Results of Michigan-Led Study Published in Modern Pathology

By Rohit Mehra | January 23 2020

Modern Pathology recently published a multi-institutional study led by pathology faculty Dr. Rohit Mehra; other participating centers included The Cleveland Clinic, Emory School of Medicine and Memorial Sloan Alex Taylor, MDRohit Mehra, MDKettering Cancer Center. Third year Pathology resident at Michigan Medicine, Alex Taylor, MD, was the first author with other major contributions by Drs. Noah Brown and May Chan. The study, PAX8 expression and TERT promoter mutations in the nested variant of urothelial carcinoma: a clinicopathologic study with immunohistochemical and molecular correlates was summarized by Drs. Taylor and Mehra as:

Nested urothelial carcinoma is a subtype of bladder cancer that can be difficult to diagnose because it appears similar to various benign lesions under the microscope. This study demonstrates that PAX-8, an immunohistochemical biomarker, usually thought to be negative in most bladder cancers, is present in more than half of nested urothelial carcinomas, thus creating a potential diagnostic pitfall when using this stain. Consequently, pathologists hoping to differentiate entities with PAX-8 should be cautious when nested urothelial carcinoma is a consideration. Moreover, this study shows that TERT promoter mutations, which are common in bladder cancer, are also common specifically in the subtype of nested urothelial carcinoma. TERT promoter mutation testing may therefore be helpful to confirm cases of nested urothelial carcinoma when morphology or immunohistochemical workup is not definitive. 

Nested urothelial carcinoma is a relatively infrequent entity; however, this tumor type is frequently associated with advanced stage and poor outcome of disease. To gather a cohort of cases large enough to reach statistical significance in the results, we were fortunate to be able to collaborate with genitourinary pathologists at other major academic medical centers to identify cases and compile specimens for testing. 

The abstract can be found here nature.com/articles.