MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms

Anne V Cheng; Douglas J Wu; Lisa Aviva Friedman; Emily Chan; Sean R Williamson; Laurence A Galea; Ankur R Sangoi

doi:10.1007/s00428-025-04031-7

MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms

Virchows Arch. 2025 Jan 25. doi: 10.1007/s00428-025-04031-7. Online ahead of print.

Authors

Anne V Cheng¹, Douglas J Wu¹, Lisa Aviva Friedman¹, Emily Chan¹, Sean R Williamson², Laurence A Galea³, Ankur R Sangoi⁴

Affiliations

¹ Department of Pathology, Stanford Medical Center, 300 Pasteur Drive, Stanford, CA, 94305, USA.
² Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
³ Department of Anatomical Pathology, Sonic Healthcare, Melbourne PathologyVIC, Australia.
⁴ Department of Pathology, Stanford Medical Center, 300 Pasteur Drive, Stanford, CA, 94305, USA. asangoi@stanford.edu.

PMID: 39862330
DOI: 10.1007/s00428-025-04031-7

Abstract

Beyond the more common TFE3 fusion partners PRCC, ASPSCR1, and SFPQ, additional less common fusion partners of TFE3-rearranged renal cell carcinoma (RCC) have been described. Herein, we present an example of TFE3-rearranged renal cell carcinoma harboring fusion partner MAPK1IP1L, a rare rearrangement with only one other reported tumor found in the literature. The currently reported TFE3-rearranged RCC demonstrates unique histological features compared to the previously reported tumor including dense eosinophilic cytoplasm and nuclear pseudoinclusions (corroborated by electron microscopic evaluation), with features not typically seen in other TFE3-rearranged RCCs. Recognizing this novel fusion may be important in the identification, classification, and development of potential therapeutic agents of kidney tumors in the future.

Keywords: MAPK1IP1L; Oncocytic; Renal cell carcinoma; TFE3; Translocation.