The document discusses the anatomy, histology, epidemiology, clinical features, diagnosis, staging, and treatment of nasopharyngeal carcinoma (NPC). Key points include: - NPC originates from the epithelial lining of the nasopharynx. - It has a strong association with Epstein-Barr virus. - Risk factors include genetic predisposition and environmental exposures like salted fish consumption. - Common symptoms are cervical lymphadenopathy, epistaxis, ear symptoms, and neurological deficits. - Diagnosis involves biopsy and serological testing for EBV markers. - Staging systems consider tumor size, node involvement, and serological factors. - Primary treatment is radiotherapy,

1. Nasopharyngeal carcinoma Dr. T. Balasubramanian M.S. D.L.O.

2. Synonyms Epipharynx Post nasal space Retro nasal cavity

3. 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.

4. 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.

5. 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.

6. 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 .

7. 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.

8. Epithelium of Nasopx. Mucosa is thrown into folds and crypts. Surface area is 50 cm 2 in adults. 60% of the surface lined by stratified squamous epithelium. It has subepithelial connective tissue rich in lymphoid tissue.

9. 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.

10. Anatomy Close association with skull base foramen Mucosa Epithelium - tissue of origin of NPC Stratified squamous epithelium Pseudostratified columnar epithelium Salivary, Lymphoid structures

11. Types of malignant neoplasms Epithelial : NPC, Adenocarcinoma, Adenoid cystic carcinoma and others. Lymphoid & Haemopoietic : Malignant lymphoma, Hodgkin’s, Burkitt’s & Plasmocytoma. Bone & Cartilage : Chondrosarcoma & osteosarcoma Miscellaneous : Malignant melanoma, Chordoma, & craniopharyngioma.

12. Epidemiology Chinese native > Chinese immigrant > North American native Both genetic and environmental factors Genetic HLA histocompatibility loci possible markers

13. 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

14. Age Distribution The age incidence of NPC is different from other cancers. It begins to rise at the end of II nd decade reaches a peak at IV th decade then stays at a plateau. Bimodal age distribution.

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

16. 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

17. Histopathology Squamous cell carcinoma 1. Well differentiated 2. Moderately differentiated 3. Poorly differentiated Non-keratinizing carcinoma Undifferentiated carcinoma WHO.

18. Sites of origin Lateral wall Superior – Posterior wall More than one wall Anterior wall and floor

19. 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

20. Clinical features Cervical adenopathy 60% Epistaxis & Nasorespiratory symptoms Audiological symptoms 30% Neurological symptoms 20%

21. 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.

22. Epistaxis & Nasal symptoms Commonly seen in advanced NPC’s. Complete nasal obstruction is a late presentation. Ozaena occurs as a result of tumour necrosis.

23. Tinnitus & Aural symptoms Serous otitis media is common Acute otitis media Aural block Tinnitus

24. 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.

25. 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.

26. 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.

27. Nasopharyngeal biopsy Methods: Transnasal a. Blind b. Post. Mirror rhinoscopy c. Endoscopy – rigid and flexible Transoral a. Yankauer speculum b. Rigid endoscopy

28. 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.

29. Complications of R.T. Mucositis Xerostomia Dental caries Radiation myelitis Optic atrophy Brain stem damage

30. Immunology EB virus antigens a. Viral capsid antigen (VCA) b. Early antigen (EA) c. Nuclear antigen

31. Serological markers IgA and IgG to viral capsid antigen IgA and IgG to early antigen Antibody to nuclear antigen Antibody – dependent cellular cytotoxic antibodies .

32. 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.

33. HLA and risk HLA A2 1.5 BW46 1.9 B17 2.1 Haplotype A2-BW46 3.4 AW19-B17 2.2

34. 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

35. 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

36. Staging Stage A = < 0 Stage B = 0 to 0.99 Stage C = 1 to 1.99 Stage D = > 2

37. 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

38. 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

39. 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

40. Treatment Surgical management Primary lesion consider for residual or recurrent disease approaches infratemporal fossa transparotid temporal bone approach transmaxillary transmandibular transpalatal

41. 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

42. Treatment Chemotherapy Variety of agents Chemotherapy + XRT - no proven long term benefit Mainly for palliation of distant disease Immunotherapy Future treatment?? Vaccine??