Aberrant Immunohistochemical stains among 573 cases of Diffuse Mesothelioma

Abstract

Background: Diagnosis of malignant mesothelioma often requires differentiating it from other metastatic malignancies including breast cancer, lung cancer, ovarian cancer, colorectal cancer, etc. Immunohistochemical stains (IHC) are important means to assist in confirming mesothelioma and ruling out metastatic cancers. Although mesothelial specific markers have been used for diagnosis, aberrant immunostains were also observed in clinical practice which often confounded the diagnosis. In this study, we analyzed the positive rate of commonly used IHC markers in the diagnosis of mesothelioma among 573 patients.

Design: 427 cases of epithelioid mesothelioma, 87 cases of biphasic mesothelioma and 59 cases with sarcomatoid mesothelioma were retrieved from the pathology consultation files between 2020-2023. The positive rates of over 50 IHC markers including over 30 aberrant IHC markers were analyzed.

Results: The positive rates of mesothelial markers, such as calretinin, WT-1 and D2-40, and epithelial markers, such as cytokeratins, were highest in epithelioid type, intermediate in biphasic type and lowest in sarcomatoid type mesothelioma. The mesenchymal marker vimentin and additional marker GATA-3 were highly expressed in sarcomatoid mesothelioma. The highest loss rate of BAP-1 was in epithelioid type, while the highest loss rate of MTAP was in sarcomatoid type. The CDKN2A (p16) deletion was observed equally in both epithelioid and sarcomatoid/biphasic types. Over 30 aberrant markers were observed. For epithelioid type, commonly observed aberrant IHC markers included MOC-31, BerEP4, PAX-8, p63, CK20, NKX3.1 and ER. For biphasic type, significant aberrant IHC markers included MOC-31, Ber-EP4, PAX8, CK20 and p40. For sarcomatoid type, notable aberrant IHC markers included p63, SMA, ERG and CD31. Among these aberrant IHC markers, MOC-31, Ber-EP4 and p63 were more commonly observed in pleural epithelioid mesothelioma, whereas PAX-8 in peritoneal epithelioid mesothelioma.

Conclusions: Our data demonstrated that aberrant immunostains were common in all of the histological types of mesothelioma. Therefore, the diagnosis of mesothelioma should be based on correlation of clinical presentation, radiological findings, and selective panel of immunostains, and should not be distracted by aberrant immunostains.