Nasopharyngeal carcinoma / Guandong tumour
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Published on: Mar 3, 2016
Transcripts - Nasopharyngeal carcinoma / Guandong tumour
Nasopharyngeal Ca = Guangdong
• IMMUNOLOGY IN NASOPHARYNGEAL CARCINOMA
• SITE OF ORIGIN
• CLINICAL PRESENTATION
• CLINICAL EXAMINATION OF NASOPHARYNX
• HISTOLOGICAL CLASSIFICATION OF NASOPHARYNGEAL CARCINOMA
• ROLE OF IMAGING IN THE DIAGNOSIS OF NASOPHARYNGEAL CARCINOMA
• TUMOUR STAGING (MODIFIED HO'S CLASSIFICATION, AJCC
Common in Chinese. asso with EBV. Histologically undifferentiated / non keratinizing carcinoma
types are common.
South China has 20% of worlds cases of Nasopharyngeal Ca. (guandong ca)
India its 1 in 1,00,000
Men : Women 3:1
This Tumour occurs at a much younger age than other cancers
Its incidence starts to rise after the second decade of life and slowly reaches a plateau, for both
sexes, after the fifth decade then very gradually drops with increasing age
Bimodal 15 to 20 yrs and 40 to 50 yrs
It has been suggested that individuals with a certain HLA haplotype may not be able to mount
specific cell-mediated immunity to infection caused by EBV.
Consistent deletion on the short arm of chromosomes 3 and 9 have been found on NPC
biopsies, supporting the hypothesis of an NPC tumour suppressor gene locus at these sites.
EBV genome was found in NPC cells. The discovery of EBV receptors on human pharyngeal
2. Exposure to chemical agents i.e. tobacco, drugs, and plant products.
3. Dietary factors: Ingestion of salted fish (volatile nitrosamines), 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. HLA-A, B and DR locus situated on the short arm of chromosome 6
9. If Infection is delayed until adolescence, the clinical syndrome of infectious mononucleosis may
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
EB virus was found in abundance in the lymphoepithelium of the nasopharynx (mainly B
Primary infection of this virus takes place in childhood and is always accompanied by
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
Demonstrable humoral immune response in patients with NPC against EB virus determined
antigens (VCA viral capsid antigens, Early antigen EA, and nuclear antigen EBNA).
Associated with nasopharyngeal carcinoma include :
a. IgA and IgG to Viral Capsid Antigen (☺ useful IgA/VCA, IgG/VCA)
b. IgA and IgG to Early Antigen (☺ useful ie IgA/EA, IgG/EA)
c. Antibody to Nuclear Antigen
d. Antigen dependent cellular cytotoxicity antibodies
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. The IgA anti-VCA appears to be more sensitive but less specific than IgA
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
Inversely proportional to mean titres of VCA & EA antibodies
Good prognosis is indicated by high Antigen Dependent Cellular Cytotoxicity Antibodies
The marked invasive and metastatic properties are responsible for its symptomatology.
50 % present with upper neck swelling
30 % present with nasal symptoms blood stained nasal discharge, nasal obstruction, post-nasal
drip or even frank epistaxis
20 % with deafness, tinnitus, Otalgia.
20 % Headache
OME and retracted tympanic membrane due to mechanical effects of tumour.
75 % present with palpable cervical lymphadenopathy
Cranial nerves 5 and 6 are the most commonly involved
Cranial nerves 3-6, when affected together, are indicative of Cavernous Sinus Involvement
Trismus, before radiotherapy, is rare and occurs only with direct infiltration of the pterygoid
Systemic metastasis at presentation is rare although eventually most NPC patients die of distant
failure. The bones and lungs are the most common sites for secondary deposits followed by the
The tumour 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
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. Poststyloid compartment causing vascular compression of carotid sheath, invasion of last
four cranial nerves (9,10,11,12) 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
o Cavernous sinus may be involved along with III, IV, V, and VI.
o The brain may also be affected by direct spread and not by haematogenous spread
5. Inferiorly into the oral cavity and retrotonsillar regions
6. Painless cervical lymphadenopathy because of its tendency for early lymphatic spread.
Lateral group of retropharyngeal node of Rouviere is the first echelon node.
The first node to become palpable is the jugulodigastric node / apical node under the
These are second echelon nodes. Ipsilateral and bilateral nodal involvement are
7. Epistaxis : only seen as blood tinged mucous secretion.
8. Audiological symptoms like tinnitus, otalgia and deafness. Caused by blockage to the
nasopharyngeal end of eustachian tube by the Tumour 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
HISTOLOGICAL CLASSIFICATION OF NASOPHARYNGEAL CARCINOMA
Earlier believed to be malignant Lymphoepithelioma
Now the tumour cells are confirmed to be epithelial in origin, since they stain positive for
The lymphocytes that infiltrate the tumour sites are reactive in nature. Analysis shows that these
are predominantly T-Lymphocytes and most of these are CD8 +
WHO classification :
EARLIER 3 subtypes
1. Type I squamous cell carcinoma (keratinizing):
- well differentiated
- moderately differentiated
- poorly differentiated
2. . Type II Nonkeratinizing carcinoma
3. . Type III Undifferentiated carcinoma
Mc Guire and Suen told type two and three of WHO classification are in continuum
Coincidentally, the WHO (1978) classification was revised in the same year into two grades:
Grade 1 – Keratinizing squamous cell carcinoma and
Grade 2 – Nonkeratinizing squamous cell or undifferentiated carcinoma. Mostly Endemic areas
In General – Grade 1 tumours are less aggressive than grade 2 tumours, however, they are also
Overall, the prognosis for patients with grade 1 tumours is less favourable when compared stage
to stage with patients having grade 2 tumours.
History, Clinical Examination
Serology (IgA anti-VCA titre is high although lacking in specificity, especially at low levels.
The IgA anti-EA titre, on the other hand, is less sensitive but its specificity is extremely high.
These tests, especially in combination, are useful)
Immunochemical staining : Stained for Epstein-Barr virus-associated nuclear antigen (EBNA)
by specific monoclonal antibodies
Sinonasal undifferentiated Ca
ROLE OF IMAGING
CT scan – preferred, to identify the site for biopsy of the submucosal lesion, help in the staging
of the disease
MRI scanning is useful and the most accurate method of evaluating primary Tumour
PET scanning is useful in diagnosis recurrent / residual lesions following RT
Biopsy of the lesion is the definitive confirmatory investigation
Modified Ho's classification:
Primary Tumour (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
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)
Tx - Primary Tumour cannot be assessed
To - No evidence of primary Tumour
Tis - Carcinoma in situ
T1 - Tumour confined to the nasopharynx
T2 - Tumour extends to soft tissues
T2a - Tumour extends to the oropharynx / nasal cavity without Parapharyngeal extension
T2b - Tumour with Parapharyngeal extension
T3 - Tumour involves bony structures / paranasal sinuses
T4 - Tumour with intracranial extension / involvement of cranial nerves, infratemporal fossa,
hypopharynx, orbit, or masticator space
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
N2 - Bilateral nodal metastasis 6 cms or less in the greatest dimension above the supraclavicular
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 N0-2 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 Tumour hence irradiation is the preferred
modality of treatment for primary, local and regional disease. For advanced disease chemotherapy is
added. Surgery only for local and regional failures.
For early disease (stage I-II), conventional radiotherapy alone is adequate
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 5
days per week for 6 weeks delivering a total dose of 60-65 Gy.
Chemotherapy (CISPLATIN) is believed to act as a radiosensitizer and helps to reduce the
chance of distant metastases.
After primary treatment, patients should be seen at least two-monthly for the first year and
three monthly for the second and third year, six-monthly thereafter. The response of
local disease is best followed up by repeated nasoendoscopy.
Annual chest radiographs in the first few years after treatment may pick up lung metastases
Persistent local disease confined to the nasopharynx can be treated with further radiotherapy or
Stereotactic radiotherapy, instead of brachytherapy, should be used when the tumour is
either too bulky or situated close to critical structures, such as the optic nerve
Any neck disease that remains, whether persistent or recurrent, thereafter should best be
treated by surgical resection
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.
The majority of relapses occur in the first three year
All patients should be restaged beforehand with full metastatic work up to exclude lung,
bone and liver metastases. For systemic metastases, PET and whole-body scan is probably the
most sensitive single test.
Involvement of the skull base, cranial nerves, vertebral bodies and carotid sheath and its
contents are absolute contraindications.
1. Lateral rhinotomy
2. Transnasal transmaxillary (A medial or subtotal maxillectomy can be performed to give
the exposure needed. The nasopharynx, the ipsilateral sphenoethmoidal complex,
Pterygopalatine fossa and the medial end of the infratemporal fossa are all within reach)
3. Midfacial degloving (This is essentially a bilateral transnasal, transmaxillary approach.
The procedure is carried out through a sub labial incision leaving no visible scar. With
both infra-orbital nerves safeguarded, the midface is degloved subperiosteally up to the root
of the nose. Sufficient access to the nasopharynx is obtained with bilateral medial
maxillectomy. The Pterygopalatine fossa and the medial end of the infratemporal fossa
on either side can be reached by extending the extent of the maxillectomy)
4. Le Fort I osteotomy
5. Maxillary swing - MC used Through a Weber-Fergusson-Longmire incision, the entire
maxilla is separated from its bony foundations and swung laterally intact with the
masseter muscle and the cheek flap.
Access to the opposite side is enhanced by removing the posterior part of the nasal
After tumour resection has been completed, the maxilla is swung back and fixed to the facial
1. Transpalatal (Access to the nasopharynx is gained by raising a palatal mucoperiosteal
flap off the hard palate so that the soft palate is separated from its bony portion. The
posterior edge (nearly half) of the bony palate is then removed as necessary. The greater
palatine neurovascular pedicle needs to be mobilized bilaterally from its bony canal so
that all soft tissues of the palate can be retracted downward during the tumour resection.)
2. Mandibular swing (This is essentially a trans cervical, transmandibular, trans palatal
approach via a Frazier incision)
Access to the nasopharynx and the adjacent areas is made through the infratemporal fossa. This
approach is limited by many critical structures including the facial nerve and the carotid sheath.
It is used mainly when the tumour extends laterally to the para pharyngeal space.
If a neck node persists in the absence of distant metastases, radical neck dissection should be
performed, as the potential benefit is greater than harm
Poor prognostic factors
Old age, male gender, cranial nerve palsy, level and fixity of lymph nodes
The average five-year survival achieved by conventional radiotherapy alone is excellent for
early disease: approximately 80-90 percent for stage I and 70-80 percent for stage II
OTHER TREATMENT MODALITIES
1. Photodynamic therapy