Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum.
ABSTRACT The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.
- SourceAvailable from: sciencedirect.com[Show abstract] [Hide abstract]
ABSTRACT: Introduction Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Presentation of case Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming “pseudorosettes”. population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. Discussion On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Conclusion Knowledge of distinctive morphological and immuno-histochemical features of this tumor can help in establishing a diagnosis of this rare subset of translocation associated RCC on routine hematoxylin and eosin (H and E) staining and immunophenotyping.12/2014; 24. DOI:10.1016/j.ijscr.2014.12.026
- [Show abstract] [Hide abstract]
ABSTRACT: Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.Morphologie 03/2014; DOI:10.1016/j.morpho.2014.02.006
- [Show abstract] [Hide abstract]
ABSTRACT: TFE3 translocation renal cell carcinoma (tRCC) is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study, we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq) as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 translocation. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNA read-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2) point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs). The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription-PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P < .001) and 22 papillary RCCs (P < .05-.07). Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) and Contactin 3 (CNTN3) expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both).Neoplasia (New York, N.Y.) 11/2013; 15(11):1231-40. DOI:10.5167/uzh-87479 · 5.40 Impact Factor