Nasopharyngeal carcinoma is a prevalent malignancy in Southeast Asia. External beam radiation therapy is the primary treatment, but recurrent disease remains challenging. Salvage nasopharyngectomy is used in some institutions for recurrent NPC after failed radiation. The nasopharynx has a complex anatomy near critical structures like the carotid artery. Staging involves imaging like CT and MRI to determine tumor extent and involvement of surrounding areas. Prognosis depends on staging, with 5-year survival rates from 24-95% depending on stage.

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Nasopharyngeal Carcinoma
Fuad Ridha Mahabot

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History of the Procedure
• external beam radiation therapy - primary mode of therapy for
previously untreated NPC
• recurrent or persistent disease remains a challenge to clinicians
• in some institutions, salvage nasopharyngectomy is used for the
treatment of recurrent disease
• 1998 - Fee and Tu published results of salvage nasopha-
ryngectomy in a series of patients with recurrent NPC that failed
previous treatment with radiation
 inspired other investigators to start using surgery in the treatment of
patients with recurrent NPC
 since then, various surgical approaches to the nasopharynx have been
proposed

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 these include the transpalatal-maxillary-cervical, maxillary
swing, transmandibular, transcervico-mandibulo-palatal, infratemporal
fossa, lateral temporal, and endoscopic approaches

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Anatomy of Nasopharynx
• 4cm high, 4cm wide and 3cm in
length
• anterior -choanal orifice and
posterior margin of nasal septum
• floor - upper surface of the soft
palate
• roof and posterior wall
 Body of the sphenoid,
Basiocciput
 First two cervical vertebrae
• lateral wall
 Eustachian Tube orifice
 Fossa of ROSSENMULLER

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Anatomical relation of FOR
• anteriorly
 eustachian tube and levator
palatini
• posteriorly
 pharyngeal wall mucosa
overlying pharyngobasilar
fascia & retropharyngeal space
• medially
 nasopharyngeal cavity
• superiorly
 foramen lacerum & floor of
carotid canal
• posterolateral
 carotid canal & petrous
apex, foramen ovale and
spinosum

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Histology
3 types of epithelium
• pseudostratified columnar ciliated epithelium - near the
choanae and the adjacent part of the roof of the nasopharynx
• transitional epithelium - roof and the lateral walls
• stratified squamous epithelium - along the posterior and
inferior portions of the nasopharynx

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Epidemiology & Frequency
Geographical and race
• is a prevalent malignancy in Southeast Asia
• southern China, Hong Kong, Singapore, Malaysia, and Taiwan -
10-53 cases per 100,000 persons per year
• eskimos in Alaska and Greenland and in Tunisians - 15-20 cases
per 100,000 persons per year
• relatively uncommon in Western countries (<1 case per 100,000
persons)
 however, prevalence rate for people of Asian descent in the United
States is 3.0-4.2 cases per 100,000 persons.

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Aetiology
Environmental factors
• geographical clustering in Southern China
• time trend - High risks among Chinese in Southern China
 incidence in Hong Kong, Singapore virtually remained unchanged 50 yrs
 2nd and 3rd generation born in USA shows decline
• NPC constitute 16% of all malignant tumors among the
chinese

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Smoking and Alcohol consumption
Occupational
• exposure to nickel, chromium
• radioactive metal
• inhalation of chemical fumes
Ingestions
• salted fish - Nitrosamine
• smoked food

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Drugs
• chinese herbal medicine
Cooking habits
• household smoke and fumes
Religious practice
• incense and joss stick smoke
Socioeconomic status
• nutritional deficiencies eg. Vitamin A & C

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Aetiological role of Epstein-Barr virus in
NPC
• more than 90% of patients having elevated antibody titres to
Epstein-Barr virus are those who have NPC of the
undifferentiated / poorly differentiated forms
• moderate to well differentiated NPC are devoid of Epstein-Barr
virus antigen
• thus the role of virus in NPC is still controversial

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Immunogenetics of NPC
prominent genetic susceptibility
 high risk among southern Chinese population
 differential high risk in emigrant Chinese compared to
indigenous population
 family clustering of NPC in Chinese
 elevated risk in people having genetic admixture with
Chinese
 low risk in other racial groups despite living in high-risk
countries eg. Indians in Malaysia / Singapore

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Classification
• WHO classes
 based on light microscopy findings
• 3 histological types
 type I – Keratinizing SCC
 type II – Nonkeratinizing Differentiated Carcinoma
 type III – Nonkeratinizing Undifferentiated Carcinoma
Type I
• 25 % of NPC
• moderate to well differentiated cells similar to other keratinizing SCC
(keratin, intercellular bridges)

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Type II
• 12 % of NPC
• variable differentiation of cells ( mature to anaplastic)
• minimal if any keratin production
• may resemble transitional cell carcinoma of the bladder
Type III
• 60 % of NPC, majority of NPC in young patients
• difficult to differentiate from lymphoma by light microscopy requiring
special stains & markers

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• Differences between type I and types II & III
 5 year survival
• Type I - 10%
• Types II, III - 50%
 Long-term risk of recurrence for types II & III
 Viral associations
• Type I - HPV
• Types II, III – EBV - full EBV genome present in all NPC epithelial cells

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Pathology
• Grossly the tumour presents in 3 forms
 Proliferative growth causing nasal obstruction
 Ulcerative causing epistaxis
 Infiltrative which causes cranial nerve involvement

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Clinical Features
• bimodal peak incidence - 30-40 years and 50-60 years
• male:female – 3:1
• early symptoms - nasal obstruction, blood-tinged sputum or
nasal discharge, tinnitus, headache, ear fullness, and unilateral
conductive hearing loss from serous otitis media or recurrent
acute otitis media
• advanced cases - cranial nerve involvement (III-VI), including
diplopia and numbness of the face

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• neck lump - 60%
• block sensation of ear - 41%
• hearing loss - 37%
• nasal bleeding - 30%
• nasal obstruction - 29%
• headache - 16%
• ear pain - 14%
• neck pain -13%
• weight loss 10%
• diplopia - 10%

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Cervical Lymphadenopathy (60%)
• tendency for early lymphatic spread
• commonest palpable node - jugulodiagastric, L2/L3/L5 level
• contralateral lymph nodes metastasis (nasopharynx is midline
structure)

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Aural Symptoms
• NPC leads to eustachian tube occlusion
 sensation of a blocked ear
 impaired hearing
 tinnitus
 serous otitis media
“Adult Chinese patients with unresolving unilateral serous otitis media
have to be presumed to have nasopharyngeal carcinoma until proven
otherwise”

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Epistaxis and Nasorespiratory Symptoms
• blood stained nasal discharge
• blood stained saliva on hawking
• profuse epistaxis
• nasal obstruction
• ozanea due to tumor necrosis

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Neurological Palsies
• Most frequently involved are:
 VI - Lateral rectus palsy - Diplopia & squint
 III, IV, VI - are commonly affected together (opthalmoplegia)
 V - High neck & pacial pain & paraesthesia
 IX, X & XI - Jugular Foramen Syndrome (involvement of the IX, X, and
XI CN)
• Isolated single C.N. palsy common with nerves V & VI
• Horner’s syndrome – due to involvement to cervical sympathetic chain
 ptosis, miosis, dilation lag, enophthalmos (the impression that the eye is
sunk in), anhydrosis (decreased sweating), loss of ciliospinal reflex and
blood shot conjunctiva

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Pain and Headache
• Hallmark of terminal disease
 Erosion of skull base (intracranial extension)
 Sepsis - sphenoidal sinusitis
• Trismus
 Inviltration of pterygoid muscles

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Diagnostic Evaluation
• Anterior Rhinoscopy Examination
 blood stain nasal discharged
 tumour extending into nasal cavity
• Post-Nasal Examination
 post nasal mirror - can assess NP space and tumour
 difficult to perform in sensitive patients
• Head and Neck Examination
 Lymph node
• Level 2/3/5
• Progressively enlarging, hard, fixed, painless swelling

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• Aural Examination
 Otoscopy
 Examination under microscope
• retracted tympanic membrane
• fluid in the middle ear
• Cranial Nerve Examination

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• Rigid Nasal Endoscope
 Inspection of the nasopharynx space
 Localisation and extent of tumour
 Biopsy under vision
• Shanmugaratnam et al - found that 26.4% of NPCs had features of
more than 1 histologic type
• Fee et al - encountered similar findings in 35% of recurrent NPC cases
• Diagnostic Nasal Endoscopy
 Flexible Nasal Endoscope
• Fine Needle Aspiration Cytology of the neck lymph node

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Imaging
• CT Scan
 Extent of tumor
 Neck node involvement
• Bone Scan
 Skeletal metastasis- thoracolumbar region

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• MRI – radiologic modality of choice
 to determine if any intracranial extension of the tumor involves the brain
parenchyma or the cavernous sinus
 intracranial spread can occur through foramen ovale, the foramen
spinosum, the foramen lacerum, the carotid canal, and the jugular
foramen that are in close proximity to the nasopharynx
 to detect any tumor extension into the retropharyngeal, parapharyngeal,
and pterygomaxillary spaces, as well as the infratemporal fossa and the
sinuses

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Seroepidemiologic Studies
• demonstrated that 80-90% of patients with WHO type 2 NPC
and WHO type 3 NPC have elevated levels of immunoglobulin A
(IgA) antibodies to viral capsid antigen (VCA) and early antigen
(EA)
• however, only 10-20% of patients with WHO type 1 NPC have
elevated levels of IgA antibodies to VCA
• elevated EBV titers may also be associated with other disease
entities, such as sinonasal undifferentiated carcinoma (SNUC),
sinonasal lymphoma, and tongue cancer

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Distant Metastasis
• Incidence rate is about 30%
• Sites commonly involved:
 skeletal - thoracolumbar spine > 50%
 lung metastasis
 liver metastasis
• 90% of patients die within the 1st year of diagnosis of the first
metastasis

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Staging of NPC - TNM Classification

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Treatment
• External Beam Radiotherapy
 primary mode of management of NPC
 at the primary site and in the neck
 mainly because of tumor's high degree of sensitivity to radiation as well
as the anatomical constraints for surgical access
 recent advances in imaging capabilities and improved radiotherapy
techniques have helped to improve the locoregional control rate
• Chemotherapy
 can be delivered before (neoadjuvant), during (concurrent), or following
(adjuvant) radiation therapy
 active chemotherapeutic - cisplatin, 5-fluorouracil (5-
FU), doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate, an
d vinca alkaloids

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 Chan et al - demonstrated that for patients with stage II and III NPC, the
5-year overall survival rate is better in patients treated with concurrent
chemoradiotherapy (70.3%) than for patients treated with radiation
alone (58.6%)
 also for distant metastases
 complications of radiotherapy
• brain - Pituitary dysfunction, brainstem encephalopathy, temporal
lobe necrosis, cranial nerve palsy
• ear - Sensorineural hearing loss, otitis media with
effusion, eustachian tube dysfunction
• eye - Dry eye syndrome, ischemic retinopathy
• thyroid - Hypothyroidism

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• gastrointestinal system - Severe
mucositis, xerostomia, nausea, vomiting, dysphagia, dehydration, eso
phageal stricture
• musculoskeletal system - Excessive fibrosis, trismus, radiation
myelitis, osteoradionecrosis, soft tissue necrosis, osteomyelitis
• vascular system - Stenosis of common carotid artery or internal
carotid artery

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• Surgery
 only for treatment of recurrent NPC with limited disease
 contraindicated in involvement of the cavernous sinus
 clear appreciation of the tumor in relation to the internal carotid artery is
essential
 approaches
• Fee - transpalatal, transmaxillary, and transcervical approach
– provides excellent exposure to both sides of the nasopharynx with
minimal morbidity to the patient
– minimal risk to the internal carotid artery and the cranial nerves

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• Fisch - infratemporal fossa approach; Gross and Panje - lateral
temporal approach
– both provide excellent exposure of tumors that extend into the
infratemporal fossa and the parapharyngeal space
– disadvantage - difficult if the tumor extends to the contralateral
nasopharynx
– morbidity - sensorineural hearing loss, CSF leak, unilateral laryngeal
paralysis, and facial nerve deficit
• Biller and Krespi - transcervico-mandibulo-palatal approach
– a wide-field exposure of the nasopharynx and excellent protection of
internal carotid artery
– Morton et al - 67% local control rate at 2 years with this approach

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Follow Up
• 1st year: once a month
• 2nd year: every 2nd month
• 3rd year: every 3 months
• 4th year: every 6 months
• >5years: Once a year

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Prognosis
• prognostic factors
extent of the primary tumor (ie, skull base invasion, cranial nerve
involvement, parapharyngeal infiltration)
level of the disease in the neck
histologic subtype
age and the sex of the patient
type and technique of radiotherapy
• 5-year overall survival (OS) rate (radiotherapy alone)
• 85-95% in stage I
• 70-80% in stage II
• 24-80% in stage III and IV

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• 5-year overall survival (OS) rate
60-80% in WHO type III NPC - high degree of radiosensitivity
20-40% in WHO type I NPC - low degree of radiosensitivity

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“ALWAYS a challenging problem, both
from diagnostic and therapeutic
standpoint, malignant lesions of the
nasopharynx are perhaps most
commonly misdiagnosed, most poorly
understood, and most pessimistically
regarded of all tumors of the upper part
of the respiratory tract”