We describe 2 cases of malignant melanotic epithelioid renal neoplasms bearing TFE3 gene fusions. Both neoplasms occurred in children (an 11-y-old boy and a 12-y-old girl), and presented with disseminated metastatic disease including mediastinal and mesenteric adenopathy. Both neoplasms featured sheets of epithelioid cells with clear to finely granular eosinophilic cytoplasm set in a branching capillary vasculature. The neoplastic cells contained variable amounts of finely brown pigment confirmed to be melanin by histochemical stains. By immunohistochemistry, the neoplastic cells labeled for melanocytic markers HMB45 and Melan A, but not for S100 protein, MiTF, or any epithelial marker (cytokeratins, epithelial membrane antigen), renal tubular marker (CD10, PAX8, PAX2, RCC Marker) or muscle marker (actin, desmin). Both neoplasms demonstrated nuclear labeling for TFE3 protein by immunohistochemistry, and the presence of TFE3 gene fusions was confirmed by TFE3 fluorescence in situ hybridization analysis. These distinctive neoplasms combine morphologic features of perivascular epithelioid cell neoplasms (PEComas), Xp11 translocation carcinoma, and melanoma, though the phenotype most closely approaches PEComa. These neoplasms represent the first documented examples in which TFE3 gene fusions coexist with melanin production, and their identification raises the possibility that TFE3 gene fusions may underlie an aggressive subset of lesions currently classified as PEComa in young patients.
Departments of *Pathology
†Oncology, The Johns Hopkins University, Baltimore, MD
∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY
¶Department of Pathology, University of Miami, Miami, FL
‡Institute of Pathology, Heidelberg University, Heidelberg, Germany
§Department of Pathology, Dalhousie University, Halifax, NS, Canada
Correspondence: Pedram Argani, MD, Department of Pathology, The Johns Hopkins Hospital, Weinberg Building, Room 2242, 401 N. Broadway, Baltimore, MD 21231-2410 (e-mail: firstname.lastname@example.org).
This work is dedicated to the memory of Dr William L. Gerald.