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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)
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
2
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
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
3
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
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
4
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
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
5
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 )
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
6
Staging
Modified Ho’s classification Endemic regions
AJCC Publicatios & non endemic region
Main difference N criteria
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
7
(for more topics & ppts, visit www.nayyarENT.com )
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
8
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
9
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
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
10
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
Dr. Supreet Singh Nayyar, AFMC 2011
www.nayyarENT.com
11
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 )