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Malignant peritoneal mesothelioma (MPM) is a rare, aggressive, and fatal neoplasm of the abdominal mesothelium with a very abysmal survival if left untreated. MPM with EWSR1-ATF1 fusion is an uncommon entity recently recognized by molecular studies. We report the first case of MPM with EWSR1-ATF1 fusion and aberrant CK20 expression. The patient was a 38-year-old man who presented to our institution with three months history of abdominal pain and distention, a significant weight loss (>30 lb), and failure to thrive. He was working in a construction company with 20 year-history of questionable asbestos exposure. Imaging studies demonstrated radiographic patterns suggestive of extensive peritoneal carcinomatosis. However, serum tumor markers were within the normal limit (CA 19–9, CEA, AFP, and βHCG). Subsequently, he underwent a biopsy of the peritoneal nodules. Biopsy showed a proliferation of epithelioid/round cells with ample cytoplasm and occasional vacuoles, displaying papillary architecture. Immunohistochemistry showed tumor cells were strongly and diffusely positive for WT1, AE1/3, CK7, CK20, desmin, and CD99, focally positive for calretinin, D2-40, and CK5/6, while negative for BerEp4, MOC-31, trypsin, TTF-1, P40, GATA3, CDX2, and PAX8. P16 and BAP1 were retained. Fluorescence in situ hybridization studies showed EWSR1 rearrangement, and the NGS fusion panel revealed EWSR1-ATF1 fusion. A diagnosis of MPM with EWSR1-ATF1 fusion was rendered. Unfortunately, the patient passed away within a month of diagnosis. Pathologists should be aware of this entity, especially when faced with tumors displaying mesothelioma morphology but showing atypical immunoprofile (co-expression of mesothelial markers with strong CK20).

Synchronous malignant mesothelioma (MM) and lung carcinoma are extremely rare in patients without a history of asbestos exposure and poses tremendous difficulties in clinical management. We report a patient without asbestos exposure diagnosed with MM during EGFR-TKI treatment of lung adenocarcinoma (LUAD), who responded to first-line chemotherapy with pemetrexed plus carboplatin and failed to subsequent systemic therapy. Clinicians should be careful about the possibility of MM comorbidity in LUAD patients whose lesions respond differently to EGFR-TKI, even in those without a history of asbestos exposure.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.