TY - JOUR
T1 - Translocation carcinomas of the kidney
AU - Argani, Pedram
N1 - Funding Information:
The author thanks Norman Barker MA, MS, RBP for expert photographic assistance. The study is supported in part by Dahan Translocation Carcinoma Fund (PA) and Joey's Wings (PA).
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2022/5
Y1 - 2022/5
N2 - The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC, and MITF. Gene fusions involving two of these transcription factors have been well-characterized in renal cell carcinoma (RCC). The TFE3-rearranged RCC (also known as Xp11 translocation RCC) was first officially recognized in the 2004 World Health Organization (WHO) renal tumor classification. The TFEB-rearranged RCC, which typically harbor a t(6;11)(p21;q12) translocation which results in a MALAT1-TFEB gene fusion, were first officially recognized in the 2016 WHO renal tumor classification. These two subtypes of translocation RCC have many similarities. Both disproportionately involve young patients, although adult translocation RCC overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the TFE3-rearranged RCCs frequently have clear cells with papillary architecture and abundant psammoma bodies, while the TFEB-rearranged RCCs frequently have a biphasic appearance with both small and large epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other or other more common renal neoplasms. Both of these RCC underexpress epithelial immunohistochemical markers, such as cytokeratin and epithelial membrane antigen, relative to most other RCC. Unlike other RCC, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, these two neoplasms are now grouped together under the heading of “MiT family translocation RCC.” Approximately 50 renal cell carcinomas with gene fusions involving the anaplastic lymphoma kinase (ALK) gene have now been reported. While those with a Vinculin-ALK fusion have distinctive features (predilection to affect children with sickle cell trait and to show solid architecture with striking cytoplasmic vacuolization), other ALK-fusion RCCs have more varied clinical presentations and pathologic features. This review summarizes our current knowledge of these recently described RCC.
AB - The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC, and MITF. Gene fusions involving two of these transcription factors have been well-characterized in renal cell carcinoma (RCC). The TFE3-rearranged RCC (also known as Xp11 translocation RCC) was first officially recognized in the 2004 World Health Organization (WHO) renal tumor classification. The TFEB-rearranged RCC, which typically harbor a t(6;11)(p21;q12) translocation which results in a MALAT1-TFEB gene fusion, were first officially recognized in the 2016 WHO renal tumor classification. These two subtypes of translocation RCC have many similarities. Both disproportionately involve young patients, although adult translocation RCC overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the TFE3-rearranged RCCs frequently have clear cells with papillary architecture and abundant psammoma bodies, while the TFEB-rearranged RCCs frequently have a biphasic appearance with both small and large epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other or other more common renal neoplasms. Both of these RCC underexpress epithelial immunohistochemical markers, such as cytokeratin and epithelial membrane antigen, relative to most other RCC. Unlike other RCC, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, these two neoplasms are now grouped together under the heading of “MiT family translocation RCC.” Approximately 50 renal cell carcinomas with gene fusions involving the anaplastic lymphoma kinase (ALK) gene have now been reported. While those with a Vinculin-ALK fusion have distinctive features (predilection to affect children with sickle cell trait and to show solid architecture with striking cytoplasmic vacuolization), other ALK-fusion RCCs have more varied clinical presentations and pathologic features. This review summarizes our current knowledge of these recently described RCC.
KW - ALK
KW - TFE3
KW - TFEB
KW - renal carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85118480049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118480049&partnerID=8YFLogxK
U2 - 10.1002/gcc.23007
DO - 10.1002/gcc.23007
M3 - Review article
C2 - 34704642
AN - SCOPUS:85118480049
SN - 1045-2257
VL - 61
SP - 219
EP - 227
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 5
ER -