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Nasopharyngeal carcinoma



Dr. T. Balasubramanian M.S. D.L.O.

Synonyms: NPC, Guangdong tumor

Introduction: This is the most common malignancy involving the nasopharynx. It is common among chinese population. In fact it is so common that it is considered to be endemic disorder in southern china. It is closely associated with Epstein Barr virus infections. Histologically undifferentiated / non keratinizing carcinoma types are common.

Anatomy of nasopharynx: Nasopharynx is at the junction of oropharynx and nasal cavity. It is lined by pseudostratified squamous epithelium. It is open inferiorly. It walls are rigid and bony.

Boundaries of nasopharynx:

. Anterior: Posterior choanae and posterior part of nasal septum

. Floor: Soft palate and part of hard palate

. Roof: It is sloping antero posteriorly. It is formed by basi sphenoid and basi occiput. C1 and C2 vertebrae also contribute.

. Posterior: It communicates with oropharynx. This area is guarded by a ring known as passavant's ridge.

. Lateral: The pharyngeal end of eustachean tube is seen here. Around the pharyngeal end of eustachean tube there is a pad of fat present. This pad of fat is known as Ostman's pad of fat. In malnourished children this pad of fat is lost causing patulous eustachean tube. Fossa of Rosenmuller is seen above and behind the pharyngeal end of eustachean tube. It is about 1.5 cms deep. Its apex is in close relation ship with the carotid canal, and its base is closely related to skull base. Foramen lacerum lies medially. Nasopharyngeal carcinoma commonly arises from fossa of Rosenmuller.


1. Highest incidence of nasopharyngeal carcinoma has been reported in southern china. This region accounts for 20% of world's reported cases of nasopharyngeal carcinoma. The incidence rates in India is about 1 per 1 lakh population

2. This disease is three times more common in men than in women.

3. This tumor occurs at a much younger age than other cancers

4. Age wise bimodal distribution is also common. This distribution suggests the influence of different aetiological factors or variations in the host response. In this type of age distribution two peaks are noted, i.e. 1. between ages 15 - 20, 2. the second peak during the 4th and 5th decades. This type of distribution is common in India.


Graph showing bimodal age distribution


1. Epstein - Barr virus: E.B. virus infections have been postulated to be the etiological agent responsible for nasopharyngeal carcinoma. The presence of raised antibody titers, and demonstration of viral genome in tumor cells are ample proof.

2. Exposure to chemical agents i.e. tobacco, drugs, and plant products.

3. Dietary factors: Ingestion of salted fish, preserved vegetables, fermented food stuff containing Nitrosamines and nitro precursors.

4. Cooking habits: Household smoke and fumes

5. Religious practices: like incense and joss stick smoke

6. Occupation: Exposure to industrial fumes / chemicals, metal smelting, Formaldehyde, wood dust

7. Other causes: Socioeconomic status, Nutritional deficiencies, weaning habits

8. Genetic susceptibility: Many HLA haplotypes have been associated with increased incidence of nasopharyngeal carcinoma. The loci involved are the HLA-A, B and DR locus situated on the short arm of chromosome 6.

Immunology in nasopharyngeal carcinoma:

Cell mediated immunity: is impaired in patients with nasopharyngeal carcinoma. This can be demonstrated by Mantoux test (in vivo), and Phytohaemagglutinin response of lymphocytes (in vitro). It is possible that this defective specific cell mediated immunity to EB virus allows the virus to be reactivated in the salivary glands. Increased EB virus loads causes increased anti EB virus IgA antibodies.

Association of EB virus with nasopharyngeal carcinoma: EB virus belongs to herpes family. It is lymphotrophic in nature. Its action is restricted to B lymphocytes. EB virus was found in abundance in the lymphoepithelium of the nasopharynx. Primary infection of this virus takes place in childhood and is always accompanied by seroconversion. EB virus is present in dormant state in small numbers of circulating B cells or in saliva. This virus may be reactivated during immunocompromised states.

The association of EB virus with nasopharyngeal carcinoma is supported by:

1. Demonstrable humoral immune response in patients with NPC against EB virus determined antigens (VCA viral capsid antigens, Early antigen EA, and nuclear antigen EBNA).

2. Presence of EB viral markers like EB viral DNA and Nuclear antigen in the tumor cells of nasopharyngeal carcinoma tumor cells.

Serologic markers of Nasopharyngeal carcinoma:

Markers assocaited with nasopharyngeal carcinoma include:

a. IgA and IgG to viral capsid antigen

b. IgA and IgG to early antigen

c. Antibody to nuclear antigen

d. Antibody dependent cellular cytotoxicity antibodies

Immunoglobulin IgA / VCA, IgG / VCA, and IgA / EA, IgG / EA are useful diagnostic markers of nasopharyngeal carcinoma. Their titers are related to the tumor load and advancing stage of the disease in untreated patients.

Normal values of these titres are:

Anti EB virus VCA / IgG = up to 1 : 160

Anti EB virus EA / IgG = up to 1 : 160

Anti EBV VCA / IgA = below 1 : 5

Anti EBV EA / IgA = below 1: 5

The titres of IgA / VCA and IgA / EA are useful clinical indices for follow up of patients after treatment. Titres may decline to a low level or remain static after successful treatment. The period between detection of raised IgA / VCA and clinical onset of stage I nasopharyngeal carcinoma ranged from 8 - 30 months.

Prognostic serological markers:

1. Prognosis and survival are inversely proportional to the geometrical mean titres of VCA and EA antibodies.

2. Good prognosis is indicated by high antigen dependent cellular cytotoxicity antibodies

Clinical presentation:

The marked invasive and metastatic properties are responsible for its symptomatology. The tumor arising from nasopharynx may spread in the following directions:

1. Anteriorly to nasal cavity, paranasal sinuses, pterygopalatine fossa and orbital apex.

2. Posteriorly to the retropharyngeal space and node of Rouviere, destruction of lateral mass of atlas

3. Laterally into the parapharyngeal space

a. Prestyloid compartment with involvement of mandibular nerve, pterygoid muscles and infiltration of deep lobe of parotid gland.

b. Post styloid compartment causing vascular compression of carotid sheath, invasion of last four cranial nerves and cervical sympathetic nerves

4. Superiorly through the body of sphenoid and sinus involving the parasellar structures and optic nerve, petrous apex and foramen lacerum. Cavernous sinus may be involved along with III, IV, V, and VI. The brain may also be affected by direct spread and not by hematogenous spread.

5. Inferiorly into the oral cavity and retrotonsillar regions.

6. Painless cervical lymphadenopathy because of its tendency for early lymphatic spread. Lateral retropharyngeal node of Rouviere is the first echelon node. The first node to become palpable is the jugulodigastric node / apical node under the sternomastoid muscle. These are second echelon nodes. Ipsilateral and bilateral nodal involvement are common.

7. Epistaxis: is commonly seen in advanced nasopharyngeal carcinoma with or without skull base erosion. It is not torrential in nature but only seen as blood tinged mucous secretion. Nasal obstruction may also be seen in advanced cases. Ozaena may also be a feature of advanced nasopharyngeal carcinoma.

8. Audiological symptoms like tinnitus, otalgia and deafness: These are common symptoms of nasopharyngeal malignancy. This is caused by blockage to the nasopharyngeal end of eustachean tube by the tumor mass.

9. Neurological symptoms like headache, cranial nerve palsy (any cranial nerve can be involved), and Horner's syndrome.

10. Distant metastasis to bone lungs and liver.

Clincial examination of nasopharynx:

Nasopharynx is one of the most difficult areas to examine clinically. Methods of examination of nasopharynx include:

1. Post nasal examination using post nasal mirror

2. Examination using nasopharyngoscope

3. Nasopharyngeal exam using nasal endoscope

Histological classification of nasopharyngeal carcinoma:

WHO classification of nasopharyngeal carcinoma is the most commonly used method. This classification divides nasopharyngeal carcinoma into three histological subtypes on the basis of light microscopic examination.

. Type I squamous cell carcinoma (keratinizing):

- well differentiated

- moderately differentiated

- poorly differentiated

. Type II Nonkeratinizing carcinoma

. Type III Undifferentiated carcinoma

Role of imaging in the diagnosis of nasopharyngeal carcinoma: CT scan is the most preferred imaging modality. It may be needed to identify the site for biopsy of the submucosal lesion. Major role of imaging in nasopharyngeal carcinoma is to help in the staging of the disease.

MRI scanning is useful and the most accurate method of evaluating primary tumor.

PET scanning is useful in diagnosis recurrent / residual lesions following RT.

Biopsy of the lesion is the definitive confirmatory investigation.

Tumor staging:

Modified Ho's classification:

Primary tumor (T)

T1 - Nasopharynx involvement only

T2n - Involvment of nasal cavity in addition

T2o - Involvement of oropharynx in addition

T2p - Involvement of parapharyngeal region

T3a - Bony involvement below the skull base including the floor of sphenoid

T3b - Involvement of skull base

T3c - Cranial nerves involvement

T3d - Orbit, laryngopharynx, infratemporal fossa

T3p - Parapharyngeal region

Regional nodes (N)

N0 - No nodes

N1 - Nodes above skin crease at laryngeal cartilage

N2 - Nodes below the skin crease but above the supraclavicular fossa

N3 - Supraclavicular nodes

Metastasis (M)

Mo - No distant metastasis

M1 - Distant metastasis


I (T1, T2n,T2o) No Mo

IIa (T2, T2n, T2o) N1, N2 Mo

IIb (T2p,T3, T3p) No Mo

IIIa (T2p, T3, T3p) N1, N2 Mo

IIIb (T1, T2n, T2o) N3 Mo

IVa (T2p, T3, T3p) N3Mo

IVb M1 (any T, any N)


AJCC classification:

Tx - Primary tumor cannot be assessed

To - No evidence of primary tumor

Tis - Carcinoma in situ

T1 - Tumor confined to the nasopharynx

T2 - Tumor extends to soft tissues

T2a - Tumor extends to the oropharynx / nasopharynx without parapharyngeal extension

T2b - Tumor with parapharyngeal extension

T3 - Tumor involves bony structures / paranasal sinuses

T4 - Tumor with intracranial extension / involvement of cranial nerves

Regional node (N)

Nx - Regional nodes cannot be assessed

No - No nodal metastasis

N1 - Unilateral metastasis in lymph nodes 6cms or less in the greatest dimension above the supraclavicular fossa

N2 - Bilateral nodal metastasis 6 cms or less in the greatest dimension above the supraclavicular fossa

N3 - Metastasis in nodes greater than 6 cms

N3a - Extension to supraclavicular fossa



Stage 0 - Tis No Mo

Stage I - T1 No Mo

Stage IIa - T2a No Mo

Stage IIb - T1 -2a N1 Mo

Stage III - T1 - 2b N2 Mo

Stage IVa - T4 No -2 Mo

Stage IVb - Any T N3 Mo

Stage IVc - Any T Any N M1


Nasopharyngeal carcinoma is a highly radiosensitive tumor hence irradiation is the preferred modality of treatment.

Megavoltage external radiotherapy is the treatment modality of choice. This is given through two lateral opposing and one anterior fold. Treatment should be delivered without interruption in five sessions per week for six weeks delivering a total dose of 60 Gy.

Role of surgery: is limited to biopsy of the lesion and confirming the diagnosis. If there is nodal metastasis then block neck dissection should be resorted to.



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