Dr.

Supreet Singh Nayyar, AFMC

2011

Nasopharyngeal Carcinoma
(for more topics & ppts, visit www.nayyarENT.com ) Epidemiology
Highest incidence -- Guangdong Province of Southern China (50 per 100,000) Other places with high incidence o Hong Kong 30/100,000 o Singapore, Malaysia, Indonesia, Thailand, Filpinos o Alaskan Eskimos o Mediterranean basin Emigration reduces but still remains higher Other countries --1 per 100,000 Recent trend in decrease in certain endemic region (Hong Kong) M:F :: 3:1 Bimodal age distribution (20 & 50)

Aetiology
Multifactorial pathogenesis

o Genetic factors supported by High in certain ethnic groups Familial clustering Low risk in immigrants Retained in successive emigrant generations HLA linkage shown by Simons (1975)
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Dr. Supreet Singh Nayyar, AFMC

2011

Loci involved are HLA-A, B & DR. Hypothesis of NPC tumour suppressor gene on chromosome 3 & 9. Chromosomal abnormalities often present

o Ebstein Barr Virus Liang in 1969 proposed the association with EBV. Factors in favour Raised antibodies Viral genome EBV receptors (Young et al) o Environmental carcinogens Salted fish, preserved food Dust, household smoke, industrial fumes & tobacco Formaldehyde, metal smelting, furnaces, wood dust Dietary carcinogens affect susceptible population

EBV - Immunology & serology

EBV - 95% of world population affected Primary infection chilhoodasymptomatic If in adultInfectious mononucleosis In either caseseroconversionpermanent immunity + some virus persistence Virus shed in salivahorizontal transmission dormant genomic form in lymphocytes & bone marrow environmental factors or immunity reactivation Cell mediated immunity impaired polyclonal proliferation of infected B cells Markers o IgA anti-Viral Capsid Antigen(VCA) sensitivity-- screening o IgA anti Early Antigen(EA) -- specificity o ADCC (Antibody dependant cytotoxicity) assay against EBV membranegood prognosis o IgA against EBV specific DNAase marker after therapy o EBV DNA also marker during & after therapy

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Dr. Supreet Singh Nayyar, AFMC

2011

Pathology
Morphology of tumour range - Bulky growth to infiltrative one Histology classification (WHO-1991) o Type I-SCC (Keratinizing) o Type II- Non keratinizing carcinoma o Type III-Undifferentiated carcinoma

Routes of spread
Direct o Through foramen lacerum called Linconi highway/ petro sphenoid route Early involvement of cavernous sinus, optic nerve & orbit without erosion of base of skull o Anteriorly nasal cavity, PNS, pterygopalatine fossa and apex of orbit. o Posteriorly retropharyngeal space and node of Rouviere. o Laterally thru sinus of Morgagni parapharyngeal space o Superiorly body of sphenoid to the parasellar regions. o Inferiorlyoral cavity Lymphatic retropharyngeal (node of Rouviere) upper cervical LN Haematogenous Bone, liver, lungs

Clinical features
Cervical lymphadenopathy 60% o Tendency for early lymphatic spread. o Retropharyngeal node of Rouviere 1st echelon node. o Commonest first palpable node Jugulodigastric node and apical node under sternomastoid muscle Epistaxis & Naso-respiratory symptoms o Commonly seen in advanced NPCs o Complete nasal obstruction is a late presentation o Ozaena occurs as a result of tumour necrosis Audiological symptoms 30% o Serous otitis media is common o Adult Chinese patient with unresolving OME NPC until proved otherwise o Acute otitis media o Aural block
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Dr. Supreet Singh Nayyar, AFMC

2011

o Tinnitus o Trotters triad decreased hearing, mandibular pain, impaired soft palate mobility Neurological symptoms 20% o All cranial nerves can be affected o Signifies spread through foramina & Para pharyngeal space involvement o Frequently involved are V, VI, IX, & X. o Nerves IX & X are invariably involved together o Nerves of the ocular muscles are the next commonly affected indicate cavernous sinus involvement o Horners syndrome Headache o Poor prognosis o Severe headache hallmark of terminal disease. o Signifies tumour erosion into skull base o If accompanied by trismusdisease very advanced extended into pterygopalatine fossa Distant metastasis 30% o Thoraco lumbar spine commonest o Followed by the lung and liver

Diagnosis
Examination of ear, neck and cranial nerves Posterior rhinoscopy o Mass in Nasopharynx Transoral retrograde naso-pharyngoscopy o Fossae of rossenmuller wide open for evaluation. o Useful in gross DNS, small nasal cavity & Nasal polyposis Antegrade Naso- pharyngoscopy o Rigid Excellent optics Wide angle of view o Flexible fibreoptic Narrow diameter & flexible tip Nasopharyngeal biopsy o Transnasal - Hildyard biopsy forceps Blind Post. Mirror rhinoscopy
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Dr. Supreet Singh Nayyar, AFMC

2011

Endoscopy rigid and flexible o Transoral Yankauer speculum Rigid endoscopy Serolgy o IgA anti-VCA( high sensitivity, low specificity) o IgA anti-EA (low sensitivity, high specificity) Cytology o Typical of undifferentiated variety. Immunochemical staining o EBNA o EBV RNA o PCR for free EBV DNA Imaging o Tumour staging, RT planning, post treatment monitoring CT o Most widely used o Bony erosion MRI o Better soft tissue resolution, multiplanar images o More sensitive for marrow infiltration o Better defines nodal metastasis o In PNS diff between mucus and tumour Ultrasound o Confined to Dx and monitoring of regional and distant spread PET Scan o Differentiate post RT oedema from cancer in recurrences o Rule out distant metastasis

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Dr. Supreet Singh Nayyar, AFMC

2011

Staging
Modified Hos classification Endemic regions AJCC Publicatios & non endemic region Main difference N criteria

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Dr. Supreet Singh Nayyar, AFMC

2011

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Dr. Supreet Singh Nayyar, AFMC

2011

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Dr. Supreet Singh Nayyar, AFMC

2011

Treatment
Radiotherapy o Extremely radio sensitive o External Beam Radio Therapy (EBRT) primary modality o Two lateral opposing and one anterior field o Nasopharynx and both sides of neck covered. o Recommended dose is not less than 65Gy o Para pharyngeal boost to extend postero-lateral coverage o Stage I and II only RT o Stage III and IVB RT + CT o Additional dose of RT given by after loading Brachytherapy in advanced cancer Advanced disease chemotherapy added o 3 types Neoadjuvant Concurrent Adjuvant o Acts as radiosensitizer o Helps in controlling distant mets o Reduce bulk o Increases disease free survival o However no long term survival o Concurrent chemoradiation most impressive results

Follow up
Majority of relapses first 3 years 2 monthly review 1st year 3 monthly review 2nd & 3rd yrs6 monthly Lifelong follow up Endoscopy biopsy, imaging for neck, thyroid function test ,X ray chest

Salvage treatment
Local recurrence <1yr persistent disease In high recurrence T stage & short disease free survival CT added For regional failure RND preferred option

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Dr. Supreet Singh Nayyar, AFMC

2011

Surgery
Limited role Patient to be restaged Preoperatively the tumour stage difficult to define Best results with rT1 & rT2 cases without neck disease Surgical approaches o Anterior approach Lateral rhinotomy Transnasal transmaxillary Midfacial degloving Le Fort 1 osteotomy Maxillary swing o Inferior approach Transpalatal Mandibular swing o Lateral approach

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Dr. Supreet Singh Nayyar, AFMC

2011

Transpalatal Approach

Prognosis
Poor prognostic factors o Old age o Male o Cranial nerve palsies o Fixity of nodes Stage I 80-90% Stage II 70-80% Stage III 40-60% Stage IV 20-40% Photodynamic therapy o Used for salvage when others fail o Laser activation of a photosensitizer taken up and retained by the tumour Tumouricidal effect of PDT o First generation haematoporphyrin+ 630 nm red light o Second generation m-thpc sensitizer + 652 nm red light o Experience less more studies required Immunotherapy o Difficult alternative o Complex structure o Latent infection o EBV structural antigen/cytotoxic T lymphocyte epitopes

Recent Advances

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