A 68-year-old former asbestos worker develops dyspnea and pleural effusion. CT shows bilateral pleural thickening with calcification and a pleural-based mass. Biopsy shows biphasic tumor with epithelioid and spindle cells, positive for calretinin, WT1, mesothelin, and CK5/6, negative for TTF-1 and CEA. Which pathological finding most reliably confirms a diagnosis of malignant mesothelioma over metastatic adenocarcinoma?
- A BAP1 loss by immunohistochemistry ✓
- B Presence of long microvilli on electron microscopy
- C Loss of MTAP (methylthioadenosine phosphorylase) by immunohistochemistry
- D Calretinin nuclear and cytoplasmic positivity
Explanation
BAP1 (BRCA1-associated protein-1) loss of expression by immunohistochemistry, reflecting CDKN2A/BAP1 deletion or inactivating mutation, is the most specific finding for malignant mesothelioma and is not seen in reactive mesothelial hyperplasia or metastatic carcinoma. BAP1 loss is present in ~60–70% of mesotheliomas and is used along with CDKN2A (p16) homozygous deletion by FISH as the most diagnostically definitive markers. Long microvilli on EM are a morphological feature but less routinely applied. MTAP loss parallels CDKN2A deletion and is a useful surrogate marker. Calretinin is positive in mesothelioma but can be positive in some adenocarcinomas and is not specific enough alone.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.