Discussion

Mesothelioma is a malignant neoplasm arising from mesothelial cells. Peritoneal mesothelioma accounts for approximately 15–20% of all mesotheliomas and typically presents with nonspecific symptoms, including abdominal pain, distension, weight loss, and ascites. Around 10% of cases are associated with germline BAP1 mutations, while 40–80% harbor somatic BAP1 inactivation. Less common genetic alterations include CDKN2A, NF2, SETD2, and DDX3X. In children and young adults, tumours often lack BAP1 and NF2 alterations but may instead harbor ALK or EWSR1/FUS-ATF1 gene fusions.

Peritoneal mesothelioma is predominantly of the epithelioid type, with tubular, papillary, and solid growth patterns, often occurring in combination. Tumour cells are typically cuboidal to low columnar with eosinophilic cytoplasm and mild to moderate nuclear atypia. Less common variants include biphasic, sarcomatoid, and deciduoid subtypes. The main histological differential diagnoses are serous and clear cell carcinomas. Immunohistochemically, mesothelioma is characteristically positive for calretinin, WT1, CK5/6, D2-40, mesothelin, and CK7, while usually negative for epithelial markers such as BerEP4, claudin-4, MOC31, B72.3, CD15, ER, and PR. Loss of nuclear BAP1 expression, present in approximately half of cases, supports the diagnosis and helps distinguish mesothelioma from reactive mesothelial proliferations, well-differentiated papillary mesothelial tumour, and serous carcinoma, which typically retain BAP1 expression.

Diagnostic molecular pathology: Homozygous deletion of BAP1 or CDKN2A (p16) detected by FISH is highly specific for malignant peritoneal mesothelioma and is useful in distinguishing it from its histological mimics. However, these alterations are present in only a subset of cases, and FISH does not identify tumours with BAP1 point mutations

References

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2. Robert J. Kurman, Lora Hedrick Ellenson, Brigitte M. Ronnett, Blaustein's Pathology of the Female Genital Tract. 7th ed, Diseases of the Peritoneum: Springer; 2019.