## Histological Classification of Nasopharyngeal Carcinoma **Key Point:** Squamous cell carcinoma, non-keratinizing (undifferentiated) type is the predominant histology in nasopharyngeal carcinoma, particularly in endemic regions like Southeast Asia and Southern China. ### WHO Classification & EBV Association | Histological Type | Frequency | EBV Association | Geographic Pattern | | --- | --- | --- | --- | | Squamous cell carcinoma, keratinizing | 15–25% | Weak | Non-endemic regions | | Squamous cell carcinoma, non-keratinizing (undifferentiated) | 60–95% | Strong | Endemic regions | | Squamous cell carcinoma, basaloid | Rare | Moderate | Variable | | Adenocarcinoma | <5% | Weak | Rare | | Small cell carcinoma | <1% | Weak | Very rare | **High-Yield:** The undifferentiated (non-keratinizing) type shows the strongest and most consistent association with EBV, particularly in endemic populations. Nearly 100% of undifferentiated NPC cases are EBV-positive by in situ hybridization. **Clinical Pearl:** In endemic regions (Southeast Asia, North Africa, Inuit populations), undifferentiated carcinoma predominates and presents at younger ages with advanced stage. In non-endemic regions (North America, Europe), keratinizing type is relatively more common and presents at older ages. **Mnemonic:** **UNK** — **UN**differentiated (undifferentiated) = **N**asopharyngeal carcinoma + **K**ey EBV association. ### Pathological Features - Undifferentiated type: loss of keratinization, syncytial growth pattern, prominent lymphocytic infiltration ("lymphoepithelioma") - Strong EBV association makes it useful for diagnosis via EBV-encoded RNA (EBER) in situ hybridization - Better chemosensitivity compared to keratinizing type [cite:Harrison 21e Ch 81] 
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