A 70-year-old man with a central lung mass is found to have scattered tumour cells arranged in small clusters in the submucosal layer of the bronchus, with prominent palisading, nuclear moulding, and Azzopardi effect (DNA encrustation of vessel walls). NCAM/CD56 is strongly positive on IHC, along with synaptophysin. What is the most likely diagnosis?
- A Large cell neuroendocrine carcinoma (LCNEC) — distinguished by larger cells with prominent nucleoli
- B Small cell lung carcinoma (SCLC) — the Azzopardi effect and nuclear moulding with neuroendocrine markers are hallmarks; it is classified separately from other high-grade neuroendocrine carcinomas in WHO 2021 ✓
- C Typical carcinoid — low-grade neuroendocrine tumour with organoid architecture and <2 mitoses/2mm2
- D Basaloid squamous cell carcinoma — shows palisading but lacks neuroendocrine marker expression
Explanation
Small cell lung carcinoma (SCLC) is a WHO Grade 3 neuroendocrine carcinoma characterised by: small cells with scant cytoplasm and 'salt-and-pepper' chromatin, nuclear moulding (cells deform against each other), crush artefact, necrosis, high mitotic rate (>10 mitoses/2mm2), and the pathognomonic Azzopardi effect (tumour cell DNA smearing on vessel walls in necrotic areas). IHC shows strong CD56/NCAM, synaptophysin, chromogranin A positivity. WHO 2021 classifies SCLC separately from LCNEC based on its distinct molecular profile (ubiquitous RB1 and TP53 mutations, ASCL1/NEUROD1 transcription factor status). LCNEC has larger cells with prominent nucleoli and geographic necrosis. Typical carcinoid is low-grade.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.