Molecular and Immunohistochemical Characterization of Mesothelioma of the Tunica Vaginalis

Histopathology 2022 April 23 [Link]

William J Anderson, Lynette M Sholl, Christopher D M Fletcher, Stephanie Schulte, Li Juan Wang, Fiona M Maclean, Michelle S Hirsch


Aims: Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare and aggressive tumor, and the molecular features and staining profile with contemporary immunohistochemical (IHC) biomarkers are largely unexplored. We characterize the clinicopathologic, molecular, and IHC features of MM (N=13) and mesothelial neoplasms of uncertain malignant potential (MUMP) (N=4).

Methods and results: Targeted next-generation sequencing was performed on 7 MMs and 2 MUMPs. IHC was performed for MTAP, BAP1 and SOX6. 13 adenomatoid tumors were also assessed with SOX6. MM were epithelioid (7/13) or biphasic (6/13). In MM, NF2 (5/7; 71%), CDKN2A (3/7; 43%), and BAP1 (2/7; 29%) were most frequently altered. Non-recurrent driver events were identified in PTCH1 and TSC1. In contrast, none of these alterations were identified in MUMPs; however, one MUMP harbored a TRAF7 missense mutation. By IHC, loss of MTAP (2/12; 17%) and BAP1 (2/9; 22%) was infrequent in MM, whereas both were retained in the MUMPs. SOX6 was positive in 9/11 (82%) MMs, and negative in all MUMPs and adenomatoid tumors.

Conclusions: Testicular MM exhibit a similar mutational profile to those of the pleura/peritoneum; however, alterations in CDKN2A and BAP1 are less common. These findings suggest that although MTAP and BAP1 IHC are specific for MM, their sensitivity in testicular MMs appears lower. In addition, rare tumors may harbor targetable alterations in driver genes (PTCH1 and TSC1) that are unusual in MMs at other anatomic sites. SOX6 is sensitive for MM; accordingly, the presence of SOX6 expression argues against a benign neoplastic process.