CASE PRESENTATION

Identity
Name
Age
Occupation
Weight
Address

: Mr. X
: 65 years old
: Retired
: 50 kg
: Jl. Koperasi , Sukabumi

Chief complaint
:
cough since 1 year ago
Additional complaint : Bloody discharge from the left nostril, hearing loss, weight loss,
enlarged gland in the neck
History of present illness
Patient came to the hospital with a chief complaint cough since 1 year ago, he has been
treated but the cough is not resolved. He has a hearing loss gradually , and he forgot when
was the first time he has problems with his hearing. The patient complaint for the recently
slight bloody discharge from the left nostril 2 weeks ago. There is a mass in the left neck,
the mass was single, round, and painless. The patient complain of weight loss up to 10 kg
since 2 months ago. The patients were a heavy smoker.
The patient denied the presence of fever, ear pain, tinnitus, other palpable mass in the
body, difficulty swallowing, purulent discharge from the mouth, nose or ear, changes in
voice.
History of past illness
The patient has no history of high blood pressure, diabetes mellitus, coagulopathies,
mechanic or noise trauma, and infection of the nose, ear and throat before.
The patient never previously had similar complaint as now.
History of family illness
History of tumor (-)
History of hypertension (-), diabetes (-), allergy (-)
Physical Examination
Right ear

Left ear

: External ear : hyperemic (-), deformity(-), laceration (-), mass (-)

Mucuos membrane: hyperemic (-), edema (-), mass (-)
Secretion (-), laceration (-), cerumen (+)
Tymphanic membrane: intact, retracted (-), light reflex (+) normal
Rinne test (+), no lateralization, normal Schwabach test
: External ear : hyperemic (-), deformity(-), laceration (-), mass (-)
Mucuos membrane: hyperemic (-), edema (-), mass (-)

Secretion (-), laceration (-), cerumen (+)

Tymphanic membrane: intact, retracted (+), light reflex deviated (+)
Rinne test (-), Lateralization to the left ear, prolongedSchwabach test
Right nose

Left nose

Throat
Neck

: Mucous membrane : hyperemic (-), edema (-), secretion (-)

mass (-), laceration (-), crust (-)
Concha
: non-hypertrophy
Septum
: no deviation
Air passage
: normal
: Mucous membrane : hyperemic (+), edema (+), secretion (+)
mass (-), laceration (-), crust (-), blood (+)
Concha
: non-hypertrophy
Septum
: no deviation
Air passage
: normal
: Uvula in the middle
Pharynx
: normal pharyngeal arch,hyperemic (-)
Tonsils
: T1 / T1, hyperemic (-)
: Lymphadenopathycervical lymph node (+) with diameter 5cm, hard

consistency, immobile, pain (-), redness (-), lesion (-)

Summary
Mr.X, men 65 years old, came with a chief complaint cough since 1 year ago. He has a hearing
loss gradually. The patient complaint for the recently slight bloody discharge from the left nostril
2 weeks ago. There is a mass in the left neck and the patient complain of weight loss up to 10 kg
since 2 months ago. The patients were a heavy smoker. According physical examination, in the
left ear, there is retraction and light reflex deviated in the tympanic membrane. Rinne test ear (-),
Lateralization to the left ear, and prolonged Schwabach test. In the left nose there is a blood
cloth. And in the neck, there is lymphadenopathy cervical lymph node (+) with diameter 5cm,
hard consistency, immobile, painless and no redness.
Working diagnosis
Suspect of nasopharynx tumor
Differential diagnosis
- Lymphoma
Workup
- Complete blood count
- EBV titer
- Rhinoscopy posterior or nasoendoscopy with biopsy

CT-scan with bone window and MRI if possible

Therapy
- If positive Nasopharungeal carcinoma use radiotherapy and/or chemotherapy

NASOPHARYNGEAL CARCINOMA
Epidemiology
NPC is a relatively rare disease in the west, but is endemic in the Far East. The highest incidence
reported is from the Guangdong Province of Southern China, where it is the third most common
malignancy among men, with an incidence rate of between 15 to 50 per 100,000. High
incidences are also seen among Hong Kong and Singapore Chinese, with intermediate incidences
in Alaskan Eskimos and in the Mediterranean basin. Emigration from high to low incidence areas
such as the United States and Canada reduces the incidence of NPC in first-generation Chinese
but still remains at seven times the rate in whites. The incidence in most other countries is low,
with an age-adjusted incidence rate of less than 1 per 100,000.
The geographic distribution of the disease suggests a multifactorial pathogenesis, resulting from
a unique interaction between genetic susceptibility, environmental factors, and migration
patterns. Chromosomal abnormalities in chromosomes 1, 2, 3, 4, 5, 6, 9, 11, 13, 14, 16, 17, 22,
and the x chromosome have been implicated in its pathogenesis. Chan recently published a
hypothesis for the development of NPC. Early dysplastic changes are associated with allelic
losses on the short arms of chromosomes 3 and 9, resulting in the inactivation of tumor
suppressor genes p14, p15, and p16. Latent infection by the Ebstein-Barr virus (EBV) is crucial

in the progression to severe dysplasia, and gains on chromosome 12 and allelic losses on 11q,
13q, and 16q lead eventually to invasive carcinoma. Mutations in p53 and aberrant expression of
cadherins propagate the further development of metastases. Specific haplotypes in the human
lymphocyte antigen (HLA), located on the short arm of chromosome 6, have also been found to
increase the risk of NPC. Dietary factors have focussed mainly on preserved foods, and salted
fish, in particular, has been found to have a strong relation to the development of NPC. [106] There
is also an increased risk with diets deficient in fresh fruits, carotene, or fiber intake; vegetables
do not provide protection against NPC.

Pathology
Although the nasopharyngeal mucosa consists of a variety of surface epithelium and soft tissue
components that include respiratory-type pseudostratified columnar and transitional epithelium,
lymphoid stroma, and mucous glands, squamous epithelium predominates in adult life. NPC is
by far the most common epithelial malignancy arising from the nasopharynx.
Three histopathologic types are described in the World Health Organization (WHO)
classification. Type I consists of keratinizing squamous cell carcinoma, having features of
squamous differentiation that include intercellular bridges and abundant keratin production. They
may be further graded as well, moderately or poorly differentiated. Although the type I variety
may account for 20% to 30% of cases seen in North America, true well-differentiated squamous
cell carcinoma is rare in the Asian context, accounting for 1% to 3% of all NPC.
WHO type II consists of nonkeratinizing carcinoma and essentially encompasses all tumors that
do not fall into either the type I or type III categories. Type III consists of undifferentiated
carcinoma, historically termed lymphoepithelioma because of an intimate admixture of
undifferentiated epithelial and lymphoid cells. Types II and III exhibit a wider degree of cellular
pleomorphism than the keratinizing variety and include microscopic patterns of spindle,
transitional, clear and anaplastic cells, lymphoepitheliomas, or a combination of these. The
commonalties in these ultrastructural features make it difficult to make clear-cut histologic
distinctions and their similar clinical behavior had led to the suggestion that these two entities

should be considered as a single entity, undifferentiated cancer of the nasopharyngeal type

(UCNT). Indeed, an increasing body of evidence supports this distinction of squamous and
nonsquamous carcinoma of the nasopharynx both in their clinical behavior and prognosis. WHO
types II and III are typically more radiosensitive and exhibit better local control rates than
keratinizing squamous cell carcinoma but have also been shown to have higher rates of distant
metastases.

Gambar 1 . NPC tipe I

Gambar 2. NPC tipe II

Gambar 3. NPC

tipe III

Clinical Presentation
NPC affects a relatively younger group of patients than the garden-variety squamous cell cancer
of the head and neck. The incidence begins to rise in the second decade of life, and peaks in the
forth and fifth decades of life. The male/female ratio is approximately 3:1.
Early symptoms and signs are subtle and variable and often are neglected by both patient and
physician. Cervical lymphadenopathy is the most common presentation and can be seen in
between 50% and 90% of patients. A rich lymphatic plexus drains the nasopharynx, and up to a
third of these patients may have bilateral cervical involvement. Involvement of the upper jugular
and jugulodigastric nodes occur first, and spread occurs in a fairly organized fashion to the lower
neck and supraclavicular nodes. This pattern of spread has been shown to be of prognostic
significance. Lymphatic spread to the first echelon nodes, the retropharyngeal nodes of Rouviere,

may only, however, be detected radiologically. In areas where NPC is endemic, it is important to
exclude NPC in any young patient who has asymptomatic cervical lymphadenopathy.
Nasal symptoms are seen in half of presenting patients and usually consist of blood-stained nasal
discharge and unilateral nasal obstruction. Aural symptoms most commonly consist of unilateral
hearing loss, although tinnitus and otalgia may occasionally be present. Hearing loss is due to
tumor producing a physiologic and/or an anatomic obstruction of the eustachian tube, causing a
serous otitis media. NPC should always be considered in high incidence regions in patients with
unilateral serous otitis media.
Neurologic symptoms, usually in the form of cranial nerve paralysis and occasionally headaches,
are seen in a fifth of patients. Unimpeded superior extension of tumor through the foramen
lacerum to the cavernous sinus results in multiple cranial nerve involvement. Cranial nerve VI is
the most commonly involved, resulting in diplopia, followed by cranial nerve V, which results in
facial or high neck pain or paresthesia. Eye signs may further be complicated by involvement of
cranial nerves III and IV. Tumor eroding into the jugular foramen and hypoglossal canal results
in any combination of cranial nerve IX, X, XI, and XII nerve paralysis, resulting in the jugular
foramen syndrome (IX, X, XI) or the Collet-Sicard syndrome (IX, X, XI, XII).
Approximately 5% of all patients have systemic metastases, most commonly to the bone
(thoracolumbar vertebrae, pelvis, and femoral heads) followed by the lungs and liver.

Diagnostic Evaluation
Clinical Evaluation
A detailed history and clinical examination should be taken, and although symptoms may be
trivial, a high index of suspicion must be present in evaluating patients within the geographic
endemic areas of the disease. A thorough visualization and examination of the nasopharynx is
also required, either with a rigid (0-, 30-, or 70-degree Hopkins rod) or flexible endoscope. Rigid
endoscopes provide excellent visualization but have limited maneuverability within the confines
of the nasopharynx or when anatomic variations in the nasal cavity preclude the introduction of a
rigid instrument. Flexible fiberoptic nasopharyngeal endoscopes are relatively atraumatic and
provide greater maneuverability at the expense of a slightly inferior image. Biopsy is required for
definite diagnosis and can be done through the biopsy channel of a flexible scope if one is
present or with a separate biopsy forceps like a Takahashi or Halyard cup forceps. The most
common sites of origin are the fossa of Rosenmller and the nasopharyngeal roof, keeping in
mind that in up to 10% of patients the disease may be entirely submucosal. Biopsy of the
nasopharynx is usually performed in the outpatient setting under local anesthesia. Transnasal
biopsies may be endoscopically directed, performed through indirect nasopharyngoscopy or
blind. If performed with separate instruments, the forceps and endoscope may be placed through
the same or through different nostrils. It may sometimes be necessary to take biopsies with the
patient under general anesthesia, either in patients with suspected recurrent submucosal disease
that may require deep biopsies or in patients with a strong suspicion of disease with repeated
negative biopsies. Nasopharyngeal curettage may also be performed at the time as a last resort.
Biopsy is sometimes necessary from a cervical node for diagnosis. Fine-needle aspiration
cytology (FNAC) is the safest and most expeditious method for tissue diagnosis. [8] Open
biopsies, either in the form of an incisional or excisional biopsy, should be avoided, because
there is evidence to suggest that it may adversely affect survival.

Serology

Latent EBV infection seems to be crucial in the pathogenesis of NPC. EBV infection is prevalent
and occurs in early life, especially during weaning. Once infected, the virus remains latent in
epithelial cells and B lymphocytes and in NPC expresses one of six possible nuclear proteins,
EBNA 1 to 6 and three membrane proteins LMP-1, LMP 2A, and 2B. [9] Latent to replicative
infection is triggered by BamH1 Z EBV replication activator (ZEBRA) protein, resulting in
extensive transcription of the viral genome and expression of the early (EA, nonstructural) and
late (VCA, structural) antigens. High antibody titers to these EBV antigens serve an important
function as diagnostic markers. An elevated IgA anti-VCA titer is highly sensitive (sensitivity
95%, specificity 80%95%), and an elevated IgA anti-EA is highly specific (specificity >95%,
sensitivity 80%). Both tests collectively provide a useful index for detecting early occult disease
or in raising the degree of suspicion of an abnormal clinical examination or radiologic finding. It
is interesting to note that although WHO types II and III exhibit between 82% to 100% positivity
with respect to the antibody titers, WHO type I showed only a 38% and 19% positivity to IgA
EA and VCA, respectively. EBV titers may be useful in posttreatment surveillance.[66]
EBV DNA titers, on the other hand, seem to be an important index for prognostication. Lo, in a
series of publications, found that EBV DNA titers correlate with stage, treatment response,
relapse, and survival. Lin also found a correlation of EBV DNA titers with overall, metastasisfree, and progression-free survival.
Radiology
MRI with gadolinium and fat suppression is the diagnostic imaging modality of choice in that it
provides multiplanar views, excellent delineation of soft tissue and fascial planes, and better
tissue specificity. Coronal views are helpful in determining tumor spread through the
petroclinoid fissure or foramen lacerum to the cavernous sinus, as well as through the foramen
ovale, rotundum, or spinosum. Axial views display extension into the retropharyngeal,
paranasopharyngeal, and pterygomaxillary space and into the infratemporal fossa. CT, however,
provides better definition of bone involvement, especially skull base erosion, and may be more
accurate in assessing cervical lymphadenopathy, especially in the presence of extracapsular
spread Indeed, both imaging modalities are complementary and may be required collectively to
obtain maximal information about the extent of disease. Imaging also provides important

information about the state of the retropharyngeal nodes of Rouvire, which are a common site
of drainage but are not evaluable by clinical examination.
When tumor extends beyond the confines of the nasopharynx, NPC can spread along several
defined ways. Lateral spread is the most common, through the pharyngobasilar fascia, resulting
in lateral displacement or effacement of the fat-filled parapharyngeal space. Anterolateral
extension leads to the pterygoids, the muscles of mastication and causes trismus. Posterolateral
spread into the carotid sheath or jugular foramen results in cranial nerve IX, X, XI, and XII
palsies.
Anterior extension is to the nasal fossa and through the sphenopalatine foramen into the
pterygopalatine fossa (PPF). The PPF may also be involved by direct invasion of the pterygoid
process or through the masticator space. The earliest sign of PPF involvement is the obliteration
of normal fat content. The maxillary nerve may then be involved and lead to spread to the
cavernous sinus through the foramen rotundum.
Superior spread results in skull base or sphenoid sinus erosion, with or without intracranial
extension. Superolateral extension involves the petrous apex and foramen lacerum, from which
the tumor may gain the cavernous sinus and cause cranial nerve III, IV, V, and VI cranial nerve
palsies.
Positron emission tomography scans are becoming an essential diagnostic tool in the
management of residual or recurrent disease. A study on its usefulness compared with CT in 36
patients evaluated for posttreatment disease reported a 100% sensitivity, 96% specificity, and
97% accuracy in diagnosis.
Staging
There exists to date no universally accepted staging classification for NPC. The classification
proposed by John Ho has been widely used in Asia since his classic publication in 1978. Ho's
system is composed of three T- and N-stages individually and five overall stages, I to V, instead
of the usual practice of four. Despite this departure from international staging systems, there are
several strengths to Ho's classification. Ho recognized that the limits of the primary tumor within

the nasopharynx were not easy to define, especially with the possibility of submucosal extension,
and, therefore, defined all tumors within the nasopharynx as T 1 regardless of subsite. Ho's T
stage takes into consideration lateral spread into the parapharyngeal space, a factor of
considerable prognostic implication. In addition, Ho's staging of the neck was into upper, middle,
and lower neck disease, which has since been shown to correlate well with prognosis, with lower
neck involvement portending a poorer prognosis. Ho's classification has withstood the test of
time and has been prognostically validated.
The UICC/AJCC staging classification is more widely used in the United States and the West
and since 1992 has been incorporated into one. The staging systems before 1992 distinguished T1
from T2 disease by the number of subsites involved within the nasopharynx. As mentioned,
clearly defining tumor extent within the nasopharynx is not always exact, and it has been shown
that this designation into T1 and T2 has no correlation with survival. T classification did not take
into account parapharyngeal spread, and N staging was more traditionally based on other staging
systems that took into account nodal size and the number of nodes involved rather than node
levels. In 1997, a new UICC/AJCC classification was formulated that took into account these
and other significant prognostic variables. The current system has been validated in both the
Asian and Western context.

Management
Primary Disease
Radiation
The management of NPC is unique for two reasons. The first is that the tumor is in a relatively
inaccessible location, especially if the tumor has extended beyond the confines of the
nasopharynx. The second is that these tumors are particularly radiosensitive. For these reasons,
radiotherapy has been the cornerstone of the definitive treatment for NPC for close to half a
century.

Effective radiotherapy requires careful simulation and treatment planning. All patients must be
referred for dental clearance before instituting therapy to reduce the development of xerostomiarelated osteomyelitis and osteoradionecrosis and continue with meticulous dental care and
flouride prophylaxis.
Radical radiotherapy may be delivered several ways. External beam radiotherapy is most
commonly delivered by opposed lateral fields to encompass the primary tumor and upper neck. A
third anterior matched field may be used to irradiate the lower cervical and supraclavicular neck
nodes with protection of midline structures such as the spinal cord and larynx. Conventional
delivery is from a linear accelerator and consists of tumoricidal radiation doses of 70 to 76 Gy in
fractions of 1.8 to 2.0 Gy per day to the primary and anatomic structures at risk within the
vicinity of the nasopharynx. Radiation boosts in the form of intracavitary brachytherapy for T 1 to
T2 lesions have been used to improve local control rates. Stereotactic radiosurgery boosts may
also be given for T3 and T4 lesions. Le reports a 100% local control rate in 45 patients with T 3
and T4 primary tumors treated with a stereotactic boost at a median of 4 years follow-up.Because
there is a high incidence of subclinical neck disease, radiation doses between 50 and 60 Gy are
used to electively treat the neck. The shrinking field technique is used to provide a range of doses
to various regions, reducing the portals in subsequent deliveries to attain tumoricidal doses
eventually only to the primary tumor and involved neck nodes.
Advances in radiation technology have resulted in the advent of three-dimensional conformal
(3DCRT) and IMRT, which have replaced conventional two-dimensional techniques as the
standard of care since the early 1990s. With better delineation of gross tumor volume (GTV) by
coregistration of images from CT and MRI scans, 3DCRT and IMRT can result in a much lower
incidence of "geographic misses" at the same time providing better sparing of vital structures in
the vicinity. The clinical target volume (CTV) includes all adjacent structures at risk of
subclinical disease, and the planning target volume (PTV) should ideally include a further safety
margin that takes into consideration systematic errors and day-to-day positional variability.
Overall survival with the use of conventional radiotherapy alone in the treatment of NPC is in the
range of 50% to 76%. The use of 3DCRT has improved both tumor coverage and dose delivery
but has not improved local control or long-term complications. The data for IMRT seem more

convincing in terms of improvement in tumor coverage, dose delivery, locoregional control, and
tissue sparing.
In addition to improved planning and delivery techniques, altered fractionation to shorten the
treatment time (acceleration) or increase total dosage (hyperfractionation) has been used to
improve local control. Although of proven efficacy in squamous cell head and neck cancers in
other sites,[26] a phase III trial comparing conventional radiotherapy to an aggressive course of
accelerated hyperfractionated radiotherapy had to be terminated early because of excessive
neurologic complications, without improvement in local control rates. Accelerated fractionation,
however, seems to be efficacious in local control. Lee, in a recent retrospective analysis of more
than 300 patients, reported on improved local control rates with the use of six fractions per week
instead of the usual five, without a significant increase in toxicity. Accelerated fractionation with
small fraction sizes is currently being studied in a phase III randomized trial of patients with
locally advanced disease.
Chemotherapy
Because the results of radiation alone in stages I and II are excellent, radiation continues to be
the mainstay of treatment for early stage NPC. For locally advanced disease (stage III and IV),
however, despite good initial response, local recurrence and subsequent systemic failure are
significant problems. Single and combination chemotherapy have been used as an adjunct to
radiation in an attempt to achieve better local and systemic control. Combination chemotherapy
produces better responses, and combination cisplatin/5-flurouracil is the most widely used and
studied. Nonrandomized studies that used induction, adjuvant, concomitant, or combinations of
these chemotherapy delivery methods have shown an improvement in survival ( Table 73-3 ). To
date, 10 phase III randomized trials have compared radiation therapy alone with radiation and
chemotherapy. The method of delivery differed significantly between the various studies, and
two did not use the cisplatin-5FU combination. Only two studies achieved a significant
difference in 5-year progression-free and overall survival. The Head and Neck Intergroup Study
reported by Al-Sarraf, which used a combination of concurrent chemoradiation followed by
adjuvant chemotherapy, achieved a significant difference in 5-year overall and progression-free
survival ( Table 73-4 ). The results of the radiation only arm, however, are sufficiently poor to

question the validity of the study. More recently, however, Jin in a study of 284 patients
receiving concurrent chemotherapy consisting of cisplatin-5FU administered during weeks 1 and
5 of radiation therapy also reported a significant improvement in progression-free and overall
survival. This study is the first to demonstrate a significant benefit of concurrent chemoradiation
in the Asian population. An improvement in regional and distant control rates was also seen,
although the difference did not reach statistical significance. A meta-analysis of more than 1500
patients from six of the randomized trials comparing combination chemotherapy with radiation
alone found that progression-free survival and overall survival increased by 34% and 21%,
respectively at 4 years for the chemotherapy arm. Since publishing the results of the Intergroup
Study, Al-Sarraf has reversed the sequence of chemotherapy delivery to neoadjuvant
chemotherapy followed by concomitant chemoradiation, and reports, from unpublished data, a
90% overall survival. The results of concomitant chemoradiation seem promising but need to be
further validated. Two ongoing phase III trials, NPC 9901 and 9902 studying further the benefits
of chemotherapy, will hopeful shed new light on its efficacy in the management of locally
advanced NPC.

Table 73-3

-- SURVIVAL IN NONRANDOMIZED STUDIES OF THE USE OF

CHEMOTHERAPY IN THE TREATMENT OF NASOPHARYNGEAL CANCER

Therapy

No. of Series

Range

% Survival (Ave)

RT only

18

2662

45

CT + RT

10

3578

62

RT + CT

5077

66

CT/RT + CT

7080

77

CT + CT/RT

8394

88

From Al-Sarraf M: Cancer Control 9:387, 2002.

Recurrent Disease

Radiotherapy
Locoregional recurrences without distant metastases are treated with radical external beam
radiation, brachytherapy, or by surgical resection. If detected early, they are potentially curable
and therefore should be treated aggressively. Because recurrent tumors are likely to be more
radioresistant, doses exceeding 60 Gy may be required for tumor eradication. Five-year local
control rates approach 50% to 60%, and survival ranges from 16% to 45% ( Table 73-5 ). Small
recurrences <5 cm in diameter may be treated with interstitial brachytherapy with gold grain
(138Au) implants. The implants may be inserted under endoscopic guidance or under direct vision
by use of a split palatal approach. Despite significant sparing of vital structures in the vicinity by
the inverse square law, morbidity in the form of headache, nasopharyngeal radiation necrosis,
skull base necrosis, and palatal fistula are not uncommon. The use of chemotherapy in both
locally recurrent and systemic disease is on a protocol basis and has not been validated by a
prospective randomized study.
Surgery
The role of surgery in NPC is largely confined to the treatment of residual or recurrent disease
either in the nasopharynx or in the neck. Neck dissection for postradiation residual or recurrent
nodal disease is the most common indication for surgery, although it should be mentioned that
unlike other squamous cell cancers of the head and neck, large bulky neck disease of up to 8 cm
can be effectively controlled with radiation. The extent and level of nodal dissection is often
more extensive than suspected and is complicated further by posttreatment changes and fibrosis.
A classical radical neck dissection is often required, consisting of a comprehensive clearance of
all neck levels, including sacrifice of cranial nerve XI, the internal jugular vein, and the
sternocleidomastoid. If the skin of the lateral neck is involved by recurrent disease, it should be
incorporated in the neck dissection specimen. The defect should then be closed by nonirradiated
healthy tissue, usually in the form of a pedicled local myocutaneous flap like a pectoralis major
flap.
There are a variety of approaches to the nasopharynx. Because surgery is very much
intracavitary, important considerations are tumor extent, access for exposure, and control of the

internal carotid artery. The transpalatal, transmaxillary, and transcervical approaches are
preferred, because they provide the most accessible routes. The transpalatal approach involves a
U-shaped incision along the mucosa of the hard palate approximately 5 mm from the maxillary
dentition. This may be extended around the maxillary tuberosity into the gingival buccal sulcus if
access to the pterygopalatine fossa is necessary. Mucoperiosteal flaps are raised based on the
greater palatine neurovascular pedicle, and bone is removed from the palatine bone and posterior
hard palate ( Figure 73-5 ). Division or resection of the soft palate may also be required for better
exposure. The transmaxillary approach to the pterygopalatine space is gained by way of the
posterior maxillary sinus wall. Ligation of the internal maxillary artery then permits entry into
this space. The transcervical approach identifies cranial nerve IX and lateralizes the internal
carotid artery to access the parapharyngeal space. Lateralization of the internal carotid
necessarily protects cranial nerves X, XI, and XII also. Resection then proceeds cranially through
the oral cavity. A Le Fort I osteotomy by means of a mid-face degloving procedure has also been
described.
The lateral infratemporal approach advocated by Fisch provides excellent exposure for tumors
extending into the infratemporal fossa and parapharyngeal space but at the expense of limited
access to the contralateral nasopharynx. It requires transecting the auditory canal and zygoma, a
radical mastoidectomy rerouting cranial nerve VII and displacing the internal carotid artery.
An anterolateral approach by means of a "maxillary swing" has also been proposed, by Wei that
involves detaching the maxilla from its bony buttresses inferior to the orbit and swinging the
entire osteocutaneous complex laterally based on the cheek flap.[101] This provides wide exposure
of the nasopharynx, paranasopharyngeal space, and the internal carotid artery below the skull
base.
Five-year local control rates range from 43% to 67%. For early disease (rT1), the Stanford
experience is of 67% survival at 5 years. Surgery, therefore, offers reasonable control and
survival in carefully selected patients with residual or recurrent disease.
Complication
Late toxicity of radiotherapy may include xerostomia, hypothyroidism, fibrosis of the neck
with complete loss of range of motion, trismus, dental abnormalities, and hypoplasia of

irradiated muscular and bony structures. Because of the high doses of radiotherapy used in

this disease, these late toxicities can be significant, especially in younger children.
Endocrinopathies and growth retardation can occur secondary to radiotherapy to the pituitary

gland. Panhypopituitarism can occur in some instances.

Sensorineural hearing loss may occur with the use of cisplatin and radiotherapy.
Renal toxicity can occur in patients receiving cisplatin.
Caries and poor dental hygiene are associated complications. Osteonecrosis of the mandible is

a rare complication of radiotherapy and is often avoided with proper dental care.
Second malignancy may occur in a child who has received previous radiotherapy. This risk is

small but continues throughout life.

With proper radiotherapy techniques, the chance for development of radiation myelitis should
be less than 1%.

Prognosis
The results of clinical trials that include both radiation therapy and chemotherapy generally

report long-term survival rates of 50-80% overall.

In a study by Serin et al, the 5-year overall survival rate was 42% with radiotherapy alone and

58% with chemoradiation.

Rodriguez-Galindo et al reported a 4-year event-free and overall survival rate of 77% and
75%, respectively, in a Phase II Pediatric Oncology Group clinical trial using radiation alone
for patients with T1-T2N0M0 disease and radiation with neoadjuvant chemotherapy for all
others. Most were treated with 4 cycles of chemotherapy consisting of methotrexate, cisplatin,
5-fluorouracil, and leucovorin prior to radiotherapy.