Cystic MED15::TFE3 translocation renal cell carcinoma: histologic mimicker of multilocular cystic renal neoplasm of low malignant potential with review of the literature.

Presented are four cystic renal masses which harbored a MED15::TFE3 gene fusion detected by RNAseq, mimicking multilocular cystic neoplasm of low malignant potential. Clinicopathologic and outcomes data were collected for all cases. Radiologically, three cases were diagnosed as complex cystic masses and one case as a renal cyst, three years prior to surgery. The tumors ranged in size from 1.8 to 14.5 cm. Grossly, all masses were extensively cystic. Microscopically, cells with a clear or minimally granular cytoplasm and nuclei with inconspicuous nucleoli lined the cysts' septa. Focally, small mass-forming aggregates of malignant cells were present between septae and were associated with psammomatous calcifications. In case one, apparent prior cyst wall rupture was associated with reactive changes and cystic spaces filled with fibrin clots. Two of the tumors were staged as T1a, one as T1b, and the other as T2b. By immunohistochemistry, the tumors were positive for TFE3, MelanA, and P504S, with apical CD10 while CAIX and CK7 were negative. RNA sequencing was performed on all cases revealing a MED15::TFE3 gene fusion. The patients were alive and without evidence of disease 11-49 months (mean 29.5) after partial nephrectomy. To date, 12 of the 15 MED15::TFE3 fusion renal cell carcinomas published in the literature are cystic, with three being extensively cystic. Thus, if a multilocular cystic renal neoplasm is encountered in a kidney specimen, translocation renal cell carcinoma should be included in the differential diagnosis as cystic MED15::TFE3 tRCCs carry an uncertain prognosis making recognition for future characterization necessary.