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TFEB -amplified renal cell carcinoma

Wednesday 14 December 2016

Definition : Some RCCs demonstrate TFEB gene amplification (most without TFEB rearrangement, rare cases with concurrent TFEB rearrangement) and demonstrate downstream consequences of TFEB overexpression.

Like the unamplified t(6;11) RCC, all TFEB-amplified RCC were associated with aberrant melanocytic marker expression.

However, several differences between TFEB-amplified RCC and the usual unamplified t(6;11) RCC are evident.

First, TFEB-amplified RCC occurred in older patients (median age, 64.5 y) compared with unamplified t(6;11) RCC (median age, 31 y).

Second, the morphology of TFEB-amplified RCC is not entirely distinctive, frequently featuring nests of high-grade epithelioid cells with eosinophilic cytoplasm associated with pseudopapillary formation and necrosis, or true papillary formations. These patterns raise the differential diagnosis of high-grade clear cell and papillary RCC.

Third, TFEB and melanocytic marker expression was more variable within the TFEB-amplified RCC. TFEB protein expression by immunohistochemistry was detectable in 6 of 8 cases in one study.

TFEB-amplified RCC represent a distinct molecular subtype of high-grade adult RCC associated with aggressive clinical behavior, variable morphology, and aberrant melanocytic marker expression.

Renal cell carcinomas (RCCs) with the t(6;11)(p21;q12) chromosome translocation are low-grade RCC which often occur in young patients. They typically feature an unusual biphasic morphology characterized by nests of larger epithelioid cells surrounding intraluminal collections of smaller cells clustered around basement membrane material.

The t(6;11)(p21;q12) translocation fuses the Alpha (MALAT1) gene with the TFEB transcription factor gene, resulting in upregulated expression of intact native TFEB that drives the aberrant expression of melanocytic markers which is a hallmark of this distinctive neoplasm.

See also

- TFEB -associated renal cell carcinoma

  • TFEB -rearranged renal cell carcinoma

Open references

- MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge. CaliĆ² A, Segala D, Munari E, Brunelli M, Martignoni G. Cancers (Basel). 2019 Aug 3;11(8). pii: E1110. doi : 10.3390/cancers11081110. Review PMID: 31382581 Free

- Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features. Inamura K. Cancers (Basel). 2017 Aug 29;9(9). pii: E111. doi : 10.3390/cancers9090111. Review PMID: 28850056 Free

- Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays. Skala SL, Xiao H, Udager AM, Dhanasekaran SM, Shukla S, Zhang Y, Landau C, Shao L, Roulston D, Wang L, Siddiqui J, Cao X, Magi-Galluzzi C, Zhang M, Osunkoya AO, Smith SC, McKenney JK, Betz BL, Myers JL, Chinnaiyan AM, Tomlins SA, Mehra R. Mod Pathol. 2018 Jan;31(1):179-197. doi : 10.1038/modpathol.2017.99 PMID: 28840857 Free

- TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management. Gupta S, Johnson SH, Vasmatzis G, Porath B, Rustin JG, Rao P, Costello BA, Leibovich BC, Thompson RH, Cheville JC, Sukov WR. Mod Pathol. 2017 Jul;30(7):998-1012. doi : 10.1038/modpathol.2017.24 PMID: 28338654 Free

Paywall References

- TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity. Argani P, Reuter VE, Zhang L, Sung YS, Ning Y, Epstein JI, Netto GJ, Antonescu CR. Am J Surg Pathol. 2016 Nov;40(11):1484-1495. PMID: 27565001