Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features

Abstract

Microphthalmia-associated transcription (MiT) family translocation renal cell carcinoma (tRCC) comprises Xp11 tRCC and t(6;11) RCC. Due to the presence of fusion genes, Xp11 tRCC and t(6;11) RCC are also known as TFE3- and TFEB-rearranged RCC, respectively. TFE3 and TFEB belong to the MiT family, which regulates melanocyte and osteoclast differentiation, and TFE3- and TFEB-rearranged RCC show characteristic clinicopathological and immunohistochemical features. Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC. Furthermore, RCC with chromosome 6p amplification, including TFEB, was identified as a unique subtype of RCC, along with ALK-rearranged RCC. This review summarizes these recent advancements in our tRCC-related knowledge.

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

“…Fortunately, all fusion proteins end with TFE3 overexpression, which is diagnostic by virtue of IHC of transcription factors [15]. Ambiguous (patch or weak) TFE3 staining should be considered negative or pending for MiT RCC, but identification of fluorescent in situ hybridization break-apart signals is more convincing [16][17][18]. The molecular approach or specific TFs IHC panels, however, are possible only when considered properly.…”

MITF—the first 25 years

“…Importantly, deregulation of the MITF/TFEB/TFE3 family is also implicated in cancer; increased nuclear localization of these key transcription factors is required for pancreatic cancer progression (Perera et al 2015), whereas Ewing's sarcoma gene (EWS) translocations leading to fusion with the CREB-related transcription factor ATF1 can lead to aberrant expression of MITF and clear cell sarcoma (Li et al 2003;Davis et al 2006). Moreover, translocations between different MiT family members are driver mutations for renal cell carcinoma (Inamura 2017) leading to deregulation of MiT-family target genes.…”

Renal Tumors of Childhood—A Histopathologic Pattern-Based Diagnostic Approach

“…This underlines the reasons why extensive sampling is required, in order to capture all tumor features [9]. The most common pediatric renal tumors have been described and reviewed extensively elsewhere [3,[13][14][15][16]], so we only briefly recapitulated their main histologic features (Table S2). Since some tumors harbor a variety of histologic patterns, they appear in more than one of these categories.…”