TFE3-Rearranged Tumors of the Kidney: An Emerging Conundrum

: Identical translocations involving the gene and various partners have been found in both renal and soft tissue tumors, like alveolar soft part sarcoma (), ossifying fibromyxoid tumor (), epithelioid hemangioendothelioma, and the clear cell stromal tumor of the lung (). : Herein, we review in detail the clinicopathologic and molecular data of TFE3-rearranged renal tumors and propose our perspective, which may shed light on this emerging conundrum. : Among the kidney tumors carrying translocations, most are morphologically heterogeneous carcinomas labeling for the tubular marker PAX8. The others are mesenchymal neoplasms known as PEComas, characterized by epithelioid cells co-expressing smooth muscle actin, cathepsin-K, melanogenesis markers, and sometimes melanin pigment deposition. Over the past 30 years, numerous fusion partners have been identified, with , , , and being the most frequent. : It is not well understood why similar gene fusions can give rise to renal tumors with different morpho-immunophenotypes, which may contribute to the recent disagreement regarding their classification. However, as these two entities, respectively, epithelial and mesenchymal in nature, are widely recognized by the pathology community and their clinicopathologic features well established, we overall believe it is still better to retain the names TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa.