## Nasopharyngeal Carcinoma: Histology and Aetiology ### WHO Classification and Epidemiology **Key Point:** Nasopharyngeal carcinoma (NPC) in endemic regions (Southeast Asia, North Africa, Southern China) is predominantly undifferentiated (WHO Type III), with EBV as the strongest aetiological agent. ### Histological Types and EBV Association | WHO Type | Histology | EBV Association | Geographic Pattern | | --- | --- | --- | --- | | Type I | Keratinizing squamous cell | Weak (20–30%) | Non-endemic (Western) | | Type II | Differentiated non-keratinizing | Moderate (60–70%) | Intermediate | | Type III | Undifferentiated (lymphoepithelioma) | Strong (95–100%) | Endemic (Asia, Africa) | **High-Yield:** In endemic regions, >90% of NPC cases are EBV-positive undifferentiated carcinoma. This patient's presentation (epistaxis, nasal obstruction, cervical lymphadenopathy, serous otitis media from Eustachian tube obstruction) and geography (Tamil Nadu—endemic region) strongly suggest Type III. ### EBV Mechanisms in NPC 1. **Latent infection** in nasopharyngeal epithelium 2. **LMP1 (Latent Membrane Protein 1)** acts as viral oncogene → NF-κB activation → cell proliferation and anti-apoptosis 3. **EBNA1** promotes genomic instability 4. **Genetic predisposition** (HLA-A2, HLA-B17) + EBV + environmental cofactors (salt-cured foods, smoking) **Clinical Pearl:** Serous otitis media ("conductive hearing loss") in an adult with unilateral nasal symptoms is a red flag for nasopharyngeal mass obstructing the Eustachian tube orifice. ### Why Undifferentiated Type III? - Strongest EBV association (95–100% positive) - Most common in endemic regions - Presents with early cervical lymphadenopathy and systemic symptoms - Highest radiosensitivity (better prognosis despite advanced stage at presentation) **Mnemonic:** **EBEN** = **E**BV + **B**iological undifferentiated + **E**ndemic + **N**asopharynx = Type III NPC 
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