Surg Oncol Clin N Am 13 (2004) 151–166 Neck dissection: current concepts and future directions Nestor R. and chronic neck and shoulder pain syndrome. and popularized by Martin et al [4]. The classic RND requires en bloc resection of the cervical lymph nodes. has remained the cornerstone of the surgical treatment of cervical lymph node metastasis throughout most of the 20th century. 1055-3207/04/$ . rationale. Roswell Park Cancer Institute. V6Z 1Y6. FRCS(C)c. These morbidities are exacerbated when postoperative radiotherapy is added. FACSa. USA c Department of Surgical Oncology. The development of lymph node metastasis is a critical factor in guiding the treatment and determining the prognosis of individuals diagnosed with head and neck carcinoma. State University of New York at Buffalo. Wiseman. cosmetic deformity. Rigual). For these reasons.R. sternocleidomastoid muscle (SCM).1 School of Medical and Biological Sciences. * Corresponding author. Rigual.2]. 1081 Burrard Street. Sam M. Vancouver. USA a This article discusses the classification.rigual@roswellpark.1016/S1055-3207(03)00119-4 . the term ‘‘head and neck cancer’’ refers to squamous cell carcinoma (SCC) of the upper aerodigestive tract. NY 14263. and because of a lack of rationale for removing all cervical lymph 1 Current address: Department of Surgery.b. British Columbia. NY 14263. Buffalo. Elm and Carlton Streets. MD. Paul’s Hospital.

Lymph node groups not located within these regions should be referred to by their specific nodal group name. 2. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 nodes. The structures defining the anatomic boundaries of the neck levels and sublevels are depicted in Fig. and level VB (supraclavicular nodes). a change in the surgical approach to managing cervical metastasis was initiated by Suarez [5] in the late 1950s. level IB (submandibular nodes). he proposed that muscles. 1). This system is easy to remember and has become widely accepted (Fig. the concept of neck sublevels has been introduced into the classification schema. Most of these anatomic boundaries are Box 1.M. The lymph node groups contained in these levels and the anatomic boundaries of the six neck levels are shown in Table 1. levels IIA and B (upper jugular nodes). Recently.8]. Neck dissection classification     Radical neck dissection Modified radical neck dissection Selective neck dissection Extended neck dissection . because areas have been identified within the six neck levels that seem to have independent oncologic significance [12]. blood vessels. In anatomic studies. and other visceral structures of the neck. Bocca et al [6] subsequently popularized this ‘‘functional neck dissection’’ concept. blood vessels. and a more recent update was published in 2002 [12]. and suboccipital nodal groups. These sublevels include level IA (submental nodes). S. In the current classification schema. and nerves that were routinely removed during an RND could be preserved without compromising regional disease control in patients who had limited neck disease. the Committee for Head and Neck Surgery and Oncology of the American Academy of Otolaryngology/Head and Neck Surgery standardized neck dissection terminology in 1991 [11]. nerves. Neck dissection classification categories are shown in Box 1.10] have been the impetus for the development of current modifications of the RND. the discovery of fascial compartments separating cervical lymph nodes from neck structures commonly removed in RND. In response to a need for an organized approach for describing and classifying neck dissection. or neck dissection with the preservation of vital structures. periparotid. separate from muscles. the location of cervical lymph node groups is delineated by the level system [11]. The development of a better understanding of lymph node drainage patterns [7. and an improved understanding of the role of adjuvant radiation therapy [9.152 N.R. level VA (spinal accessory nodes). Rigual. Suarez demonstrated that cervical lymphatics are contained within well-defined fascial compartments. Thus. Examples include retropharyngeal.

MD. S. medical illustrator. Rigual.N. with few exceptions. The anterior border of level IIA is defined by the stylohyoid muscle (see Table 1). 1.R. (Drawing by Paul Tomljanovich. Level IB includes nodes that also lie below the . and below the mylohyoid muscle. These cervical plexus sensory nerve branches also define the anterior boundary of level V. superior to the body of the hyoid bone. This radiologic classification was designed as an adjunct to the clinically based nodal classifications. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 153 Fig.M. Imaging-based classification of cervical lymph node groups Imaging studies were not used in the initial neck dissection classification scheme in 1991 [11]. The posterior boundary of levels II through IV is delineated by the posterior border of the SCM or by the sensory branches of the cervical plexus. Using imaging landmarks.) familiar and well-defined anatomic structures. level IA includes the lymph nodes that are located between the medial margin of the anterior belly of the digastric muscles. Radiologists therefore have recently identified landmarks that accurately define the location of lymph nodes and have devised an imaging-based classification scheme for the cervical lymph node groups [13]. The levels of the neck.

or cervical plexus sensory branches Trapezius muscle.R. S. lateral border. anterior border Common carotid artery IV VA VB Plane (horizontal) defined by inferior aspect of cricoid cartilage Clavicle VI Sternum . posterior border. or cervical plexus sensory branches Sternocleidomastoid muscle. lateral border Sternocleidomastoid muscle. lateral border Sternohyoid muscle.154 N. lateral border Sternocleidomastoid muscle. or cervical plexus sensory branches Sternocleidomastoid muscle. or cervical plexus sensory branches Common carotid artery Lateral (posterior) Ipsilateral digastric muscle. anterior belly Anterior belly of digastric muscle Stylohyoid muscle Plane (vertical) defined by spinal accessory nerve Sternohyoid muscle.M. anterior border Trapezius muscle. lateral border. posterior border. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 Table 1 Neck level anatomic landmarks Level IA IB IIA IIB III Superior Mandibular symphysis Mandibular body Base of skull Base of skull Plane (horizontal) defined by inferior border of body of hyoid Plane (horizontal) defined by inferior border of cricoid cartilage Apex of the point of convergence of the trapezius and sternocleidomastoid muscles Plane (horizontal) defined by inferior border of cricoid cartilage Hyoid bone Inferior Hyoid bone body Posterior belly of digastric muscle Plane (horizontal) defined by inferior border of hyoid bone Plane (horizontal) defined by inferior border of hyoid bone Plane (horizontal) defined by inferior border of cricoid cartilage Clavicle Medial (anterior) Contralateral digastric muscle. Rigual. anterior belly Stylohyoid muscle Plane (vertical) defined by spinal accessory nerve Sternocleidomastoid muscle.

The deep border of level II is defined by the internal carotid artery in that any nodes lying medially to this vessel are considered to belong to the retropharyngeal nodal group. Level II nodes are contained in the space defined superiorly by the skull base. and posterior to a transverse line drawn on each axial image through the posterior edge of the SCM. inferiorly by the hyoid bone. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 155 Fig. S.R. Neck dissection classification The neck dissection classification system has arisen because radical neck dissection remains the standard procedure for cervical lymphadenectomy. (Drawing by Paul Tomljanovich. which are located laterally to level IV nodes. anteriorly by the posterior border of the submandibular gland. the medial margin of the carotid arteries separates the level III nodes.) mylohyoid muscle and above the hyoid bone but are posterior and lateral to the anterior belly of the digastric muscles and anterior to the posterior border of the submandibular gland.M. 2. On both sides of the neck. The boundaries of levels V and VI are the same as in the clinical classification. Rigual. Level III nodes are located between the lower border of the hyoid bone and the lower margin of the cricoid cartilage. MD. which lie medially to the vessels. . The sublevels of the neck.N. These nodes lie laterally to the common carotid artery. medical illustrator. Level IV nodes lie inferiorly to the lower border of the cricoid cartilage and superiorly to the clavicle.

MD. If one or more lymph node levels that are routinely removed in an RND are preserved. one or Fig. the SCM. In describing an mRND. with preservation of one or more nonlymphatic structures that are routinely removed during the course of an RND. and posteriorly.156 N. inferiorly. the clavicle. the anatomic structure or structures preserved should be clearly specified (eg. medical illustrator. the internal jugular vein (IJ). the inferior border of the mandible.) . and the internal jugular vein. and accessory spinal nerve (cranial nerve XI). In general. mRND with preservation of the internal jugular vein). Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 with other operations representing alterations of this classic operation (see Box 1). Radical neck dissection. the procedure is termed a ‘‘selective neck dissection’’ (SND). Finally.R. currently preserved structures include the SCM. the anterior border of the trapezius muscle. In this type of neck dissection. the operation is termed an ‘‘extended neck dissection.M. 3. SNDs are commonly used in the staging and treatment of the clinically undetectable (or N0) neck tumor.’’ The anatomic boundaries of the RND include the following: superiorly. The term ‘‘modified radical neck dissection’’ (mRND) is used when one or more nonlymphatic structures routinely removed in an RND is preserved. the midline. medially. the accessory nerve. Rigual. An mRND refers to the removal of lymph node levels I through V. Included within these boundaries are lymph node levels I through V. (Drawing by Paul Tomljanovich. S. 3). which are removed at surgery (Fig. if the procedure includes removal of additional nonlymphatic structures or lymph node groups (relative to the RND).

M. Rigual. and larynx have bilateral lymphatic drainage patterns. retropharyngeal nodes. Patients who have SCC of the larynx rarely present with metastases at the submandibular triangle (level I) [19]. and IV. For thyroid cancer and subglottic cancers. Therefore. VI). The procedure would be termed SND II–IV. the nodes in level VI are at greatest risk of harboring metastatic disease. III. In cancers involving the walls of the hypopharynx and oropharynx. With the exception of the glottic larynx. and the posterior border of the SCM and cutaneous sensory branches of the cervical plexus posteriorly (Fig. Skip metastasis to level IV may potentially represent a problem in patients who have oral tongue carcinoma [16]. hypopharyngeal.18]. and IV (SND II–IV). Selective neck dissection for oropharyngeal.14. hypopharynx. in this circumstance.15]. removal of this nodal group should be considered. Although this change in treatment philosophy has been applied mostly to patients with N0 nodal disease. because they are at risk [21]. S. II. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 157 more lymph node levels are preserved. the lateral border of the sternohyoid muscle medially. laryngeal. Lymph nodes in levels I. and hypopharyngeal cancer The lymphadenectomy of choice in the treatment of cancers affecting these anatomic sites includes the removal of lymph node groups in levels II. . The lymph nodes at risk for laryngeal.N. cancers of the oropharynx. Thus. The anatomic limits of this lymphadenectomy are as follows: the clavicle inferiorly. 4). and oropharyngeal carcinomas are usually found within levels II. the procedure of choice for patients with N0 primary tumors in these locations is a bilateral SND II–IV in cases where the neck is managed surgically. The most significant paradigm shift in the management of cervical lymph node disease over the past decade has been the selective removal of lymph node groups that are at greatest risk of harboring metastases. In laryngeal and hypopharyngeal carcinomas extending below the glottic larynx. Data from two recent studies support the use of SND II–IV for the treatment of N0 laryngeal and hypopharyngeal carcinomas [20] and transglottic carcinomas (supraglottic tumors that cross the laryngeal ventricle and invade the glottis) [21]. large-scale.R. the retropharyngeal nodes may harbor metastatic disease. The lymph node levels removed are based on the location of the primary tumor because the clinical patterns of cervical lymphatic metastasis from head and neck tumors have been shown to be predictable in multiple. and III are at greatest risk of harboring microscopic metastatic disease in patients who have oral cavity primary cancers. III. the skull base superiorly. level VI lymph nodes are usually included in the neck dissection (SND II–IV. retrospective studies [8. SND also has a role in the treatment of N-positive neck tumors [17.

The procedure of choice is SND I–III (Fig. 5). S. central compartment neck dissection refers to the removal of bilateral. including . The adequacy of SND I–III for treating clinically negative neck tumors in patients who have oral carcinomas has been examined thoroughly [9. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 Fig.158 N. and perithyroiidal lymph nodes. Some evidence suggests that. II. Therefore. including the floor of the mouth. the indicated procedure is a bilateral SND I–III. delphian.) Selective neck dissection for cancer of the oral cavity In oral cavity cancer. 6). medical illustrator. and III [8]. In addition. paratracheal. In cancers involving midline structures.R. investigators have demonstrated that. because the lymph nodes on both sides of the neck are at risk for containing metastases.M.22]. level IV nodes may contain metastatic disease [16]. MD. (Drawing by Paul Tomljanovich. the addition of postoperative radiotherapy following SND I–III can achieve regional control comparable to that of level I–V dissection and postoperative radiotherapy [9]. Rigual. it is recommended that lymph nodes in level IV be removed in patients who have cancer of the tongue (Fig. Selective neck dissection II–IV. Anterior neck dissection (selective neck dissection VI) Level VI. the nodal groups at risk are located in levels I. in patients with pathologically positive lymph nodes. 4. in cancer of the anterior tongue.10.

Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 159 Fig.) . Rigual. medical illustrator.N. Selective neck dissection I–IV for oral tongue cancer. (Drawing by Paul Tomljanovich.R. Selective neck dissection I–III. S. 6. 5. medical illustrator. MD.) Fig. (Drawing by Paul Tomljanovich. MD.M.

The lateral margins are defined by the common carotid arteries. or central compartment neck dissection. (Drawing by Paul Tomljanovich. S.R. and is designated SND II–VI. either preoperatively or intraoperatively. the procedure of choice also would include levels II to V. 7. suboccipital. The anatomic structures and lymph node groups removed during the course of this operation must be documented.160 N. carotid artery. Examples of nonlymphatic structures that may be removed include the vagus nerve. Examples of such lymph node groups include the retropharyngeal. Selective neck dissection VI. 7). medical illustrator. Extended neck dissection involves the removal of additional lymph node groups or nonlymphatic structures not included in an RND. and cervical esophageal carcinoma (Fig. Extended neck dissection Extended neck dissection is by definition more extensive than an RND.) . In thyroid cancer where there is clinical evidence of nodal metastases in the neck. The superior boundary of the dissection is the body of the hyoid bone. and the strap muscle (Fig. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 nodes adjacent to the recurrent laryngeal nerves [7]. MD. SND VI is most commonly indicated in the treatment of thyroid cancer. 8). Rigual. advanced laryngeal cancer with subglottic extension. and the inferior margin is the suprasternal notch.M. and paratracheal nodes. Fig.

Similar to SND. MD. in accordance with preexisting lymphatic anatomy. digastric muscle. 9). SND II–V (postauricular. Extended neck dissection (common carotid artery. performed . postauricular lymph nodes. medical illustrator.M. The superior limit of the dissection is the base of skull and the nuchal line. but rather predictably. Sentinel lymph node biopsy: a new paradigm for staging N0 neck tumors Sentinel lymph node biopsy (SLNBX) has become an accepted technique for staging the first extratumoral echelon of draining lymph nodes in individuals diagnosed with melanoma or breast cancer. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 161 Fig.R. Rigual. The lateral (posterior) limit is the anterior border of the trapezius muscle inferiorly and the midline of the neck superiorly [24. hypoglossal nerve). The inferior limit of the dissection is the clavicle. (Drawing by Paul Tomljanovich. SLNBX is based on the principle that lymphatic metastases do not occur in a random manner. 8. As discussed.N. The anterior (medial) limit of the dissection is the lateral border of the sternohyoid muscle.) Posterolateral neck dissection Posterolateral neck dissection is an SND that involves removal of the suboccipital lymph nodes. suboccipital) is the procedure of choice to treat the neck in patients with cutaneous carcinomas of the posterior scalp and neck [23]. S. the practice of Staging SND.25]. and lymph nodes in levels II through V (Fig.

Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 Fig. medical illustrator. It is this group of ‘‘understaged’’ patients with head and neck cancer that may especially benefit from SLNBX. SLNBX has the potential of avoiding either overtreatment or undertreatment of the neck. Hamakawa et al [30] determined that routine histologic evaluation of neck dissection specimens miss micrometastatic disease in up to 28% of patients. Wiseman et al [31] presented the results of a pilot study using an isosulfan blue dye technique to carry out SLNBX in patients with early- . In addition. S. however. is based on studies examining the pattern and incidence of metastases in large patient cohorts. SLNBX is a lymphatic mapping technique that allows for the direct evaluation of the lymph node or nodes that initially receives metastatic disease.162 N.M.29]. which may be more extensively evaluated by either immunohistochemical or molecular techniques. or posterolateral neck dissection. approximately two thirds of patients who have N0 head and neck cancer will have no pathologic evidence of metastatic disease [26. 9. Approximately 20% to 40% of patients who have N0 disease harbor microscopic tumor foci [26–28]. with a tumor at a specific location. Taking a ‘‘wait and see’’ approach in patients with N0 cancer has been associated with disease recurrence and a worsened prognosis [26]. suboccipital). Selective neck dissection II–V (postauricular. Patients who have N0 head and neck cancer may benefit most from SLNBX. Thus. Rigual.R. MD. Unlike SND. SLNBX has the added benefit of improved disease staging by directing the pathologist to the ‘‘highest risk’’ lymph node or nodes. (Drawing by Paul Tomljanovich.) by removing nodal levels with the highest probability of harboring metastatic disease. in a specific individual. Recently.

of SLNBX being performed on 316 patients who had N0 head and neck cancer. the sensitivity was 57%. Other investigators have used a combined vital dye/radiotracer technique and have reported that these methodologies complement one another and also have high rates of sentinel node identification (90%–100%) and accurate nodal staging (97%–100%) [43–45].R. The classification of neck dissection and the definition of precise anatomic landmarks have allowed . Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 163 stage N0 oral cavity head and neck cancer. vital dye. and even when identified. and when identified. In addition. 100% of sentinel nodes were identified) [34–44]. the sentinel node almost always accurately reflected the pathologic status of the neck. Recently. the sentinel node often did not accurately predict the pathologic status of the neck (0%–75%) [32. neck dissection may be performed for therapy or disease staging. from 22 centers. these investigators reported a 95% rate of sentinel node identification and an overall sensitivity of 90% for this procedure. uncontrolled.M. The negative predictive value for the absence of cervical metastases was 67% [31]. stage. however. they must be interpreted with caution because this study was performed in a patient cohort that was nonrandomized. radiotracer. Summary For individuals diagnosed with head and neck cancer. S. SLNBX does seem to be a technically feasible and accurate method for staging N0 neck cancer. the sentinel node identification rate was only 57%. using the radiotracer technique. retrospectively collected. At centers that performed 10 or fewer procedures. The results reported in the current literature are encouraging. Ross et al [46] reported pooled results. Although SLNBX was technically feasible. Although the data reported by Ross et al [46] are provocative. and heterogeneous. The authors’ experience was similar to that of other investigators who found that a vital dye technique alone had a low rate of sentinel node identification (0%–67%).N. and the study population was treated heterogeneously. There remain many issues that must be addressed before SLNBX becomes integrated into the management algorithm of N0 neck cancer. or combination technique) most appropriately applied to these individuals. centers that performed more than 10 procedures had a sensitivity of 92% [46].33]. The poor clinical utility of the vital dye methodology is a sharp contrast to the high rate of sentinel node identification reported when a radiotracer technique is used (in most series. the sentinel node accurately predicted the pathologic status of the neck in 75% of patients. site. Although this study was not prospective. Critical unresolved issues include the identification of patient/tumor characteristics appropriate for this methodology (eg. Rigual. and no adverse effects were observed in the authors’ patient population. subsite) and a determination of the technique (eg.

Nauta JJP. [10] Medina JE. Tiwari RM.47:1780–6.117:601–5. Cahan WG.29:1446–9. Nauta JJP. Arch Otolaryngol Head Neck Surg 1990. S. El Problema de las metastasis linfatica y alejadas del cancer de laringe e hipofaringe. Levine PA. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Curtin HD. Pignataro O. Medina JE. Kothari K. Tiwari RM. Del Valle B.12:197–203. Head Neck Surg 1990.4:441–99.R. Arch Otolaryngol Head Neck Surg 1999. Cancer 1972. Shah J. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 for this operation. Shah JP. Regardless of the future role of SLNBX in the management of head and neck cancer. Supraomohyoid neck dissection: rationale.160:405–9. Hicks WL Jr. Shaha A. References [1] Leemans CR. Jacques DP. Cancer 1951. Cancer 1993. [13] Som PM. Arch Otolaryngol Head Neck Surg 2000. for his excellent artwork. Standardizing neck dissection terminology. Neck dissection. Excision of cancer of the head and neck. [9] Kolli VR. Am J Surg 1990. Cancer 1994. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications.116:432–5. theoretic. et al. [7] Lindberg R. Clayman G. Wolfe ET. Pruet C. SLNBX shows promise in its ability to accurately stage N0 head and neck cancer and may allow patients with no micrometastatic disease to avoid neck dissection. Sessions R. Patterns of cervical node metastases from squamous carcinoma of the oropharynx and hypopharynx.11:111–22.126: 413–6. [11] Robbins KT. Loree TR. Mancuso AA. it must first be prospectively scrutinized in large patient populations. however. Before this technique becomes adopted into routine clinical practice. and surgical technique. JAMA 1906. Ehrlich H. Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. . Sessions R.128:751–8. Cappa C.164 N.73:187–90.125:388–96. Patterns of cervical node metastases from squamous carcinoma of the larynx. [5] Suarez O. Laryngoscope 1984. Arch Otolaryngol Head Neck Surg 1991. The role of supraomohyoid neck dissection in patients with positive nodes. Rev Otorhinolaringol 1963. to become standardized worldwide. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. [4] Martin HE. [14] Candela FC. Rigual. [12] Robbins KT. currently it is only through a complete understanding of the clinical. Medina J. [3] Crile GW.94:942–5. Levine P. Byers RM. indications. et al. Acknowledgment The authors thank Paul Tomljanovich. Datta RV. Neck dissection classification update. [8] Shah JP. MD. Oldini C. Functional neck dissection: an evaluation and review of 843 cases. [15] Candela FC.M. Patterns of cervical lymph node metastasis from squamous carcinoma of the upper aerodigestive tract. and technical aspects of neck dissection that surgeons may benefit individual patients and the head and neck cancer patient population as a whole. [2] Leemans CR. Arch Otolaryngol Head Neck Surg 2002. and its many variations. [6] Bocca E. Orner JB.71:452–6. Shah JP.23:83. Head Neck 1989.

MacLennan K. Weber RS. Loree T.124:455–9. Eur Arch Otolaryngol 1993. Helliwell TR. [24] Goepfert H. Johnson LFP. Brandt D. Pyle PB.172:654–7. [36] Koch WM. Andrews T.110:198–203. Soares JF. Br J Oral Maxillofac Surg 1995.19:260–5. Rigual N. Evolving role of modifications in neck dissection for oral squamous carcinoma. Shah JP.8(3):156–63. S.106:618–20. Virchows Arch 2000. Saunders JR. Eisele DW. et al. Ear Nose Throat J 2002. Cancer 1972. Magrin J. Spiro RH. Tobias MJ.156:286–90. [27] Shah JP. Singh A. Sumida T.N. Cervical node metastases in laryngeal and hypopharyngeal cancer: a prospective analysis of prevalence and distribution. Filho JG. Am J Surg 1988. Arch Otolaryngol Head Neck Surg 1998. [34] Alex JC. Head Neck 1999.160:405–9. 124:790–3. Jesse RH. 1938. Otolaryngol Head Neck Surg 2000.437:116–21. . Am J Surg 1990. Ann Arbor.19:14–9. Selective neck dissection and the management of the node-positive neck. Am J Surg 1996. Takemura K. Gray J. Edington H. Prosser JE. Wolf P. Gamma probe-directed biopsy of the sentinel node in oral squamous cell carcinoma. [31] Wiseman S. [38] Zitsch RP. [19] Dos Santos CR. Posterolateral neck dissection. Laryngoscope 2000.M. [18] Pellitteri PK. Sessions RB. Ballantyne AJ. [25] Rochlin D. Everts EC. Phillips DE. [17] Traynor SJ.22: 380–5. [35] Werner JA. Dunne AA. Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.21(8):728–33.250(8):446–9. et al. translator. Mauri S. Sasaki CT. Johnson JT. Wenig B.33(1):3–8. Ferlito A. Involvement of level I neck lymph nodes in advanced squamous carcinoma of the larynx. [20] Buckley JG. Renner GJ. Head Neck 1997. Kayahara H. Hicks W. et al. End results of a prospective trial on elective lateral neck dissection vs type III modified radical neck dissection in the management of supraglottic and transglottic carcinomas. Head Neck 1997. Studies on significance of sentinel lymphadenectomy in pharyngeal and laryngeal carcinoma.29:1446–9. Krag DN. Head Neck 2000. Histological study on pN upgrading of oral cancer. MI: Edwards Brothers. Rigual. Todd DW. Roland NJ. [30] Hamakawa H. Lymphatic system of the head and neck. McGill D. Critical assessment of supraomohyoid neck dissection. Occult node metastases in head and neck squamous carcinoma. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 165 [16] Byers RM. Ann Otol Rhinol Laryngol 2001.21:694–702. Andersen PE.128(1):16–21. Laryngorhinootologie 1999. Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: a major advance in staging of the N0 neck. [32] Pitman KT. Civelek AC. [23] Rouviere H. [22] Spiro JD. et al. Andersen PE.R. [29] Lindberg R. [26] Jones AS. Lymphatic mapping with isosulfan blue dye in squamous cell carcinoma of the head and neck. Arch Otolaryngol 1980. Posterolateral neck dissection. Kare R. Kowalski LP. Kowalski LP. Intraoperative radiolymphoscintigraphy for detection of occult nodal metastasis in patients with head and neck squamous cell carcinoma.78(12):663–70. Is there a role for sentinel node biopsy in early N0 tongue tumors? Surgery 2000. Surg Gynecol Obstet 1962. [37] Chiesa F. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. [33] Shoaib T. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Grana C. Expanded application of selective neck dissection with regard to nodal status. Head Neck 1999. Frequency and therapeutic implications of ‘‘skip metastases’’ in the neck from squamous carcinoma of the oral tongue. [28] Shah JP. Strong EW. Robbins KT. et al. Choti MA.115:369–73. Cohen JI. Arch Otolaryngol Head Neck Surg 1998. Neuman T. A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck.122(5):662–6.110:982–4. [21] Brentani RR. Soutar DS.

Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms. Sharma PK. et al. Wahl RL. Giuliano A.91(11):2077–83. Lymphoscintigraphy and ultrasoundguided fine needle aspiration cytology of sentinel lymph nodes in head and neck cancer patients. Ann Surg Onc 2001.R. [40] Nieuwenhuis EJC. Soutar DS. Sentinel node biopsy in head and neck cancer. Botti G. Ann Surg Oncol 2002. Sentinel node localiztion in oral cavity and oropharynx squamous cell cancer. [45] Bilchik AJ. The First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer and adoption of a multicenter trial protocol. Colnot DR. et al. Pijpers HJ. et al. .9(4):406–10. van den Brekel MWM. Essner R.M. [42] Taylor RJ. Chiesa F.8(9S):103–5. et al. A suggested method for sentinel node biopsy in SCC of the head and neck [letter]. Radiology 2001. et al. Head Neck 2000. Rigual. et al.4(6): 351–8. [46] Ross GL. Shoaib T. Wiseman / Surg Oncol Clin N Am 13 (2004) 151–166 [39] Meijer S. [41] Colnot DR.127:970–4. van den Brekel MWM.218(1):289–93. Arch Otolaryngol Head Neck Surg 2001. Nieuwenhuis EJC. Recent Results Cancer Res 2000.157:206–17. S. MacDonald DG.166 N. Cancer J Sci Am 1998. Cancer 2001. Head and neck squamous cell carcinoma: US-guided fine-needle aspiration of sentinel lymph nodes for improved staginginitial experience. The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck. [43] Mozzillo N. et al. [44] Shoaib T.22:733–5. Soutar DS.

University of Texas Southwestern Medical (L. Oxford.myers@utsouthwestern. multimodality therapies and radiation therapy and chemotherapy protocols have had little impact on improving the traditionally poor prognosis. Each frontal sinus drains inferiorly by way of the nasofrontal duct. 1055-3207/04/$ . staging. which continues inferiorly to drain into the medial meatus of the lateral nasal wall. and outcomes for these heterogeneous neoplasms arising from the anatomically complex region of the paranasal sinuses. E-mail address: larry. Myers. The dura of the * Corresponding author. and frontal sinuses (Figs. with an emphasis on epithelium-derived malignancies. The paranasal sinuses consist of the paired maxillary. Myers). Dallas. complex defects with free-tissue transfers. 5323 Harry Hines Boulevard. Paranasal sinuses are inaccessible on routine examination and cancers of this region typically do not become manifest until critical adjacent structures are involved. This article presents the diagnosis. MD*. Anatomy A fundamental knowledge of the anatomy of the paranasal sinuses is crucial in any discussion of malignancies of this region.1016/S1055-3207(03)00115-7 . Lance E. The frontal sinus is located between the outer and inner tables of the frontal bone. TX 75390-9035. The middle meatus is the area found inferior to the middle turbinate and superior to the inferior turbinate. Each sinus is named according to the bone that it pneumatizes. The poor overall and disease-free survival rate is commonly attributed to the advanced stage at presentation of most tumors. 1 and 2).see front matter Ó 2004 Elsevier Inc. ethmoid. these rare malignancies remain a complex and difficult problem. All rights reserved. USA Despite major advances in the diagnosis and treatment of paranasal sinus cancers. including the ability to safely reconstruct large. doi:10. MD Department of Otolaryngology–Head and Neck Surgery. sphenoid.Surg Oncol Clin N Am 13 (2004) 167–186 Differential diagnosis and treatment options in paranasal sinus cancers Larry L. Improved surgical techniques.L. treatment options.

PE. It is surrounded by numerous vital structures. Myers. The sphenoid sinus is the most posterior of the paranasal sinuses. middle ethmoid ostium. with a base formed by the lateral nasal wall and an apex projecting toward the zygomatic arch. The lateral border is formed by the lamina papyracea of the medial orbital wall. a bony structure that supports the middle turbinate by attachment to the lamina papyracea and anterior skull base. L. The superior boundary is formed by the orbital floor. OB. The soft tissues of the face . The anterior cranial base forms the superior border of the ethmoids. Each of the sphenoid ostia is located on the anterior wall of the sphenoid sinus.E. 2. The sphenoid sinus and posterior ethmoid cells drain into the sphenoethmoid recess in the posterior superior lateral nasal cavity. sphenoid ostium. ME.168 L. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 Fig. Its superior surface forms the sella turcica and contains the pituitary gland. anterior ethmoid. Sagittal section of head.L. Each maxillary sinus is shaped similar to a pyramid. posterior ethmoid. depicting position of paranasal sinuses and sectioning planes 1 and 2 of Fig. and the nasal cavity is located medially. SO. The internal carotid artery and optic nerve are located along its lateral wall. The pterygopalatine fissure is located immediately posterior to the sinus. The ethmoid sinuses are divided into anterior and posterior ethmoid cells by the basal lamella. which also forms the posterior wall of the nasal cavity superior to the choanae. The ethmoid sinuses consist of 3 to 18 thin-walled air cells. and the inferior boundary is formed by the alveolar and palatine process of the maxilla. The maxillary sinuses are the largest sinuses and are the only ones separated from the skull base. 1. anterior cranial fossa is located immediately posterior to the sinus. olfactory bulb. AE.

Etiology The precise cause of paranasal sinus malignancies is unknown. are located anteriorly and laterally to the sinus.L. The maxillary sinuses and the anterior ethmoid cells drain into the middle meatus [1. and more adherent to the surrounding bone [1]. however. include . Incidence Paranasal sinus cancers account for less than 1% of all malignancies and comprise 3% of all head and neck malignancies [3]. Myers.0 case per 100. The normally airfilled sinuses surround the nasal cavity and are lined by ectodermally derived respiratory epithelium. The lining of the sinuses is continuous with the mucosa of the nasal cavity. Epithelium-derived neoplasms are almost nonexistent in children [5. 1 for planes of sections 1 and 2). the overall male-to-female incidence is 3 to 2.E. Coronal section of head to illustrate relationships of paranasal sinuses (see Fig. The incidence is 2 to 3 times higher in Japan [7]. The incidence rate of sinonasal cancer progressively increases after age 35. columnar epithelial cells and interspersed mucus producing goblet cells. The incidence rate is 0.3 to 1. L. consisting of ciliated. The sinus mucosa is thinner. with a strong predilection for whites.2]. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 169 Fig. 2.6]. pseudostratified.000 people per year in Western populations [4–6]. In the United States.L. Known risk factors for the development of cancer in this region. however.

and heavy metals. then endoscopic or open biopsy is best performed in the operating room. neural tissue. L.L. If there is concern for bleeding or the lesion is not easily accessible. smoke. maxillary dental symptoms. Epithelium-derived malignancies Squamous cell carcinoma Non–squamous cell carcinoma Adenocarcinoma Adenoid cystic carcinoma Mucoepidermoid carcinoma Melanoma Olfactory neuroblastoma Sinonasal undifferentiated carcinoma Presenting symptoms/history Patients typically present after symptoms have been present for several months and the tumor has involved adjacent structures. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 wood and leather dust. With involvement of surrounding structures. Small tumors are often asymptomatic but may present with nasal obstruction. minor salivary glands. and bone. Office nasal endoscopy under topical anesthesia allows assessment of the extent of a mass and its fixation to surrounding structures. Most patients have a history of exposure to carcinogens for more than 10 years [8]. A formal ophthalmologic evaluation is recommended if there is concern for orbital involvement. infraorbital nerve deficits. A neoplasm may arise from any type of tissue present in the paranasal sinuses. or possibly neurologic deficits secondary to intracranial extension. lymphatics. epistaxis. including lymphomas.170 L. patients may experience diplopia or vision changes. such as headache or rhinorrhea. A biopsy can usually be performed in the office setting. Myers. Evaluation A suspected paranasal sinus malignancy requires a thorough head and neck examination complemented by imaging studies. . This article discusses epithelium-derived malignant neoplasms. Pathology The paranasal sinuses contain diverse components: schneiderian mucosa. A complete cranial nerve examination may disclose skull base or direct nerve involvement by the tumor.E. or symptoms consistent with chronic sinusitis. vessels. including nickel.

floor. Often on CT scans. MRI with gadolinium is superior in delineating soft tissue detail. Tumors of the infrastructure are associated with a better prognosis because of decreased involvement of the orbit and cranial base. A 6-ft Caldwell view is occasionally used to create a template of the outline of the frontal sinus to guide frontal bone osteotomies. and not exposing the patient to ionizing radiation.L. both intra. The infrastructure of the maxillary sinus lies anterior and inferior to the line and the suprastructure lies posterior and superior. skin of the cheek. allows the best assessment of involvement of surrounding bone. In addition. This modality provides the best assessment of tumor extent and can easily differentiate between tumor and inspissated mucus (Fig. The extension of a paranasal sinus malignancy through the skull base is best evaluated with fine-cut coronal imaging. including fine bony structures such as the lamina papyracea. A formal staging system has been developed only for maxillary sinus carcinomas. L.L. nasopharynx. Coronal imaging readily demonstrates the anatomy of the paranasal sinuses. or ethmoid sinuses T4: Tumors invading orbital contents beyond the floor or medial wall. In 1997. subcutaneous tissue. MRI has the advantage of avoiding dental filling artifacts. cribiform plate. the American Joint Committee on Cancer revised its 1977 criteria to more accurately correlate tumor stage and survival [10]. Plain radiographs are generally not useful in assessing a sinus malignancy. 3). Contrast infusion may help demonstrate regions of enhancement containing neoplasm. it is difficult to determine the soft tissue extent of a malignancy. except for the posterior wall. imaging in the sagittal plane. Tumor classification T1: Tumors limited to antral mucosa. Myers. and cribiform plate. The 1997 staging system is described in the following sections [11]. Staging Staging paranasal sinus malignancies as a whole is imprecise and controversial. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 171 CT imaging. base of skull. infratemporal fossa. Ohngren [9] differentiated maxillary sinus tumors based on whether they primarily involved the suprastructure or the infrastructure of the maxillary sinus. In 1933. Ohngren’s line runs from the medial canthus inferiorly and laterally to the angle of the mandible. including extension into the hard palate or middle nasal meatus T3: Tumors invading any of the following: posterior wall. orbital floor.E.and extracranially. including any of the following: orbital apex. Sinus opacification on CT images may be secondary to tumor infiltration or the result of accumulations of mucus from obstruction of the sinus. without bone erosion or destruction T2: Tumor causing bone erosion or destruction. and sphenoid and frontal sinuses . pterygoid plate. with at least 3-mm cuts. or medial wall of the orbit.

none more than 6 cm in greatest dimension N2b: Metastasis to multiple ipsilateral nodes.172 L. Black arrow indicates actual tumor. White arrow indicates inspissated mucus. 3. L. all less than 6 cm in greatest dimension N3: Metastasis of more than 6 cm Metastasis classification M0: No distant metastasis M1: Distant metastasis present .L. Node classification N0: No regional node metastasis N1: Metastasis to single ipsilateral node. Axial contrast-enhanced MRI depicting actual extent of left posterior ethmoid sinus adenocarcinoma. or in multiple ipsilateral lymph nodes. Myers. more than 3 cm and less than 6 cm in greatest dimension. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 Fig. all less than 6 cm in greatest dimension N2c: Metastasis to bilateral or contralateral nodes. less than 3 cm in greatest dimension N2a: Metastasis to single ipsilateral node.E.

exophytic. Nibu et al [15] reported an overall 5-year survival rate of 86% in 33 patients with maxillary sinus SCC. The surgical group demonstrated a significantly higher 5-year disease survival rate of 64%. Tiwari et al [13] reviewed 35 cases of SCC of the maxillary sinus. L. Lymph node or distant metastases are rare on presentation [15]. accounting for 58% to 73% of malignancies [12–14].E. and 50%. compared with the chemotherapy/radiation therapy group. The neoplasm more commonly affects men and typically presents in the sixth and seventh decades of life [1].L. for each decade respectively. The tumors may exhibit either papillary.L. 7 infrastructure maxillectomies with preservation of the orbital floor. 45%. Reported risk factors include a history of inverted papilloma and exposure to radioactive thorium dioxide (thorotrast) contrast and nickel [1].13]. 80% of cases demonstrate keratinization and the remainder are the nonkeratinizing subtype. and the use of these agents may be an effective adjuvant treatment for paranasal sinus SCC. The most common treatment approach used was surgery and radiation therapy. a 60% . The maxillary sinus is the most common location for paranasal sinus SCC. Even with skull base involvement. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 173 Disease stage Stage Stage Stage Stage I: T1N0 II: T2N0 III: T3N0 or T1-3N1 in greatest dimension IV: T4N0 or T1-4N2-3 Squamous cell carcinoma Squamous cell carcinoma (SCC) is the most common paranasal sinus neoplasm. or inverted growth patterns [1]. The authors reviewed the literature and demonstrated a significant improvement in survival compared with previous publications. followed by the ethmoid sinuses. The standard treatment of paranasal sinus SCC is combined therapy involving resection and radiation [10. 22. Twenty-six patients were treated with surgery and postoperative radiation and nine were treated with chemotherapy and radiation therapy. The reported survival rates in articles published in the 1960s through 1990s were 25%. most commonly in the infratemporal fossa. SCC arises from the respiratory ciliated columnar epithelium of the paranasal sinuses.13]. Histologically.12. more than 80% of patients present with stage III or IV tumors [10. however. The favorable response of head and neck SCCs to the chemotherapeutic agents 5-fluorouracil (5-FU) and cisplatin recently has been reported.5% of patients treated with resection developed a local recurrence. Duelguerov et al [12] reported a 58% 5-year survival rate for 126 patients treated at the University of California– Los Angeles and Geneva University Hospital. The frontal and sphenoid sinuses each account for 1% of SCC [1. Resections included 12 maxillectomies. SCC typically presents at an advanced stage. and 1 craniofacial resection. Myers. 6 radical maxillectomies with orbital exenteration.12]. 34%.

Intestinal. Woodworkers in England have greater than a 1000-fold increased incidence of ethmoid adenocarcinoma [17–24]. however. surgical resection. Adenocarcinomas account for 17% to 90% of ethmoid malignancies. with follow-up periods ranging from 9 months to 5 years. High-grade lesions may demonstrate glandular structures but are characterized by a solid growth pattern containing pleomorphism and increased mitotic activity. L. Selection bias likely contributed to the high survival rate. Only one patient had positive margins secondary to brain involvement and died of local recurrence at 8 months. three of these recurrences were salvaged with repeat resection [15]. including five patients who were observed for more than 3 years. and high-grade lesions adjacent to the cribiform plate [28]. The 5-year survival rates after craniofacial resection ranged from 39% to 57% [29–31]. In addition.174 L. Postoperative radiation therapy is recommended for positive margins. Histologically. All intestinal types are considered to be high-grade lesions [1]. The patients received biweekly packing changes. Sinus adenocarcinomas may develop from either minor salivary gland tissue or the epithelium. Low-grade adenocarcinomas contain numerous glands lined by a single layer of cuboidal to columnar cells with uniform nuclei. irregular cystic spaces may be present. Wax et al [27] reported on eight patients with adenocarcinoma of the ethmoid sinuses who were treated with craniofacial resection. or intestinal type. Myers. depending on geographic location and occupational risk factors [25–27]. Chronic exposure to wood or leather dust has been cited as a risk factor for the development of sinonasal adenocarcinoma in numerous studies. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 survival rate was achieved.or colonic-type adenocarcinoma resembles intestinal adenocarcinoma and may contain goblet or signet ring cells. Seven patients have no evidence of disease. high grade. and postoperative radiation therapy. Multimodality treatment included preoperative cisplatin. because advanced tumors with invasion of dura or the orbit were excluded from the protocol.L. dural or cribiform plate invasion. Ethmoid adenocarcinoma typically requires a craniofacial approach for resection. and topical chemotherapy for 4 weeks. Papillary formations or large.E. Four patients received postoperative radiation therapy. surgical resection. and postoperative radiation therapy [16]. 5-FU. removal of necrotic tissue. Nine patients developed a local recurrence. Orbital contents were preserved in 67% of patients. . and radiation therapy. Knegt et al [32] reported a 5-year survival rate of 87% in 70 patients treated with surgical debulking and topical chemotherapy with 5-FU. Adenocarcinoma Paranasal sinus adenocarcinomas differ from SCC in risk factors and typical location. a University of Chicago study reported 11 of 12 patients with no evidence of disease at a median follow-up period of 55 months after preoperative chemotherapy. adenocarcinomas are classified as low grade.

Salvage therapy yielded no evidence of disease for at least 2 years in only 1 of 17 patients with a local recurrence. including cribiform. With a median follow-up period of 8 years. In a longer-term follow-up period of 22 patients with ACC of the maxillary antrum. It is an aggressive neoplasm characterized by early neural invasion and a high incidence of local recurrence and distant metastases.36].40]. including 21% with distant metastases. however. ACC is characterized by varied growth patterns. Pitman et al [36] reviewed 35 patients with ACC of the sinonasal tract and reported a 46% disease-free survival rate with a median follow-up of 40 months. Myers. and solid arrangements of hyperchromatic cells with indistinct cell borders. All 12 of the patients treated with a single modality developed local recurrence. Melanoma Sinonasal melanomas are rare neoplasms characterized by a poorer prognosis than cutaneous melanomas. which may develop years after initial resection.E. It may arise from minor salivary gland tissue located throughout the upper respiratory tract. Five-year survival rates of approximately 50% have been reported for advanced cases of ACC [39. L.L.6%. The most common location of ACC of the sinonasal tract is the maxillary sinus. Craniofacial resection in 23 patients allowed a similar rate of control of advanced tumors compared with patients treated with a maxillectomy for limited tumor extension. The standard treatment for ACC of the paranasal sinuses is combined therapy with resection and radiation therapy [36–38].34]. accounting for 66% of cases [36].6% and a 10-year disease-free survival rate of 13. The neoplastic cells may form nests of ducts or tubules. tubular. ACC of the paranasal sinuses has the highest incidence of local recurrence. Kim et al [37] reported a 10-year survival rate of 37. compared with a local recurrence rate of 40% in patients receiving resection and radiation therapy. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 175 Adenoid cystic carcinoma Adenoid cystic carcinoma (ACC) most commonly develops in the major salivary glands. Malignant melanoma occurs in the . the 20-year survival rate is only 13% [1]. however. Approximately 71% of patients developed a recurrence.5 years. Patients with unresectable ACC or residual disease after resection should be evaluated for neutron radiotherapy. including the paranasal sinuses.L. the median survival time for all patients was 7. Neutron therapy delivers a higher linear energy transfer compared with conventional radiotherapy. Although the 5year survival rate of ACC of all head and neck sites is 75%. Histologically. which are sharply demarcated from the surrounding myxoid or hyalinized interstitial stroma [1]. likely secondary to its advanced stage at presentation and vicinity to cranial nerves and the skull base [35. Negative predictors for survival were perineural invasion and single-modality treatment. ACC is the second most common malignancy of the paranasal sinuses in some series [33.

In a review of 72 cases of sinonasal melanoma. L. patients may develop local recurrences or distal metastases years later [50. bones. Surgical resection is the standard treatment for sinonasal melanomas. prominent neurofibrillary material. and upper surface of the superior turbinate [52]. On histology. Higher-grade neoplasms are characterized by anaplastic tumor cells with increased mitotic . and lungs [53]. The ethmoid sinuses are the most common paranasal sinuses to be affected by this neoplasm. but distant spread may involve the brain. The incidence of sinonasal melanoma is much higher in certain populations. viscera. rare neoplasms derived from the olfactory mucosa present on the superior septum. and most patients present in their sixth or seventh decade of life [46]. It accounts for more than 25% of melanoma cases in Japan and 7% to 11% of sinonasal neoplasms [43–45]. melanomas may exhibit various growth patterns. The overall 5-year survival rate was 36%. especially the lateral nasal wall. with variable melanin deposition [1]. Immunohistochemical staining for S-100 protein and HMB45 allows the diagnosis to be made with amelanotic melanomas [1.49]. The cervical lymphatics are the most common site of metastasis. variable calcification. and well-differentiated cells. and sinonasal melanoma accounts for less than 4% of sinonasal malignancies [42].176 L. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 sinonasal tract in less than 1% of cases [41]. with peaks in the second and sixth decades of life. The ethmoid and maxillary sinuses are the most common location for paranasal sinus melanomas [47]. are aggressive. Olfactory neuroblastoma (esthesioneuroblastoma) Olfactory neuroblastomas. Despite initial resection with negative margins. Sinonasal melanomas develop from neural crest–derived melanocytes found in the lamina propria of respiratory epithelium and around sinonasal minor salivary glands [48]. Olfactory neuroblastomas commonly extend intracranially and are associated with a high local recurrence and metastatic incidence.51]. low-grade olfactory neuroblastomas exhibit lobular architecture with pseudorosette formations. Myers. The tumor displays a bimodal distribution for patient age. including epithelioid and spindle cell formations. There is an equal male-to-female incidence. Recurrences amenable to surgery should be resected to help prolong survival [46]. Lund et al [47] reported a 5-year survival rate of 28%.L. Histologically.E. Despite advances in chemotherapy and radiation therapy. Brandwein et al [46] reviewed 25 cases from Mount Sinai Hospital and performed a meta-analysis of 163 reported cases. There was no improvement in local control or survival rates with the addition of radiotherapy or chemotherapy compared with surgical resection. cribiform plate. also known as esthesioneuroblastomas. Sinonasal melanoma most commonly develops in the nasal cavity. there was no improvement in survival in patients reported before 1980 compared with patients from 1980 to 1995.

Duelguerov et al [12] reviewed 30 cases and reported a 10-year survival rate of 33%.58]. such as epistaxis. there has not been an improvement in survival times. . SNUC is characterized by nests of small.5 to 1 [57. highly aggressive neoplasm. The authors performed a meta-analysis of cases reported since 1960 and demonstrated no significant improvement in survival rates during the past 40 years. and there is a male-to-female incidence of approximately 2.E. and chemotherapy. or bone. obtained complete surgical resection in 62% of patients with craniofacial resection. Cells contain numerous mitotic figures. The most common locations are the ethmoid sinuses and the nasal medium-sized cells with extensive necrosis.L. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 177 activity. Patients present with rapid onset of symptoms. hyperchromatic nuclei [57]. Histologically. Proposed risk factors include smoking and prior radiation therapy [56–58].85%. Standard treatment consists of combined therapy with surgical resection and postoperative radiation therapy. The survival rates with surgery or radiation alone were 62. Jeng et al [57] reported a high incidence of metastasis. High-grade olfactory neuroblastomas may retain a lobular configuration with rosette formation [1]. Broich et al [54] reported a 5-year survival rate of 72. In a recent review of 36 cases of SNUC. radiation therapy. and 28%. Chao et al [55]. which was not described until 1986 [56]. Resto et al [53]. Despite advances in craniofacial resection. including surgery. a high nuclear-tocytoplasmic ratio. lungs.2% for irradiation alone. Myers. at Washington University Medical Center. All five of the patients with no evidence of disease at a median follow-up time of 31 months received surgical resection as part of their treatment.6 years. 42%. The survival rates for articles from the 1960s through the 1990s were 23%.4% for combined therapy and 51. The tumor typically presents with involvement of multiple sinuses and extension through the skull base and into the orbit. nasal obstruction. observed a 5-year local control rate of 87.5% and 53. Craniofacial resection is frequently necessary because of the high incidence of anterior cranial fossa involvement.L. yielded only a 10-month median survival time. or proptosis. most commonly to the liver. Sinonasal undifferentiated carcinoma Sinonasal undifferentiated carcinoma (SNUC) is a rare. and moderate pleomorphic. The mean age of presentation is the sixth decade of life. respectively. L.5% with combined therapy. for each decade respectively. and radiation therapy. 30%. Approximately 80% of patients with negative margins had no evidence of disease at a median follow-up period of 5. at Johns Hopkins. In patients with unresectable tumors. chemotherapy. chemotherapy may be given in conjunction with radiation therapy for palliation. cranial nerve deficits. Others proposed that craniofacial resection is sufficient treatment when negative margins are obtained with limited tumors. Approximately 17% of patients had cervical node involvement and 31% had distant metastasis. Various protocols.

60]. Formal ophthalmologic evaluation is helpful when there is concern for orbital involvement. Because T-cell–derived lymphomas are associated with Epstein-Barr virus. Imaging studies are reviewed by a neuroradiologist.2% to 2% of extranodal lymphomas in Western populations [59. diversity of Epstein-Barr strains in the different populations may contribute to the marked difference in disease course [62]. Approximately 11 of 15 patients were alive at a median follow-up period of 10 years. CuadraGarcia et al [62] reported a significantly improved prognosis with patients who had T-cell/natural killer cell lymphomas treated at Massachusetts General Hospital compared with Eastern reviews. the patient is referred to an oral surgeon so that any needed dental extractions may be performed at the time of surgery. whereas T-cell lymphomas more commonly involve the nasal cavity [62].E. medical oncology.178 L. it is necessary to send biopsy specimens in formalin and in saline to allow permanent section analysis and flow cytometry. compared with a median survival time of 6 to 25 months in Asian populations [67–69].L. are large B-cell–type lymphomas diagnosed in elderly men [59–66]. A neurosurgeon is consulted if there is skull base involvement and a craniofacial resection is anticipated. however. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 Lymphoma Lymphomas of the paranasal sinuses are rare but are the most common non–epithelial-derived neoplasm of the sinuses. yielding a 67% overall survival rate [61]. There is significant geographic diversity in the incidence and histology of paranasal sinus lymphomas. A review of 70 patients who had sinonasal lymphoma and who were treated at M. with margins clear of neoplastic cells. Lymphomas of the sinonasal tract account for less than 0. most cases are T-cell derived neoplasms affecting young men. maxillec- .D. Most Western cases. Treatment Surgical treatment A multidisciplinary approach is often used before resection of a paranasal sinus cancer. For maxillary sinus neoplasms. The goal of surgical resection is to remove the cancer en bloc. Orbital extension is more often associated with diffuse. Myers. A combined modality approach with chemotherapy and radiation therapy is the treatment of choice. Patients are presented to a tumor board consisting of specialists in head and neck oncologic surgery. and radiation therapy. Anderson Cancer Center reported improved prognosis with combined therapy versus radiotherapy alone. The maxillary sinus is the most common site of involvement. If a patient is expected to require radiation therapy. If lymphoma is suspected. In Asian populations and in Peru. large B-cell lymphomas. L.

or sphenoid sinuses usually require a craniofacial approach because of skull base involvement. The incision begins in the inferior hairs of the medial one third of the eyebrow. with exposure of the pterygopalatine fissure. It continues slightly on the nasal side of the nasofacial groove until it curves around the ala and into the floor of the nose. and the ethmoid sinuses. L. such as medial maxillectomy. Neoplasms involving the ethmoid. and the nasal tip and dorsal nasal soft tissues are elevated as with a rhinoplasty. nasal cavity. and may be freed with osteotomies [74]. 2 to 4 units of blood are made available for the patient.L. The lateral rhinotomy technique provides access to the nasal cavity. The hemitransfixion incisions are connected. and clivus. This technique provides access to the midfacial skeleton. Bilateral intranasal incisions include a transfixion. The medial canthal ligaments may be detached from the lacrimal crest in the subperiosteal plane. In addition. may be used depending on tumor extent. a Weber-Ferguson incision may be made. The maxillary soft tissues may then be elevated in a subperiosteal plane to the orbital rims. frontal. and radical maxillectomy. infrastructure maxillectomy. and an incision along the nasal floor. however.E. The incision is carried deep through the periosteum. suprastructure maxillectomy. After general endotracheal anesthesia. which combines the lateral rhinotomy incision with an upper lip–splitting incision. The medial nasal floor incision may include a small Z-plasty or triangular incision to decrease postoperative stenosis. sinuses. Cefuroxime and metronidazole are most commonly given upon entering the operating room and every 8 hours for at least 24 hours postoperatively. Numerous modifications. The two most commonly used incisions for approaches to the midface and anterior skull base are the lateral rhinotomy and the facial degloving technique. The infraorbital neurovascular bundle is preserved. Exposure is compromised. Before beginning surgical resection. The mucosa of the gingivobuccal sulcus is incised between the maxillary tuberosities. Myers. the extent of the tumor is assessed with rigid telescopes and indirect mirror examination of the nasopharynx. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 179 tomy is the standard surgical procedure. If a total maxillectomy is required. The incision curves downward midway between the nasion and the medial canthus. an intercartilaginous incision along the cephalic border of the lower lateral cartilage. if possible. subtotal maxillectomy. After periosteal elevation. The midfacial degloving technique offers the advantage of avoiding facial incisions.L. a curved osteotome is used to make low lateral osteotomies through the frontal process of the maxilla. Placing the vertical component of the incision on the philtral crest minimizes the visibility of the subsequent scar [70–72]. The lateral nasal wall may then be out-fractured and retracted medially. in patients with decreased distance between the oral commissures [73]. medial third of the maxilla. Anterior craniofacial resection is most commonly used for resection of tumors originating in the sinonasal tract with invasion of the floor of the . patients receive broad-spectrum intravenous antibiotics.

Once transfacial exposure has been obtained.180 L. Optic nerve decompression is not required if the posterior limit of resection is limited to the cribiform region. A diamond burr may then be used to remove the posterior table to expose the dura. maxillary. and orbital regions. Osteotomies of the zygoma and palate are included if a total maxillectomy is required. fovea ethmoidales. Stents may be placed in the canalicular system to help prevent dacrostenosis [75. The dura is then elevated to expose the planum sphenoidale. control of anterior and posterior ethmoid vessels. orbital exenteration is indicated . orbital roofs. and medial and inferior orbital rims. The periosteum is elevated from the maxilla. a neurosurgeon performs the bifrontal craniotomy. Once the bone flap is removed. the optic nerve should be decompressed. all resections for maxillary sinus carcinomas included an orbital exenteration [77]. Because the pericranial flap traverses the frontal sinus. In the early 1900s. A contralateral Lynch incision facilitates elevation of the contralateral periorbita. the frontal lobe is then elevated from the cranial base. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 antezrior cranial fossa. attention is directed at reconstruction of the anterior skull base defect. nasal bones. care is taken to separate the superior sagittal sinus contained in the dural folds from the frontal bone before making the lower horizontal bone cut.E. an upper lip incision is included with the lateral rhinotomy incision. A vascularized. An osteoplastic frontal sinus flap may be used in patients with large frontal sinuses to avoid cosmetic deformity from the placement of burr holes in the forehead region. Cutting the anterior horizontal bone inferiorly within 1 cm of the supraorbital rims minimizes the amount of subsequent brain retraction required. In patients with small frontal sinuses. With the realization that the entire orbit is lined by a periosteum (periorbita). Traditionally. which is resistant to tumor infiltration [78]. If the posterior limit of resection involves the planum sphenoidale. the frontonasal duct should be obliterated. During closure of the facial wound. and exposure for osteotomies. orbital preservation became more accepted. The olfactory nerves are severed at the cribiform plate. Myers. This approach combines a bifrontal craniotomy with transfacial exposure of the nasal cavity. The frontal sinus may either be obliterated or cranialized. Once margins have been cleared and the dura is closed. anterior-based pericranial flap is placed over the defect. ethmoid. a guarded osteotome is introduced by means of burr holes above the hairline or in the temporal regions to create the frontal bone flap. A less aggressive approach toward orbital exenteration with resection of sinonasal malignancies has developed during the past century.76]. the medial canthal ligaments are resuspended to the medial orbital wall. and the base of the anterior clinoid processes. Removing the optic canal allows an osteotomy to be made in the planum sphenoidale with decreased risk of injury to the optic nerve.L. if the tumor involves the periorbita or other intraorbital structures. L. If a total maxillectomy is also planned. and the distal end may be sutured to dura. In the midline.

Thus far. The risk of regional failure is higher with SCCs and undifferentiated carcinomas. middle ear effusions. hypothyroidism. without reconstruction of the bony orbital wall [80]. The neck should be included in the postoperative radiation field if there are two or more pathologic nodes or if one node exhibits extracapsular spread.E. At the University of Virginia. Radiation therapy is typically started approximately 4 weeks after surgical resection.L. have included chemotherapy. Multiple studies have demonstrated improved survival with paranasal sinus malignancies with combined therapy compared with single-modality treatment. such as the nasopharynx. including surgical resection. Approximately 10% of paranasal sinus cancers are found to have regional spread at the time of diagnosis. There are no standard criteria for the treatment of N0 neck tumors. such as SNUC. L. Patients who have advanced lesions. Chemotherapy In general. Jiang . and the defect is closed primarily or with temporalis fascia. chemotherapy is of limited use for most sinus malignancies.L. Patients are counseled regarding potential adverse effects. positive margins of resection. patients are evaluated by an oral surgeon for extractions of diseased dentition to decrease the risk of osteoradionecrosis.82]. and blindness. such as xerostomia. Recent studies for aggressive cancers. no improvement in overall survival rates has been demonstrated with such regimens compared with surgery and radiation therapy. oropharynx. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 181 [79]. Nodal metastasis should be treated with neck dissection at time of surgical resection of the primary cancer. Recent articles report similar local control rates with orbital preservation in selected cases of infiltration of the periorbita. The most common locations for cervical involvement are the submandibular and jugulodigastric nodes [81. and hypopharynx. The 5-year incidence of post-treatment regional nodal failure with N0 disease is reported to range from 12% to 29% [81–83]. the invaded periorbita is resected. oral cavity. Chemotherapy regimens may be used with radiation therapy for palliation of unresectable neoplasms. Radiation therapy Radiation therapy is often used with combination therapy. however. in addition to surgery and radiation therapy. Myers. Management of cervical nodes Regional metastasis to cervical nodes is less common with paranasal sinus malignancies compared with other head and neck sites. however. Before referral for radiation therapy. or regional metastasis should be evaluated for radiation therapy. Chemotherapy is the primary treatment for paranasal sinus lymphomas.

Most patients present with advanced lesions. Several centers have reported improved regional control with elective neck irradiation. Patients presenting with T3 or T4 maxillary sinus carcinomas routinely receive cervical radiation therapy [81]. improvements in radiation therapy can allow more accurate administration to the desired region. Finally. characterized by local recurrence and metastatic spread. Anderson Cancer Center. In contrast. the most of these patients develop a local recurrence or a metastasis.E. L. with decreased damage to surrounding structures such as the orbit and brain. Five-year survival rates range from 35% to 40% [12. advances in the diagnosis and staging by use of molecular or DNA markers of tumor behavior may allow for more directed therapy. an advanced stage. With a long-term follow-up period of 20 years. even in light of advances in surgical techniques. Craniofacial resection techniques developed in the past few decades have cured many patients with skull base invasion. who would have been considered unresectable in the past.L. Survival rates are higher for maxillary sinus neoplasms compared with other paranasal sinuses because of decreased incidence of skull base involvement. radiation delivery techniques. nodal metastasis. . and have a poor overall prognosis. Oxford / Surg Oncol Clin N Am 13 (2004) 167–186 et al [84] reported a regional recurrence rate of 38% with SCC and SNUC at the M. Melanoma and SNUCs are both aggressive neoplasms associated with a dismal prognosis. and new chemotherapeutic agents.182 L. In Myers et al’s [14] series of 141 patients with paranasal sinus malignancies. There is a wide variety in the clinical courses of paranasal sinus malignancies depending on the histopathologic type. Jeremic et al [85] achieved a 10-year regional control rate of 97% with elective radiation and surgical salvage in 44 patients. Improving the prognosis of these cancers continues to be a difficult task. randomized clinical trials to compare different treatment approaches. Given the low incidence and diverse pathologies of paranasal sinus cancers. Myers. and distant metastasis negatively influenced survival.86. whereas physicians at Loyal University of Chicago Medical Center use radiation therapy with all maxillary sinus carcinomas [82]. Aggressive and oncologically sound surgical resection combined with radiation therapy remains the treatment of choice for most patients.87]. Furthermore. Prognosis/outcome The overall survival prognosis for paranasal sinus malignancies remains poor. Summary Paranasal sinus malignancies are challenging to treat.D. it is extremely difficult to perform prospective. often with intracranial or intraorbital extension. patients who have ACC often seem to have no evidence of disease during the first 5 years after treatment.

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this article * Corresponding author. MD. yet functionally impaired. Box 1 lists physiologic functions that can be altered significantly by either head and neck cancer or its treatment.*. Furthermore. and multimodality therapy and limb-sparing surgery for sarcoma. In many cancers. The issue of organ preservation in patients who have head and neck cancers often is centered on the larynx. doi:10. USA a In recent years. NY 14263. but progress has been made in lessening the negative impact that cancer treatments may have on patients. Anatomic organ preservation does not necessarily equate to functional preservation. Schwarz). USA b Department of Radiation Oncology. Therefore. This article addresses issues of organ preservation in the treatment of patients who have head and neck cancers. JDb Department of Medicine. It is less clear in the case of a patient with persistent swallowing or speech difficulties after treatment with radiation and chemotherapy.1016/S1055-3207(03)00120-0 .K. Elm and Carlton Streets. Examples of this progress include preoperative chemotherapy and radiation followed by sphincter-sparing surgery for rectal cancer. Buffalo. This situation is fairly obvious in the case of radiation-induced xerostomia. (J. Roswell Park Cancer Institute.Surg Oncol Clin N Am 13 (2004) 187–199 Organ preservation in patients with squamous cancers of the head and neck James K. in which the salivary glands are anatomically intact. significant progress has been made in improving survival in some types of malignancies. adapts a broader perspective to include several head and neck functions that are impacted significantly in patients who undergo treatment for head and neck cancer.see front matter Ó 2004 Elsevier Inc. This article addresses only a subset of these issues. however. William Giese. Elm and Carlton Streets. All rights 1055-3207/04/$ . and this is the impetus for development of treatment regimens that result in maximum functional organ preservation. Buffalo. This article. MDa. NY 14263. survival times have not increased significantly. Roswell Park Cancer Institute. issues of organ preservation are inexorably linked with quality of life. E-mail address: james.

patients have been assessed at different intervals in different studies. W. First.188 J. For organ preservation for head and neck cancer. however.K. different assessment tools have been used in different studies. specific functional assessment (subjective and objective) is not routinely performed in treatment trials. new radiation techniques) have not been compared with each other. the larger issue of whether that preserved organ remains functional is tainted by patient perception. Finally. In addition. radiation can have significant. Among . Although the patient may be seduced by an alternative that does not include the surgical extirpation of their tongue or larynx. it often will not restore function of an organ destroyed by tumor. it is necessary to realize that although irradiation may eradicate the primary tumor and sterilize nodal metastases. Schwarz. It is therefore important that the advising physician be cognizant of the potential temporary and permanent side effects and complications of radiation. new surgical techniques. and that they be fully disclosed. and new technical changes in modalities of treatment (ie. this is a difficult task. the risks of full-course head and neck irradiation are not trivial. Some reasons for this difficulty include the following: the number of randomized trials (particularly trials of surgery versus a nonsurgical modality) are limited. whether adjuvant or definitive. Radiation as an alternative to surgery: the nature of side effects and complications Head and neck irradiation. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 Box 1. long-term detrimental effects on speech and swallowing. Functions impacted by head and neck cancers and their treatment Speech Swallowing Salivary function Hearing Dental function Neuromuscular function Taste Cosmetic function briefly addresses the issue of quality of life in patients who have head and neck cancer before discussing specific functions. an article of this type should be able to make recommendations as to what treatment regimens would be most appropriate for a given situation. has certain side effects and complications. Irradiation does result in anatomic organ preservation.

The Veterans’ Administration (VA) trial was initiated in 1985 and randomized 332 patients with larynx cancer to primary laryngectomy or a nonsurgical approach [8]. Good oral hygiene seems to help reduce the temporal appearance and severity of the reaction. treatment trials (randomized and nonrandomized) rarely include prospective and ongoing assessment of organ function. the most aggressive treatment option (in terms of survival) for patients with advanced larynx cancers was total laryngectomy. It is difficult to draw definitive conclusions from much of this work. Acute oral mucositis is painful. and often the patient groups studied are selected from a single institution. Quality of life in patients with head and neck cancer Numerous articles have been published on quality of life in patients who have head and neck cancer [1].K. the tools (subjective and objective) are varied. certain amino acids (glutamine). because severe mucositis can result in breaks in treatment that may translate into a reduced cure rate. Several phase 2 trials demonstrated that some patients with advanced larynx and hypopharynx cancer who responded to induction chemotherapy could be subsequently treated successfully with radiation therapy and avoid a total laryngectomy [5–7]. and photodynamic therapy. What is clear is that the quality of life of patients who have head and neck cancer is profoundly impacted by the disease and its treatment. Approximately 64% of the . The issue is important. These studies provided the rationale for three trials in which patients were randomized between initial surgery or induction chemotherapy followed by radiation for those patients who responded to chemotherapy. Patients who did not have a 50% or greater decrease in the primary lesion after two cycles of chemotherapy underwent surgery. amifostine. Schwarz. W. possibly followed by adjuvant radiation therapy. Speech In the early 1980s. Patients with a 50% or greater response (and no progression in neck disease) received a third cycle of chemotherapy followed by definitive radiation. In addition. Treatment has been largely based on patient symptoms. however. growth factors. for the following reasons: the patient populations and their treatments are varied. and that treatment choices made by patients and providers are influenced by perceptions of the impact of treatments on the patients’ quality of life [1–4].J. using salt and baking soda gargles/rinses and antifungal and antibiotic therapy. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 189 the other significant radiation-associated factors that affect a patient’s quality of life are acute mucositis and acute and long-term xerostomia. Preventative measures under investigation include systemic or topical prostaglandins. The nonsurgical approach started with two cycles of cisplatin and 5-fluorouracil (5-FU) chemotherapy.

there was no statistical difference in survival between groups assigned to surgery or induction chemotherapy. Schwarz.K. resectable cancers of the hypopharynx or larynx. lack of CT scan assessment of the tumor extent at the beginning of the trial.190 J. it is important to confirm the benefits of anatomic larynx preservation in the patients whose larynx was spared versus those who underwent laryngectomy. A meta-analysis that pooled updated survival data from these three trials concluded that there was not a statistically significant difference in the survival rates of patients randomized to the two different arms in each of these studies [11]. however. The 3. A second randomized trial of similar design was performed by the European Organization for Research and Treatment of Cancer in 194 patients who had resectable cancers of the aryepiglottic fold or pyriform sinus [9]. but this was not statistically significant. respectively.5 y) follow-up of 46 patients from the VA trial also has been reported [13]. This trial has been criticized for its small size. Long-term (mean. There were no significant differences in swallowing and employment in the two groups. 8 of the 21 patients had undergone laryngectomy at some point.and 5-year estimates of having an intact larynx in the patients assigned to induction chemotherapy were 42% and 35%. for patients with large. Approximately 54% of the patients assigned to the induction chemotherapy arm achieved a complete response. There was a slightly decreased overall survival rate in the induction chemotherapy group. Given that these trials were performed to provide support for a larynxsparing approach. A third trial randomized 68 patients who had laryngeal cancers to either induction chemotherapy followed by radiation or upfront surgery [10]. A complete clinical response to two to three cycles of cisplatin and 5-FU chemotherapy was required for patients randomized to the nonsurgical arm to proceed to radiation. Again. Twenty-five of the patients had been randomized to initial surgery and 21 to induction chemotherapy. swallowing. The VA trial assessed patients periodically for 2 years after treatment for parameters related to speech. but there was a decreased survival rate for patients randomized to the nonsurgical arm. There was a difference in parameters for speech and voice. In addition. and less stringent evaluation of response after chemotherapy and after radiation. The conclusion from these trials was that. 10. and employment [12]. W. Larynx preservation was achieved in 41% of the 36 patients randomized to induction chemotherapy. favoring the group that received induction chemotherapy. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 patients assigned to the induction chemotherapy arm had an anatomically intact larynx at a median follow-up time of 33 months. This strategy may provide comparable survival rates to a strategy of upfront surgery and result in rates of anatomic larynx sparing of approximately 50%. The 21 patients . a strategy of induction chemotherapy followed by radiation for those patients who respond to chemotherapy is a reasonable treatment option.

Schwarz. this could not be attributed to speech. Radiation therapy has evolved to include altered fractionation schedules and powerful new planning techniques. It is generally assumed that patients with an intact larynx will have more favorable speech function than patients . W. the use of hemilaryngectomy. Furthermore. or concurrent chemotherapy and radiation [15]. It is too early to tell if concurrent chemotherapy and radiation should be considered a standard larynx-sparing approach. Close monitoring of these patients by a head and neck surgeon (particularly during the assessment of response to chemotherapy) is an intrinsic part of this strategy. such as intensity-modulated radiation therapy (IMRT). Preliminary analysis suggests that concurrent chemotherapy may be superior to induction chemotherapy followed by radiation or radiation alone for larynx preservation. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 191 randomized to the induction chemotherapy arm had significantly better quality of life scores for mental health and pain compared with those randomized to surgery. Comparing voice quality in patients treated with different modalities Numerous studies have been performed documenting quality of speech and voice in patients after treatment for larynx cancers. Few studies have assessed speech prospectively. Technical improvements and larynx-preservation strategies Numerous advances in treatment modalities have been made since the previously discussed randomized trials were initiated.K. induction chemotherapy followed by radiation. the use of chemotherapy concurrent with radiation has been demonstrated to be superior to radiation alone in several randomized trials. supraglottic laryngectomy. and measurement of vocal function is generally not part of treatment trials. Induction chemotherapy followed by radiation (in those who respond to chemotherapy) is currently considered a reasonable treatment option for patients with larynx and hypopharynx sinus cancers who would otherwise require total laryngectomy. Thus. patient-reported assessment of speech was not significantly different between any of the groups. With respect to surgery. Two things are worth mentioning: (1) the laryngectomy patients may have learned to adapt well to their state and (2) differences in the domain scores for speech were partly minimized because the speech scores for patients with an intact larynx were well below that of healthy control subjects. In addition.J. although the self-reported quality of life was better in those patients randomized to initial chemotherapy. however. The Intergroup Trial R91-11 randomized 547 patients with larynx cancers to radiation alone. or supracricoid laryngectomy may allow for laryngeal voice preservation while still providing a sound oncologic operation [14]. This finding was also true of the 13 patients with anatomically preserved larynges.

in whom a total laryngectomy traditionally would be considered. This assumption has not been clearly documented. and esophageal voice with augmentation by a tracheoesophageal prosthesis (TEP) [18]. Furthermore. Swallowing There are at least two basic considerations when evaluating swallowing function in patients who have head and neck cancer: (1) the ability to swallow itself and (2) whether there is aspiration. The perception of speech by trained and untrained listeners was higher in patients who had received radiation. Poor vocal function after radiation for larynx cancer could be caused by the treatment or by irreversible damage from the cancer. patient-reported speech quality of life was similar in patients with and without an intact larynx [13].192 J. W. As mentioned previously. This type of surgery can also obviate a permanent tracheostomy. Voice function in patients who have larnyx cancer treated with radiation has been compared with voice function in patients who have had a total laryngectomy and speech rehabilitation with a TEP [19. although a TEP can result in good voice quality.20]. but this is not known with certainty [21]. regardless of vocal function. this approach has not been successful in some patients. Oncologically successful treatment of this population with radiation should not be expected to restore excellent vocal function in most of these patients. newer surgical techniques involving less than a total laryngectomy may allow for reasonable voice production [14]. Patients who have advanced larynx cancer. often have significant impairment of voice before treatment. esophageal voice. moderate-sized larynx cancers. . In patients who have small. Whether radiation therapy can have adverse effects on larynx function is not clearly known. but the difference was not large. in long-term follow-up from the VA trial. Options for speech rehabilitation in patients who have undergone a total laryngectomy include an electrolarynx. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 who have undergone a total laryngectomy. Because a tracheostomy contributes significantly to negative quality of life [17]. there were clear differences in patients who had received radiation compared with control subjects who did not have larynx cancer. Surgical procedures that preserve some form of laryngeal voice and avoid a permanent tracheostomy have the potential to be associated with quality of life that might equal that associated with nonsurgical treatments. Most of the poor voice quality in the patients who received radiation is likely caused by irreversible damage from the cancer rather than the radiation.K. In addition. improvement in self-assessed speech has been shown to occur at 6 months after treatment with radiation [16]. surgical options that avoid this procedure will result in improved quality of life. however. As noted previously.

and patients treated with postoperative radiation have had swallowing function that is inferior to patients treated by either surgery or radiation alone [31]. Radiation can have detrimental effects on swallowing function (discussed later). Swallowing changes have been attributed to decreased compliance in tissues after radiation. in patients with base of tongue cancer.K. Several randomized trials have demonstrated that administration of chemotherapy concurrent with radiation has been associated with more favorable outcomes for control of disease and survival compared with radiation alone. This type of treatment also has been clearly associated with . In one study using videofluoroscopy. Thus. Impairment of swallowing was more closely associated with hypopharynx and larynx cancers in another study [23]. and a nonsurgical treatment approach may not result in restoration of function. however. Harrison et al [25] reported that.33]. patients with larynx cancers did not have the worst swallowing function [24]. Swallowing abnormalities after radiation have been documented [34–36]. 11 of 27 patients with advanced head and neck cancers were found to have aspiration [22]. Schwarz. Radiation effects on swallowing Swallowing symptoms after radiation in patients who have head and neck cancercan been separated into those symptoms that are caused by xerostomia versus a mechanical problem with the tongue or pharyngeal function [32. even if the treatment is effective.J. Surgery for head and neck cancer in sites other than the tongue of head and neck cancer surgery can result in difficulty swallowing. whereas in a third series. Patients with xerostomia may or may not have difficulties with the mechanical act of swallowing. but modern methods of reconstruction have had reasonable functional outcomes [27–30]. swallowing function was better in those patients treated with radiation rather than surgery. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 193 Patients who have head and neck cancer often have abnormal swallowing before treatment. patients who have advanced head and neck cancers often have abnormal swallowing function before treatment. A later series from the same institution noted that patients treated surgically may have swallowing function that is more comparable to patients treated with radiation [26]. Swallowing after surgery for patients with head and neck cancers Much of the literature concerning swallowing function after surgery has focused on patients who have base of tongue cancer. and the experience and opinion of the consulting surgeon is invaluable in estimating the degree of swallowing function to be expected after surgery. The extent of surgical resection for the base of the tongue is hard to quantify. W.

For example. Pretreatment hydration and antiemetic agents seem to be helpful. Practically. WR-2721 (commonly known as amifostine. The randomized trials of concurrent chemotherapy and radiation versus radiation alone did not report long-term swallowing function. Schwarz. Another agent with a differing mode of action touted as potentially useful in the prevention or treatment of radiation-induced xerostomia is pilocarpine hydrochloride. nausea. This free-radical scavenger is concentrated preferentially by normal rather than tumor cells [45]. the drug seems to be tolerable for some patients. quality of life and swallowing in particular need to be carefully evaluated in these patients [42]. Severe. The drug may be useful for radiation-induced mucositis as well. the chemotherapy regimens are experimental and may result in greater toxicity than more commonly used regimens.K. but may be because of the lower concentration of alkaline phosphatase in tumor tissue [46]. and rash (both in and outside the irradiated portals) limit its use in others. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 more severe short-term toxicity. given just before irradiation. WR-1065 [44]. but is limited to intravenous administration at 200 mg/m2 daily. long-term swallowing problems also have been noted in several phase 2 trials of concurrent chemotherapy and radiation [35. with no evident tumor protection [47]. although the results of concurrent chemotherapy and radiation are attractive from a survival standpoint. Thus.194 J. in a trial in which gemcitabine was used concurrent with radiation (in patients with mostly oropharynx and nasopharynx cancers). 14% of patients aspirated pretreatment versus 62% post treatment. Data from randomized trials have concluded that amifostine reduces both acute and chronic xerostomia in patients who have head and neck cancer. This parasympathomimetic agent stimulates secretion from salivary glands.37–41]. It is possible that long-term swallowing problems are more prevalent in patients treated with concurrent chemotherapy and radiation. In some of these trials. Salivary function Radioprotective agents The concept that certain agents taken systemically might render a protective effect against ionizing radiation is not new [43]. The drug has received Food and Drug Administration approval to be marketed for that purpose. although hypotension. The prodrug form becomes dephosphorylated to form an activated free thiol. Ethyol) was developed circa World War II by the US Army at the Walter Reed facilities with the hope it might prove protective to troops in the field when and if they became exposed to atomic fallout. trade name. however. The precise reasons for this behavior is unclear. W. particularly mucositis. The theory is that stimulation of output from those acini that remain functional translates into a reduction in the sensation of dry- .

The computer modulates fluence as a function of entry angle for each defined point and simply ‘‘grinds out’’ a plan by shear power of repetition in a trial-and-error format. The physician must first define the acceptable radiation exposure to all tissues. This was despite statistically significant presence of salivary output in the pilocarpine arm [38]. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 195 ness. There exist logistical constraints to these approaches. If IMRT can be used to limit a significant portion of the total volume of major salivary gland tissue to below this dose. Perhaps most important.K. a function uniquely suited to this tool. The output of major salivary glands decreases with doses of 10 Gy and worsens with dose escalation. Limiting salivary gland exposure to radiation Another avenue for the reduction of the xerostomia inherent to head and neck irradiation is to limit the dose that the salivary gland receives. A recent phase 3 placebo-controlled trial failed to demonstrate a benefit with respect to subjective parameters of swallowing and taste. Chao et al [49] noted that. Schwarz. while limiting dose to a sufficient volume of the saliva-producing organs. Although the appropriate doses should become clearer with the test of time and analysis of failure patterns. however. both those that are normal and those at risk. it applies to those patients . A current technique to reduce xerostomia is to physically transfer the submandibular gland to a region of the head and neck outside the anticipated irradiation portal. however. W. whereas limiting parotid gland dose resulted in both an objective (stimulated and unstimulated salivary flow rate) and subjective improvement of quality of life scores (by quality of life questionnaire). close follow-up and frequent reimaging are mandatory. it remains unclear just what daily and overall dose is appropriate for closely juxtaposed structures heretofore similarly exposed. It has been theorized that this may be accomplished through the use of computergenerated three-dimensional dose distributions that conform to the tumor and tissues deemed at risk. Surgical relocation of this gland to the submental space is technically feasible. IMRT uses sophisticated computer algorithms to design a treatment beam array. both current IMRT and non-IMRT techniques could achieve this. This study limited eligibility to a planned dose of more than 50 Gy to at least 50% of both parotid glands. although uncomfortable. the sparing of minor salivary gland–rich tissues is also protective.J. Physicians need to weigh the risk of locoregional failure. It is the intersection of multiple noncoplaner beams that results in the dose delivered to any one point. to the possible benefit of some degree of salivary gland sparing that. this output stimulation may prove beneficial. Although research has largely focused on the major salivary glands (parotids and submandibular/sublingual complex). a potentially life-threatening event. Cheng et al [48] compared the fractional volume of parotid gland receiving 30 Gy by conventional versus other techniques and showed that IMRT nearly reduced this volume by half (from 93% to 48%). remains tolerable.

K. treatment decisions concerning the neck often necessitate using both surgery and radiation. . sparing of the spinal accessory nerve.120:427–36. In patients who have advanced head and neck cancers (ie. Advances in surgical techniques. the patients for whom the question of organ preservation is an issue). is limited to those in which the submental space can safely be shielded. the development of treatment strategies that result in improved outcomes in neck function have lagged behind that of the primary sites. has been limited by the lack of standardized. References [1] De Boer MF. but well-planned and executed clinical trials are necessary to determine how best to apply these techniques to patient care. Schwarz. This technique is also limited to those surgeons familiar with how to move the particular gland with limited trauma to the gland duct. sternocleidomastoid muscle. and larynx. Otolaryngol Head Neck Surg 1999. It is not known if a neck dissection is required after a complete response following concurrent chemotherapy and radiation for patients with N2 or N3 nodal disease [56]. McCormick LK. W. Neuromuscular function Neck function can be significantly altered by surgery and radiation. Giese / Surg Oncol Clin N Am 13 (2004) 187–199 deemed surgical candidates and. Clinical research in this field. Thus. objective criteria of organ function post treatment and by lack of prospective assessment of organ function in treatment trials [56]. In general. however. and combined-modality therapies are promising. Surgical morbidity associated with neck dissection depends largely on the extent of surgery. radiation protectants. Radiation can result in long-term decreased mobility of the neck tissues [51]. In experienced hands. Summary Treatment strategies that have the potential to improve functional organ preservation in patients who have head and neck cancer are emerging. van den Borne BW. Ryckman RM. and internal jugular vein are associated with improved function [52–55]. perhaps more significantly. eligibility criteria limit applicability to squamous cell carcinomas of the oropharynx. Pruyn JF. radiation techniques. Physical and psychosocial correlates of head and neck cancer: a review of the literature. For example.196 J. hypopharynx. this technique seems to be useful. a clinically complete response to primary radiation alone in patients with N2 or N3 disease in the neck would typically require a neck dissection. with either no or unilateral neck node involvement [50].

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and treatment of CMM. University of Texas M. it was estimated that 53. diagnosis. In contrast. doi:10. Myers.see front matter Ó 2004 Elsevier Inc. PhD* Department of Head and Neck Surgery. Box 441. but far more fatal.600 new cases of CMM and about 34.49% at * Corresponding author. late-stage disease has a dismal chance for cure.13% at birth. in 2002 [1]. 1515 Holcombe Boulevard. the lifetime risk for developing CMM is 1. In 2002. up to 0. Because as many as one third of CMMs arise from the skin of the head and neck region. In the United States. It is also important that clinicians are aware of the less common types of melanoma arising in the head and neck.Surg Oncol Clin N Am 13 (2004) 201–229 Melanoma of the head and neck: current concepts in staging. Jeffrey N. All rights reserved. Houston. staging. respectively.N. early detection is paramount and is associated with a high chance of cure. E-mail address: jmyers@mdanderson. up to 0. and management Maher N.19% at birth. Myers). Younes. TX 77030-4009. respectively [1].1016/S1055-3207(03)00125-X . This lifetime risk increases with age (0. including mucosal melanoma and desmoplastic melanoma. Epidemiology It is estimated that cutaneous melanoma of the skin comprised 5% and 4% of all new cancer cases in the United States among men and women.72% (1 in 58) for men and 1.22% (1 in 82) for women.300 new cases of melanoma in situ were diagnosed. MD.97% at 60–79 y for men. diagnosis. CMM is less common than basal cell and squamous cell carcinoma (SCC). MD. USA Cutaneous malignant melanoma (CMM) is an aggressive malignant neoplasm of the melanocytes.D. 0. Therefore. Anderson Cancer Center. it is critical that head and neck surgeons have a thorough understanding of the natural (J. 1055-3207/04/$ . This statistic makes CMM the fifth and the sixth most common cancer in the United States among men and women.

Edwards BK. National Cancer Institute: Bethesda. The Surveillance. (From Ries LAG. and eyelids Fig. nose (2%). including sun exposure and the regional variation in the skin distribution of melanocytes. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 60–79 y for women) [1].N. the estimated lifetime risk of developing CMM was 1 in 1500.) . Hankey BF. J. 00-2789. NIE pub. In 2001.202 M. Incidence and mortality rates by gender. no. The most common sites in decreasing order are the skin of the cheek (46%). because the melanocytic content in the head and neck is 2 to 3 times higher than it is elsewhere in the body [4]. although the head and neck region accounts for a mere 9% of the total body surface area [3]. MD. and End Results [SEER] Cancer Statistics Review 1973-1997. 1. 1) [2]. Epidemiology. Kosary CL. external ear (125).N. The overall incidence of CMM is increasing at a disturbing rate of 5% per year. with permission. Clegg LX. Eisner MP. Primary melanoma of the head and neck accounts for approximately 25% to 35% of all melanomas. In 1935. Miller BA. 2000. neck (20%). There are many reasons for that predilection to the head and neck area. There are different sites in the head and neck region where CMM can be found. scalp (18%). it was estimated that 1 in 75 Americans developed CMM (Fig. Younes.

Myers / Surg Oncol Clin N Am 13 (2004) 201–229 203 (1%) [5]. followed by those of the temple. This represents a 2% annual surge in total mortality since 1960.N. Ballantyne AJ. In addition. cheek.132:484–89. J. 2) [6]. Mortality The number of deaths attributed to melanoma was projected to be approximately 7400 persons in the United States for 2002 [1]. (From Ames FC. Younes. 2. with the skin of the scalp tumors with the worst rate. the survival rates differ depending on the specific location of the melanoma in the head and neck. Despite of the increase of melanoma. Sugarbaker EJ.) . Analysis of survival and disease control in stage I melanoma of the head and neck. to Fig. ear. Am J Surg 1976. Actuarial survival rates by site of primary tumor for patients with melanoma of the head and neck. The explanation for this increase in mortality is a parallel increase in incidence. with permission.M.N. the 5-year survival rates for all ethnic groups in the United States for CMM is on the rise: from 80% for 1974 to 1978. and neck (Fig.

however. acute exposure during childhood and adolescence is more damaging to the skin [7]. and even visible light radiation. These rates can be attributed to an increase in earlier detection of the disease. First. protective clothing [12] and hats. the development of sunburns. This in turn induces a ‘‘safe’’ feeling among users.N. is an integral part of an overall sun protection regimen [13. There are several reasons behind this counterintuitive finding. Precursor lesions Most patients who have head and neck melanoma have a history of a preexisting lesion. there is also evidence for their inefficiency. rather than to a true improvement in treatment. to 89% for 1992 to 1997 [1]. particularly between 10 AM and 2 PM.204 M. Despite the conflicting data. may also play a role [8]. J. Many investigators believe that intermittent. intermittent exposure to sunlight. Younes. allowing more effective treatment in the earliest stages. most sunscreens are effective against UV-B. there is a consensus that sun protection in its different forms: sunscreens. and a decrease in daily exposure to sunlight. Studies have shown that excessive lifetime exposure to sunlight. Although there is an expanding body of epidemiologic evidence for the effectiveness of sunscreens in the prevention of CMM [9].N. The conclusions drawn from a European case control study [10] and one animal study [11] suggest that sunscreens may not be protective. the body’s alarm system against sunlight overexposure. including the use of sunscreens. Second. much interest has been focused on prevention strategies. at least delaying. Because of the pivotal role of sunlight exposure in the development of CMM. sunscreens help in preventing or.14]. Whether cumulative exposure versus early exposure is more important is still a debatable issue. not UV-A or the visible light spectrum. Ultraviolet (UV) B radiation (280–320 nm) has long been believed to be the most critical factor in the pathogenesis of CMM. and a history of sunburns are risk factors for developing CMM later in life. recent evidence shows that UV-A (320–400 nm). which results in longer time exposures to sunlight. where it has been shown that the incidence of CMM can be decreased and the melanomas that develop can be diagnosed earlier by raising public awareness through education [15]. both of which have been implicated in the pathogenesis of CMM. One report found that one third of melanomas arise from . Myers / Surg Oncol Clin N Am 13 (2004) 201–229 85% for 1983 to 1995. Causes and risk factors Sun exposure The most important predisposing factor in the development of CMM is exposure to sunlight. These practices have been tested in Australia.

The lifetime risk for CMM in the sporadic form is unknown. history of 3 or more blistering sunburns before the age of 20 years. a freckling pattern. Three types of lesions are known to be precursors to CMM. These characteristics include blue or green eyes. one third arise in nevi present for more than 5 years. blonde or red hair. and melanoma. The onset of skin cancers often occurs in individuals younger than 10 years who are affected with this syndrome [27]. a fair complexion. The rate of progression of lentigo maligna to melanoma is between 5% and 33% [18]. and an inability to tan [19]. Clinical features of XP include early onset of freckling (by age 2 y) and multiple skin cancers. Congenital nevi are usually present at birth. Patient characteristics Certain phenotypic characteristics increase the risk for developing CMM. An early. whereas those with three or more factors has a twentyfold increased risk [20].N. and one third arise in newly acquired nevi (nevi present for \5 y) [16]. Genetics Familial melanoma/dysplastic nevus syndrome Members of familial melanoma and DNS families have a lifetime risk for developing CMM approaching 100% [21]. Rigel [20] used multivariant analysis to identify six independent risk factors for CMM: family history. Linkage analysis has shown the involvement of several genes. Dysplastic nevi may either occur sporadically or as a part of a familial syndrome called dysplastic nevus syndrome (DNS). history of 3 or more years at an outdoor job as a teenager. Subsequent investigations showed that the gene of interest at 9p21 was the previously described p16 gene [26]. and presence of actinic keratosis. Lentigo maligna is considered to be a preinvasive lesion of lentigo maligna melanoma and frequently occurs on the head and neck region. Individuals with one or two of these risk factors had a fivefold increased risk of developing CMM. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 205 congenital nevi. basal cell carcinoma. Younes. .M. freckling of upper back. Patients with large congenital nevi (>20 cm) have a lifetime risk between 5% and 20% for developing CMM [17].N. Xeroderma pigmentosum Xeroderma pigmentosum (XP) is a hereditary syndrome that predisposes individuals to the development of skin cancers. blonde or red hair. unconfirmed study that showed a linkage of familial melanoma to chromosome 1p36 was followed by multiple studies that demonstrated linkage to chromosome 9p21 [22–25]. but the lifetime risk of CMM in the DNS is believed to be close to 100% [18]. including SCC. This rare autosomal-recessive disease increases the risk of skin cancer in individuals with this syndrome by 1000 times more than that of the general public. J.

J. Younes. The neoplastic melanocytes remain at the dermoepidermal junction.’’ These lesions are often not pigmented. Its main characteristics include a prolonged radial growth phase. these tumors are fairly slow to invade.N. and skin cells in these patients exhibit decreased survival and increased mutagenesis after UV radiation because of defects in nucleotide excision repair [28]. and the intraepithelial growth is along hair follicles and sweat ducts. . A differentiating feature of lentigo maligna melanoma from lentigo maligna lies in the requirement of this melanoma to invade into the papillary dermis.206 M. It is marked by an initial radial growth spread that is eventually followed by a vertical growth. forming aggregates in all levels of the epidermis. When this occurs.N. the term ‘‘neurotropic melanoma’’ is often used. maintain a uniform appearance throughout the epidermis. although atypical. It is invasive almost from the onset. Pathology Lentigo maligna melanoma Lentigo maligna melanoma is the least common subtype of melanoma. The melanocytic neoplastic cells are uniform. This affinity for perineural spread is crucial to consider during evaluation and treatment [29]. which may last for decades. These lesions also have been found to infiltrate and expand nerves and may show neural-like differentiation. Nodular melanoma Nodular melanoma accounts for 10% to 15% of all melanoma cases. The pathogenesis of skin cancers in XP patients highlights the important role for UV-induced DNA damage in the development of all three types of skin cancer. Therefore. It is characterized by a lack of radial growth and early vertical growth. comprising 5% to 10% of all cases. a pattern that has been likened to a ‘‘school of fish. Desmoplastic melanoma This subtype of melanoma is characterized by a dermal population of spindle cells among a fibrous stroma. The hallmark feature of this form of melanoma is that all tumor cells. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Patients with XP are hypersensitive to the sun. accounting for 75% of cases. which can be heralded by ulceration and bleeding. Superficial spreading melanoma Superficial spreading melanoma is the most common subtype.

border. The most common presenting signs are color change or growth of a pre-existing lesion. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 207 Diagnostic evaluation History The key to effective treatment of malignant melanoma lies in early recognition and diagnosis. (2) irregularly raised surface. Lesions that show border irregularities are likely to be melanoma. color. Assymetric growth patterns are caused by uneven growth rates. especially red. All these factors have been found to predict malignant lesions to a varying degree.N. Any increase in the size of a lesion. and blue [32]. Either the patient or a family member detects approximately 75% of the cases. other signs may include itching. In addition.M. In addition. These signs usually are ominous. and surface characteristics (irregularly raised) of moles. or a diameter greater than 6 mm. late signs. and pain. ABCD checklist The ABCD checklist is used by clinicians to identify potentially malignant lesions [31]. J. a bright light and a magnifying lens are needed to assess the size. ulceration. with border irregularity being the strongest predictor [33]. On examination.N. which occur more often in thick melanomas rather than thin ones. paresthesis. Differential coloring and shading indicates malignant potential. (3) an irregular border. with the remaining 25% detected by physicians [30]. Younes. family history of melanoma. Hallmarks of melanoma include the following: (1) variation in color. The following clinical factors are included: Assymetry. Diameter. and (4) ulceration. These features are what characterize benign from malignant lesions. and about their history of sunburns. Physicians need to ask patients about overall sun exposure. the biopsy method of choice should not interfere with subsequent . Physical examination A comprehensive assessment of the total number and types of moles present is required. is suspicious. Biopsy All suspicious lesions should undergo biopsy to confirm the diagnosis of melanoma and for accurate staging once the diagnosis is established. and lentigo malignas. Border irregularities. Physicians should look for congenital nevi. bleeding. dysplastic nevi. white. Color variegation.

Needle biopsies are useful to assess suspicious lymph nodes or distant metastasis. J. 2-mm margins is recommended.N. although both remain widely used in the literature and in clinical practice (Table 1). For lesions that are either large or inaccessible to excisional biopsy without significant disfiguration.41]. and scalp) have lower survival rates than those individuals with tumors arising in non-BANS regions [37. Currently. posterior neck. however. several studies have revealed that patients with tumors arising in the so-called ‘‘BANS’’ region (upper back. and neck (see Fig. upper arm.208 M. face. WLE before lymphscintigraphy makes it difficult to accurately access sentinel lymph nodes (SLNs) and drainage basins [35]. 2) [39]. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 resection and reconstruction efforts if needed later on. incisional biopsy through the thickest part of the tumor is recommended. Breslow [43]. Balch et al [36] showed that patients with head and neck primary tumors are believed to have a worse prognosis than patients with extremity tumors. was set. The depth of invasion became the most important prognostic factor for stage I and stage II melanoma tumors.D. In an analysis of prognostic factors in 8500 patients with CMM. demonstrated the importance of tumor thickness. Anderson Cancer Center revealed that melanoma lesions on the scalp do significantly worse than lesions on the ear.38]. the landmark histologic staging of Clark [42]. which is critically important for further treatment options. Furthermore. excisional biopsy with 1. are sufficient and easy to perform in the office or the clinic. compared with wide local excision (WLE). Patients who underwent excisional biopsy have had better overall survival rates [34]. Needle and shave biopsies of the primary tumor are strongly discouraged because they do not properly assess the thickness. Punch biopsies. if they encompass the entire thickness of the tumor. who defined the levels of invasion. excisional biopsy does not interfere with or affect subsequent staging procedures. Several methods of biopsy are available to clinicians to choose from. Although controversial. If the lesion is small and the location is amenable. A review from the M. This finding has been confirmed by other studies [40. Staging Anatomic location of the primary tumor Numerous studies have shown the prognostic significance of anatomic site of the primary tumor on survival rates. Depth of invasion During the 1960s.N. Breslow thickness represents a more powerful prognostic tool than do Clark’s levels. Younes. such as lymphoscintigraphy. .

50 mm III 1. Younes.0 mm IV !4. with cutoff levels of 1 mm. 5. not an invasive lesion Invasion of the papillary dermis but does not reach the papillaryreticular dermal interface Invasion fills and expands the papillary dermis but does not penetrate the reticular dermis Invasion into the reticular dermis but not into the subcutaneous tissue Invasion through the reticular dermis into the subcutaneous tissue American Joint Committee on Cancer First published in 1978.51–4. It is based on the tumor-node-metastasis (TNM) classification and incorporates the Breslow system into the primary tumor stages.N. 6. (2) regional disease . the AJCC published a new staging system for CMM (Box 1) [44].N. Ulceration of the primary tumor is included in this system. Level of invasion (Clark’s level) is replaced by tumor thickness. as the prognostic variable of primary tumor invasion that best predicts survival. Distinct definitions for clinical and pathologic staging incorporate the new staging information gained from intraoperative lymphatic mapping and SLN biopsy [48]. Patients are categorized into clinical and pathologic staging to incorporate lymphatic mapping data and micrometastatic disease.47]. Staging: clinical versus pathologic In the past. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Table 1 Histopathologic staging systems—Clark’s levels and Breslow thickness Classification Clark’s levels I II III Characteristics 209 IV V Breslow thickness stage I 0. 4. This new melanoma staging system includes five major changes from the 1997 version as follows [45]: 1. and patients with ulceration in each T-stage subgroup are upstaged accordingly.M. The number of lymph nodes involved in staging replaces the size of lymph nodes. Subcategorization of stage IV metastatic disease is based on anatomic site and inclusion of an elevated serum lactate dehydrogenase (LDH) [46. J. and 4 mm.76–1. the TNM classification system of melanoma had been broadly based on a clinical staging system that recognized three general categories: (1) localized melanoma (stages I and II). 2 mm. In 2002. 2. the American Joint Committee on Cancer (AJCC) staging system of CMM has undergone several changes in an effort to incorporate current knowledge into each version.0 mm Lesions involving only the epidermis (in situ melanoma).75 mm II 0. 3.

Coit DG. Macrometastases are defined as clinically detectable lymph node metastases confirmed by therapeutic lymphadenectomy or when any lymph node metastasis exhibits gross extracapsular extension.0 mm (a) without ulceration (b) with ulceration N classification N1: one lymph node (a) micrometastasisa (b) macrometastasisb N2: two to three lymph nodes (a) micrometastasis (b) macrometastasis (c) in-transit metastasis/satellites without metastatic lymph nodes N3: four or more lymph nodes. A new American Joint Committee on cancer staging system for cutaneous melanoma.N. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Box 1. or combinations of in-transit metastasis/satellites and metastatic lymph nodes M classification M1: distant skin. elevated LDH levels Micrometastases are diagnosed after sentinel or elective lymphadenectomy.0 mm (a) without ulceration (b) with ulceration T3: 2. normal LDH levels M3: all other visceral or any distant metastasis. Houghton A Jr. Younes. Revised AJCC TNM classification T classification T1: 1. J. Cancer 2000.01 to 2. et al. subcutaneous. Fleming ID.88(6):1484–91. Buzaid AC.N. or lymph node metastasis.210 M. Atkins MB. matted lymph nodes. normal LDH levels M2: lung metastasis. with permission. Cascinelli N. From Balch CM.0 mm or less (a) without ulceration (b) with ulceration or level IV or V T2: 1. b a .01 to 4.0 mm (a) without ulceration (b) with ulceration T4: greater than 4.

nccn. including alkaline phosphatase and LDH levels. Ulceration of the primary tumor up-stages each T stage [50].nih. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 211 (stage III). The AJCC melanoma staging committee recommends that. the new AJCC staging system incorporates clinical and pathologic staging (Table 2).D. preoperative lymphoscintigraphy is warranted.N. For this patient In situ and/or Clark’s level I lesions are effectively treated with WLE and require no further workup. liver function tests. and therefore consideration should be given to a metastatic workup (complete blood count. J. abdomen. The hallmark of stage III is the involvement of regional lymph nodes.mdanderson. and (3) distant disease (stage IV) [49]. especially if elective lymph node dissection may be part of the treatment plan. however. Younes. nodal staging is particularly important. chest radiograph. Similarly. The general guidelines followed at the M. Similar guidelines are available from the National Comprehensive Cancer Network at www. a more comprehensive workup is recommended. The IIC patients have an equivalent prognosis as those with multiple metastatic lymph nodes [51]. a chest radiograph and an evaluation of LDH levels is recommended [50]. and pelvis. Pretreatment evaluation by stage Although there are general stage-specific guidelines. In asymptomatic patients with primary melanoma (stage I or II). and LDH). The presence of micrometastasis in the lymph nodes using SLN biopsy is differentiated by the pathologic staging [52]. and MRI of the brain). satellite or intransient metastases have a poor prognosis and are up-staged to For patients with lesions of intermediate thickness (1–4 mm) and thin lesions that are either ulcerated or extend into Clark’s level IV. Anderson Cancer Center are summarized in Table 3 and are available at www. Because of major advances in the diagnosis and staging of CMM brought about primarily by the development of SLN mapping and/or biopsy for the identification of micrometastases. there is a high risk for distant metastasis. For patients with thick lesions (>4 mm) or those who have regional metastatic or recurrent locoregional disease. each patient’s evaluation and treatment should be and the National Cancer Institute at www. selective metastatic . For patients with signs or symptoms of metastatic disease.N. nodal staging should be performed and that. All patients with clinically evident regional disease (stage III) must undergo imaging of the cervical lymphatics and metastatic screening (CT or ultrasound of the head and neck. A new staging category of IIC was designed for ulcerated T4 lesions. Patients with multiple lymph node metastases and ulcerated primary tumors do worse are categorized as having stage IIIC disease. Stage IV is defined by distant metastasis and remains the same in the new system. Early-stage (I and II) localized melanoma is a primary tumor without evidence of lymph node metastasis.M.nci. when possible. for clinical trials. a CT of the chest.

however. Newer modalities. Other studies (eg. Jr.212 M. Accordingly. Finally. bone scan) are performed according to symptoms [53]. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Table 2 New stage groupings for cutaneous melanoma Clinical staginga Stage 0 1A 1B IIA IIB IIC IIIc T Tis T1a T1b T2a T2b T3a T3b T4a T4b Any T — — — — — — — — — — — — Any T N N0 N0 N0 N0 N0 N0 N0 N0 N0 N1 N2 N3 — — — — — — — — — — Any N M M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 — — — — — — — — — — — — Any M1 Pathologic stagingb T Tis T1a T1b T2a T2b T3a T3b T4a T4b — — — T1–4a T1–4a T1–4b T1–4b T1–4a T1–4a T1–4a/b T1–4b T1–4b Any T Any T N N0 N0 N0 N0 N0 N0 N0 N0 N0 — — — N1a N2a N1a N2a N1b N2b N2c N1b N2b N3 Any N M M0 M0 M0 M0 M0 M0 M0 M0 M0 — — — M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 Any M1 IIIA IIIB IIIC IV a Clinical staging includes microstaging of the primary melanoma and clinical/radiologic evaluation for metastases. Buzaid AC.N. and MRI of the brain. Fleming ID. By convection. who do not need pathologic evaluation of their lymph nodes. et al. gastrointestinal series. Cascinelli N. and pelvis. A new American Joint Committee on Cancer staging system for cutaneous melanoma. including the following: chest radiograph. Younes. Coit DG. and their role in the detection of melanoma of the head and neck are currently being investigated. they require a full metastatic workup. its role in the evaluation and follow-up of patients with CMM awaits further studies [54–56]. including positron emission tomography (PET).N. CT of the chest. b Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or complete lymphadenopathy. Cancer 2000. PET is one of the new modalities that has shown promise in detecting regional and metastatic lesions. Data from Balch CM. Houghton A. imaging should be performed. Atkins MB. abdomen. . J. except for pathologic stage 0 or stage 1A patients. LDH levels. patients with known systemic disease (stage IV) should be more comprehensively evaluated. it should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases. CT or ultrasound of the head and neck. c There are no stage III subgroups for clinical staging.88(6):1484–91.

in the head and neck. The type of neck dissection must be tailored to the disease. Data from the American Joint Committee on Cancer (AJCC). a substantial number of patients . Chicago. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York. chest X ray. J. MRI of brain) CXR. Younes.M. visit www. Patients with stage I disease have a low rate of occult metastasis and thus may not need surgical treatment of the neck. US. abdomen. In contrast. consider lymphoscintigraphy CXR. LDH Consider metastatic imaging (CT of chest. LDH (CT or US of the neck for regional lymphatics). Inc. The treatment for clinically N0 neck disease is less definite. 1-cm margins provide equivalent local control and survival [58]. LDH CXR. A sound knowledge of the anatomy of the pathways of lymphatic spread for CMM of the head and neck is essential. it is important to address all the intervening lymphatics between the primary tumor and the positive node or nodes.N.cancerstaging. on behalf of the AJCC. chest. 6th edition (2002) published by Springer-Verlag New York (For more information. MRI of brain) Abbreviations: CXR. Any citation or quotation of this material must be credited to the AJCC as its primary source. LDH. ultrasound. metastatic imaging (CT or US of the head and neck. consider metastatic imaging for patients with signs and symptoms of metastatic disease CXR.. pelvis. the surgeon may not have the luxury of being able to take 1. In these patients.N. Complete surgical excision is recommended in most patients who have local or regional disease in the absence of systemic 2-cm margins without running the risk of significant functional disability or cosmetic deformity. Management General treatment options Surgery Surgery is well accepted as the primary treatment modality for CMM. It is generally accepted that clinically positive neck disease requires surgical treatment. CT of abdomen. For thinner lesions. Recent studies have indicated that a 2-cm margin around the primary tumor for intermediatethickness melanoma is sufficient [57]. The original and primary source for this information is the AJCC Cancer Staging Manual. pelvis. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Table 3 Recommendations for workup based on stage Stage Melanoma in situ Stage I or II Stage I or II with ulceration or T3 T4 or recurrent primary melanoma Workup 213 Stage III Stage IV None CXR. A crucial reminder is that these recommendations are derived from studies of truncal and extremity melanoma and that. Illinois.

p. J. 377. Predicted patterns of lymphatic drainage from primary sites in the head and neck. there are no prospective data to support the use of any elective neck dissection for N0 neck disease to improve either locoregional control or overall survival. If END is undertaken. There exists a limited set of regional lymph nodes as a first stop along the route of Fig. preauricular. B. Houghton AN. To date. and posterior triangle lymph nodes. Milton GW. retroauricular. a posterolateral neck dissection is recommended [59]. 1992. D. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 with stage II disease harbor an occult regional metastasis and need to be considered for elective treatment. Philadelphia: JB Lippincott. a parotidectomy and lateral neck dissection are recommended. Tumors located anteriorly on the face and neck tend to spread to the facial. In: Balch CM. with permission. H. The most commonly used elective treatment is elective neck dissection (END). F. C. G.) . submandibular. Tumors arising on the scalp and occiput posterior to a line drawn through the external auditory canal most commonly spread to postauricular. 2nd edition. Cervical and parotid node dissection. thus. it should be guided by a comprehensive knowledge of the pathways of lymphatic spread (Fig. 3. In general. posterior cervical. submental. Cutaneous melanoma. 3).214 M. The rationale behind SLNB is as follows.N. E. and deep cervical nodes. supraclavicular. submandibular. occipital. (From Byers RM. tumors arising on the scalp and the forehead anterior to a line drawn through the external auditory canal most commonly spread to the parotid/periparotid lymph nodes and upper jugular lymph nodes. therefore. submental. Location of nodes: A. and I. et al. jugular chain. A newer option for elective treatment of the neck is sentinel lymph node biopsy (SLNB). a supraomohyoid neck dissection is advocated. suboccipital. Younes. editors. consequently. jugulodigastric.N.

SLNB has proved to be a well-accepted method in the treatment of truncal and extremity melanoma. 4). Based on the result. J. Kaplan-Meier survival for patients undergoing sentinel lymph node biopsy. with permission. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. Thompson W. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 215 lymphatic drainage. et al. 4. Disease-free survival and disease-specific survival according to sentinel lymph node status. Using dyes.N.M. Mansfield PF. a decision can be made as to whether to perform a more extensive lymphadenectomy or provide systemic adjuvant therapy. (A) Diseasefree survival. The same group of investigators also has shown that among the benefits of this method is that it allows the pathologist to focus on fewer lymph nodes than found in an END. these ‘‘sentinel’’ lymph nodes can be localized and surgically removed.N. In a multi-institutional study. which allows for a more comprehensive Fig. Gershenwald et al [61] showed the status of SLNs was the strongest predictor of disease-free survival in patients who have stage I and II disease (Fig. J Clin Oncol 1999. It provides accurate staging and important prognostic information [60]. (B) Disease-specific survival. or radioactive tracers. radiographic contrasts agents. (From Gershenwald JD.17:976–83.) . Younes.

and (2) the frequent need for the removal of the SLN from the parotid gland.N. have shown disturbingly high rates of regional recurrence in patients with negative SLNB results [66].63]. Younes. their widespread distribution (42% with noncontiguous nodal basins). significant improvements in locoregional control have been noted with the use of adjuvant radiotherapy [68]. This situation is attributed to many factors: (1) the complexity of the lymphatic drainage patterns in the head and neck. Also. and that postauricular and contralateral metastatic node involvement was uncommon [65]. Anderson Cancer Center. Thus. three groups of patients were investigated: (1) those who underwent excision of stage III primary tumors. Currently. thus placing the facial nerve at risk of injury.N. there seems to be a steep learning curve associated with the technique and potential risks to the facial nerve and other cranial nerves during the biopsy procedure. however. Anderson Cancer Center designed a prospective trial of intraoperative lymphatic mapping and SLN identification in 43 patients who had head and neck CMM.D. and their frequent location within the parotid gland (44%). At M.D. may preclude SLNB in many patients. In this trial.64]. the recommendations from that study are that selective lymphadenectomy of the SLN basins allows histologic staging of the regional lymphatics with limited morbidity. (2) those with palpable lymphadenopathy who underwent WLE and neck dissection. however. Despite its promise in truncal and extremity melanoma. data reveal the possibility of attaining a locoregional control rate of 88% in patients with stages II and III disease when postoperative radiotherapy is used at a dose of 30 Gy given in 5 fractions [69]. The multiplicity of the nodes. The locore- . have shown that different dosimetric and fractionation schemes are needed for CMM treatment than those used to treat other tumors. Most studies have reported that SLNs can be identified in almost 95% of cases and that false-negative results are low [63. investigators at M. the role of SLNB in the management of CMM of the head and neck has yet to be defined.216 M. J. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 search for metastasis by applying molecular methods to increase the sensitivity of detection [62. Moreover. the data from head and neck studies concerning SLNB are conflicting. however. The past 20 years. Radiotherapy In the past. To properly assess the accuracy and applicability of the SLNB in the management of CMM of the head and neck. This trial showed that intraoperative lymphatic mapping accurately depicts the SLN and that false-negative results were 0% (no patient who had a negative SLN had a positive nonsentinel lymph node [67]. CMMs of the head and neck were found to metastasize to clinically predicted nodal groups in 92% of patients. melanoma was believed to be a radioresistant tumor. For example. More studies are warranted to establish the role of SLNB in the management of head and neck CMM [67]. Other studies. and (3) those with nodal relapse who underwent neck dissection.

N. the use of . Immunotherapy Because melanoma is the most immunogenic type of solid tumor. Overall and disease-specific survival rates for all patients at 10 years was 30% and 36%. In a more recent study. The M. (2) immunostimulants. that dosimetry is harmful to nervous tissues and cannot be used for lesions near the eyes or central nervous system. Clinicians should bear in mind. both in animal models and in the clinic. The study showed that patients who have malignant melanoma with nodal involvement have significant risk of nodal basin failure after LND if they have cervical involvement. the overall survival rate in patients with stage II disease was higher than in historical control subjects (Fig. Younes. Using combination chemotherapy leads to a small. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 217 gional control rates in all three groups were higher than in historical control subjects.N. however. or any node that is larger than 3 cm. worse overall survival rates were found with chemotherapy [73]. The rate of cervical nodal basin recurrence at 10 years was 43%. remain investigational. Moreover. Response rates to decarbazine alone are 10% to 20%. J.72]. and (3) vaccines. insignificant improvement in response rates. though promising. Anderson Cancer Center recommends postoperative radiotherapy for all patients with stage II lesions in which regional lymph nodes are not treated surgically and in patients with pathologically proven nodal disease or nodal recurrence. and in the third study. however. Three major randomized trials have been performed using adjuvant chemotherapy postoperatively [71–73]. 5) [69]. respectively. All three approaches. chemotherapy served two main purposes: (1) as a palliative therapy for patients with stage IV disease and (2) as an adjuvant therapy in high-risk patients. it serves as a primary model for immunotherapy. The approaches used to boost the body’s immune system include the following: (1) biologic response modifiers (interleukins and interferons). This study concluded that patients with such risk factors should be considered for adjuvant radiotherapy to the lymph node basins to reduce the incidence of recurrence [70]. The use of chemotherapy as an adjuvant therapy for CMM still needs to be substantiated by prospective randomized trials. In two of these studies. was performed. clinically involved nodes.M. more than three positive lymph nodes. Chemotherapy Traditionally. Currently. the single most effective chemotherapeutic agent approved for the treatment of advanced melanoma is decarbazine.D. a retrospective analysis of 338 patients with lymph node involvement who underwent complete lymph node dissection (LND) of the nodal basin. there was no difference in disease-free interval or overall survival rates with chemotherapy [71. which had pathologically involved lymph nodes. extracapsular extension. after nodal dissection has been performed. As in chemotherapy.

) . (B) Group 1. treated with irradiation after nodal recurrence. Postoperative radiotherapy for cutaneous melanoma of the head and neck region. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Fig. (A) All patients. treated with adjuvant irradiation after WLE plus neck dissection. (From Ang KK. with permission. 5. J. (C) Group 2. treated with elective irradiation.218 M.N. Locoregional control and survival rates of patients treated with elective or adjuvant radiotherapy.N. Int J Radiat Oncol Biol Phys 1994. Younes. et al. (D) Group 3. Peters LH. Weber RS.30:296–8.

At the M. Biologic response modifiers have been extensively studied. Moreover. however. interferon a2b (IFN-a2b) is the most promising of these agents [74]. although their use has yielded either negative or conflicting data. antibody-based vaccines. The lack of difference in the overall survival rate. Furthermore. Melanoma vaccines seem to be promising. both as a postoperative adjuvant treatment and for treatment of systemic disease.81]. . Younes. J. Biochemotherapy Biochemotherapy is the combination of two modalities of treatment: immunotherapy and chemotherapy. the effect of adjuvant INF-a2b therapy on overall survival rate awaits further investigation.M. This study confirmed the improvement in the relapse-free survival rate in patients given the high-dose INF-a2b. This form of therapy attempts to achieve responses higher than those achieved when either treatment is used alone. Several phase 2 trials have shown feasibility and suggested efficacy. dendritic cell–based vaccines. Consequently. vinblastine. These agents do not yet play a role in the treatment of melanoma [79]. no phase 3 trial has yet established any improvements in disease-free survival or overall survival rates in vaccinated patients [80. A more recent ECOG trial (number 1690) aimed at verifying these results and assessing the efficacy of low-dose IFN-a2b [75]. and increased toxicity as compared with immunotherapy and chemotherapy alone [83–85]. many clinical trials of melanoma vaccines are now underway and include carbohydrate-based vaccines. and decarbazine with interleuken 2 and IFN-a2b [82]. Several large-scale trials are currently underway to further evaluate the potential role of biochemotherapy.N. The Eastern Cooperative Oncology Group (ECOG) trial E1684 is a prospective randomized trial that revealed significant improvements in relapse-free and overall survival rates in patients who had node-positive disease treated with high-dose IFN-a2b as a postoperative adjuvant drug [74]. DNA vaccines. ´ Other immunostimulants include Calmette-Guerin bacillus [76]. trials have usually combined cisplatin. low-dose IFN-a2b showed no efficacy. however. and levamisole [78]. many advances in melanoma vaccination have been made during the past 15 years.N. Thus. however. was because of a significant increase in the survival rate in the trial’s observation group: patients in this group who had experienced a relapse had been given INFa2b as salvage therapy. Corynebacterium parvum [77]. peptide vaccines. the difference was not as significant as was found in the ECOG 1690 trial. higher response rates. and heat-shock protein vaccines [80]. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 219 immunotherapy has been primarily in the form of adjuvant therapy for high-risk patients or for patients with metastasis or recurrent disease. Anderson Cancer Center.D. The few prospective randomized trials showed similar survival rates.


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Treatment by stage Three different aspects need to be addressed in the management of CMM of the head and neck: the primary tumor, the regional lymphatics, and distant metastasis. Although an acceptably high rate of locoregional control has been established, many patients who have stage II disease and higher eventually die of distant disease. The recommendations for treatment on the basis of stage are presented in Table 4. Melanoma in situ For patients with melanoma in situ, the treatment of choice is surgical excision with conservative margins (0.5–1cm) because the risk of metastasis is essentially zero. No regional or metastatic workup is required. Stage I The recommended treatment in patients with stage I melanoma is WLE [6]. Margins of 1 cm are generally acceptable. The defect can be closed primarily or reconstructed using local flaps or skin grafts. Delayed reconstruction is often advisable, given the limitations of frozen section analysis of margins for pigmented lesions. As in melanoma in situ, no regional or metastasis workup is needed because of the low risk of metastasis in this group.

Table 4 Recommendations for treatment based on stage Stage I II III Treatment Primary tumor: WLE Primary tumor: WLE Regional lymphatics: observation vs, END vs SLNB vs ENI Primary tumor: WLE Regional lymphatics: neck dissection +/ÿ parotidectomy Consider postoperative radiotherapy Primary tumor: WLE Regional lymphatics: neck dissection +/ÿ parotidectomy if node-positive Metastasis site–directed surgery or radiotherapy Consider systemic adjuvant therapy trials Supportive care


Abbreviations: END, elective neck dissection; SLNB, sentinel lymph node biopsy; WLE, wide local excision. Data from the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, 6th edition (2002) published by Springer-Verlag New York (For more information, visit Any citation or quotation of this material must be credited to the AJCC as its primary source. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York, Inc., on behalf of the AJCC.

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Stage II The adopted treatment in patients with stage II melanoma is WLE. If possible, 2-cm margins are taken. If 1-cm or smaller margins are obtained, adjuvant radiotherapy should be contemplated. As in stage I lesions, the defect can be closed either primarily or reconstructed using local flaps or skin grafts. Given the substantial percentage of patients with stage II disease harboring occult regional metastasis, elective neck treatment is often considered. There are, however, no prospective trials to support the use of any type of elective neck treatment for improving the locoregional control and the overall survival rates. Once elective neck treatment is decided on, there are several options to choose from. END is the most widely adopted treatment option. The nodes of interest are those considered to be at risk. A major advantage to END is the prognostic information it provides. If occult metastasis is present, then patients can be up-staged and are eligible for adjuvant systemic treatment (immunotherapy, chemotherapy, or biochemotherapy). Elective neck irradiation constitutes the second option. Locoregional control rate is achieved in 85% of stage III patients who were given irradiation to the primary site after WLE [68]. Finally, SLNB is still under investigation as a possible modality for the evaluation of patients who have stage II melanoma. Stage III The recommendations for stage III disease include treating the primary tumor by WLE and obtaining, if possible, a 2-cm margin. In addition, to attain locoregional control, regional disease can be addressed by neck dissection. If the disease allows, a selective or modified radical neck dissection is advised rather than a classic radical neck dissection. In addition, postoperative radiotherapy seems to increase locoregional control. Unlike with stage I and stage II disease, systemic therapy, in the form of chemotherapy, immunotherapy, or biochemotherapy, should be contemplated in patients with stage III disease because of the high risk for distant metastasis. Stage IV Despite the dismal prognosis in this subgroup of patients, locoregional control remains an important consideration because of the devastating effects of uncontrolled locoregional disease. The overall treatment approach in the treatment of stage IV metastatic melanoma is best determined by a multidisciplinary team, including a surgeon, radiation oncologist, and medical oncologist, and is often best performed in the context of a prospective clinical trial. Palliative and supportive care is also an important issue to address in these patients.


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Recurrent disease Recurrent disease is usually associated with a poor prognosis. The recurrence can be locoregional or distant. For locoregional recurrence, reexcision [86], if possible, and adjuvant radiotherapy (if it has not been administered before) are indicated. If surgery is not an option, radiotherapy and systemic therapy are secondary options, but they can only be palliative at this stage. Distant metastases that are surgically resectable should be aggressively treated because, in rare instances, a cure or long-term progression-free interval can be achieved. Sometimes, however, isolated distant metastases are kept in place to initially ‘‘monitor’’ the response to systemic treatment, and then depending on the result, excised later on. The prognosis for pulmonary metastasis is better than brain and liver metastasis, which carries with it a dismal expected survival time of 2 to 4 months [87]. Even in the context of recurrent disease, every effort should be made to achieve locoregional control, if only to improve the patients’ quality of life. Follow-up Because CMM is a disease of young people (average age, 45 y), both the clinical and financial aspects of the patient’s follow-up are important and need to be addressed. Weiss et al [88] reported that intensive follow-up in the post-treatment phase (5 y) costs around $421,000 for laboratory tests alone [88]. Thus, the need arises to establish equilibrium between what can be called an ‘‘adequate’’ surveillance and fiscal responsibility. An estimated 28% to 56% of recurrences are usually detected by physicians [89,90]. Therefore, physical examination when supplemented with periodic laboratory testing and radiologic assessment is a good basis for follow-up. At the M.D. Anderson Cancer Center, the follow-up depends on the stage of the disease at diagnosis (Table 5). Special issues in melanoma Mucosal melanoma Mucosal melanoma of the head and neck is rare (1%–2% of melanomas). In the head and neck, the most common sites of occurrence include the nose, paranasal sinuses, oral cavity, and nasopharynx. If located in the sinonasal cavity, mucosal melanoma typically presents with symptoms of nasal obstruction, epistaxis, pain, visual disturbances, or facial deformity. Patients who have mucosal melanomas of the oral cavity most often present with asymptomatic masses; however, symptoms of dysphagia are not uncommon. Because most of these symptoms are indolent and nonspecific, there is often a delay in presentation and a worse prognosis. Mucosal melanoma tumors may lack melanin, making the diagnosis difficult from the histopathologic standpoint. The 5-year disease-specific

M.N. Younes, J.N. Myers / Surg Oncol Clin N Am 13 (2004) 201–229 Table 5 Recommendations for follow-up based on stage Stage Melanoma in situ Stage 1 or II (no ulceration, thickness \1.0 mm) Stage I or II (with ulceration or thickness >1.0 mm) Stage III or recurrent primary melanoma Stage IV Physical examination Radiology Labs None LDH LDH


Every 6 moÂ4 y, then annually None Every 6 moÂ4 y, then annually CXR Every 6 moÂ2 y, then every 6 moÂ2 y, then annually Every 3 moÂ2 y, then every 6 moÂ3 y, then annually Individualize CXR CXR


Individualize Individualize

Abbreviations: CBC, complete blood count; CXR, chest X-ray. Data from the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, 6th edition (2002) published by Springer-Verlag New York (For more information, visit Any citation or quotation of this material must be credited to the AJCC as its primary source. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed written permission of Springer Verlag New York, Inc., on behalf of the AJCC.

survival rates depend on the anatomic site of the primary lesion [91] and are 40% for oral lesions and 47% for sinonasal lesions [93]. In addition, most of the staging criteria for CMM, including depth of invasion and regional lymphadenopathy, fail to impact or affect the prognosis in mucosal melanoma. The only significant and independent predictors of the development of distant failure and death in patients who have mucosal melanoma of the head and neck are as follows: the clinical stage at presentation, whether the tumor thickness is greater than 5 mm, whether there is vascular invasion on histologic studies, and the development of distant failure [92,93]. As a group, mucosal melanomas of the head and neck are highly aggressive and rapidly fatal [91]. Radical surgery with aggressive resection of the primary tumor is the primary treatment used to achieve locoregional control [93]. Adjuvant radiotherapy does improve locoregional control; however, it probably does not affect overall survival rates because of the high rates of distant metastasis at the time of initial presentation [94]. Overall 5-year survival rates are usually between 15% and 20%, although rates as high as 40% have been reported [92,95]. Desmoplastic melanoma Desmoplastic melanoma (DM) was first described by Conley et al [29], in 1971, as a rare variant of spindle cell melanoma. These lesions are often nonpigmented and may appear only slightly abnormal or harmless when actually an aggressive malignant lesion is present. The seemingly benign appearance of this tumor can be misleading to patients and physicians alike, causing a delay in proper therapy. Previous studies have noted that DM was


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more commonly diagnosed in elderly men [91,96] and more frequently reported in the head and neck region [97,98]. At presentation, the lesions are usually thicker (median tumor thickness, 2.5 mm; Clark’s level IV or V) [103] than other forms of melanoma; however, the thickness of DM lesions is not as useful a predictor of prognosis as it is in other forms of melanomas. This subtype of melanoma is characterized by its neurotropism. This trait is of critical importance in the head and neck because even small DM lesions can spread to cranial nerves, causing palsies and leading to intracranial spread. The particularly high rate of local recurrence with these tumors has been attributed to this propensity for perineural spread [99], which is a strong adverse factor for prognosis [100,101]. WLE with a 2-cm margin, if possible [96], and a meticulous analysis of the specimen for evidence of perineural spread are important. Adjuvant radiotherapy is also recommended for patients with this pathologic finding. Finally, the rate of regional lymph node metastasis in DM (15.4%) is lower than for other forms of CMM [101], regardless of tumor thickness. The overall survival rates, however, tend to be similar to other forms of CMM [102]. Metastatic melanoma of unknown origin In rare cases, melanoma is discovered in the cervical and parotid lymph nodes without evidence of a primary tumor. The hypothesis is that, in most cases, these metastases result from primary melanomas that have regressed spontaneously. Clinicians must first rule out mucosal or ocular melanoma, however. The treatment of choice is appropriate lymphadenectomy and postoperative radiotherapy. These patients also need to be considered for clinical trials of adjuvant systemic therapy. The prognosis for this group of patients is similar to that for other patients who have stage III disease [104].

Summary Major advances in the understanding of the causes and risk factors for melanoma and for the prevention and management of this tumor have taken place since the beginning of the past century, when the diagnosis of melanoma was synonymous with death. As many as 80% of early melanomas can be cured, and a high rate of locoregional control for even far-advanced melanoma is plausible. The major challenge for the years to come lies in curtailing the steady rise in the incidence of melanoma by increasing patient education and adopting measures to prevent the increasing mortality rates associated with this disease. Cure rates can be improved by early diagnosis by physicians and instant referral to experienced oncologists. Finally, new advances in diagnostic and treatment strategies carry the hope for further improvements in locoregional control and survival rates.

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Acknowledgments The authors thank Bradley A. Schiff, MD, for his review and critique and Ms. Yolanda Luna for her administrative assistance.

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com (K. are not considered candidates for resection because of concerns about stroke or residual disease. and real-time image acquisition. even if the ICA is not invaded directly. Neurosurgical techniques have evolved over the past 60 years. NY 14209. These problems greatly limited early efforts in cranial base surgery. 3 Gates Circle. from a point in time when any cranial surgery involved great uncertainty and risk. advanced head and neck malignancies. albeit a large one. State University of New York–Buffalo. is the integration of imaging into the operative suite for surgical planning.J. USA Skull base surgery requires integrating surgeons of differing specialties. with complication rates approaching 40% to 50% in some early series. The major advance in cranial base surgery. and remain pertinent for skull base surgeons today. proximity by preoperative imaging or by direct operative inspection prevents adequate oncologic margins. Buffalo. MD*. Gibbons. A significant number of patients. Malignant disease involving the internal carotid artery (ICA) limits the resectability of disease. to complete a technically difficult surgery without complication. to surgery in the modern era in which complex operations are routinely performed to treat lesions that were. This apparent revolution in technique application is actually more of an evolving step. E-mail address: kgibbons@Buffns. Dare. Amos O. School of Medicine and Biomedical Sciences. until recently. doi:10. considered inoperable. All rights reserved. This article initially focuses on the avoidance and management of cerebrospinal fluid (CSF) leak and wound reconstruction. * Corresponding author. and neurosurgery in general. Gibbons). particularly those who have recurrent.1016/S1055-3207(03)00116-9 . and appropriate techniques specific to each specialty.Surg Oncol Clin N Am 13 (2004) 231–239 The integration of neurosurgical techniques in current head and neck skull base surgery Kevin J. This article reviews current protocols for assessment and management of these patients. 1055-3207/04/$ . MD Department of Neurological Surgery. localization.see front matter Ó 2004 Elsevier Inc.

this step generally involves temporary lumbar CSF diversion. however. All patients were treated with primary dural closure or cadaveric dural reconstruction. In cases of persistent hydrocephalus. and a 4% incidence of symptomatic pneumocephalus requiring intervention. permanent diversion may be required. Cerebrospinal fluid diversion The first step in prevention and treatment of fistula formation is elimination of any pressure gradient between compartments. and fibrin sealant has resulted in significant improvement in avoiding this problem. The development of CSF diversion. Select cases undergo intraoperative localization.J. and benefit of postoperative CSF diversion remains controversial. skull base surgeons link the intracranial subdural space with the nasapharyngeal compartment. Most patients who have skull base malignancies now undergo multimodality multiplanar preoperative imaging to aid in surgical planning. and uncal and other herniation syndromes. or may have presaged. The role. These leaks resulted in. Subgroups included 25 patients with documented postcraniotomy fistulae. but this is generally delayed until any question of perioperative contamination or postoperative infection has been resolved. and 38 patients who experienced successful augmentation of ‘‘tenuous dural closure.O. In skull base surgery. serious wound complications. A. Lumbar root irritation. In many centers. The authors reported a 94% success rate. Similar results were subsequently reported by McCutcheon et al [2] in 1996. intraoperative imaging is available. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 in the neurosurgical challenge of localization. and 4 days of lumbar drainage. A report by Dagnew et al [3] described three cases of acute foramen magnum syndrome with arrest and quadriplegia secondary to .232 K.’’. Cerebrospinal fluid leaks In most patients. such as dehiscence and infection. with a combination of preoperative images and intraoperative localization with computer-assisted navigation (frameless stereotaxy). with real-time data acquisition. with a 4% rate of transient CSF leak. acute foramen magnum syndrome. however. multilayered closures. with a 5% infection rate and a 3% rate of temporary decline from overdrainage. using MRI obtained in the operative theater and updated as needed to demonstrate location and extent of residual disease. again only temporary in this series. was reported in 14% of patients. an overall 7% rate of pneumocephalus. CSF leaks seemed to be a nearinsurmountable problem early in the development of the specialty. Complications of overdrainage include pneumocephalus. with an 87% success rate. risk. A series describing the role of lumbar CSF diversion was reported by Shapiro and Scully [1] in 1992. Gibbons. pericranial flap base reconstruction.

The decision to place a lumbar drain is usually made before surgery.K. which could result in uncontrolled drainage into the soft tissues of the back and further herniation. ideally in an ICU setting). Dare / Surg Oncol Clin N Am 13 (2004) 231–239 233 lumbar drainage. 5. this procedure is easier to perform under general anesthesia. 3. either subarachnoid or intraventricular. 2. Gibbons.O. after induction of general anesthesia. however. CSF drainage may avoid these periods of intracranial hypertension. with the recommendation to attempt cranial catheter placement. minimal duration. Securing the catheter at multiple sites by suture fixation of the looped catheter is often essential to maintain a working catheter for 5 days or more. The most tenuous cranial/dural base repairs can be disrupted by even brief periods of intracranial hypertension associated with Valsalva’s maneuvers and other events during emergence from anesthesia. including the . in cases where significant dural reconstruction is likely to be required. to avoid the pressure gradient across the foramen magnum when possible [4]. Another study reported two patients with coma associated with overdrainage from a lumbar catheter. A. The authors also reviewed the syndrome and its management. serious central nervous system (CNS) infection. Controlled drainage during surgery facilitates exposure and minimizes brain retraction.or 16-gauge) Tuohy needles are more comfortably placed in patients under general anesthesia (from both the patient’s and surgeon’s perspective). as opposed to removing the catheter. 4. The placement of a catheter into the subarachnoid space before craniotomy. A recent review of ventriculostomy-related infection and specific risk factors was published by Lozier et al [5]. with potentially devastating results. in particular.. Large-bore (14. Ventriculostomy placement is not without risk.J. which is uncommon with lumbar drains. Dural repair and multilayered closure Adequate resection of lesions extensively involving the skull base requires meticulous wound closure and repair for several reasons. volume drainage targets. An important practical point is the need to clamp the catheter at the first sign of neurologic decompensation. and the practical details of successful lumbar drainage (eg. the theory of cranial spinal pressure gradients. is advantageous for the following reasons: 1. The lumbar subarachnoid space is easily and safely entered before drainage of large amounts of CSF at the primary surgical site (dry taps are more likely to result in root injury or irritation). Risks include intraparenchymal hemorrhage and. Uncal or transtentorial herniation syndromes occur in the setting of temporal lobe edema or hemorrhage and lumbar drainage. and careful frequent nursing care.

If so. and the predominance of cases in most surgeons’ personal series. Most of the literature regarding closure of complex wounds after skull base surgery. with or without titanium mesh. maintaining attachment and vascular supply during the procedure. The dura should be kept moist during any lengthy procedure. a practice aided by well-positioned irrigation catheters. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 avoidance of CNS infection. This method allows the alteration of the size of both the free graft used for dural closure and the vascularized graft used as a sling for floor reconstruction. The current authors’ preference is to mobilize as large a pericranial flap as possible. The grafts are secured with 4-0 silk or polyglactin 910 (Vicryl) sutures for the dural patch. . using autologous fascia or pericranium. the next issue is to determine whether a margin of native dura exists circumferentially around the defect such that a graft can be sewn in a watertight fashion. Numerous techniques have been developed to optimize closure and repair. Posterior fossa cases are usually neurosurgical cases. Viability in this instance describes dura that is of adequate thickness and has been kept hydrated during the procedure up until closure. Primary dural closure is possible in limited situations in skull base surgery. is primary dural closure. when the opening is limited and the adjacent dura is substantial and able to be mobilized: an example is primary closure or oversewing of the subfrontal dura after division of an olfactory tract involved with a small esthesioneuroblastoma. When available. Gibbons. It may be harvested early on in the procedure and kept moist on the table as a free devascularized graft. involves anterior cranial fossa surgery. if viable. CSF leaks. a moist collagen sponge over exposed dural surfaces. techniques of repair and tissue acquisition for repair are determined in advance of surgery. The goal. and 3-0 and 4-0 silk for attachment of the sling to the surrounding bone of the defect (usually the orbital roofs for anterior craniofacial resections).J. in most cases with proper preoperative imaging and planning. Preparing the closure during the exposure is a hallmark of the successful surgeon. The repair is reinforced with fibrin glue [6]. In this location. autogenous pericranium is ideal. Drill holes are placed with a 2-mm round bit in the adjacent bone. Temporal bone and lateral skull base cases are less likely to involve difficult or impossible dural repairs in direct connection with a sinus. Although the findings at surgery may require a deviation from the planned approach and procedure. A recent report described a sutureless fixation. A. and structural support of the CNS and important end organs. and anchoring it with titanium screws. When dural grafting is required because of an extensive defect. when possible. cosmetic deformity. a watertight dural closure and a viable tissue barrier providing separation from the upper respiratory tract are essential. More extensive defects can be repaired primarily with mobilization of surrounding dura. with complex repair schemes rarely necessary.234 K. This method may be useful when the dural margin is inadequate to place or hold a suture. the next question is which type of graft to place.O. and general attention to detail.

First. preservation.K. they should not be used. if there is not enough vascularized native tissue to provide a viable barrier between the airway and the subdural compartment. In certain instances. and rectus abdominis free flaps. in one large-scale series) than in aneurysm patients . Carotid involvement seen on preoperative imaging limits intervention to the following options: debulking without oncologic margins (peeling tumor off the ICA).8]. assessment of adequate cerebral vascular reserve. the series that have reported testing and carotid sacrifice were primarily in patients before elective ICA occlusion for aneurysms: vascular complications in patients who have skull base tumor occur at a higher rate (eg. Traditionally. tumor involvement of the ICA relegated the patient to palliative care for malignancies in which surgical resection was the main therapy. and the safety of elective carotid occlusion and sacrifice. Balloon test occlusion with hypotensive challenge is an accepted means of assessing cerebrovascular reserve and is used by the authors in selected patients. sacrifice. particularly if native tissue is not available because of prior surgery or radiation. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 235 Dural substitutes and allogenic cadaveric dura may be used. Radial forearm free flaps are used for smaller defects. Considerable work in the past 10 years has reported on the preoperative assessment of adequate collateral circulation. Carotid artery assessment. resection with carotid sacrifice (preoperative with endovascular balloon occlusion or intraoperative). the use of vascularized free flaps is increasing. and bypass Tumor involving the ICA presents a major surgical management issue. there are several key issues to understand.O. Vascularized muscle flaps may be used if rotated in (temporalis. Although these substitutes are acceptable for dural closure in limited circumstances. latissimus) with adequate tissue and length. even as a dural patch.J. are placed for larger defects. The decision process is aided in many centers with preoperative assessment of collaterals and reserve. 22%. however. Collaterals are located by means of the circle of Willis and the external carotid branch anastomosis to the intracranial vasculature. Although identification of an isolated hemisphere or middle cerebral artery (ie. This technique and subsequent ICA sacrifice has been used successfully for more than a decade. resection after revascularization (bypass). those without apparent collaterals by means of the circle of Willis) may be obtained with conventional angiography with the addition of simple cross compression tests (further testing has been advocated and used) [7. Gibbons. For squamous carcinoma of the head and neck nonoperative treatment is associated with a dismal prognosis of 1-year survival time. and delegation to nonoperative therapy (often palliative care) [7]. with or without subcutaneous fat and/r skin. Before routine incorporation into a surgical head and neck oncology practice. A.

Before routine application. carotid blowout. before a scheduled tumor resection [7]. with thick (5–10 mm) slices. likely from a transient hypercoagulable state.236 K. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 after a simple hunterian ligation [9]. and contrast angiography. the risks of pseudoaneurysm formation. after successful test occlusion with hypotensive challenge.O. and very limited nonaxial slice imaging or reconstruction capability. with toxic agents delivered by direct carotid puncture. and the durability of this construct needs to be established. Neurosurgery as a specialty was reborn based on modern neuroimaging.J. The current authors have reported a single case of a stump embolus resulting in a fatal dominant hemisphere stroke. prior radiation and surgery are likely to impair and. however. the location and extent of lesions were no longer in doubt. In patients who have head and neck cancer. however. A. In view of these results. cerebral ischemia of varying degrees of severity may affect 20% to 50% of patients undergoing elective ICA occlusion and represents a major ongoing area of concern in the treatment of patients with head and neck cancer. This practice does not seem to reduce or eliminate the risk of stroke. antiplatelet agents were not protective. which occurred after permanent balloon occlusion. in many cases. Gibbons. establishing the presence of adequate collaterals does not eliminate the risk of embolic stroke. Stump emboli occur at a higher rate during and following extensive tumor resection. This method involves the removal of the diseased ICA around the endothelialized stent. The routine use of bypass surgery to prevent ischemic complications of carotid sacrifice is intuitively attractive. Second. In a series reported by Abruzzo et al [10]. pneumoencephalograms. Anticoagulation may have lessened the risk of stroke in carotid sacrifice with or without bypass. and occlusion need to be determined. from the days of Harvey Cushing until the advent of CT in the 1970s. Standard CT acquisition was slow. followed by ‘‘exarterectomy’’ has been tested [11]. Endoluminal stenting of the ICA. Crossover bypass from the contralateral side (bonnet bypass) may be an option in selected cases. followed by a delay to allow in-stent endothelialization. Imaging Neurosurgeons relied on clinical acumen and knowledge of neurology and anatomy to guide surgery for the first 70 years of the specialty. MRI provided better views of nonosseous . eliminate the donor and recipient vasculature. neurodiagnostic testing included air ventriculograms. a novel approach for carotid artery management has been proposed and tested in animal models. and the use of extensive revascularization procedures. Despite careful assessment of collaterals and cerebrovascular reserves. Until CT became available. The stent itself may be removed. 7 of 15 patients undergoing bypass suffered an ischemic event. significant volume averaging. With the introduction of CT and subsequently MRI.

and transfer to the operating suite with frame attached. Operative localization of a predetermined target is useful. and more accurately displays the information than either modality alone [14]. Those images initially were only preoperative. or reference blocks and less invasive localizing points.J.O. and adjust windows and plan approaches before incision. and. improved computer capabilities has returned the modality to equal footing with MRI. however. CT had been relegated to a distant second place in terms of value to the surgeon. This fusion technique. with accurate three-dimensional renderings. Combining these modalities in overlaid sections and rendered threedimensional images is the result of image fusion. those with tool localization based on ultrasound.13]. tumor–bone and tumor–vessel) [15]. which are then referenced in the operating room with a system that allows the surgeon to reorient the location of a probe or any surgical instrument to a three-dimensional display in the operating suite. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 237 structures in three standard planes but required lengthy scan times and a cooperative patient. magnify. however. . The concept of frameless stereotaxy involves preoperative imaging with fixed reference points. provides better depiction of individual anatomic structures and key structural relationships (eg. Now. The use of frameless systems for intraoperative navigation is increasing in neurosurgery and otolaryngology. These systems include those with reference points with fixed arcs attached to typical neurosurgical head frames.K. and often included significant artifacts. Image fusion permits accurate localization and target identification. were only images on a light box in the operating room. intraoperative localization (frameless stereotaxy). not always readily or accurately transferable in the surgeon’s mind to the three-dimensional field in which he or she must work. those with localized skull pins. and although of great use to the surgeon. Thin-slice high-resolution CT with multiplanar reconstruction and workstation capabilities allows the surgeon to rotate. as described later. and intraoperative MRI. framed stereotactic surgery did not allow for reorienting the surgeon. and articulated arms that allow the surgeon to know where in three-dimensional space he or she is working. particularly in cranial base surgery. image acquisition in the ring. CT and MRI have advanced the specialty of neurosurgery in general and skull base surgery in particular. dental stents. Gibbons. optics. The use of fusion techniques in preoperative frameless guidance combines the submillimetric accuracy of CT with the tissue-imaging capabilities of MRI. however. In addition. and numerous systems are available [12. either anatomic structures or fiducials. operating around a frame is difficult for extensive or lengthy procedures. thin-slice multiplanar imaging. A. imaging is available with threedimensional reconstruction. Framed stereotactic techniques in neurosurgery involve the application of a head frame and localizer ring. The introduction of improved hardware and software in both CT and MRI modalities greatly aids modern-day skull base surgeons. in surgery.

The use of frameless guidance clearly is more surgeon-friendly and quicker than framed stereotactic systems. Summary The recent advances in neurosurgery.20: 241–5.J. References [1] Shapiro S. . This hindrance is far less likely to occur in skull base surgery [19]. Frameless guidance is particularly useful in repeat operations in which normal. and hospital length of stay [16. In the future. The authors’ practice is to use frameless guidance in cases of repeat operation and tumors involving multiple anatomic compartments. Intraoperative MRI The latest and potentially most useful imaging modality in the surgical suite is real-time intraoperative image acquisition that demonstrates the surgical anatomy and remaining pathology as the procedure evolves.5-T field strengths now available. consisting of anesthetic and surgical instruments. the routine use of intraoperative MRI may provide intraoperative quality assurance in neurosurgery and skull base surgical procedures. in which image guidance is likely to prolong surgery [16. brain shift is a particular problem. to improve patient selection by reducing the risk of stroke while expanding the operative options available to patients with head and neck malignancies. The transition period from research tool to widespread clinical applications is now upon us. The use of updated images eliminates the concern of brain shift and should reduce the occurrence of unsuspected tumor remnants and the need for return trips to the operating room. A. Closed continuous drainage of spinal fluid via a lumbar catheter for treatment or prevention of cranial/spinal cerebrospinal fluid fistula. with intraoperative magnets of 0. and to aid operative care through improved surgical planning and intraoperative localization. Gibbons. Intraoperative MRI is now available.12to 1.238 K. with the possible exceptions of simple biopsy. intraparenchymal surgery of primary brain tumors. Scully T.17]. In intradural. from equipment and prolonged setup and operative time. in which framed systems are both accurate and quick. provide surgeons with new techniques to avoid the devastating complication of CSF leak. are now available [20]. with several studies documenting no increases or actual decrease in operative time. and uncomplicated primary transphenoidal surgery. adjoining anatomic reference points are distorted or destroyed. MRI surgical suites and compatible operating equipment.O.18]. Neurosurgery 1992. these disadvantages are generally eliminated with routine use. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 Incorporating frameless image–guided surgical technique involves increased cost initially. applied to the growing field of skull base surgery.

Boor S. Combined and three dimensional rendered multimodal data for planning cranial base surgery: a prospective evaluation. DeMonte F. Luebben B. [9] Origitano TC.J. Patel N. Sciacca R. Neurosurgery 2002.35:463–71. Loree T. Comparison of different computer aided surgery systems in skull base surgery. Reid J. Neurosurgery 1994.13:43–50. Gibbons K. Alberti O. vanLoveren H. Neurosurg Focus 2003. Griffith HB. et al. Prevention of complications resulting from endovascular carotid sacrifice: a retrospective assessment. Neurosurgery 1999. Neurosurgery 1994.191:447–54. [14] Hill DL. Dare / Surg Oncol Clin N Am 13 (2004) 231–239 239 [2] McCutcheon I.35:351–63. [8] Standard S. and bone screws: technical note.8:529–44. Neurosurgery 2000. Accurate frameless registration of MR and CT images of the head: applications in planning surgery and radiation therapy. Petermeyer M. Levine PA. Freysinger W. Villalobos H.O. [15] Gandhe A. Kaibara T. Lam MK. Ventriculostomy-related infections: a critical review of the literature. [7] Dare A. Dawson RC. Minim Invasive Neurosurg 2001. Anterior transcranial (craniofacial) resection of tumors of the paranasal sinuses: surgical technique and results. A. Guterman L. Mann W. Hill D. Neurosurgery 2002. Connolly E. Thumfart WF. Al-Mefty O. . Dural reconstruction with fascia. titanium mesh. Skull Base 2003. 126:390–5.51:170–82. Advances in image-directed neurosurgery: preliminary experience with the ISG Viewing Wand compared with the Leksell G frame. Barrow D. J Craniofac Surg 1992. Intravascular stents for endoluminal cerebrovascular bypass.44:99–103. Ahuja A. Newman SA. [11] Lopes D. Acute foramen magnum syndrome caused by an acquired Chiari malformation after lumbar drainage of cerebrospinal fluid: report of three cases. [5] Lozier A.K. Tew J. [10] Abruzzo T.3:1–4. Nelson RJ. Intraoperative magnetic resonance: an inflection point in neurosurgery? Techniques in neurosurgery 2002. Surg Neurol 2000. [12] Gunkel AR. Hicks W. Poon WS. Becker R. Br J Neurosurg 1994. Maurere J. Boston.45:261–70. Presented at the Annual Meeting of the Congress of Neurological Surgeons. et al. Neurosurgery 1996. Blacklock J. Gillihan M.46:910–7. 1999. Neurosurgery 2001. AJNR Am J Neuroradiol 1995. [4] Francel PC. Louw D. Experience with various 3-dimensional navigation systems in head and neck surgery. The impact of an armless frameless neuronavigation system on routine brain tumour surgery: a prospective analysis of 51 cases. [20] Sutherland G. Post K. Joseph G. Weber R. Wakhloo A. Vascular considerations and complications in cranial base surgery. Clinical use of the optical digitizer for intracranial neuronavigation.7:246–51. Guterman L.38: 471–80.51:823–9. Advanced image-guided skull base surgery. Radiology 1994. Reichman OH. [6] Sekhar L. Chandler C.49:749–52. [3] Dagnew E. Leonetti JP. [17] Germano I. et al. [13] Ecke U. Sarma S. Silver A. Morita A. Coakham HB. Romagnoli M. [19] Sure U. Gleeson MJ. Bertalanffy H. [16] Wong GK. Persing JA. [18] Sandeman DR.3:145–8.16:1453–8. Hawkes DJ. Gibbons. Studholme C. Owens D. Neurological deterioration after lumbar cerebrospinal fluid drainage. Balloon test occlusion of the internal carotid artery with hypotensive challenge. et al. Arch Otolaryngol Head Neck Surg 2000. Cantrell RW. Hypotensive endovascular test occlusion of the carotid artery in head and neck cancer.53:563–72 [discussion: 572].

of paranasal sinuses. in skull base surgery for head and neck cancer. of laryngeal carcinoma. expanding role in head and neck surgery.see front matter Ó 2004 Elsevier Inc. doi:10. to protect salivary function during radiation therapy of head and neck cancer patients. integration of neurosurgical techniques into skull base surgery for head and neck cancer. 118 Adjuvant therapy. and bypass of. 13–35 in skull base surgery. See Thyroid carcinoma. 218 Chermotherapy. 56 upper. 161–163 C Cancer predisposition. 107–108 for oropharyngeal carcinoma. 28–29 of cutaneous melanomas of head and neck. assessment.Surg Oncol Clin N Am 13 (2004) 241–247 Index Note: Page numbers of article titles are in boldface type. surgical treatment of. in head and neck oncology. 4–5 Carotid artery. 188–189 Computed tomography (CT). 5–6 genomic instability and. 1055-3207/04/$ . 168–169 B Biochemotherapy. 40–41 long-term considerations. 2–4 genes for. of paranasal sinuses. sacrifice. 236–237 Cutaneous malignant melanoma. 223 Differentiated thyroid carcinoma. 207–208 sentinel lymph node. lower. iodine 131 for welldifferentiated thyroid cancer. 120–121 Adenoid cystic carcinoma. D Dental oncology. squamous cell carcinoma of. of paranasal sinuses. 93–94 Chemotherapy. dental oncology and. All rights reserved. 235–236 Cerebrospinal fluid leaks. salivary gland. 56–57 Amifostine. 175 salivary gland. for staging N0 neck tumors.1016/S1055-3207(03)00146-7 . preservation. 194–195 Anatomic landmarks. See Melanoma. as alternative to surgery for head and neck cancers. 206. for paranasal sinus cancers. 41–43 Desmoplastic melanoma. for identification of cervical lymph nodes. in head and neck cancer. A Acinic cell carcinoma. anatomic landmarks for identification of. of cutaneous melanomas of head and neck. 181 Complications. imaging in head and neck oncology. imaging-guided. 78 in management of oral cavity squamous cell carcinoma. 39–40 for laryngeal carcinoma. 37–46 assessment. 153–154 Anatomy. 174 salivary gland. in patients with squamous cell carcinoma of head and neck. 119 Adenocarcinoma. 108–109 of radiation therapy. 63–64 of cutaneous melanomas of head and neck. 232–233 Cervical lymph nodes. for hypopharyngeal carcinoma. 219 Biopsy. 153–154 Chemoradiation therapy. 38–40 considerations during treatment. 129–149 Alveolus.

81–98 of larynx. of paranasal sinuses. carcinoma of. surgery for carcinoma of. for cancer predisposition. 55–56 Function. 157 surgical treatment. 82–85 primary radiation therapy. 167–186 salivary gland cancer. 218–219 Internal carotid artery. 205–206 Fine-needle aspiration. 194–196 speech. risk factors for cutaneous malignant melanoma. 86–87 Hypopharynx. 205–206 E Esthesioneuroblastoma. as risk factor for cutaneous malignant melanoma. in head and neck cancer patients. 187–199 thyroid cancer. role in pathogenesis of squamous cell carcinoma of head and neck. 113–127 squamous cell carcinoma. iodine 131 as adjuvant therapy for well-differentiated. 1–11 Glottic carcinoma. 114–116 Floor of mouth.242 Index / Surg Oncol Clin N Am 13 (2004) 241–247 other applications. in skull base surgery for head and neck cancers. 13–35 anatomic landmarks for identification of cervical lymph nodes. 13–35 nodal staging. of cutaneous melanomas of head and neck. preservation of. 129–149 Hypopharyngeal wall. 99–112 of oral cavity. as risk factor for cutaneous malignant melanoma. 22–28 of primary tumor. 71–80 organ preservation in patients with. expanding role of. 22–28 of primary tumor. 187–199 neuromuscular function. 176–177 F Familial melanoma/dysplastic nevus syndrome. 114–116 other applications. 238 Dysplastic nevus syndrome. 205–206 familial melanoma/dysplastic nevus syndrome. subsite treatment heterogeneity. squamous cell carcinoma of. 105–106 H Hard palate. 140–142 Immunotherapy. genomic instability. of salivary gland tumors. 201–229 neck dissection. posterior. 37–46 assessment. 14–16 melanoma. 93–94 clinical behavior. current treatment options. 16–22 of salivary gland tumors. role in pathogenesis of. 92–93 selective neck dissection for. Intraoperative magnetic resonance imaging (MRI). 16–22 . 236–238 nodal staging. 47–70 of oral pharynx. 14–16 with iodine 131. surgical treatment of. See Carotid artery. in patients with squamous cell carcinoma of head and neck. squamous cell carcinoma of. 1–11 of hypopharynx. 41–43 imaging in. 205–206 Genomic instability. in head and neck oncology. 85–92 I Imaging. 56–57 Head and neck cancer. 151–166 neurosurgical techniques in skull base surgery. 189–192 swallowing. 1–239 dental oncology. 196 salivary function. 5–6 Genetics. 28–31 techniques. 81–98 chemoradiation therapy. surgical treatment of. 205 xeroderma pigmentosum. as follow-up to radioiodine ablation of thyroid remnant or tumor. 38–40 considerations during treatment. 28–31 techniques. 40–41 long-term considerations. 192–194 G Genes. 153–154 integration of neurosurgical techniques into skull base surgery in. major. surgical treatment of. 231–239 paranasal sinus cancers.

L-thyroxine therapy. 101–102 pathology. 57–58 Lymph nodes. 99–112 anatomy. 153–154 sentinel. 223 metastatic melanoma of unknown origin. 222–223 staging. of head and neck. dental oncology in head and neck cancer. of oropharyngeal carcinoma. 201–229 causes and risk factors. anatomic landmarks for identification of. See Melanoma. 122 M Magnetic resonance imaging (MRI). 178 of parotid salivary gland. 223–224 of paranasal sinus cancers. 116–117 Mucosal melanoma. 213–222 biochemotherapy. 203 of paranasal sinuses. 107–108 selective neck dissection for. 219 by stage. 222 management. 16–22 metastatic melanoma of unknown origin. 142–144 serum Tg testing and rhTSH. therapy with. 129–149 acute and long-term effects of therapy. biopsy of for staging N0 neck tumors. of hypopharyngeal carcinoma.Index / Surg Oncol Clin N Am 13 (2004) 241–247 Iodine 131. 207–208 epidemiology. surgical treatment of. imaging of nodal disease in head and neck oncology. 218–219 radiotherapy. 189–192 radiotherapy and chemotherapy in treatment of. 137–140 further management. after iodine 131 therapy for differentiated thyroid carcinoma. 102 surgical treatment. 134–135 therapy of metastases from. 161–163 Lymphoma. 135–137 L L-Thyroxine. 152–153 squamous cell carcinoma of. surgical treatment of. squamous cell carcinoma of. 221 salivary gland. 104 preserving speech in patients with. 223–224 mucosal melanoma. 222–223 N Neck. See Head and neck cancer dissection of. squamous cell carcinoma of. 175–176 pathology. salivary gland. 100–101 complications and outcomes. See Neck dissection. 90 to neck. 213–216 mortality. 204–206 diagnostic evaluation. due to melanoma of head and neck. 108–109 diagnosis. of salivary gland cancers. 142 postsurgical remnant ablation. 58–61 . levels of. 238 Malignant melanoma. 145 imaging and follow-up. 142–144 Larynx. cancer of. for adjuvant therapy of well-differentiated thyroid carcinoma. of paranasal sinuses. 140–142 outcomes. cervical. 206 Lip. squamous cell carcinoma of. 208–213 Metastases. 236–238 intraoperative. 219–221 chemotherapy. 77–78 Molecular biology. 121–122 special issues. 206 recurrent disease. 222–224 desmoplastic melanoma. 157 staging and prognosis. 218 immunotherapy. 216–218 surgery. 181–182 to neck. 122–123 Mortality. imaging in head and neck oncology. Mandible. surgical treatment of. 13–35 in skull base surgery. 104–107 Lentigo maligna melanoma. 102–104 lymphatic and distant spread. 40 Melanoma. 58 243 Maxillofacial prosthodontics. 201–203 follow-up. 203–204 Mucoepidermoid carcinoma.

see Hypopharynx oral. 76–77 tonsillar complex. 43 Outcome. 169 lymphomas. 56–57 Palate. 142 P Palate. imaging of. 178–182 chemotherapy. carcinoma of. hypopharynx. 161–163 for salivary gland cancers. and hypopharyngeal cancer. 157 soft palate. of paranasal sinuses. in patients with squamous cancers of head and neck.244 Index / Surg Oncol Clin N Am 13 (2004) 241–247 Organ preservation. analysis of subsite treatment heterogeneity. 206 O Olfactory neuroblastoma. See Oropharynx. 235–236 cerebrospinal fluid leaks. carcinoma of. 187–199 Oropharynx. 158–160 classification systems. 233–235 Nodal disease. olfactory. 182 treatment. 176–177 Neuromuscular function. sacrifice. preservation of. 167–169 epithelium-derived malignancies. 157–158 for oropharyngeal. 47–70 etiology. differential diagnosis and treatment options. 48–51 Oral pharynx. squamous cell carcinoma of. 176–177 Oral cavity. 124–125 Neuroblastoma. in laryngeal carcinoma. 160 for cancer of oral cavity. 71–72 selective neck dissection for. 73 relevant anatomy. 65–66 of paranasal sinus cancers. 182 with iodine 131 therapy of differentiated thyroid carcinoma. 167–186 anatomy. squamous cell carcinoma of. 51–53 prognostic factors and outcome. 65–66 radiotherapy and chemotherapy. 77–78 posterior pharyngeal wall. 169–170 incidence. 73 Pharynx. 170–178 etiology. 157 posterolateral. 16–22 Nodular melanoma. 181 surgical. 73–74 tongue base. carcinoma of. 160–161 sentinel lymph node biopsy for staging N0 neck tumors. 64 selective neck dissection for. 181 management of cervical nodes. 62–64 reconstruction. laryngeal. in head and neck cancer patients. 178–181 Pharyngeal wall. in head and neck oncology. 78 histopathology. see Oropharynx . 232–233 imaging in. integration of in current head and neck skull base surgery. 231–239 carotid artery assessment. surgical treatment of. 73–74 Neck dissection. 51–66 diagnostic investigations. 48 management. and bypass. of paranasal sinuses. preservation. 108–109 in oral cavity squamous cell carcinoma. 157–158 specific sites. hard. 74–76 Osteoradionecrosis. 72 chemotherapy. soft. 71–80 assigning tumor to subset of origin. 196 Neurosurgical techniques. current concepts and future directions. 170 prognosis and outcome. 151–166 anterior (selective VI). Paranasal sinus cancers. dental oncology in head and neck cancer. 152–157 imaging-based. 72 management of regional spread to neck. 61–62 rehabilitation. 236–238 wound closure. 181–182 radiation therapy. posterior. 178 pathology. 53–61 pathology. 153–155 extended.

177 Sinus cancers. 188–189 xerostomia induced by. as alternative to surgery for head and neck cancers. 16–22 Prognostic factors. See Iodine 131 Reconstruction. 107–108 for paranasal sinus cancers. in patients with head and neck cancers. Skull base surgery. in head and neck oncology. to cancer. 189 R Radiation therapy. 231–239 Q Quality of life. patient-specific. 119 adenocarcinoma and related classification. major. 194–196 limiting salivary gland exposure. dental oncology in head and neck cancer. 29 Precursor lesions. See Neck dissection. use of imaging in. 87–89 245 Radical neck dissection. of salivary gland cancers. 121–122 molecular biology. 194–195 Salivary gland tumors. 2–4 genes for. 122 Selective neck dissection. as alternative to surgery for head and neck cancers. 65–66 in well-differentiated thyroid carcinoma. imaging of. 62–63 of cutaneous melanomas of head and neck. 194–195 Positron emission tomography (PET). integration of neurosurgical techniques in. for cutaneous malignant melanoma. in head and neck oncology. 188–189 Sinonasal undifferentiated carcinoma. 121 treatment. 125–126 squamous cell carcinoma. 131–134 Prosthodontics. 114–116 lymphoma. in patients with squamous cell carcinoma of head and neck. 123–124 undifferentiated carcinomas. 38 for laryngeal carcinoma. 56 Risk factors. 40 Pyriform sinus. 13–35 Postcricoid tumors. 161–163 Side effects. 194–196 . 125 in management of oral cavity squamous cell carcinoma. 204–206 S Salivary function. squamous cell carcinoma of. in oral cavity squamous cell carcinoma. preservation of. 216–218 primary. 125 salivary gland surgery. 120 melanoma. to protect salivary function during radiation therapy of head and neck cancer patients. 89–90 Postoperative evaluation. 120–121 adenoid cystic carcinoma. See Paranasal sinus cancers. Sentinel lymph node biopsy. after surgery for squamous cell carcinoma of oral cavity. 204–205 Predisposition. imaging in head and neck oncology. 125–126 Rehabilitation. 92–93 side effects of. 4–5 Primary tumor. 124–125 radiation therapy. 61–62 Recurrence. 113–127 acinic cell carcinoma. surgical treatment of. in head and neck cancer. after treatment of oral cavity squamous cell carcinoma. in patients with head and neck cancers. 116–117 recurrence. 122 malignant mixed tumors. Radioiodine ablation. 122–123 mucoepidermoid carcinoma. of radiation therapy. See Neck dissection. strategies to reduce. surgery for carcinoma of. risk factor for cutaneous malignant melanoma. for head and neck cancer. 195–196 radioprotective agents. for hypopharyngeal carcinoma. for staging N0 neck tumors.Index / Surg Oncol Clin N Am 13 (2004) 241–247 Pilocarpine hydrochloride. 117 imaging and fine-needle aspiration. 64 Retromolar trigone. dental oncology and. 123–125 neck dissection. 130–131 tumor-specific. surgery for. 181 for salivary gland cancers. 5–6 genomic instability and.

231–239 carotid artery assessment. current treatment options. 71–80 of paranasal sinuses. 85–92 for laryngeal squamous cell carcinoma. 137–140 further management. and bypass. and bypass. L-thyroxine therapy. preservation. 232–233 imaging in. 130–131 tumor-specific. in patients with head and neck cancer. 178–181 T Thyroglobulin assay. 191–192 Squamous cell carcinoma. of salivary gland. 40–41 for hypopharyngeal carcinoma. 235–236 cerebrospinal fluid leaks. 134–135 therapy of metastases from. 145 Thyroxine. integration of neurosurgical techniques in. 145 Thyroid carcinoma. 191 voice quality with different treatment modalities.246 Index / Surg Oncol Clin N Am 13 (2004) 241–247 skull base surgery for head and neck cancer. carcinoma of. 73–74 Speech. 236–238 wound closure. 189–192 technical improvements in. preservation of. 233–235 Soft palate. 104–107 for oropharyngeal carcinoma. 122 sinonasal. dental oncology and. 235–236 cerebrospinal fluid leaks. 71–80 for salivary gland cancers. 236–238 wound closure. 151–166 of cutaneous melanomas of head and neck. 121 organ preservation in patients with. patient-specific. L-. surgical treatment of. 233–235 Swallowing. surgical treatment of. 208–213 Subglottic carcinoma. preservation of. 177 . 192–194 after radiation. 140–142 outcomes. genomic instability. 123–125 for squamous cell carcinoma of oral cavity. subsite treatment heterogeneity. 74–76 U Undifferentiated carcinoma. iodine 131 as adjuvant therapy of well-differentiated. sacrifice. preservation. surgical treatment of. 145 imaging and follow-up. 142–144 Tongue. 105 Surgical treatment. carcinoma of. 173–174 of salivary gland. 53–54 Tongue base. 99–112 of oral cavity. 131–134 Thyrotropin administration. 206 Supraglottic carcinoma. 106–107 Sun exposure. 142 postsurgical remnant ablation. therapy with. 193 Skull (continued) carotid artery assessment. 204 Superficial spreading melanoma. 129–149 acute and long-term effects of therapy. in patients with head and neck cancers. of cutaneous melanomas of head and neck. according to subsite. after postoperative iodine 131 therapy for differentiated thyroid carcinoma. 47–70 of oral pharynx. after postoperative iodine 131 therapy for differentiated thyroid carcinoma. sacrifice. 1–11 of hypopharynx. 232–233 imaging in. 76–77 Tonsillar complex. role in pathogenesis of. 187–199 Staging. 135–137 prognostic factors. after iodine 131 therapy for differentiated thyroid carcinoma. squamous cell carcinoma of. of head and neck. 81–98 of larynx. carcinoma of. 142–144 serum Tg testing and rhTSH. 193–194 after surgery. 53–62 neck dissection in head and neck cancers. 213–216 of paranasal sinus cancers. risk factor for cutaneous malignant melanoma.

integration of neurosurgical techniques into skull base surgery for head and neck cancer. 205–206 Xerostomia. 233–235 247 X Xeroderma pigmentosum.Index / Surg Oncol Clin N Am 13 (2004) 241–247 V Voice. preservation of salivary function in patients with head and neck cancer. preservation of. See Speech. 194–196 . W Wound closure. as risk factor for cutaneous malignant melanoma.