ArticleVirchows Archiv : an international journal of pathology2026
ASPSCR1::TFE3-rearranged renal cell carcinomas: clinicopathologic, molecular, and survival analysis of 30 cases.
Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
ASPSCR1::TFE3-rearranged renal cell carcinoma (RCC) represents the most common subtype of TFE3-rearranged RCC, yet clinicopathologic and prognostic data remain limited. We analyzed 30 cases confirmed by fluorescence in situ hybridization or RNA-based next-generation sequencing, representing the largest single-center series to date. The cohort demonstrated an overwhelming female predominance, with a median age of 23.6 years. Microscopically, tumors exhibited diverse histological patterns, including papillary, nested, or tubular architectures, with papillary structure being the most prevalent. Tumor cells characteristically showed abundant clear to eosinophilic cytoplasm with discrete cell borders. Psammoma bodies were frequently present. Rare morphologic patterns included TFEB-rearranged RCC-like and cystic changes that, to our knowledge, have not been reported previously. Immunohistochemically, all tested tumors showed nuclear TFE3 positivity, with variable PAX8 expression, weak or absent staining for epithelial markers (CK7 and EMA), and negativity for melanocytic markers (HMB45 and Melan-A). PD-L1 was positive in 4 of 18 cases. Over 5-173 months of follow-up, the 5-year disease-free survival (DFS) rate was 37.9%, while the corresponding overall survival (OS) rate was 61.4%, with 3 patients developing recurrences and 16 developing metastases. Univariate analysis linked larger tumor size (> 4 cm), grossly solid appearance, tumor necrosis, psammoma bodies, microvascular tumor thrombi, high Ki-67 (≥ 5%), advanced stage (≥ III), and synchronous metastasis to worse prognosis. On multivariate analysis, tumor necrosis was independently associated with shorter DFS. Our findings expanded the clinicopathologic, immunohistochemical, molecular, and prognostic spectrum of ASPSCR1::TFE3-rearranged RCC and underscored the importance of precise morphologic and molecular assessment for risk stratification.
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