Renal cell carcinomas with t(6;11)(p21;q12): A clinicopathologic study emphasizing unusual morphology, novel alpha-TFEB gene fusion point, immunobiomarkers, and ultrastructural features, as well as detection of the gene fusion by fluorescence in situ hybridization.
Renal cell carcinomas (RCCs) with t(6;11)(p21;q12) are extremely rare and characterized by specific chromosome translocation, involving the transcription factor EB (TFEB). Fewer than 30 cases have been described in the literature. We examined 7 additional cases of this rare tumor by clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Four tumors had the typical morphologic features of TFEB RCCs, whereas 3 cases demonstrated uncommon morphologic features, mimicking epithelioid angiomyolipoma, chromophobe cell RCC, and clear cell RCC, respectively. Immunohistochemically, aside from TFEB and cathepsin K, kidney-specific cadherin was another sensitive and relatively specific marker for TFEB RCCs, supporting a distal nephron origin for these renal tumors. We also observed different ultrastructures including mitochondrion with areas of lipofuscin pigment in the smaller cells in these cases. An identical Alpha-TFEB fusion gene, 486 bp, was identified in 2 cases. In addition to the polymerase chain reaction method, we also developed a fluorescence in situ hybridization assay to serve as a cost-effective and time-efficient diagnostic tool. We detected a TFEB gene rearrangement in all 7 cases using the fluorescence in situ hybridization method. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none of the cases developed tumor recurrence, progression, or metastasis.
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Qiu
Q
Rao
Biao
B
Liu
Liang
L
Cheng
Yun
Y
Zhu
Qun-Li
QL
Shi
Bo
B
Wu
Shao-Jun
SJ
Jiang
Yan
Y
Wang
Xuan
X
Wang
Bo
B
Yu
Ru-Song
RS
Zhang
Heng-Hui
HH
Ma
Zhen-Feng
ZF
Lu
Pin
P
Tu
Jian-Dong
JD
Wang
Xiao-Jun
XJ
Zhou
D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C064972:TFEB protein, human