TFE3/TFEB altered renal cell carcinomas in end-stage renal disease setting: A single institution clinicopathological study of 4 cases
Related Experiment Video
Updated: Jun 14, 2025
Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression
Published on: January 31, 2025
Andrea Mladenovic1, Lara R Harik1, Kristin K Deeb1
1Department of Pathology and Laboratory Medicine, Emory University, School of Medicine, Atlanta, GA, 30322, USA.
Introduction:
Translocation renal cell carcinoma (tRCC) are morphologically distinct tumors having an underlying disease defining molecular alterations (commonly TFE3/TFEB gene alterations). Their occurrence in the setting of end stage renal disease (ESRD) has been rarely reported. This study was undertaken to assess the occurrence of TFE3/TFEB altered RCCs in ESRD setting at our institution.
Design:
By retrospective review, we searched our pathology database for tRCC in ESRD setting over a 14-year period. We analyzed and documented the clinical, histopathological, immunohistochemical, and molecular findings in these tumors.
Results:
Out of 223 patients of ESRD associated with RCCs, we found 4 cases of molecularly confirmed TFE3/TFEB-altered RCCs. Three of four patients were on pharmacologic immunosuppression (2 for underlying SLE and 1 for prior liver transplant). The ages ranged from 36 to 74 years (median 48 years) with an equal sex ratio. Tumors were solitary and ranged in size from 1.3 to 4.7 cm (median 2 cm). All four cases were confined to the kidney (pT1) and did not exhibit any necrosis, small vessel invasion, or sarcomatoid/rhabdoid features. The tumors exhibited characteristic morphology (solid, nested and papillary architectures with clear and eosinophilic cytoplasm in TFE3-rearranged RCCs, and biphasic morphology with basement membrane-like material in TFEB-altered RCCs). On immunohistochemistry, tumors consistently expressed cathepsin-K (3/3) & Melan-A (3/3). On molecular studies one case was confirmed via FISH study (TFEB gene rearrangement) and three cases were confirmed via RNA fusionplex (PRCC::TFE3, MED15::TFE3 and MALAT1::TFEB fusion transcripts). The median follow-up was 13 months (range 10-95 months), none of the 4 patients had any local or metastatic recurrences. One patient died of other comorbidities. Background kidney in all 4 patients exhibited variable features of ESRD.
Conclusion:
TFE3/TFEB-altered RCCs are rarely encountered in ESRD. Morphological and immunohistochemical findings of tRCC in ESRD replicate those found in sporadic settings. To the best of our knowledge, our study is the first to identify TFEB-rearranged RCCs in an ESRD setting.
