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Microphthalmia family of transcription factors associated renal cell carcinoma |
Ling Xiea,b,Yifen Zhanga,Chin-Lee Wub,*()
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a Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China b Department of Pathology and Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA |
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Abstract The microphthalmia (MiT) subfamily of transcription factors includes TFE3, TFEB, TFEC, and MITF. In the 2016 World Health Organization classification, MiT family translocation renal cell carcinoma (tRCC) including Xp11 tRCC and t(6;11) RCC, was newly defined as an RCC subtype. Xp11 and t(6;11) RCC are characterized by the rearrangement of the MiT transcription factors TFE3 and TFEB, respectively. Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC. Furthermore, RCC with TFEB amplification, melanotic MiT family translocation neoplasms, was identified may as a unique subtype of MiT family associated renal neoplasms, along with MITF associated RCC. In this review, we will collect available literature of these newly-described RCCs, analyze their clinicopathological and immunohistochemical features, and summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of these rare subtypes of RCCs, and eventually promote clinical management strategies.
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Received: 10 May 2018
Available online: 03 May 2019
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Corresponding Authors:
Chin-Lee Wu
E-mail: cwu2@partners.org
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Neoplasm | Fusion | Translocation | Age range (year) | ASPS | ASPSCR1-TFE3 | der(17)(X;17)(p11.2q25) | 1-71 | RCC | ASPSCR1-TFE3 | t(X;17)(p11.2;q25) | 1-75 | RCC | PRCC-TFE3 | t(X;1)(p11.2;q21) | 2-69 | RCC | SFPQ-TFE3 | t(X;1)(p11.2;q34) | 3-68 | RCC | NonO-TFE3 | inv(X)(p11.2;q12) | 39 | RCC | CLTC-TFE3 | t(X;17)(p11.2;q23) | 14 | RCC | LUC7L3-TFE3 | t(X;17)(p11.2;q21) | 20 F | RCC | KHSRP-TFE3 | t(X;19)(p11.2;p13) | | RCC | PARP14-TFE3 | t(X;3)(p11.2;q23) | 45 F | RCC | DVL2-TFE3 | t(X;17)(p11.2;p13.1) | 73 M | RCC | RBM10-TFE3 | Inv(X)(p11.2;p11.23) | 32-61 | RCC | GRIPAP1-TFE3 | inv(X)(p11.23,p11.23) | 40 F | RCC | MED15-TFE3 | t(X;22)(p11.2;q11.2) | 34 F | RCC | Unknown | t(X;3)(p11.2;q23) | 32 | RCC | Unknown | t(X;10)(p11.2;q23) | 77 | Melanotic Xp11 translocation cancer | SFPQ(PSF)-TFE3 | t(X;1)(p11.2;q34) | 11-55 | ARID1B-TFE3 | T(X:6)(p11.2;q25.3) | | Melanotic t(6;11) renal cell carcinoma | MALAT1(Alpha)-TFEB | t(6;11)(p21;q12) | | Xp11 PEComa | SFPQ-TFE3 and others | t(X;1)(p11.2;q34) and others | 9-55 | Subset of epithelioid hemangioendothelioma | YAP1-TFE3 | t(X;11)(p11.2;q13) | 14-50 | RCC | MALAT1(Alpha)-TFEB | t(6;11)(p21;q12) | 3-68 | RCC | CLTC-TFEB | t(6;17)(p21;q23) | | RCC | KHDRBS2-TFEB | inv(6)(p21q11) | | RCC | COL21A1-TFEB | inv(6)(p21p12) | | RCC | TFEB-CADM2 | t(3;6)(p12;p21) | | RCC | ACTG1-MITF | t(17;3)(q25.3;p13) | | RCC | PRCC-MITF | t(1;3)(q21;p13) | 45 |
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TFE3, TFEB and MITF gene fusions.
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Xp11 translocation renal cell carcinoma (RCC). (A-C: Hematoxylin and eosin stains) (A) Xp11 tRCC showing compact nested and papillary architecture at low power; (B) Xp11 tRCC showing solid nested architecture with eosinophilic cytoplasm; (C) Xp11 tRCC at higher power showing cells with voluminous clear cytoplasm and vesicular nuclei with prominent nucleoli; (D) Immunohistochemistry for TFE3 showing nuclear labeling of neoplastic cells; note the absence of labeling in native endothelial cells.
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The t(6;11) renal cell carcinoma (RCC). (A,B) The t(6;11) RCCs typically show a biphasic morphology, with larger epithelioid cells at the periphery of the nests and smaller cells clustered around hyaline basement membrane material in the center; (C) Immunohistochemistry for TFEB showing strong nuclear labeling of neoplastic cells; note the absence of labeling in native endothelial cells; (D) Diffuse cytoplasmic staining with Melan A in both types of cells.
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