title: Melanotic Xp11 translocation renal cancer: a case with PSF-TFE3 gene fusion and up-regulation of melanogenetic transcripts.
abstract: Melanotic Xp11 translocation renal cancer is a recently recognized aggressive epithelioid neoplasm with features overlapping between PEComa, carcinoma, and melanoma. We describe morphologic and immunohistochemical characteristics of a melanotic Xp11 translocation renal cancer occurring in an 18-year-old girl and perform molecular genetic studies to analyze its genetic alterations and related melanogenetic activities. The tumor was composed of solid nests of epithelioid cells bearing abundant clear to finely granular eosinophilic cytoplasm and separated by delicate vascular septa. Finely granular and nonrefractile brown melanin pigments, highlighted by Fontana-Masson stain, were scattered through the tumor. By immunohistochemistry, the tumor was diffusely and strongly labeled by TFE3 and focally stained by HMB45 in a patchy pattern. In contrast, all other applied immunomarkers, including cytokeratins, epithelial membrane antigen, vimentin, CD10, S-100, smooth muscle actin, desmin, c-kit, CD68, and microphthalmia-associated transcription factor, were nonreactive to the tumor. Reverse transcription-polymerase chain reaction and validating sequencing demonstrated PSF-TFE3 gene fusion, a novel exon composition juxtaposing PSF exon 9 to TFE3 exon 5. Up-regulations of melanogenesis-associated regulators, including microphthalmia-associated transcription factor, tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP1), were identified in the tumor by semiquantitative reverse transcription-polymerase chain reaction. The morphologic and immunohistochemical discrepancies between this intriguing melanotic tumor and other documented renal cell carcinomas bearing identical PSF-TFE3 gene fusion may suggest melanotic Xp11 translocation renal cancer is a distinct entity among the MiT/TFE family neoplasms.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chang
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Ming-Tse
authors.initials: MT
authors.lastname: Sung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D008543:Melanins / Q000096:biosynthesis / Q000235:genetics*; D008545:Melanoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D000072670:PTB-Associated Splicing Factor; D054973:Perivascular Epithelioid Cell Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C497234:MITF protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins; C069203:TFE3 protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase