Dr. Supreet Singh Nayyar,MS ENTnayyarent.com/wp-content/uploads/2012/07/Nasopharyngeal... · 2012....

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Dr. Supreet Singh Nayyar, AFMC 2011 www.nayyarENT.com 1 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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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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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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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 NPC’s

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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o Tinnitus

o Trotter’s 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 Horner’s 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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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

(for more topics & ppts, visit www.nayyarENT.com )

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Staging

Modified Ho’s classification Endemic regions

AJCC Publicatios & non endemic region

Main difference N criteria

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(for more topics & ppts, visit www.nayyarENT.com )

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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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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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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%

Recent Advances

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

(for more topics & ppts, visit www.nayyarENT.com )