Nasopharyngeal Carcinoma

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Nasopharyngeal carcinoma

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

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Synonyms

• Epipharynx

• Post nasal space

• Retro nasal cavity

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Anatomy

Histological studies show that the anterior portion proximal to the tubal orifice resembles the nasal cavity, while the posterior portion possess features resembling oropharynx. The junctional zone is the belt along the tubal orifice where the first and third arches meet.

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Anatomy

The portion proximal to the tubal orifice is innervated by the maxillary division of the trigeminal nerve, and that posterior to the tubal orifice by the glossopharyngeal nerve.

Functional studies reveal structural differences between the two. Contractility is observed only in the posterior portion.

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Anatomy

• The average dimensions of nasopharynx in adult are 4cm high, 4 cm wide, and 3 cm long.

• The anterior wall is formed by choana and posterior end of nasal septum.

• The floor is formed by upper surface of soft palate, and the nasopharyngeal isthumus.

• The roof and posterior wall is formed by basisphenoid, basiocciput and first two cervical vertebrae.

• Lateral wall is formed by the pharyngeal end of E.T.

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Fossa of Rosenmuller

• It is situated in the corner between the lateral and dorsal walls.

• It can measure up to 1.5 cm in adults.

• It opens into the nasopharynx at a point below foramen lacerum.

• It is a hidden area.

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Fossa of Rosenmuller relations

• Anterior – E.T. & Levator palatini• Posterior – Pharyngeal mucosa, pharyngobasilar

fascia, retropharyngeal space with node of Rouviere.• Medially – Nasopharynx• Superiorly – Foramen lacerum and floor of carotid

canal.• Posterolateral or apex – Carotid canal opening and

petrous apex posteriorly, foramen ovale and spinosum laterally.

• Laterally – Tensor palatine and mandibular nerve, prestyloid compartment of parapharyngeal space.

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Epithelium of Nasopx.

• Mucosa is thrown into folds and crypts.• Surface area is 50 cm2 in adults.• 60% of the surface lined by stratified

squamous epithelium.• It has subepithelial connective tissue rich in

lymphoid tissue.

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Sinus of Morgagni

• The superior constrictor does not reach the base of skull.

• A lateral gap sinus of Morgagni is created.

• This gap is bridged only by pharyngobasilar fascia.

• Through this opening the E.T. along with its two muscles enter the nasopharynx.

• Tumors can easily breach this area and spread into the parapharyngeal space.

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Anatomy

• Close association with skull base foramen

• Mucosa – Epithelium - tissue of origin of NPC

• Stratified squamous epithelium• Pseudostratified columnar epithelium

– Salivary, Lymphoid structures

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Types of malignant neoplasms

1. Epithelial : NPC, Adenocarcinoma, Adenoid cystic carcinoma and others.

2. Lymphoid & Haemopoietic : Malignant lymphoma, Hodgkin’s, Burkitt’s & Plasmocytoma.

3. Bone & Cartilage : Chondrosarcoma & osteosarcoma

4. Miscellaneous : Malignant melanoma, Chordoma, & craniopharyngioma.

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Epidemiology

• Chinese native > Chinese immigrant > North American native– Both genetic and environmental factors

• Genetic– HLA histocompatibility loci possible

markers

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Epidemiology

• Environmental– Viruses

• EBV- well documented viral “fingerprints” in tumor cells and also anti-EBV serologies with WHO type II and III NPC

• HPV - possible factor in WHO type I lesions

– Nitrosamines - salted fish– Others - polycyclic hydrocarbons, chronic

nasal infection, poor hygiene, poor ventilation

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Age Distribution

• The age incidence of NPC is different from other cancers.

• It begins to rise at the end of IInd decade reaches a peak at IVth decade then stays at a plateau.

• Bimodal age distribution.

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Sex distribution

NPC is more common in men with age standardized male: female ratio between 2-3 : 1.

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Epidemiology

• Environmental– Viruses

• EBV- well documented viral “fingerprints” in tumor cells and also anti-EBV serologies with WHO type II and III NPC

• HPV - possible factor in WHO type I lesions

– Nitrosamines - salted fish– Others - polycyclic hydrocarbons, chronic

nasal infection, poor hygiene, poor ventilation

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Histopathology

Squamous cell carcinoma

1. Well differentiated

2. Moderately differentiated

3. Poorly differentiated

Non-keratinizing carcinoma

Undifferentiated carcinoma

WHO.

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Sites of origin

• Lateral wall

• Superior – Posterior wall

• More than one wall

• Anterior wall and floor

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Spread of tumor

• Anteriorly to the nasal cavity,PNS, pterygopalatine fossa and apex of orbit.

• Posteriorly to the retropharyngeal space and node of Rouviere.

• Laterally into the parapharyngeal space• Superiorly through the body of sphenoid to

the parasellar regions.• Inferiorly into the oral cavity

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Clinical features

• Cervical adenopathy 60%

• Epistaxis & Nasorespiratory symptoms

• Audiological symptoms 30%

• Neurological symptoms 20%

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Cervical adenopathy

• NPC has a tendency for early lymphatic spread.

• Retropharyngeal node of Rouviere is the first echelon node.

• Commonest first palpable node is the J.D. node and the apical node under sternomastoid muscle.

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Epistaxis & Nasal symptoms

• Commonly seen in advanced NPC’s.

• Complete nasal obstruction is a late presentation.

• Ozaena occurs as a result of tumour necrosis.

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Tinnitus & Aural symptoms

• Serous otitis media is common

• Acute otitis media

• Aural block

• Tinnitus

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Nerve palsies

• All cranial nerves can be affected

• Frequently involved are v, vi,ix, & x.

• Nerves ix & x are invariably involved together.

• Nerves of the ocular muscles are the next commonly affected.

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Pain & Headache

• This is an ominous symptom

• Severe pain is hallmark of terminal disease.

• Signifies tumour erosion into skull base.

• If accompanied by trismus,the disease is very advanced and has extended into pterygopalatine fossa.

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Distant Metastasis

• Incidence is 30%

• Skeletal metastasis account for more than one half.

• Thoraco lumbar spine is the commonest site followed by the lung and liver.

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Nasopharyngeal biopsy

Methods:1. Transnasal

a. Blind

b. Post. Mirror rhinoscopy

c. Endoscopy – rigid and flexible

2. Transoral

a. Yankauer speculum

b. Rigid endoscopy

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Treatment

• Radiotherapy is the definitive treatment.

• Chemotherapy is used to supplement R.T. in advanced cases with cervical metastasis

• Role of surgery is only to take biopsy or to deal with cervical metastasis after the primary has been sterilized.

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Complications of R.T.

• Mucositis

• Xerostomia

• Dental caries

• Radiation myelitis

• Optic atrophy

• Brain stem damage

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Immunology

• EB virus antigens

a. Viral capsid antigen (VCA)

b. Early antigen (EA)

c. Nuclear antigen

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Serological markers

• IgA and IgG to viral capsid antigen

• IgA and IgG to early antigen

• Antibody to nuclear antigen

• Antibody – dependent cellular cytotoxic antibodies.

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Prognostic serological markers

• Prognosis is inversely proportional to the geometric mean titres of VCA and Early antigen antibodies.

• Good prognosis is indicated by high antibody – dependent cellular cytotoxicity.

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HLA and risk

• HLA A2 1.5

BW46 1.9

B17 2.1

Haplotype A2-BW46 3.4

AW19-B17 2.2

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Staging

• Variety of systems used– Am Jt Comm for Ca Staging– International Union Against Ca– Ho System

• Unique NPC prognostic factors often not considered and similar prognosis between stages

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Staging

• Neel and Taylor System– Extensive primary tumor +0.5– Sx’s present < 2 months before dx - 0.5– Seven or more sx’s +1.0– WHO type I +1.0– Lower cervical node dx +1.0– -------------------------------------------------------

• ADCC assay titer considered if available

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Staging

• Stage A = < 0

• Stage B = 0 to 0.99

• Stage C = 1 to 1.99

• Stage D = > 2

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Treatment

• External beam radiation– Dose: 6500-7000 cGy– Primary, upper cervical nodes, pos. lower

nodes– Consider 5000 cGy prophylactic tx of clinically

negative lower neck

• Adjuvant brachytherapy– mainly for residual/recurrent disease

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Treatment

• External beam radiation - complications– More severe when repeat treatments required– Include

• xerostomia, tooth decay• ETD - early (SOM), later (patulous ET)• Endocrine disorders - hypopituitarism, hypothyroidism,

hypothalamic disfunction• Soft tissue fibrosis including trismus• Ophthalmologic problems• Skull base necrosis

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Treatment Surgical management

• Mainly diagnostic - Biopsy– consider clinic bx if cooperative patient– must obtain large biopsy– clinically normal NP - OR for panendo and bx

• Surgical treatment– primary lesion – regional failure with local control– ETD

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Treatment Surgical management

• Primary lesion – consider for residual or recurrent disease– approaches

• infratemporal fossa • transparotid temporal bone approach• transmaxillary• transmandibular• transpalatal

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Treatment Surgical management

• Regional disease– Neck dissection may offer improved survival

compared to repeat radiation of the neck

• ETD– BMT if symptomatic prior to XRT– Post XRT

• observation period if symptoms not severe• amplification may be more appropriate

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Treatment

• Chemotherapy– Variety of agents– Chemotherapy + XRT - no proven long term

benefit– Mainly for palliation of distant disease

• Immunotherapy– Future treatment??– Vaccine??