Well-Differentiated Papillary Mesothelioma of the Peritoneum is Genetically Distinct from Malignant Mesothelioma

Abstract

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process, and if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPM of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C>A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1 and SMARCC1 that are frequently altered in malignant mesotheliomas. We conclude that WDPMs are genetically distinct from malignant mesotheliomas, and based on observed mutations do not appear to be precursors of malignant mesotheliomas.

A case report of typical well-differentiated papillary mesothelial tumor diagnosed by internal thoracoscopy and literature review

“…At the genetic level, some researchers have studied the mutations in WDPMT. Shrestha found that EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 mutations are present in WDPMT, but they are rare in malignant mesotheliomas pointing out that these mutations may be specific to WDPMT (15). Another study suggesting the presence of TRAF7 or CDC42 missense mutations in WDPMT can be used to distinguish it from mesothelioma (16).…”