肾癌的新类型-黑色素性Xp11易位肾癌。

1. Chang IW, Huang HY, Sung MT. Melanotic Xp11 translocation renal cancer: a case with PSF-TFE3 gene fusion and up-regulation of melanogenetic transcripts. Am J Surg Pathol. 2009;33:1894-901.

Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center,Chang Gung University College of Medicine, Kaohsiung, Taiwan.

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.

2. Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM.Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. Am J Surg Pathol. 2009 ;33:609-19.

Department of Pathology, The Johns Hopkins Hospital , The Johns Hopkins

University, Baltimore, MD 21231-2410, USA. pargani@jhmi.edu

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.

  谢谢金主任！

先学习一下，晚上再细细体会。

望月老师，能否请您根据HE形态和IHC标记与经典型肾细胞癌和PEComa 做一鉴别诊断总结？因为，毕竟不是一般医院能进行融合基因检查的；我想这种新型肾癌还是有些形态学特点帮助大家识别的。

谢谢！