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CH 41
CH 41
NEOPLASMS OF THE
NASOPHARYNX
Frank G. Ondrey, MD, PhD
Simon K. Wright, MD
NASOPHARYNGEAL CARCINOMA
Epidemiology
Nasopharyngeal carcinoma (NPC) is unique among squa-
mous cell carcinomas of the head and neck (SCCHN) in its
geographic epidemiologic profile. Although it is a rare tumor
in most parts of the world, in regions of southeastern Asia, its
incidence soars to 27.3 in 100,000. The highest incidence
occurs in Taiwan, where 98% of the population is Chinese,
90% of whom originate from the Guangdong province. There
is a decrease in incidence in northern China, falling to 3 in
100,000 in northern provinces. The Japanese, who trace their
origins to the Mongoloid region, have an incidence of just
1 in 100,000 for both men and women. In Europe and North
America, the incidence is 1 in 100,000. In China, the disease
rate rises after age 20 and falls after age 60; the mean age is
40 to 50 years. The male-to-female ratio is 3 to 1.
Dietary Associations
Because of the strikingly high incidence of NPC among the
“boat people” of southern China (54.7/100,000), specula-
tion about their unique environmental exposures led to the
examination of salted fish as a risk factor. Salted fish has
been shown to contain strong carcinogens and mutagens.
Animal studies support the association, demonstrating a
484
Neoplasms of the Nasopharynx 485
Serologic Studies
Elevated levels of IgA and IgG antibodies directed against
viral capsid antigen and early antigen in patients with NPC
have been documented by many studies. Immunoglobulin A
can be detected in 80 to 85% of patients with NPC. Response
to treatment yields a corresponding decrease in levels;
increasing titers are associated with progression of disease.
Anti-EBV nuclear antigen 1 IgA has also proven to be a sen-
sitive indicator of the presence of NPC.
Biomarkers
Vascular endothelial growth factor, a potent angiogenic
growth factor, has been shown to be elevated in patients with
metastatic NPC but not in patients with nonmetastatic NPC.
486 Otorhinolaryngology
Histology
The World Health Organization (WHO) has classified NPC
into three histopathologic groups. WHO type I is a keratiniz-
ing squamous cell carcinoma similar to others of the head
and neck. It exhibits abundant keratin formation with inter-
cellular bridges and various degrees of differentiation. It can
be subdivided into well-differentiated (G1), moderately dif-
ferentiated (G2), or poorly differentiated (G3) grades. WHO
type II is a nonkeratinizing form with greater pleomorphism,
scant keratin formation, and a variety of patterns. It exhibits
a pavemented or stratified pattern with clear cell margins.
WHO type III is an undifferentiated tumor, characterized by
greater heterogeneity of cell size, indistinct cell borders, and
prominent nucleoli. Types II and III both typically demon-
strate lymphocytic infiltration; these are endemic forms of
NPC and are classically associated with EBV. The clinical
implications of the differential types are considerable. In a
National Cancer Data Base study of 5,069 patients diagnosed
with NPC in the United States between 1985 and 1989, there
were substantial differences between 5-year survival of ker-
atinizing (37%) versus nonkeratinizing (65%) and undiffer-
entiated (64%) NPC.
Staging Systems
The epidemiologic idiosyncrasies of NPC are reflected in the
controversies surrounding the staging of this disease. All stag-
ing of NPC begins with a thorough physical examination
including endoscopy. Imaging studies, including computed
tomography (CT) and magnetic resonance imaging (MRI),
are performed to define soft tissue and bony extension. Ho
developed a staging system based on his extensive experi-
ence treating NPC in endemic areas of southeastern Asia. His
system divides all disease into three T categories that do not
account for nasopharyngeal subsite involvement. Ho’s stag-
ing system divides the neck into three zones, with increasing
Neoplasms of the Nasopharynx 487
Clincical Presentation
Poor access and confounding early symptoms account for the
high proportion of advanced disease at the time of diagnosis.
Generally, symptoms fall into one of four general areas of
complaint: aural, nasal, neck, and miscellaneous accounted
for by cranial nerve (CN) involvement, the most common
being CN VI. The classic presentation is a neck mass, partic-
ularly in the superior part of the posterior cervical triangle,
and conductive hearing loss, often with bloody drainage.
Nasopharyngeal carcinoma often arises from the lateral wall
of the nasopharynx, near the fossa of Rosenmüller, inducing
a serous otitis media as it enlarges and obstructs the
eustachian tube.
Nodal involvement is extremely common in NPC, occur-
ring in 75 to 90% of WHO type II and III histologies at the
time of diagnosis. In type III, nodal involvement is bilateral in
60% of cases. Distant dissemination is reported by most major
series to be between 5 and 11% at the time of presentation.
Diagnosis
The diagnosis of NPC begins with an accurate history and
complete physical examination, including endoscopic visu-
alization of the nasopharynx. This is followed by endoscopic
488 Otorhinolaryngology
Treatment
Radiotherapy
Historically, external beam radiotherapy (XRT) has been
the standard of treatment for locoregionally confined NPC.
In such patients, it is administered with the intent to cure.
The location of primary disease with respect to vital struc-
tures and the propensity toward bilateral lymphatic metas-
tasis pattern along with the inherent radiosensitivity of NPC
have made XRT the primary treatment modality. The entire
nasopharynx and bilateral retropharyngeal, jugulodigastric,
low neck, posterior chain, and supraclavicular lymph nodes
are included in the initial XRT target. At least 45 to 50 Gy
at 1.8 to 2.0 Gy per fraction (day) are delivered. The dose to
the primary tumor is usually boosted to 66 to 70 Gy based
on tumor stage. Because NPC is generally more radiosen-
sitive than other SCCHN, moderate-dose XRT followed by
neck dissection is not recommended. However, proven
residual disease after full-course XRT should be addressed
with neck dissection 6 to 8 weeks following completion of
XRT. The M. D. Anderson Cancer Center has reported sur-
vival on a consecutive series of 378 patients. Respective
actuarial survival rates at 5-, 10-, and 20-year follow-up
were 48%, 34%, and 18%. Local control rates with radiation
alone for T1, T2, T3, and T4 tumors are 85 to 95%, 80 to
90%, 60 to 75%, and 40 to 60% respectively.
Neoplasms of the Nasopharynx 489
JUVENILE NASOPHARYNGEAL
ANGIOFIBROMA
A clinical presentation of epistaxis and nasal obstruction in an
adolescent male patient classically represents a juvenile
nasopharyngeal angiofibroma (JNA) until proven otherwise.
This is a relatively rare sporadic neoplasm that represents
approximately 0.05% of all head and neck neoplasms.
Neoplasms of the Nasopharynx 493
Differential Diagnosis
The differential diagnosis of lesions within the nasopharynx in
the age group affected by JNA includes both benign and malig-
nant processes. Other benign conditions associated with nasal
obstruction include adenoid and turbinate hypertrophy, nasal
polyposis, antral choanal polyps, and nasopharyngeal cysts.
Other benign neoplasms of the nasopharynx include chordo-
mas, angiomatous polyps, teratomas (eg, dermoids), fibromas,
hemangiomas, gliomas, fibrous dysplasia, chondromas, and
rhabdomyomas. Soft tissue malignancies in the differential
diagnosis include rhabdomyosarcomas, NPCs, and lymphomas.
Clinical Presentation
The average and median ages for the presentation of JNA are
12.5 and 14 years, respectively. Early lesions will present
with epistaxis and nasal obstruction. Symptoms and signs
have predictive value for the anatomic extent of the disease.
494 Otorhinolaryngology
Diagnostic Workup
Once the clinical presentation suggests a possible differential
diagnosis, a radiologic workup is performed. The MRI is par-
ticularly helpful in identifying soft tissue characteristics of
the lesion that would increasingly suggest that it is a JNA as
opposed to another neoplasm. The lesion will demonstrate
contrast enhancement on CT scans and MRI, and any vascu-
lar flow voids within the lesion will be identified on MRI.
The usual, nearly uniform enhancement of this lesion radi-
ographically distinguishes it from other vascular entities such
as arteriovenous malformations. Additionally, other accom-
panying features of soft tissue, including reactive inflamma-
tion of the sinus or nasal mucosa or postobstructive sinusitis,
will be well delineated on MRI.
Because of the characteristic clinical presentation and radio-
graphic appearance, few clinicians would feel compelled to
obtain tumor biopsies as part of the workup. Clearly, a biopsy
of this lesion could lead to massive hemorrhage and is dis-
couraged. Lesions currently undergo preoperative emboliza-
tion with carotid angiography at many major centers. This
technique allows for a decrease in blood loss during surgery
by 60 to 80%. Typically, embolization agents are directed via
the external carotid circulation through the internal maxillary
artery, but significant blood supply can be derived directly
from the internal carotid artery and ethmoidal arteries.
Treatment
Surgery
Because JNAs can involve multiple anatomic sites at the skull
base, surgical treatment options can be applied on a stage-
Neoplasms of the Nasopharynx 495
Other Modalities
Juvenile nasopharyngeal angiofibromas are known to have
recurrence rates up to 25%, and extension of disease into
extranasopharyngeal sites correlates with increased rates of
recurrence. For these reasons, several investigators have con-
sidered additional modalities of treatment for extensive JNA.
Some institutions will employ radiation therapy as standard
care for intracranial disease extension. Typically, 30 to 40 Gy
are used in standard fractions to gain lesion control. Signi-
ficant further growth of tumor is not noted, but lesions do
not completely regress after treatment. Because these tumors
are associated with puberty in young males, considerable
effort has been expended in hormonal therapies as primary
or adjunctive treatment for these tumors. Hormonal thera-
pies for this lesion have included the use of diethylstilbestrol
and flutamide.