title: Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma.
abstract: 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.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, The Johns Hopkins University, Baltimore, MD 21231-2410, USA. pargani@jhmi.edu
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.forename: Zarir
authors.initials: Z
authors.lastname: Karanjawala
authors.forename: Robert B
authors.initials: RB
authors.lastname: Fraser
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Maria M
authors.initials: MM
authors.lastname: Rodriguez
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D015622:Epithelioid Cells / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000556:secondary*; D009378:Neoplasms, Multiple Primary; D054973:Perivascular Epithelioid Cell Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D014178:Translocation, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D008543:Melanins; C069203:TFE3 protein, human