In summary, VEGFA amplification/increased gene copy number and VEGFA mRNA expression occur in TFEB-amplified renal cell carcinoma, but also in a subset of t(6;11) renal cell carcinoma demonstrating aggressive behavior, and in unamplified conventional t(6;11) renal cell carcinoma suggesting VEGFA as potential therapeutic target in these neoplasms even in the absence of TFEB amplification.
The NEAT1-TFE3 RCC arose in a 59-year-old male; which demonstrated overlapping morphological features seen in NEAT2(MALAT1)-TFEB t(6;11) renal cell carcinoma, including biphasic alveolar/nested tumor cells with eosinophilic cytoplasm.
Three novel fusions were identified: a complex rearrangement involving three genes (EWSR1/RBFOX2/ERG) in Ewing sarcoma, a EWSR1/TCF7L2 fusion in a colon adenocarcinoma, and a EWSR1/TFEB fusion in a translocation-associated renal cell carcinoma.
Comprehensive study of three novel cases of TFEB-amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome.
HOT should be considered as an emerging renal entity because it does not meet the diagnostic criteria for other recognized eosinophilic renal tumors, such as oncocytoma, chromophobe renal cell carcinoma (RCC), TFE3 and TFEBRCC, SDH-deficient RCC, and eosinophilic solid and cystic RCC.
In summary, TFE3 and TFEB FISH evaluation aids in identification and accurate classification of renal cell carcinomas with MITF aberrations, including TFEB-amplified renal cell carcinoma, which may demonstrate aggressive behavior.
Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion.
Together with one recent case in another report, our findings suggest that extensive sclerosis and ossification may be a less common recurring histology of TFEB-rearrangement renal cell carcinoma.
One tumor had the typical morphologic features of SFPQ-TFE3 RCC, whereas other 3 cases demonstrated the unusual morphologic features associated with pseudorosettes formation or clusters of smaller cells, mimicking TFEBRCC.
Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology.
The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia.
A total of five TFE3 gene fusions (PRCC-TFE3, ASPSCR1-TFE3, SFPQ-TFE3, NONO-TFE3, and CLTC-TFE3) and one TFEB gene fusion (MALAT1-TFEB) have been identified in RCC tumours and characterized at the mRNA transcript level.
Molecular confirmation of t(6;11)(p21;q12)renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.
Using tissue microarray, immunohistochemistry, cytogenetic examination, and fluorescence in situ hybridization, we identified 6 (∼5%) cases of TFE3 translocation RCC and 1 (<1%) case of TFEB translocation RCC in 121 consecutive adult RCC cases between 2001 and 2009.
We selected 54 patients with renal cell carcinoma with positive nuclear transcription factor E3 and transcription factor EB expression from the Juvenile RCC Network.
We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB.
Translocations of the genes encoding the related transcription factors TFE3 and TFEB are almost exclusively associated with a rare juvenile subset of renal cell carcinoma and lead to overexpression of TFE3 or TFEB protein sequences.