Xp11.2 Translocation Renal Cell Carcinoma in an Elderly Woman: A Diagnostic Challenge - A Case Report

Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC) characterized by transcription factor E3 (TFE3) gene rearrangements. It typically occurs in children and young adults, but cases in older patients have also been reported. An accurate diagnosis of Xp11.2 tRCC is often challenging because of its overlapping histological features with other RCC subtypes.

We report the case of a 68-year-old woman who was diagnosed preoperatively with left RCC, clinical stage cT1aN0M0, and underwent robot-assisted partial nephrectomy. The gross and histological tumor findings were atypical for clear cell RCC (ccRCC), suggesting ccRCC with numerous granular tumor cells. Immunohistochemistry (IHC) showed focal positivity for CA9 and cytokeratin (AE1/AE3), negativity for c-kit, and positivity for PAX8. Initial consultation suggested that microphthalmia-associated transcription factor family tRCC was less likely because of negativity for human melanoma black 45 and Melan-A, and the tumor was diagnosed as ccRCC (WHO/ISUP grade 3, pT1a). However, additional IHC results revealed nuclear positivity for TFE3, and subsequent consultation demonstrated break-apart and fusion signals on TFE3 break-apart fluorescence in situ hybridization (FISH), confirming the diagnosis of Xp11.2 tRCC. The patient remained disease-free for >4 years postoperatively.

This case illustrates the diagnostic difficulty of Xp11.2 tRCC, particularly in atypical renal tumors, and emphasizes the possibility of such cases being overlooked. The limited availability of facilities capable of performing TFE3 IHC and FISH highlights the need for heightened awareness and molecular testing for the accurate diagnosis and management of this rare tumor.