Nasopharyngeal Carcinoma

Overview

NPC is the second most common head and neck cancer in Kenya. It has a high incidence in Southern China and a moderate incidence in Kenya and Northern Africa. Areas with high incidence have a single peak incidence at age 35-50 years while low incidence areas have a double peak at 9-15 years and 35-50 years. It affects males more than females with a M:F ratio is 3:1. Site of origin is the Fossa of Rosenmuller.

WHO classification of NPC

WHO Type	Histology	Subtypes
WHO Type I	Keratinizing SCC	Squamous differentiation, not associated with EBV, sporadic, worse prognosis, less sensitive to radiation
WHO Type II	Non-Keratinizing SCC	No definite squamous differentiation, associated with EBV, endemic, better prognosis and sensitive to radiation
WHO Type III	Undifferentiated SCC	Lymphoepithelioma, anaplastic and clear cell variants. Indistinct cell margins, may have lymphocytic stroma. EBV, endemic (Souther China), bette rprognosis, sensitive to radiation

Other types of NPC: Lymphoma, adenocarcinoma, plasma cell myeloma, cylindroma, adenoid cystic carcinoma, melanoma, carcinosarcoma, unclassified spingling malignant neoplasm

• Forms of NPC
  • Proliferative: extends locally causing obstructive nasal symptoms
  • Ulcerative: a lot of bleeding (epistaxis)
  • Infiltrative: bony involvement, may spread to the brain

Anatomy of the Nasopharynx

The post-nasal space measures 4cm high, 4cm wide, and 2 cm deep. It is lined by stratified squamous columnar epithelium and pseudostratified columnar epithelium. It also contains lymphoid tissue.

Fossa of Rosenmuller: a slit-like region medial to the medial crura of the eustachian tube orifices. It is the most common site of nasopharyngeal tumors.

Passavant’s Ridge: Interdigitating superior constrictor muscles that form a band at the posterior pharyngeal wall during swallowing. It abuts the soft palate.

Boundaries of the post-nasal space

Boundary	Structure
Anterior boundary	Choana and nasal septum
Posterior boundary	Superior pharyngeal constrictor muscles, Bodies of C1-C2 in continuity with the roof
Roof	Base of skull (body of sphenoid)
Floor	Soft palate and opening of oropharynx
Lateral boundary	Eustachian tube orifices and fossae of Rosenmuller

Clinical Features and Treatment

• Risk factors
  • Demographics
    • Male
    • Regional distribution: More common in Chinese or Mongolians. Southern China, Northern Africa, Southeast Asia, Alaska and Greenland)
  • Infections
    • Epstein-Barr Virus (EBV) – Viral Capsule Antigen (VCA) and Early Intracellular Antigen (EA)
    • Elevated IgA VCA and EA can be used to screen for NPC in high-risk regions
    • Low titers of IgA VCA and EA predicts poor prognosis, Higher titres predict good prognosis
  • Genetic predisposition:
    • Inheritance of certain HLA genes- HLA A2, HLA B17, HLA B46
    • Family history
  • Environmental factors: as evidenced by the regional distribution
    • Dietary habits: Nitrosamines in salted fish (most notable in China) and other preserved foods
    • Burning of incense stick and wood
    • Cigarette smoking
    • Lack of vitamin C
    • Alcohol consumption
    • Occupational exposure to wood, dust, or smoke
  • Polycyclic hydrocarbons
  • Chronic nasal infection
  • Poor hygiene
  • Poor ventilation
  • Smoke
• Signs and symptoms
  • Neck mass (70%)
    • Painless
  • Otitis media with effusion (secondary to eustachian tube obstruction, 50%)
  • Nasal obstruction
  • Cranial nerve palsies (abducens nerve palsy is the most common)
  • Recurrent epistaxis
  • Trismus
  • Headache
  Nasal symptoms are unilateral in the early stages A painless neck mass is the most common presentation of NPC Ear symptoms are the second most common presentation of NPC Eye symptoms can occur in advanced disease
• Diagnosis
  • Routine labs: CBC, LFT (r/o metastasis)
  • Rigid nasal endoscopy with biopsy
  • To rule out metastasis:
    • Fine needle aspiration of enlarged lymph nodes
    • CECT base of skull to thoracic inlet: metastasis
    • CECT Abdomen
    • CXR
• Treatment
  • Stage I-II (non-surgical)
    • Radiotherapy to the primary site and bilateral necks (regardless of nodal status)
  • Stage II-IV
    • Concurrent Chemoradiation w/Cisplatin/5-FU
    • Followed by adjuvant chemotherapy
  • Neck dissection for post-radiation salvage surgery
  • Tracheotomy if there are airway issues
  • Supportive treatment: analgesia
• Differentials
  • Other nasopharyngeal tumors Benign Malignant Angiofibroma Lymphoma Choanal polyp Rhabdomyosarcoma Squamous papilloma Chordoma Craniopharyngioma Plasmacytoma Hamartoma Malignant salivary tumor

Signs and symptoms according to region

Nose	Nasal obstruction, Epistaxis, Rhinorrhoea, Nasal mass
Neck	Painless Neck mass
Ear	Ear blockage, Fullness, CHL, OME, Otalgia
Throat	Oropharyngeal mass, Displaced palate, Post-nasal drip, Hyponasal speech, Dysphagia, Odynophagia, Airway obstruction
Eye	Proptosis, Visual disturbance, Impaired eye movement
Central Nervous System	Xerophthalmia (greater superior petrosal nerve), Facial pain (trigeminal nerve), Diplopia (CN VI), Ophthalmoplegia (CN II, IV, VI), Horner syndrome (sympathetic trunk), Headache, Convulsions

Staging of NPV (AJCC, 2017)

Tumor

Stage	Definition
Tx	Primary tumor not assessed
T0	No primary tumor
Tis	Carcinoma in situ
T1	Tumor confined to the nasopharynx, or extension to the oropharynx/nasal cavity w/o parapharyngeal involvement
T2	Tumor extends to the parapharyngeal space and/or adjacent soft tissue (pterygoid mm, prevertebral muscles)
T3	Tumor involves bony structures of skull base/cervical vertebrae/pterygoid and/or paranasal sinus
T4	Tumor invades intracranially/cranial nerves/hypopharynx/orbit/parotid gland and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid

Node

Stage	Definition
Nx	Nodes cannot be assessed
N0	No regional LN metastasis
N1	Unilateral metastasis in cervical LN and/or unilateral or bilateral metastasis in retropharyngeal LNs, ≤ 6 cm above the caudal border of cricoid cartilage
N2	Bilateral metastasis in Cervical LNs, ≤ 6 cm above the caudal border of the cricoid cartilage
N3	Unilateral or bilateral metastasis in cervical LNs >6cm and/or extension below the caudal border of the cricoid cartilage

Metastasis

Stage	Definition
M0	No distant metastasis
M1	Distant metastasis