759 Renal Cell Carcinoma with Inconclusive TFE3/TFEB Fluorescent in Situ Hybridization (FISH) Results: A Clinical and Pathological Study
Recommended Citation
Agarwal P, Hassan O, Dadhania V, Alhamar M, Gupta N, Al-Obaidy K. 759 Renal Cell Carcinoma with Inconclusive TFE3/TFEB Fluorescent in Situ Hybridization (FISH) Results: A Clinical and Pathological Study. Lab Invest 2025; 105(3).
Document Type
Conference Proceeding
Publication Date
3-24-2025
Publication Title
Lab Invest
Keywords
molecular marker, adult, aneuploidy, chromosome 6, clinical article, conference abstract, cytoplasm, diagnosis, diploidy, end stage renal disease, eosinophilia, female, fluorescence in situ hybridization, follow up, histology, human, human cell, human tissue, immunofluorescence, immunohistochemistry, kidney biopsy, male, middle aged, nephrectomy, nephroblastoma, overtesting, renal cell carcinoma, retrospective study, treatment response
Abstract
Disclosures: Priti Agarwal: None; Oudai Hassan: None; Vipulkumar Dadhania: None; Mohamed Alhamar: None; Nilesh Gupta: None; Khaleel Al-Obaidy: None Background: Renal cell carcinoma (RCC) presents with a wide spectrum of morphologic and immunohistochemical (IHC) findings that are used to characterize various subtypes. Molecular markers not only help identify the unique signatures of these entities but also serve as predictors of therapeutic response. The 2022 WHO classification introduced, for the first time, a subset of RCCs defined by molecular alterations, the accurate diagnosis of which is crucial for guiding therapy, prognostication, and follow-up. TFE3/TFEB-rearranged and amplified RCCs, prime examples of these subtypes, are diagnosed through molecular analysis, with Fluorescent In Situ Hybridization (FISH) being the gold standard. However, a subset of RCCs shows atypical morphological and/or IHC features, with inconclusive TFE3/TFEB FISH results, often in the form of aneuploidy. Thus, we sought to investigate the clinicopathological features of these tumors. Design: We retrospectively reviewed the clinicopathologic features of RCCs analyzed by FISH between 2021 and 2024. Results: Thirty-seven patients who underwent renal biopsy or nephrectomy were included (24 males, 13 females; mean age 62 years, range 30–86), seven of whom had end-stage kidney disease. Tumors were mostly left-sided (22; 60%) and unifocal (35; 95%), with a mean size of 5.6 cm (range 1.3–9.5 cm). Most tumors were WHO/ISUP grade 3 (19; 51%), followed by grade 4 (9; 24%), with pT3a (11; 30%) and pT1a (10; 27%) being the most common pathological stage categories. The presence of clear cells with abundant cytoplasm, clear cells with areas of cytoplasmic eosinophilia, and/or papillary structures by histology, along with positivity for TFE3 and/or melanocytic markers by IHC (Table 1), were the most common findings prompting FISH analysis. Of the 37 tumors submitted for FISH analysis, 6 had TFE3 rearrangement, 14 had chromosome 6 &/or X aneuploidy, and 17 were diploid. Aneuploidy tumors were eventually diagnosed as clear cell renal cell carcinoma (10; with complete membranous CA9 staining), unclassified (2 had oncocytic features and chr. 6 aneuploidy), ESC-RCC (1; with chr. 6 aneuploidy)and adult Wilms tumor (1). [Formula presented] Conclusions: In our findings, most tumors that showed chromosomal aneuploidy were consistent with clear cell renal cell carcinoma, although they exhibited some immunohistochemical positivity for TFE3.This positivity must be interpreted with caution, especially in the absence of other features of TFE3/TFEB-rearranged renal cell carcinoma, to avoid unnecessary testing.
Volume
105
Issue
3
