Malignant Neoplasms of the Nasal Cavity, Paranasal
Chapter
14 Sinuses and Nasopharynx
Sherif Said and Robert O. Greer
Introduction
Malignancy in the sinonasal and nasopharyngeal tract in the
pediatric age group is an exceedingly rare and serious event;
however, there are limited reports documenting such
tumors.1,2 Thus, the non-specific nature of these neoplasms
and their similarity to benign and infectious conditions can
lead to delays in diagnosis.
As a rule, and in stark contrast to malignancies of the
sinonasal tract in the adult population, most tumors in the
pediatric age group are not epithelial in origin, but instead
belong to the sarcomatous, neuroectodermal or hematolym-
phoid groups of malignancy.
It is extremely difficult to separate the various types of nasal
malignancies that occur in the pediatric age group based on
clinical or imaging studies (MRI and CT) alone, largely
because the symptoms and signs for most such malignancies
tend to be similar, and the imaging findings overlap.
Biopsy and tumor tissue evaluation, including immunohis-
tochemical, and frequently molecular studies are essential if
one is to determine the true biologic nature of the different
childhood malignancies that occur in the region. Benoit et al.1
in a review of the symptoms related to malignancies involving
the sinonasal tract of pediatric patients, found that the most
common complaint was a unilateral nasal obstruction,
followed by ophthalmic manifestations, including diplopia,
proptosis, lid discoloration and vision loss. Additional less
common signs and symptoms included; epistaxis, headache,
weight loss, lethargy, obstructive sleep apnea, anosmia, foul
nasal discharge and cervical lymphadenopathy. In tumors that
showed intracranial extension, seizures sometimes occur.2
Sarcomas
Rhabdomyosarcoma (RMS)
RMS represents the most common malignancy of the sinona-
sal tract in the pediatric age group.1 RMS in general constitutes
approximately 3.5 percent of all childhood cancers in individ-
uals up to 14 years of age and 2 percent of adolescent cancers
in individuals up to 19 years of age. Thirty-five to forty percent
of all RMSs occur in the head and neck region.1,2,3
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RMS has not been causally related to a specific carcinogen
or virus and is largely in fact a result of sporadic or inherited
gene mutations. As a highly malignant and extremely primitive
tumor that recapitulates the biologic features of embryonic
skeletal muscle,4 RMS has a poor prognosis.
The tumor has a bimodal distribution pattern of occur-
rence, with one tumor peak occurring in the first decade of life
and a second peak occurring during adolescence.4 A host of
staging systems, including the international union against
cancer (UICC) staging system, the TNM staging system and
the intergroup RMS study staging system have been used to
classify and stage RMS.4-6
The radiographic presentation of the tumor will most often
demonstrate an extensive radiodense mass involving the max-
illary, nasal or ethmoid sinuses. CT or MRI scans should
include sections through the skull base to assess possible inva-
sion and exclude brain metastases.
Pathologic Features
Grossly sinonasal RMS will be an ill-defined fleshy mass,
although the spindle cell variant of embryonal RMS tends to
be firm to rubbery, and the botryoid histologic tumor subtype
tends to be polypoid in appearance. Quite frequently the
tumor will have an intact epithelial surface.
Histologically,1,2,3,4,5 three RMS tumor subtypes can be
seen in the sinonasal tract: 1) embryonal, 2) alveolar and 3)
pleomorphic forms of the neoplasm.
Embryonal RMS is the most frequent subtype of RMS to be
seen in the sinonasal tract of pediatric age patients, and will
consist of primitive mesenchymal cells (rhabdomyoblasts)
simulating various stages of myogenesis. At one end of that
primitive spectrum rhabdomyoblasts will appear stellate, with
centrally placed tumor cell nuclei and amphophilic cytoplasm
(Figure 14.1 & 14.2). With greater tumor differentiation, tumor
cells become elongated with more eosinophilic cytoplasm and
will appear tadpole or strap-like. In well differentiated tumors,
cells will show cytoplasmic cross striations and multinuclea-
tion. The tumor stroma is usually loose and myxoid, although
variable alternate areas of dense cellularity may be seen.
The botryoid variant of RMS will often contain a linear
dense layer of tumor cells that abuts surface epithelium, or a
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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.1 Embryonal RMS showing primitive mesenchymal cells in various
stages of myogenesis including a dominant small blue round cell morphology.
Figure 14.2 Eosinophilic predominantly round tumor cells with
multinucleation dominate the histopathology of this embryonal RMS.
so-called cambium layer. Polypoid nodular tumor cell aggre-
gates will also be recognizable in this histological variant.
The spindle cell variant of the tumor (Figure 14.3) will
show a fascicular, whorled or storiform pattern of growth.
Individual tumor cells that simulate smooth muscle cells will
have centrally placed nuclei and eosinophilic cytoplasm that
tends to elongate and taper. Only rarely will cross striations be
seen. A rare anaplastic variant of the tumor will show enlarged,
bizarre, hyperchromatic tumor cell nuclei.
Alveolar RMS (Figure 14.4) will be composed of small
round primitive cells that tend to be blue in color and thus
they may simulate other small blue round cell tumors includ-
ing lymphoma, small cell carcinoma and neuroblastoma.
Three histomorphologic variants of alveolar RMS are seen: a
classic variant with nests of small round tumor cell surrounded
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Figure 14.3 RMS, spindle cell variant demonstrating a swirling aggregation of
spindle cells set in a primitive myxoid matrix.
Figure 14.4 Alveolar RMS composed of nests of monotonous aggregates of
small round blue cells.
by fibrous septae, (Figure 14.5), a solid variant which will lack
fibrous septae and a mixed variant that will demonstrate both
alveolar and embryonal components. The small tumor cells in
all these variants can show variable degrees of rhabdomyoblas-
tic differentiation.
In pediatric age group patients, embryonal RMS tends to
occur in younger children, while alveolar RMS is seen more in
older children and adolescents. Pleomorphic RMS is seen exclu-
sively in adults.
The differential diagnostic considerations for RMS can
be rather extensive, and include neural, epithelial, melanotic
and malignant lymphoproliferative neoplasms. However,
careful morphologic, immunohistochemical and cytogenetic
studies should enable the pathologist to render a proper
diagnosis.
 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.5 High power photomicrograph of an alveolar RMS demonstrating
tumor cells confined to a central alveolar like space.
Figure 14.6 Alveolar RMS showing desmin immunohistochemical target cell
reactivity.
Immunohistochemical Assessment
IHC markers can be quite helpful in appropriately diag-
nosing a RMS.4,7 Primitive tumor cells may only exhibit
vimentin reactivity. Both muscle specific actin and desmin
(Figure 14.6) will be reactive in tumor cells that are more
differentiated.
Nuclear skeletal muscle-specific myoregulatory proteins
including MyoD1 and myogenin (Figure 14.7) will demon-
strate highly specific nuclear staining. Acetylcholine recep-
tor antigens can be seen in cells that become terminally
differentiated.
Aberrant tumor cell reactivity to other IHC markers may
also occasionally seen including reactivity to S100 protein,
CD99, CD20, NSE, Cam5.2 and CD57.
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Figure 14.7 Positive myogenin nuclear staining characterizes this
alveolar RMS.
Molecular Studies
Most embryonal RMSs have allelic loss in the chromosomal
region 11p15,8 which contains an important tumor suppressor
gene.9 Complex numerical and structural chromosomal
changes can also be present, including extra copies of chromo-
somes 2, 8 and 13. Rearrangement of 1p11q11 and 12q13
gene rearrangements have also been documented in some cases
of RMS.10
Genomic amplification is rare in RMS except for rare cases
of anaplastic disease. Mutations of TP53 and CDKN2A as well
as mutations in the RAS family genes have been seen in subsets
of RMS.
Alveolar RMS shows consistent translocations including t
(2;13)(p35;q14) in the majority of cases, and t(1;13)(p36;q14)
in a minority of cases.11
In approximately 33 percent of all pediatric alveolar RMSs,
there will be chromosomal translocations that generate PAX3-
FKHR or PAX7-FKHR fusion genes, which exert their onco-
genic effect by activating down-stream transcriptional targets
that control cell proliferation apoptosis and differentiation.12,13
FKHR fusion can be detected using a FISH break apart probe.
Significant differential diagnoses include lymphoma, primi-
tive neuroectodermal tumor/Ewing sarcoma (PNET/EWS),
aural polyp, melanoma and fetal rhabdomyoma. B and T cell
markers can be used to identify lymphomas. PNET/EWS will
lack a myogenic immunophenotype and thus stain negatively
for muscle markers. Melanoma will mark positively for S100
protein and HMB-45 and fetal rhabdomyomas will lack cytolo-
gic atypia.
Treatment and Prognosis
An international classification schema for RMS is used to
categorize RMS aggressiveness and, thus its prognosis based
on tumor histologic type. Botryoid and spindle cell tumor
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Box 14.1 Pre-treatment TNM-UICC classification system for

pediatric rhabdomyosarcoma*
Status Definition
Tumor size
T1: Tumor confined to anatomical site of origin
(a): Tumor size  5 cm in diameter
(b): Tumor size  5 cm in diameter
T2: Extension or fixation to surrounding tissue
a) < 5 cm in diameter
b) > 5 cm in diameter
Regional lymph nodes
N0: Regional lymph nodes not clinically involved
N1: Regional lymph nodes involved by neoplasm
Nx: Clinical status of regional nodes unknown
Metastasis
M0: No distant metastasis
M1: Metastasis present Figure 14.8 Undifferentiated pleomorphic sarcoma showing a storiform-
pleomorphic morphology with giant cells.
T = Tumor; N = nodes; M = metastasis; UICC = International Union
against Cancer
*Lawrence W, Anderson JR, Gehan EA, Maurer, H. Pretreatment TNM
staging of childhood rhabdomyosarcoma study group. Cancer 1997;
80:1165–1170.

types have a favorable prognosis. Embryonal RMS has an

intermediate prognosis, and alveolar RMS and undifferentiated
tumors have an unfavorable prognosis. The TNM-UICC
staging system for pediatric RMS can be seen in Box 14.1.
The classification of RMS in the head and neck region has
prognostic importance.14 The nasal cavity, paranasal sinuses
and nasopharynx together with the infratemporal fossa, pter-
ygopalatine fossa, middle ear and mastoid region are con-
sidered to be parameningeal regions and thus tumors in
these anatomic regions carry a poor prognosis with a marked
risk of intracerebral extension.15 Patients less than 10 years of
age with parameningeal embryonal RMS have the most favor- Figure 14.9 Marked pleomorphism of giant cells and cytologically bizarre
nuclei are seen in this higher power view of undifferentiated pleomorphic
able prognosis. sarcoma. Note the primitive myxoid stroma.
Over the past four decades, surgery in association with
multiagent chemotherapy has improved the five-year survival
inflammatory.1,2,3 Only 3 to 10 percent of tumors occur in the
rate for RMS in children. Adriamycin, actinomycin D, Cyclo-
head and neck region,4,5 and less than 20 cases have been
phosphamide, ifosfamide and vincristine, used in combination
reported in this site in the pediatric age group.2,3 Most cases
with selective/individually adapted radiotherapy has improved
have been reported to involve the maxillary sinus with only
patient survival significantly.
rare tumors occurring in the nasal cavity and nasopharynx.

Other Sarcomatous Lesions Pathologic Features

Apart from RMS, other soft tissue sarcomas are rarely reported
in the sinonasal tract of pediatric patients. The following
discussion represents a brief account of some of the most
frequently reported entities.
Undifferentiated Pleomorphic Sarcoma
Undifferentiated pleomorphic sarcoma was first described
in 1963 by Ozzelo et al.1 and includes five tumor histologic
subtypes: pleomorphic, angiomatoid, myxoid, giant cell and
On microscopic examination, tumors will display a storiform-
pleomorphic pattern of fascicular growth in which spindle
to epithelioid cells with marked cellular pleomorphism and
increased mitotic activity aggregate (Figure 14.8). Multinu-
cleated giant cells are common and a mixed acute and chronic
inflammation cell infiltrate, rich in eosinophils and foamy cells
set in a myxoid stroma may be seen (Figure 14.9). The tumor’s
collagenous stoma will show areas of hyalinization and myxoid
change which will occur in 50 percent of tumors, in association

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.10 Sinonasal osteosarcoma demonstrating malignant osteoid
formation.
with spindle and epithelioid cell aggregation. Tumors will be
CD68 and vimentin reactive and actin can be focally positive.
Treatment and Prognosis
Treatment includes complete excision with post-operative
radiation for local and regional tumor control. Chemother-
apy does not seem to play a significant role in the manage-
ment of this tumor, and five year recurrences are in the
35 percent range.
Osteosarcoma
Primary osteosarcoma of the head and neck in pediatric age
patients, not associated with previous radiation, chemotherapy
or a syndrome, are quite rare.6 Those tumors that do involve
the sinonasal region of children most often occur in the max-
illary sinus,7 and the vast majority of osteosarcomas involving
the sinonasal region will occur in individuals in the third and
fourth decades of life. Males are slightly more often affected
than females and most tumors present as a slow growing mass
or swelling.
Pathologic Findings
Tumors will demonstrate the classic histopathologic morph-
ology of osteosarcoma seen elsewhere in the body with the
production of malignant primitive osteoid by the proliferating
neoplastic pleomorphic osteoblasts (Figures 14.10 & 14.11).
Tumors are generally graded as low, intermediate or high
grade, based on their degree of osteoid production, pleo-
morphism, mitotic activity and necrosis. Additionally, osteo-
sarcomas will demonstrate a high rate of mutation in the Rb,
MDM-2 and p53 oncogenes.
Treatment and Prognosis
Treatment modalities vary from surgical resection alone to
combined radiation or chemotherapy. Tumors of the nasosi-
nus most often behave as low grade neoplasms with good
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Figure 14.11 Pleomorphic cells with hyperchromatic nuclei can be seen
between zones of malignant osteoid formation in this osteosarcoma.
long term survival. Osteosarcoma is discussed in greater
detail in Chapter 16.
Chondrosarcoma
Chondrosarcomas represent mesenchymal tumors of cartila-
ginous origin. Less than 10 percent of Chondrosarcomas
involve the craniofacial region, and fewer than two dozen cases
have been reported in the sinonasal region in children.8,9,10
The maxillary sinus is the most common site for the tumor,
and patients can present with a painless mass or include
symptoms that range from nasal obstruction to proptosis.
Pathologic Features
On microscopic examination, malignant cartilage formation in
which disorganized hyper-cellular hyaline cartilage tumor cells
that demonstrate lacunae with irregular, atypical binucleated
or multinucleated forms will be seen (Figure 14.12). Tumors
can be classified as grade I, II or III (Figure 14.13) (low,
intermediate or high grade). Low grade chondrosarcomas tend
to predominate pediatric cases. Treatment generally involves
surgical resection. The use of adjuvant chemotherapy and
radiation therapy is controversial but it has been employed
in some pediatric cases. Pediatric age patients demonstrate an
overall good prognosis when tumors are low grade. High grade
tumors tend to be more biologically aggressive and have an
unfavorable prognosis.8
Angiosarcoma
The maxillary antrum and the nasal cavity are the most common
sites for angiosarcoma in the pediatric patient.11,12,13 On micro-
scopic examination, tumors will show irregularly arranged and
poorly formed vascular channels lined by malignant, frequently
pleomorphic and often spindle appearing cells with highly atyp-
ical nuclei and marked mitotic activity (Figure 14.14). Vascular
cell markers including CD31, CD34, FLI-1 and Factor VIII will
all characteristically highlight tumor cells.
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Figure 14.12 Sinonasal, well differentiated (grade I), chondrosarcoma
showing atypical chondrocyte nuclei and central tumor necrosis.
Figure 14.13 Increased cellularity with atypical pleomorphic chondrocytes
are seen in this grade II chondrosarcoma.
Although the angiosarcoma is radiosensitive, it is rarely
cured by this modality alone and radical surgical resection is
commonly employed. Radiation is typically reserved for recur-
rent lesions.
Infantile Fibrosarcoma (IFS)
IFS, is a spindle cell sarcoma that arises from fibroblasts. The
neoplasm usually involves the extremities, but rare tumors can
be found in the head and neck region including the nasal cavity
and sinuses, primarily the maxillary sinus.14,15,16,17,18 IFS which
can be congenital, usually arises in the first five years of life,
most often before the age of two. Seventy to seventy-five percent
of IFSs are characterized by a chromosomal t(12;15)(p13;q26)
translocation which gives rise to the ETV6-NTRK3 gene fusion.
Tumors can grow to 20 or 30 cm in size and appear
exceedingly large compared to the size of the host.
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Figure 14.14 Sinonasal angiosarcoma demonstrating vascular channels lined
by highly pleomorphic malignant cells with dark nuclear chromatin and
significant mitotic activity.
Pathologic Features
On gross inspection, tumors are typically fleshy to gelatinous
and may show cystic degeneration. On microscopic examin-
ation, the tumor will be composed of a poorly circumscribed
fasciculated growth of spindle cells with scant cytoplasm and
indistinct cell borders. In the case of low grade tumors, the
fasciculated pattern is easily recognizable and will consist of
uniform cells with mild pleomorphism, scattered mitosis and
focal collagen formation (Figure 14.16). In contrast, high grade
tumors are hypercellular and rich in pleomorphic and hyper-
chromatic cells that are ovoid to spindle in shape and which
will show increased mitosis, focal necrosis and little collagen
formation. The tumor will be infiltrative at the margins and
may show areas resembling a solitary fibrous tumor. IFS will
be vimentin reactive with variable staining for S100 protein,
CD34 and SMA.
Treatment and Prognosis
Treatment modalities for IFS most often include surgical
resection and or chemotherapy. The five-year survival rate
for IFS is 85 percent and is quite a bit better than that of
fibrosarcomas encountered in adults.
Neuroendocrine and Neuroectodermal Tumors
Olfactory Neuroblastoma (ONB) (Esthesioneuroblastoma - ENB)
ONB is an aggressive and rare malignant neuroectodermal
tumor of the sinonasal tract that arises from olfactory epithe-
lium1,2,3,4,5,6 that is located along the cribriform plate and
along the sides of the upper nasal cavity. Ectopic foci of
olfactory epithelium within the nasal sinuses can give rise to
the tumor as well.
First described in 1924,1 ONB has an incidence in children
of 0.1/100.000 children up to 15 years of age.2 Recognized as
the most common type of nasal cavity cancer in children,2,3,4
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Figure 14.15 Low grade IFS demonstrating a spindle cell neoplasm with a
fasciculated growth pattern.

Figure 14.17 Low power photomicrograph of ONB of the sinonasal

tract demonstrating irregular nests of dark staining tumor cells set in a
myxoid matrix.

Figure 14.16 Tumor cells show mild pleomorphism but no significant mitotic
activity in this higher power photomicrograph of the tumor seen in
Figure 14.15.

the tumor which shows no gender preference, is more aggres-

sive in the pediatric age group patients than in adults. Tumors
can be clinically classified and staged as: (1) tumor confined to
the nasal cavity, (2) tumor within the nasal cavity that is also
infiltrative of the paranasal sinuses, (3) tumor extending
beyond the nose and paranasal sinuses and (4) primary tumor
with metastasis, using the so-called Kadish staging system.9
Most tumors will involve the nasal vault and distant metastases
will occur in approximately 20 percent of cases. Imaging
studies will generally show a nasal mass that may demonstrate
on an origin within the cribriform plate.
Pathologic Features
On macroscopic inspection, tumors will be a mucosal covered
polypoid mass that will often be richly vascular. Histologically
Figure 14.18 Grade I ONB with circular groupings of dark staining tumor cells
with minimal cytoplasm and round nuclei with an indistinct nuclear membrane.
Tumor cells in many areas surround a central neurofibrillary matrix (Homer
Wright pseudorosettes).
ONB will be composed of a lobular monotonous accumulation
of dark staining, small, round, uniform cells with round nuclei
(Figure 14.17). Tumor cells will thus have a neuroendocrine
like appearance. Tumor cells will have limited cytoplasm and
nuclear chromatin will be punctate.
Tumor cells often aggregate in circular Homer Wright
pseudorosettes where a neurofibrillary background will be prom-
inent (Figure 14.18). Less differentiated tumors will demonstrate

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.19 Grade II ONB demonstrating a moderate degree of nuclear
pleomorphism including occasional mitosis, and a loss of tumor lobular
architecture.
Figure 14.20 Grade IV ONB showing marked nuclear pleomophism and
significant mitotic activity among tumor cells.
a gradual shift toward increased cellular pleomorphism, with a
loss of the tumor’s lobular architecture. (Figure 14.19) Increased
mitoses, necrosis and appearance of the true Flexner–
Wintersteiner rosettes characterize high grade tumors (Fig-
ures 14.20 & 14.21).
Tumor cells will be strongly reactive to neuroendocrine
markers including; chromogranin, synaptophysin, CD56
and NSE. S100 protein stains will stain the sustentacular cells
at the periphery of tumor lobules (Figure 14.22). Tumor
cells are usually negative for immunohistochemical epithelial
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Figure 14.21 Grade IV neuroblastoma showing Flexner–Wintersteiner rosette
formation (clusters of cuboidal or columnar tumor cells arranged around a
central lumen). Note that tumor cell nuclei tend to be displaced away
from lumen.
Figure 14.22 S100 protein stain highlighting sustentacular cells surrounding
tumor lobules in this well differentiated ONB.
markers, melanocytic markers, lymphoid markers, muscle
markers and CD99.
Molecular and cytogenetic studies of ONB have shown
overexpression of DNA chromosomal material on chromo-
some 19, partial gains on the long arm of chromosomes 8,
15, 22, deletion of the entire long arm of chromosome 4 and
several gains and losses on chromosomes 3p, 6q, 9q, 10q, 13q
and 17q.10,11,12
The differential diagnoses for ONB are lengthy and
include: 1) sinonasal undifferentiated carcinoma (SNUC),
2) nasopharyngeal undifferentiated carcinoma, 3) small cell
carcinoma, 4) sinonasal lymphoepithelial carcinoma, 5)
malignant melanoma, 6) NK/T-cell lymphoma, 7) RMS
and 8) PNET/EWS. Perhaps the most significant differential
 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.23 Sinonasal malignant melanoma showing solid sheets of
malignant melanocytes with foci of pigmentation.
diagnostic consideration, PNET/EWS, can be excluded on
the basis that ONB will show a t(11;22) (q24;q12) fusion
transcript.
Treatment and Prognosis
Complete surgical resection with post-operative radiation is
the treatment of choice for ONB. Endoscopic resection can be
employed for small tumors. Chemotherapy has shown limited
success; however, it can be employed as a palliative measure
for unresectable or disseminated disease.
Low grade tumors in children have an 80 percent five-year
survival rate, while high grade tumors show only a 40 percent
survival after five years.
Sinonasal Mucosal Malignant Melanoma
Nasal mucosal malignant melanomas are of neuroectodermal
origin and arise from neural crest derived melanocytes in the
nasal mucosa. These tumors are extremely rare in the pediatric
population.14,15 Most patients will present with a mass in the
nasal cavity or nasal sinus and accompanying non-specific
symptoms, including nasal obstruction, recurrent epistaxis
and epiphora.
Although formaldehyde exposure and smoking have been
implicated in the etiology of melanoma in adults, it is not clear
in the pediatric population that these agents play a role in
tumor development.
Pathologic Features
Grossly, tumors will be polypoid, often pigmented and rarely
larger than 2 cm in diameter. On microscopic examination,
tumor cells will show a varied morphology that can include a
proliferation of small round cells, spindle cells, plasmacytoid
or epithelioid appearing cells. Fifty to seventy percent of cells
will contain pigment (Figure 14.23). Tumor cells usually
exhibit prominent eosinophilic nucleoli and a high nuclear
cytoplasmic ratio, along with cellular pleomorphism, bizarre
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Figure 14.24 High power photomicrograph illustrating the marked
pleomorphism of tumor cells and an abundance of melanin pigment in this
mucosal malignant melanoma.
shaped nuclei (Figure 14.24) and occasionally increased
mitosis. Tumors will usually express S100 protein, HMB45,
Tyrosinase and Melan A/MART1. CD4, CD8 and CD56 stains
as well as stains for cytokeratins, smooth muscle markers and
lymphoma will be negative.
Differential diagnoses can include many of the undifferen-
tiated malignant neoplasms of the sinonasal region including
RMS, ONB, PNET/EWS and SNUC. All of the aforementioned
tumors, unlike melanoma, will be HMB45, melan A/MART1
and tyrosinase negative. Immunohistochemical staining pat-
terns for significant malignant pediatric nasosinus tumors can
be seen in Table 14.1.
Treatment and Prognosis
Although mucosal melanoma of the nasosinuses carries a
grave prognosis in adults, the prognosis in the pediatric popu-
lation is somewhat better. Treatment includes complete exci-
sion of the tumor, with adjuvant chemotherapy, radiation
therapy and high dose immunotherapy.
Small Cell Undifferentiated Neuroendocrine Carcinoma (SCUNC)
Malignant neuroendocrine tumors include the carcinoid
tumor (well differentiated neuroendocrine carcinoma,
low grade), atypical carcinoid (well differentiated neuroen-
docrine carcinoma), intermediate grade(moderately differ-
entiated neuroendocrine carcinoma), and high grade
tumors (including SCUNC and large cell neuroendocrine
carcinoma).16
Among this group of neoplasms, only extremely rare
reports of SCUNC have been identified with any frequency
in the sinonasal tract of pediatric age patients.2 Most such
tumors have occurred in the nasal cavity while the ethmoid
are maxillary sinuses have been spared.
Clinical symptomatology can include epistaxis nasal
obstruction, facial pain or exophthalmos.
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Table 14.1 Immunohistochemical staining patterns in malignant pediatric nasosinus tumors

S100 NSE CG SYN CK HMB LCA CD56 CD99 VIM DES Myf-4
Mucosal melanoma + – – – – + – – – + – –
T/NK lymphoma – – – – – – (+ –) + – (+ –) – –
a
ONB + + (+ –) (+–) – – – – – – – –
SNUC – (+ –) – – + – – – – – – –
RMS – – – – – – – – – + + +
SCC – – – – + – – – – – – –
PNET/EWS (+–) (+–) – (+–) – – – – + + – –
SCUNC + + + + + – – – – – – –
NSE = Neuron-specific enolase
CG = Chromogranin
CK = Cytokeratin
DES = Desmin
HMB45 = Melanin marker
LCA = Leukocyte common antigen
S100 = S100 protein
CD56 = Neuroendocrine marker
VIM = Vimentin
CD99 = Ewing sarcoma/PNET marker
CG = Chromogranin
SYN = Snaptophysin
Myf-4 = Rhabdomyosarcoma markers
+ –= variable
ONB = Olfactory neuroblastoma
SNUC = Sinonasal undifferentiated carcinoma
RMS = Rhabdomyosarcoma
SCC = Squamous cell carcinoma
PNET/EWS = Primitive neuroectodermal tumor (Ewing sarcoma)
SCUNC = Small cell undifferentiated neuroectodermal carcinoma

Pathologic Features
On microscopic examination, SCUNC will be composed
of hypercellular, hyperchromatic small blue cells or spindle
shaped cells, typically growing in sheets, cords and
ribbons.17,18 The tumor may show increased mitotic activity
as well as single cell and confluent necrosis with significant
associated crush artifact. (Figure 14.25) Tumors show a pro-
pensity for lymphovascular invasion, perineural invasion and
metastasis, and tumor cells may demonstrate a high degree of
pleomorphism and hyperchromatism. SCUNC tumor cells will
stain positively for CD56 and variably positive for synapto-
physin (Figure 14.26), chromogranin and neurone specific
enolase. Cytokeratin staining shows variable positivity and
Cam 5.2 is usually positive.

Treatment and Prognosis
In the adult population, SCUNC is a highly malignant
tumor that is associated with a guarded prognosis. The
paucity of cases in the pediatric population does not allow
for a definitive assessment of the tumor’s behavior in that
population. Most SCUNCs in pediatric age group patients
have been treated with systemic chemotherapy and thera-
peutic radiation.
Figure 14.25 SCUNC showing infiltrating sheets of small, round, blue tumor
cells that exhibit significant and characteristic crush artifact and necrosis.
Sinonasal Ewing Tumor Family (ETF); Ewing Sarcoma / Primitive
Neuroectodermal Tumor (EWS/PNET)
EWS/PNET represents a malignant high grade primitive
round cell neuroectodermal neoplasm that primarily affects

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx

Figure 14.26 SCUNC demonstrating strong synaptophysin reactivity. Figure 14.27 Low power photomicrograph of SNUC showing clusters of
basophilic staining round to polygonal shaped cells.

pediatric age group and young adult patients.19,20,21,22,23 Most

individuals of EWS/PNET in the sinonasal region will present
with nasal obstruction, pain and epistaxis. Extra-sinonasal
extension into the orbit or brain has also been recorded.
A complete discussion of the clinicopathology of EWS/PNET
can be found in Chapter 16.

Epithelial Neoplasms
Sinonasal Undifferentiated Carcinoma (SNUC)
Most malignant neoplasms of the sinonasal tract will represent
keratinizing or non-keratinizing squamous cell carcinomas.
However, non-epithelial malignancies that are undifferentiated
can also occur. SNUC is an aggressive malignancy for which
the causation and histogenesis are unknown. The tumor was
first described in 1986 by Frierson et al.1 and radiation has
been postulated as a possible etiologic factor, along with som-
atic mutation at the RB1 locus.2 Epstein Barr virus (EBV) has
also been implicated in the genesis of this tumor.3 Only rare
sporadic cases have been reported in the pediatric age group.4,5
Most SNUCs will be large nasal obstructive tumors which
may extend intracranially on presentation.1,2,3,4,5,6 Symptoms
can include sinusitis, epistaxis, cranial nerve palsies, convul-
sions, drowsiness, severe headaches, orbital symptoms that
include proptosis, visual disturbance and paresis.5 Symptoms
usually have a rapid onset of just a few weeks to a few months.
Pathologic Features
Grossly the tumor will consist of a rubbery fungating mass with
poorly defined margins. Histologically SNUC will be composed
of pleomorphic small to large, polygonal shaped cells with a
high nuclear to cytoplasmic ratio and hyperchromatic round to
oval nuclei (Figures 14.27 & 14.28). One or more prominent
nucleoli may be seen. Multiple foci of apoptosis and confluent
necrosis will be seen and the tumor’s growth pattern can be
sheet-like, trabecular, lobular or organoid.
Figure 14.28 SNUC characterized by sheets of oval to spindle shaped cells
admixed with lymphocytes.
SNUC, which shows a high propensity for angiolymphatic
and perineural invasion, must be differentiated from similar
poorly differentiated tumors occurring in the region including,
RMS, ONB, SCUNC, nasopharyngeal undifferentiated carcin-
oma, poorly differentiated squamous carcinoma and NK/T
Cell lymphoma. Immunohistochemical stains of SNUC tumor
cells will show positive reactivity for keratins including pancy-
tokeratin, cam 5.2 and occasionally for simple keratins
(CK7, 8, 9).
The tumor will mark negatively for muscle markers, hema-
tolymphoid markers, melanocytic markers and Ewing / PNET
markers (CD99). Only rare sporadic staining for S100 protein,
synaptophysin and chromogranin will be seen. Focal staining
for NSE and CD56 may also be observed.
Genetic polymorphism has recently been reported within
the promotor region of VEGF in SNUCs.7

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx

Treatment and Prognosis

Following surgical tumor resection, multimodality therapy is
usually employed in the treatment of SNUC, including neoad-
juvant chemotherapy. Although the tumor’s prognosis in pedi-
atric age patients is difficult to determine due to the paucity
of cases, adult patients have an overall poor survival rate with a
high incidence of local recurrence and local and distant
metastasis.

Sinonasal Adenocarcinoma
Extremely rare instances of sinonasal adenocarcinoma have
been reported in the pediatric population.1 Two main categor-
ies of tumor are encountered in the sinonasal region.1 An
intestinal type tumor that can appear papillary, colonic, solid,
mucinous or mixed (Figures 14.29, 14.30 & 14.31); and a non-
intestinal form of tumor that can be either low or high grade
(Figure 14.32). All of the tumor variants are mucosal surface
epithelially derived with adenomatous differentiation, and
most will occur in the lateral nasal walls, causing nasal obstruc-
tion. EGFR alterations are common to intestinal type tumors,
while KRAS and BRAF mutations are infrequent.2 Complete
surgical excision is curative.

Basaloid Squamous Cell Carcinoma (BSCC)

BSCC represents a high grade variant of squamous cell carcin-
oma. The tumor is rare in the nasosinus and generally affects
adults, rather than pediatric age individuals. Laryngeal tumors
and tumors of the hypopharynx far exceed the number of
sinonasal tumors, and laryngeal tumors tend to be more bio-
logically aggressive than sinonasal tumors, often presenting as
multifocal growths. Symptoms depend on the anatomic site of
presentation of the tumor and may include hoarseness, dyspla-
sia, swelling of the neck or pain.
Microscopically BSCC will be composed of a predomin-
ance of basaloid cells with an associated squamous cell carcin-
oma component that will show a trabecular, cribriform, solid,
glandular or cystic growth pattern.

Treatment and Prognosis

Tumors are treated by radical surgical excision and neck dis-
section and nasosinus tumors tend to have a better prognosis
than BSCC in other head and neck sites.

Germ Cell Tumors (GCT)

Yolk Sac Tumor (YST) (Endodermal Sinus Tumor)
The vast majority of GCTs in children that develop in the head
and neck area are benign.1,2,3,4 Extragonadal YST, a malignant
Figures 14.29 (top), 14.30 (middle) & 14.31 (bottom) Intestinal type
germ cell neoplasm is extremely uncommon in children2,3 sinonasal adenocarcinomas that are papillary, mucinous, and colonic
although it represents the leading non-seminomatous type of respectively can be seen in these three photomicrographs. Note the classic
GCT to occur in the perinatal period and throughout child- glandular pattern of each tumor subtype.
hood.3 Even so, YST is extremely rare in the sinonasal
tract.4,5,6,7 Tumor related symptoms will vary and are rather
non-specific. Nasal obstruction, epistaxis and sinusitis may be

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.32 Non intestinal sinonasal type adenocarcinomas. This high
power photomicrograph demonstrates a low grade oncocytoid (non-intestinal
type) adenocarcinoma.
Figure 14.33 Low power photomicrograph of a YST showing microcystic,
interconnected web-like collections of tumor cells.
seen. The tumor produces alpha-fetoproteins, (AFP) a homo-
logue of albumin, and thus AFP can be used as a diagnostic
marker in follow-up of the patient during post treatment.
Clinically tumors of the nasosinus in pediatric patients will
be characterized by persistent nasal bleeding, and CT and MRI
will tend to demonstrate a lobulated soft tissue mass in the
sinus or paranasal sinus region.
Pathologic Features
Microscopically the YST will demonstrate pleomorphic
cuboidal type cells arranged in a microcystic pattern that
results in an interconnected web-like network (Figures 14.33
& 14.34). The tumor can also demonstrate an endodermal
sinus pattern in which a central vessel will be surrounded by
malignant cells that lie within a cystic space that will be lined
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Figure 14.34 High power photomicrograph showing pleomorphic tumor
cells that marginate a cystic spaces in a YST.
Figure 14.35 “Schiller–Duvall” bodies showing a centrally placed blood
vessels surrounded by flattened malignant tumor cells that marginate a
cystic space.
by flattened tumor cells, or so called Schiller–Duvall bodies.
(Figure 14.35)
Tumors can also appear solid, glandular, myxomatous,
macrocystic, hepatoid, polyvesicular, festooned or parietal.
The tumor will commonly contain hyaline globules (1–50u)
that are periodic acid positive (PAS)/diastase resistant,
as well as aggregates of an eosinophilic band-like protein
product representing extracellular basement membrane
material.
Tumor target cells will stain for AFP (Figure 14.36) and
low molecular weight cytokeratin, AFP and occasionally for
Placental alkaline phosphatase (PLAP) and Glypican 3.8
Microscopic differential diagnoses include RMS, adenocar-
cinoma, ONB, undifferentiated carcinoma and other GCT
types (embryonal carcinoma, choriocarcinoma, dysgermi-
noma and teratoma). Molecular studies have demonstrated
loss of the long arm of chromosome 6, the short arm of
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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.36 AFP positive immunohistochemical staining of YST cells.
Figure 14.37 Sinonasal teratocarcinosarcoma. Teratoid tumor component
composed of immature small round blue tumor cells set in a neurofibrillary
matrix.
chromosome 1 or gains in the long arm of chromosomes 1 and
20 in YST.9 These cytogenetic findings can be helpful in
differentiating YST from the more common small round cell
neoplasms that are seen in pediatric age patients.
Treatment and Prognosis
Surgical excision with combined chemotherapy and radiation
therapy is the treatment of choice for YST. The most common
chemotherapy employed is a combined carboplatin based JEB
regimen.6 Although the tumor is biologically aggressive, most
cases reported in children have shown a good prognosis with
survival rates ranging from 4 to 14 years. However, it should
be noted that the number of cases assessed to date is too
limited to make firm conclusions about the prognosis of YST
in the sinonasal tract of children.
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Figure 14.38 Malignant epithelial tumor component of a sinonasal
teratocarcinosarcoma composed of pleomorphic poorly differentiated cells that
show focal glandular formations.
Sinonasal Teratocarcinosarcoma / Teratocarcinoma
Sinonasal teratocarcinosarcoma is an extremely rare highly
malignant polymorphous paranasal sinus neoplasm that
shows combined histologic features of both a teratoma and
carcinosarcoma. With fewer than 100 reported cases in the
literature, tumors in pediatric age patients are exceptionally
rare.10,11,12,13,14,15,16,17 Most reported tumors have involved the
ethmoid sinus, maxillary sinus, sphenoid sinus and nasophar-
ynx. Tumors are thought to arise from either primitive naso-
sinus embryonic tissue or from a multipotential adult somatic
stem cell with divergent pathway differentiation.18
Patients can present with a myriad of symptoms ranging
from nasal obstruction and epistaxis to dizziness. Clinical
examination will often reveal an ulcerated nasal mass. MRI
and CT will commonly demonstrate a mass filling the affected
sinus cavity.
Pathologic Features
Microscopically tumors will demonstrate a teratoid component
and a carcinosarcoma component. The teratoid component can
be composed of neuroepithelium and neuroectodermal/blaste-
mal cells that will be small, round and blue and resemble
neuroblastoma. Tumor cells are generally set in a neurofibrillary
matrix (Figure 14.37).
The tumor’s epithelial component will consist of benign
appearing glandular or ductal structures, fetal type clear cell
squamous epithelium and foci or aggregates of squamous
carcinoma and/or adenocarcinoma (Figure 14.38).
The tumor’s mesenchymal component can demonstrate an
admix of benign or malignant fibroblasts, myofibroblasts,
zones of RMStous tissue, foci of osteoid formation or osteo-
sarcoma (Figure 14.39). Benign, mature and immature cartil-
age or foci of chondrosarcoma may also be seen.
Differential diagnoses can include ONB, EWS/PNET, RMS,
craniopharyngioma, adenocarcinoma, poorly differentiated
 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx

Figure 14.39 Sinonasal teratocarcinosarcoma demonstrating osteosarcoma Figure 14.40 Low power photomicrograph of a chordoma showing large
in its mesenchymal component. round (physaliphorous) tumor cells set in an abundant fibro-myxoid stroma.

squamous carcinoma, adenocarcinoma, SNUC and high grade

sarcomas.

Treatment and Prognosis

The sinonasal teratocarcinoma is a highly malignant neo-
plasm that requires aggressive therapy in adults, including
surgical resection, adjuvant chemotherapy and radiation
therapy. In the adult population the average patient survival
is less than two years. Follow-up of reported pediatric cases
is too limited to draw any firm conclusions about long term
prognosis. However, Agrawal et al. have reported a case in a
15-year-old male, in which the patient was treated with
combined surgery and chemoradiation. The patient at the
time of follow-up had no evidence of recurrence after 45
months.

Notocord Derived Tumor Figure 14.41 Physaliphorous cells show mild to moderate nuclear atypia in
Chordoma this medium power photomicrograph.

Chordomas represent malignancies of low grade to inter-

mediate grade potential that arise along the length of the
neuraxis from embryonic notochordal remnants. Chordomas
only rarely occur in extraaxial locations including the
nasopharynx and the sinonasal tract.1,2,3,4 They are more
commonly present in a sacro-coccygeal or sphenooccipital
location.5 Most tumors will affect adults; however, tumors
have been recorded in the pediatric age group. Tumors occur
at the rate of less than 0.7 per 100,000 of the population on an
annual basis, and they represent less than 0.2 percent of all
tumors that involve the nasopharynx.6 Males are more often
affected than females.
Clinically lesions commonly present as a lobulated or
expansile mucoid, friable nasosinus mass, accompanied by
gradual nasal obstruction, headaches, diplopia, sensory motor
compromise or pain.
Pathologic Features
Histologically chordomas will be composed of sheets and cords
of large round to epithelioid polygonal cells with vacuolated
cytoplasm (Physaliphorous cells). (Figure 14.40) Tumor phy-
saliphorous cells may show mild to moderate nuclear atypia
(Figure 14.41). The tumor stroma will most often appear either
myxoid or chondroid. Tumors displaying a chondroid stromal
matrix are more common in pediatric age group patients
and women.
Immunohistochemical staining of the tumor target cells
will be positive for pancytokeratin, S100 protein and epithelial
membrane antigens.
Genes showing increased expression in chordoma7 are
frequently located on chromosomes 2, 5, 1 and 7. Interphase

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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
cytogenetics studies have demonstrated gains of chromosomal
material in chordoma, with gains being most prevalent on
chromosome 7q.7
Differential diagnoses include chondrosarcoma, which will
lack physaliphorous cells; chordoid meningioma, which will be
S100 protein negative, liposarcoma, which will be keratin and
EMA negative and chordoid glioma, which will stain positively
for glial markers.
Treatment and Prognosis
Surgery remains the treatment of choice for chordomas,
although adjuvant radiation therapy can be used in cases where
there has been incomplete surgical resection. Traditional
chemotherapy has not been shown to be effective; however,
clinical trials have shown clinical efficacy of imatinib mesylate
in the treatment of chordoma.8
Malignant Tumors of the Nasopharynx
Nasopharyngeal carcinoma (NPC) carcinoma is a form of
squamous cell carcinoma that arises from nasopharyngeal
mucosa. In order to be classified as such, a tumor must dem-
onstrate light microscopic or ultrastructural evidence of squa-
mous differentiation.
NPC can be classified histologically as: 1) keratinizing or 2)
non-keratinizing. Non-keratinizing NPC can be further classi-
fied as differentiated or undifferentiated. A rare BSCC variant
is also recognized.
In the pediatric age group the median age of occurrence for
NPC is 13 years. The tumor is more common in males than
females and occurs more frequently in the black population
with a significant northern and central African demographic.
NPC also accounts for nearly 20 percent of all cancers in China
with the non-keratinizing type accounting for 60 percent of
such cases. However, only 15 to 20 percent of NPC cases in
China occur in the pediatric patient age group.2,3 As a whole,
NPC constitutes from 20 to 50 percent of all primary naso-
pharyngeal malignant tumors in children.4,5
NPC has a close causal association with EBV which has
been found in the genome of NPC tumor cells, and the tumor
is associated with a type of neoplastic latency in which
EBNA1 nuclear protein, LMP1, LMP2 nuclear proteins and
EBER proteins are ultimately expressed in a clonal fashion
in tumor cells.6 Antibody titers of IgG and IgA against early
EBER antigen or viral capsid antigens are encountered in
patients with NPC at high levels, and titer expression assess-
ment is currently widely used for early screening of high risk
groups.
Differences in the world-wide incidence of NPC are
thought to be related to genetic and environmental factors.
Individuals with a HLA.AW33 haplotype are reported to have
a lesser risk for development while polymorphism of some
metabolic enzymes including Glutathione-S-transferase and
Cytochrome – P450 2E1 are related to an increased NPC
incidence and risk.7,8
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The undifferentiated NPC common to southern China
and Hong Kong, Southeast Asia, the Mediterranean basin
particularly northern Africa and Alaska has been related
causally to the consumption of food stuffs that are rich in
volatile nitrosamines, such as salted fish, the use of tobacco,
exposure to chemical fumes and dust, formaldehyde and
radiation exposure.9
NPC can be a symptomless lesion or it can present with
nasal obstructive symptoms including, blood tinged nasal dis-
charge, bleeding and blockage of the Eustachian tubes with
consequential otitis media, earache and tinnitus. Many patients
will present initially with a painless cervical neck mass that will
represent metastatic NPC that is ultimately determined by
clinical investigation to be of nasopharyngeal origin. As many
as 25 percent of NPCs invade the skull base, causing cranial
nerve deficits.6
MRI assessment is the method of choice for determining
the extent of the tumor’s soft tissue involvement and for
assessing any intracranial extension, while CT scans are
more helpful in determining evidence of bone erosion.8,10,11
Detection of EBV using in situ hybridization or by employing
PCR will demonstrate EBV in 80 to 90 percent of non-
keratinizing NPC.
Cytogenetic abnormalities in the form of deletions in
chromosome 3p, 9p, 11q, 13q and 14q have been found in
patients with NPC, suggesting that tumor suppressive genes
are deficient. Other significant genetic alterations include
inactivation of P53, rearrangement of retinoblastoma tumor
suppressor genes and genetic polymorphism of the CYP2E1
gene. Tumor associated chromosome 12 gene gains, and allelic
loss on 11q, 13q and 16q have been linked to the neoplasms
invasive potential.6,12,13,14 Children with NPC have been
shown to have significant T- lymphocyte suppression.15
Non-keratinizing NPC, which rarely occurs in patients
under 40, has an affinity for the lateral nasal wall. Clinical
symptoms are similar to the non-keratinizing form of the
disease, however this form of the disease has not been linked
to EBV.
Pathologic Features
NPC in the pediatric population will most frequently be of the
non-keratinizing undifferentiated histologic subtype. Tumors
will demonstrate a cellular syncytium of often highly baso-
philic, large, sometimes overlapping tumor cells (Figure 14.42).
Tumor cell nuclei will be vesicular to round to ovoid with
nuclei, prominent nucleoli and amphophilic cytoplasm
(Figure 14.43).
Less frequent differentiated tumors, common to adults, will
demonstrate a pattern reminiscent of what in the past has been
referred to as transitional cell carcinoma, with cellular stratifi-
cation and tumor cell pavementing.
The growth pattern of differentiate NPCs can be solid,
plexiform or trabecular. Tumor cells will have well-defined cell
margins and sometimes vague intercellular bridges, and there
may be occasional keratinizing cells. Tumor cells will have
 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.42 Low power photomicrograph of undifferentiated non-
keratinizing NPC, demonstrating the tumor’s considerable basophilia and
lobularity.
Figure 14.43 Undifferentiated NPC showing a diffusely infiltrative tumor cell
syncytium made up of large cells with vesicular hyperchromatic oval nuclei.
Tumor cells characteristically have indistinct cell margins.
high nuclear cytoplasmic ratios and the nuclei will be small
and less prominent than in the undifferentiated form of
the tumor. More differentiated tumors may show focal
keratinization.
Lymphocytes and plasma cells have a great affinity for NPC
and they will be seen in the stroma between tumor islands or
infiltrating tumor islands. The tumor’s lymphoid cells will
represent a mixture of T and B cells in which T cells and
polyclonal plasma cells predominate. Spindle cells, sometimes
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Figure 14.44 Positive in situ hybridization stain showing EBV (encoded for
early RNA (EBER) in a non-keratinizing NPC.
arranged in a fascicle-like pattern, are more common to dif-
ferentiated NPC than non-keratinizing undifferentiated forms
of the tumor.16
EBV, which is associated with non-keratinizing NPC in
nearly all cases, can be demonstrated by in situ hybridization
for EBV, encoded for early RNA (EBER) (Figure 14.44).
Immunohistochemical staining of non-keratinizing forms
of NPC will show strong staining for pancytokeratin, and high
molecular weight keratins (CK5/6). Epithelial membrane anti-
gen will be focal to absent, while low molecular weight keratins
such as CK7 and 20 will be negative or weak.
Differential diagnoses for the more common undifferenti-
ated NPC that affects pediatric age group patients can include
melanoma, RMS, lymphoma, ONB, EWS/PNET, SNUC and
primitive neuroectodermal tumors.
Immunohistochemical markers, including B cell markers
for lymphoma, HMB-45, melan-A and tyrosinase for mela-
noma and myogenic markers including desmin for RMS
should allow one to distinguish these tumors which can appear
similar on routine H & E staining from one another.17,18
Treatment and Prognosis
The treatment of choice for NPC is super voltage radiother-
apy.17 Surgery is reserved for radioresistant and recurrent
tumors. Direct tumor extension into the skull base, paranasal
sinuses, orbit and basal foramina is common. NPC will dem-
onstrate a high incidence of both hematogenous spread and
lymph node metastasis at presentation, particularly, to the
jugulo-digastric node and the posterior cervical chain. Chemo-
therapy is usually reserved for disseminated advanced stage
disease and is generally given in concert with radiation ther-
apy. If metastases develop, they usually occur within three
years of the initial presentation of the neoplasm.
Pathologists should be aware that the radiation changes
induced in fibroblasts can last for years in a NPC patient,
and thus such changes should not be over interpreted to
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 Chapter 14: Malignant Neoplasms of the Nasal Cavity, Paranasal Sinuses and Nasopharynx
Figure 14.45 Low power photomicrograph of papillary nasopharyngeal
adenocarcinoma demonstrating the tumors’ characteristic papillary nature.
represent spindled carcinoma, in those instances where there is
a re-biopsy or re-excision.
Pediatric NPC has a better prognosis than the adult form of
the disease. The overall five-year survival rate for patients in all
age groups ranges as high as 98 percent for stage I disease to as
low as 73 percent for stage IV disease.
Low Grade Papillary Nasopharyngeal
Adenocarcinoma (LGNPPA)
Glandular nasopharyngeal tumors have two sources of origin:
minor salivary glands and surface mucosal epithelium.
LGNPPAs arise from mucosal surface epithelium.1 These
tumors which are exceedingly rare in pediatric age patients2,3
have a median occurrence age of 37, and can arise from the roof,
lateral wall or posterior wall of the nasopharynx. Most patients
will present with obstructive nasal symptoms including nasal
fullness, blood tinged saliva and nasal discharge. Pediatric age
patients will have increased otitis media symptomatology.
References 4.
Introduction
1. Benoit M, Bhattacharya N, Faquin W,
Cunningham W. Cancer of the nasal
5.
cavity in the pediatric population.
Pediatr 2008; 121:e141–e145.
2. Yi JS, Cho GS, Shim MJ. Malignant
tumors of the sinonasal tract in the
pediatric population. Acta Otolaryngol
6.
2012; 132 Suppl (1):S21–S26.
Rhabdomyosarcoma
3. Benoit M, Bhattacharya N, Faquin W,
Cunningham W. Cancer of the nasal
cavity in the pediatric population.
Pediatr 2008; 121:e141–e145.
364
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https://doi.org/10.1017/9781316661949.015
Figure 14.46 Papillary glandular formation, lined by columnar cells with
bland, round to oval nuclei characterize this LGNPPA.
Pathologic Features
Histologically, LGNPPA will be composed of delicate papillary
fronds and back to back, often cribriform glandular forma-
tions that are neoplastic (Figure 14.45). Glandular spaces will
be lined by pseudostratified columnar or cuboidal epithelium
with large round to oval often overlapping nuclei with small
nucleoli (Figure 14.46). Psammoma bodies may be seen within
the fibrovascular tumor stroma.3
Immunohistochemical staining will demonstrate target
cells that will stain positively for CK7, CK19. Tumor cells will
stain negatively for thyroglobulin, CK5/6 or CK20,4 and
tumors will be EMA and TTF-1 positive. Mucicarmine stains
will be positive for intraluminal mucin.
Treatment and Prognosis
LGNPPA is an indolent, slow growing tumor that does not
metastasize. Complete surgical excision is accompanied by
cure and an excellent prognosis.
Fyrmpas G, Wurm J, Athanassiadou F,
et al. Management of pediatric
7. Lawrence W, Anderson JR, Gehan EA,
Maurer H. Pretreatment TNM staging
sinonasal rhabdomyosarcoma. of childhood rhabdomyosarcoma
J Laryngol Otol 2009; 123:990–996. study group. Cancer 1997; 80:
1165–1170.
Wurm J, Constantinidis J, Grabenbauer
G, Iro H. Rhabdomyosarcoma of the 8. Newton WA, Gehan EA, Webber BL,
nose and paranasal sinus: treatment et al. Classification of
results in 15 cases. Otolaryngol Head rhabdomyosarcoma and related
Neck Surg 2005; 133:42–50. sarcomas: pathologic aspects and
proposal for a new classification – an
Parham DM, Barr FG. Embryonal
intergroup rhabdomyosarcoma study.
rhabdomyosarcoma. In: Fletcher C,
Cancer 1995; 76:1073–1085.
Unni K, Mertens F, editors, WHO
Classification of Tumors. Pathology and 9. Parham DM, Webber B, Holt H, et al.
Genetics of Tumors of Soft Tissue and Immunohistochemical study of
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