[1563] Melanotic XP11 Translocation Renal Cancer: A Distinctive Neoplasm with Overlapping Features of Pecoma, Carcinoma, and Melanoma

P Argani, S Aulmann, Z Karanjawala, R Fraser, M Ladanyi, M Rodriguez. Johns Hopkins Medical Institutions, Baltimore, MD; Heidelberg University, Heidelberg, Germany; Dalhousie University, Halifax, NS, Canada; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Miami, Miami, FL

Background: Gene fusions involving the transcription factor gene TFE3 have been implicated in 2 types of cancer, alveolar soft part sarcoma (ASPS) and the Xp11 translocation renal cell carcinoma (RCC). Recent reports of strong nuclear labeling for TFE3 protein by immunohistochemistry (IHC) in perivascular epithelioid cell neoplasms (PEComas), comparable in intensity to that seen in neoplasms with documented TFE3 fusions, have suggested the possibility of TFE3 gene fusions in some PEComas.
Design: We describe two cases of malignant melanotic epithelioid renal cancers bearing TFE3 gene fusions. Their phenotype overlaps with PEComa, Xp11 translocation RCC, and melanoma, but most closely resembles PEComa.
Results: Both neoplasms occurred in children (ages 11 and 12), and presented with distant metastases. Both 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 fine brown pigment confirmed to be melanin by Fontana Masson histochemical stain. By IHC, the neoplastic cells labeled for melanocytic markers HMB45 and Melan A, but not for S100 protein, MiTF, or any epithelial, renal tubular, or muscle markers. Both neoplasms demonstrated nuclear labeling for TFE3 protein by IHC, and the presence of TFE3 rearrangements was confirmed by fluorescence in situ hybridization (FISH) analysis using a TFE3 break-apart probe. In case 1 (male), the rearrangement was unbalanced, while in case 2 (female), the rearrangement was balanced with loss of the second X chromosome.
Conclusions: These distinctive neoplasms combine morphologic features of PEComa, Xp11 translocation RCC, and melanoma, although the phenotype most closely resembles PEComa. The present 2 cases represent the first documented examples in which TFE3 rearrangements co-exist 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.
Category: Pediatrics

Monday, March 9, 2009 11:00 AM

Platform Session: Section H2, Monday Morning