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http://vet.sagepub.com/ A Clinicopathologic and Ultrastructural Study of Undifferentiated Malignant Tumors of the Oral Cavity in Dogs
A. K. Patnaik, P. H. Lieberman, R. A. Erlandson, E. G. Macewen and A. I. Hurvitz Vet Pathol 1986 23: 170 DOI: 10.1177/030098588602300210 The online version of this article can be found at: http://vet.sagepub.com/content/23/2/170
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New York. ERLANDSON. Antibodies against epithelial membrane antigen (EMA) and desmin were from DAKO. The dogs were examined because of pain and swelling of the upper molar or premolar areas. was an ill-defined. E. privately by DAKO. fixed in 10%buffered formalin. LIEBERMAN. Three dogs were German shepherds. The salivary glands were not involved in any dog. Memorial Sloan-Kettering Cancer Center. Pathol. Four dogs were males and two were females. the primary neoplasm. The only abnormal finding on hematologic and biochemical testing was high WBC counts (range. I. desmin. AE2 and AE3 were generously supplied by Dr. As the tumors grew. New York. and osteosarcoma were among the neoplasms reported in the young dogs. The average age of the dogs was 12. New York University School of Medicine. Antibodies against vimentin were supplied Results Undifferentiated. buffered with s-collidine. In the sixth dog (dog 2). and sometimes into brain tissue. and five were large-breed dogs. PATNAIK. Ny.’ Antibodies against three human epidermal keratins designated AE1.000 WBC/mm3). The tumor extended into maxillary. 2010 .5 months (range. 13. Inc. Selected slides were stained with Mayer’s mucicarmine. ~study of neoplasms in the dog. In all six dogs. Schmorl’s femc femcyanide reduction stain for melanin. HURVITZ Department of Pathology and Donaldson-Atwood Cancer Clinic. 6 to 22 months). Benign and malignant neoplasms in dogs under 2 years of age are r a ~ e . nasal and ocular discharge. Tung-Tien Sien. MACEWEN. the tumors were initially misdiagnosed as infections or carnasal abscesses. 23:170-175 (1986) A Clinicopathologic and Ultrastructural Study of Undifferentiated Malignant Tumors of the Oral Cavity in Dogs A. one ~ . G. R. Immunoperoxidase studies for cytokeratins.000 to 33. Three dogs were 12 months old or younger. K. post fixed in osmium tetroxide. The Animal Medical Center.s Lymphoma. and malignant melanoma. Immunoperoxidase procedures were used according to the methods of SternbergerI4and further modification by Erlandson et al. Ltd. Specimens were processed routinely. embryonal rhabdomyosarcoma. and difficulty eating were observed. Radiographs showed soft tissue swelling and bony erosion. actin.and Department of Pathology.Vet. Diffuse metastases were 170 Downloaded from vet. Five dogs were necropsied. located in the right side of the oral cavity. Diagnosis was based on histologic examination of tissue specimens. Only those cases with complete case records and follow-up information were chosen for the study. In five dogs. malignant neoplasm of the oral cavity was diagnosed in six young dogs (Table 1). mesenchymal chondrosarcoma.com by guest on December 22. We conclude that these tumors be designated undifferentiated malignant tumors of the oral cavity until histogenesis is established. Three of the cases were examined immunohistologically. and orbital tissues. and vimentin were also negative. and ulceration and bleeding from the mouth. gray-tan. Materials and Methods The case records of six dogs under two years old with undifferentiated tumors of the oral cavity diagnosed over a 15-year period were reviewed. osteosarcoma. and Gridley’s reticulum stains. Inc. Most dogs were examined because of pain and swelling ofthe upper molar or premolar areas. AND A. H. Undifferentiated malignant tumors of the oral cavity were diagnosed in six dogs under 2 years of age. suborbital swelling. Tissues for electron microscopy were fixed in Karnovsky’s fixative (paraformaldehyde and glutaraldehyde). A. and embedded in Maraglas epoxy resin. ~ In. soft. nasal.2% of the tumors in dogs under two years old. and stained with hematoxylin and eosin. Antibodies against actin and myosin were from Miles-Yeda. malignant tumors accounted for only 3.5 The purpose of this report is to describe six cases of undifferentiated neoplasm of the oral cavity in dogs under 2 years of age. hemorrhagic tumor involving the upper premolar and molar areas. loose molar and premolar teeth. P. Other clinical findings included exophthalmos. N Y Abstract. epithelial membrane antigen. myosin. Department of Dermatology. facial edema.sagepub. The differential diagnosis included malignant lymphoma. leukemia. Electron microscopy of three neoplasms showed that there were no specific features characteristic of carcinoma or sarcoma. the neoplasm involved the soft palate and surrounding tissue.
lung metastasis on X-ray Swelling under R eye. 2010 .Undifferentiated Tumors of the Oral Cavity in Six Dogs 171 Table 1. tur- binates. Breed Sex (mo) Age Clinical Signs on Physical Examination Gross Pathology Sites of Metastasis (microscopic) 1 German shepherd M 9 2 Giant schnauzer F 14 3 German shepherd M 6 Firm. polygonal and spindle-shaped cells in stroma Downloaded from vet. they had remarkably similar ultrastructural features. liver. tissue specimens were examined by transmission electron microscopy. There was little morphologic variation among the neoplasms and the metastatic sites. frontal sinuses & cranial cavity. anorexia & lethargy. nose. lungs (four). the cranial cavity. liver. no bone involvement Mass behind eye of 2’/2 month’s duration. heart (three). There were large areas of necrosis often coagulative. ovaries. The cells were round or ovoid to spindle-shaped with round to elongated nuclei containing small amounts of chromatin and granular cytoplasm. In three cases (dogs 1. 5 ) .sagepub. intestines. lymph nodes. adrenal glands. The average time from diagnosis to death was 22 days (range. adrenal glands. submandibular swelling 1 month’s duration. lungs. heart. loose molars (1st & 2nd) extracted 1 week before examination Swelling of R nasal & buccal areas. fluctuating swelling R* side of face with exophthalmos. 2 to 60 days). in three cases. and brain (three). mesentery. Because of rapid progression of disease and poor prognosis. lymph nodes. intestines. lymph nodes. no bone involvement initially (surgery two times before examination) Bleeding from nose & mouth. ulceration of gum & palate Brain. Survival (days) After Diagnosis No. and adjoining bones. lungs. all dogs were killed. lungs. gastric mucosa. The tumors consisted of patternless sheets of loosely-organized. heart. In all cases there was histologic evidence of tumor extension into the maxillary and frontal sinuses. kidneys. pleura Liver. kidneys (three). pancreas. liver. skeletal muscle Lungs. The primary and metastatic tumors were characterized by groups of small to medium-sized cells with scant stroma (Figs. R nasal disease. The most common sites of metastasis were lymph nodes (five). pleura. palate & gum Mass involving buccal & nasal cavities & intraorbital tissue Mass involving R eye. lung metastasis on X-ray Mass in back of mouth & soft palate. gastric mucosa. mesentery. Clinical and pathologic findings in six dogs with undifferentiated malignant neoplasm of the oral cavity. no oral lesion Ulcerated mass involving R molar arcade & surrounding tissue 6 German shepherd Mixed breed M 12 2 F 22 60 6 Doberman pinscher M 13 Lymph nodes 2 present in all but dog 5 in which only liver metastasis was seen. swelling on R side of face & mandible Mass with deformity involving R maxilla & nasal passage. adrenal glands. The number of mitotic cells per high power field ranged from 23 to 30. heart. & enlarged R mandibular & pharyngeal lymph nodes. 2. testes Brain. friable mass involving soft palate & nasal cavity bilaterally 42 Mass involving R maxilla extending to turbinates.com by guest on December 22. lymph nodes. 1-3). adrenal glands 20 Grayish. kidneys. and. mesentery. kidneys. liver (four). mammary glands Brain. The two dogs that lived for 42 to 60 days had multiple surgical resections.
7. Fig. Loosely organized neoplastic cells surrounding lymphocytes. Low magnification electron micrograph of tumor in dog 5. HE. Neoplasms were suspected when there was no response to antibiotics and when evidence of metastasis was observed. 8). The relatively scanty cytoplasm contained scattered cisternae of rough endoplasmic reticulum. Highly cellular neoplasm. 6. Fig. desmin.com by guest on December 22. Immunoperoxidase studies for AE1. Irregularly-shaped nuclei. 8). 7. spindle and round pleomorphic cells. Undifferentiated neoplastic cells. Nuclei are less atypical than in dog 1. and a small Golgi apparatus (Figs. AE3. EMA. and multiple nucleoli. The differential diagnosis in young dogs with clinical --t Fig. Low magnification electron micrograph of tumor in dog 1. 7. 8.8. 4). 1. 2. Pleomorphic cells with many mitotic figures invading the mucosa. undifferentiated cells with scanty cytoplasm. 2010 . Low magnification electron micrograph of tumor in dog 2. The irreguIarly-shaped nuclei displayed clumped chromatin and one to three nucleoli (Fig. Fig. and many mitotic cells. HE. actin. Discussion Because of the age and clinical signs of the dogs of this report.172 Patnaik et al.000 x). Polysomes were prominent in many of the neoplastic cells (Fig. 5. 4. rudimentary cell junctions (Figs. Small to medium-sized. Fig. 12. and thus accurate diagnoses were delayed. inconspicuous mitochondria. coarsely clumped chromatin. myosin. Except for scattered.8). little stroma. containing scattered collagen fibrils (Figs. their lesions were diagnosed as infections or carnasal abscesss. no structures indicating tumor cell differentiation were seen. Downloaded from vet. Higher magnification of Fig. Fig. 4-6. and vimentin were negative. small to medium-sized cells.000 x and Figs.sagepub. 3. Haphazardly arranged. AE2. 2.
2010 .com by guest on December 22.Undifferentiated Tumors of the Oral Cavity in Six Dogs 173 Downloaded from vet.sagepub.
and Maryann D.sagepub. embryonal rhabdomyosarcoma.^^ Ultrastructuralexamination of tissue specimens from three tumors confirmed results of light microscopy that these tumors were undifferentiated neoplasms. sarcomas.e. i.6 The cells of embryonal rhabdomyosarcoma usually are partially surrounded by basement membrane and contain arrays of actin and myosin filaments in the cytoplasm.-T. Christine MacMurray for editorial assistance. Dr. ~ . 8. Immunocytochemical studies further support the truly undifferentiated nature of this neoplasm. and basement membrane were not evident making a diagnosis of carcinoma untenable. Saba SR.com by guest on December 22. 7. ~ sAlso. Hum Pathol 13:323. Wang T: ‘Undifferentiated’ large cell malignancies: an ultrastructural and immunocytochemical study.^. Electron micrograph of tumor in dog 1. 1982 Brodey RS: Canine and feline neoplasia. Adv Vet Sci Comp Med 14:309. mesenchymal chondrosarcoma. lumens. The presence of cell junctions ruled out lymphoma. Brodey RS. References Azar HA. Fig. tonofilaments. and malignant melanoma. Electron micrograph of tumor in dog 1.’ Acknowledgements Authors thank the Bodman Foundation for support. T. Rudimetary cell junctions have been seen in poorly-differentiated carcinomas and. Chen SM: Epidemiologic aspects Downloaded from vet. signs similar to those of our dogs includes malignant lymphoma. Tumor cells joined by two rudimentary cell junctions.174 Patnaik et al. and the absence of premelanosomal organelles is not compatible with malignant melanoma.6 Features of epithelial differentiation. Two polygonal tumor cells joined by rudimentary cell junction adjacent to a spindle-shaped cell. Sien and DAKO. The light microscopic features of the tumors in our dogs excluded all of t h e ~ e . Gangi and Daisy JimenezJoseph for the immunocytochemical procedures. 1970 Cohen D. There are no diagnostic structures. The fine structural findings indicate an undifferentiated tumor and do not permit further subclassification. Numerous polysomes often were found in rapidly-growing anaplastic tumor cells. Richman AV. A. microvilli. for supplying antibodies for immunocytochemistry. Inc. osteosarcoma. occasionally.. 2010 . Fig. Espinoza CG. there are neoplasms which are not possible to subclassify with presently available techniques. Polysomes are prominent. In humans also.l ~melanomas usually develop in older dog^.
Masson Publishing USA. Animal Medical Center. In: Tumors in Domestic 9 10 11 12 13 14 Animals. 82. ed. Vet Pathol 11:558. Downloaded from vet. 1984 Pool RR: Tumors of bone and cartilage. Erlandson RA. Lieberman PH. Moulton JE. ed. Patnaik. University of California Press. Klauber MR: Survey of animal neoplasms in Alameda and Contra Costa counties.. 2nd ed. 156. 107. Hibbard HH. University of California Press.. 33. p. K. John Wiley and Sons.. p.. 2nd ed.sagepub. 75.. ed.Undifferentiated Tumors of the Oral Cavity in Six Dogs 175 4 5 6 7 8 of oral and pharyngeal neoplasms of the dog. 2010 . 1978 Moulton JE. 62. 1978 Patnaik AK. Berkeley. 2nd ed. California. In: Tumors in Domestic Animals. New York. 1984 Hulland TJ: Tumors of muscle. Berkeley. Brodey RS. Moulton JE. New York. J Natl Cancer Inst 40:307. 1974 Stannard AA..com by guest on December 22. In: Tumors in Domestic Animals. 1964 Cohen D. Cardon-Cardo C. Vet Pathol 21:475. Cancer Res 34:2859. University of California Press. Moulton JE. 1978 Seibold HR: Juvenile alveolar rhabdomyosarcoma in a dog. Higgins PJ: Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands. Liu S-K: Canine sinonasal skeletal neoplasms: chondrosarcomas and osteosarcomas. Moulton JE. p. Dungworth D L Tumors of the lymphoid and hemopoietic tissues. 1974 Dorn CR. 1978 Sternberger LA: Immunocytochemistry. In: Tumors in Domestic Animals. 11. Cancer morbidity in dogs and cats from Alameda County. Berkeley. Taylor DO. 2nd ed. 1968 Erlandson RA: Diagnostic Transmission Electron Microscopy of Human Tumors: The Interpretation of Submicroscopic Structures in Human Neoplastic Cells. Department of Pathology. Keiser H: Epidemiological analysis of the most prevalent sites and types of canine neoplasia observed in a veterinary hospital. N Y 10021 (USA). 1981 Erlandson RA. 1979 Request reprints from Dr. Donaldson-Atwood Cancer Clinic. University of California Press. Pulley LT: Tumors of the skin and soft tissue. A. pp. Am J Vet Res 251776. Am J Surg Pathol8:803. p. 11 1. ed. Inc. p. An ultrastructural and immunohistochemical study. 2nd ed. Reif JS. New York. Schneider R. Berkeley.
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