We report two novel cases of Xp11 translocation renal cell carcinomas with the MED15::TFE3 gene fusion in adult females aged 40 and 74 years. Both cases were extensively cystic and contained only minimal clear cells lining cysts and within septal walls, raising the differential diagnosis of multilocular cystic renal neoplasm of low malignant potential. By immunohistochemistry, both neoplasms labeled for PAX8, TFE3, cathepsin K and Melan A but not for HMB45. On review of the published literature and the two cases reported herein, over 90% of MED15::TFE3 renal cell carcinomas (RCCs) have been described as cystic. The correlation of the MED15::TFE3 fusion with extensively cystic morphology represents the strongest association of TFE3 fusion partner with clinicopathological features among TFE3-rearranged RCC reported to date.
GandhiJSMalikFAminMBArganiPBahramiA. Mit family translocation renal cell carcinomas: a 15th anniversary update. Histol Histopathol. 2020;35(29):125‐136.
2.
ArganiP. Translocation carcinomas of the kidney. Genes Chromosomes Cancer. 2022;61(5):219‐227. doi:10.1002/gcc.23007
3.
ArganiP. Mit family translocation renal cell carcinoma. Semin Diagn Pathol. 2015;32(2):103‐113. doi:10.1053/j.semdp.2015.02.003
4.
TretiakovaMS. Chameleon TFE3-translocation RCC and how gene partners can change morphology: accurate diagnosis using contemporary modalities. Adv Anat Pathol. 2022;1(29):131‐140. doi:10.1097/PAP.0000000000000332
5.
ArganiPAntonescuCRIlleiPB, et al.Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol. 2001;159(1):179‐192. doi:10.1016/S0002-9440(10)61684-7
6.
ArganiPAntonescuCRCouturierJ, et al.PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol. 2002;26(12):1553‐1566. doi:10.1097/00000478-200212000-00003
7.
ClarkJLuYJSidharSK, et al.Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. Oncogene. 1997;15(18):2233‐2239. doi:10.1038/sj.onc.1201394
8.
ArganiPZhongMReuterVE, et al.TFE3-fusion variant analysis defines specific clinicopathologic associations among Xp11 translocation cancers. Am J Surg Pathol. 2016;40(6):723‐737. doi:10.1097/PAS.0000000000000631
9.
ArganiPZhangLReuterVETickooSKAntonescuCR. RBM10-TFE3 renal cell carcinoma: a potential diagnostic pitfall due to cryptic intrachromosomal Xp11.2 inversion resulting in false-negative TFE3 FISH. Am J Surg Pathol. 2017;41(5):655‐662. doi:10.1097/PAS.0000000000000835
10.
GreenWMYonescuRMorsbergerL, et al.Use of a TFE3 break-apart FISH assay in a renal tumor consultation service. Am J Surg Pathol. 2013;37(8):1150‐1163. doi:10.1097/PAS.0b013e31828a69ae
11.
ArganiPLalPHutchinsonBLuiMYReuterVELadanyiM. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions, a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27(6):750‐761. doi:10.1097/00000478-200306000-00005
12.
ClasseMMaloufGGSuX, et al.Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas. Histopathology. 2017;70(7):1089‐1097. doi:10.1111/his.13167
13.
PeiJCooperHFliederDB, et al.NEAT1-TFE3 and KAT6A-TFE3 renal cell carcinomas, new members of MiT family translocation renal cell carcinoma. Mod Pathol. 2019;32(5):710‐716. doi:10.1038/s41379-018-0191-7
14.
SunGChenJLiangJ, et al.Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma. Nat Commun. 2021;12(1):5262. doi:10.1038/s41467-021-25618-z
15.
YeHQinSLiNLinMXuYLiX. A rare partner of TFE3 in the Xp11 translocation renal cell carcinoma: clinicopathological analyses and detection of MED15-TFE3 fusion. Biomed Res Int. 2019:5974089.
16.
SongYYinXXiaQ, et al.Xp11 translocation renal cell carcinoma with morphological features mimicking multilocular cystic renal neoplasm of low malignant potential: a series of six cases with molecular analysis. J Clin Pathol. 2021;74(3):171‐176. doi:10.1136/jclinpath-2020-206681
17.
WangXTXiaQYYeSB, et al.RNA sequencing of Xp11 translocation-associated cancers reveals novel gene fusions and distinctive clinicopathologic correlations. Mod Pathol. 2018;31(9):1346‐1360. doi:10.1038/s41379-018-0051-5
18.
ArganiPOlgacSTickooSK, et al.Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol. 2007;31(8):1149‐1160. doi:10.1097/PAS.0b013e318031ffff
19.
AntonescuCRZhangLChangNE, et al.EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer. 2010;49(12):1114‐1124. doi:10.1002/gcc.20819
20.
SuziganSDrutRFariaP, et al. Jr. Xp11 translocation carcinoma of the kidney presenting with multilocular cystic renal cell carcinoma-like features. Int J Surg Pathol. 2007;15(2):199‐203. doi:10.1177/1066896906295891
21.
TretiakovaMMehtaVKocherginskyM, et al.Predominantly cystic clear cell renal cell carcinoma and multilocular cystic renal neoplasm of low malignant potential form a low-grade spectrum. Virchows Arch. 2018;473(1):85‐93. doi:10.1007/s00428-018-2371-8
22.
WestermanMEChevilleJCLohseCM, et al.Long-term outcomes of patients with low grade cystic renal epithelial neoplasms. Urology. 2019;133:145‐150. doi:10.1016/j.urology.2019.07.017
23.
EllisCLEbleJNSubhawongAP, et al.Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage. Mod Pathol. 2014;27(6):875‐886. doi:10.1038/modpathol.2013.208
24.
MartignoniGGobboSCamparoP, et al.Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions. Mod Pathol. 2011;24(10):1313‐1319. doi:10.1038/modpathol.2011.93
25.
WeitenRMüllerTSchmidtD, et al.The mediator complex subunit MED15, a promoter of tumour progression and metastatic spread in renal cell carcinoma. Cancer Biomark. 2018;21(4):839‐847. doi:10.3233/CBM-170757
26.
BakounyZSadagopanARaviP, et al.Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Rep. 2022;38(1):110190. doi:10.1016/j.celrep.2021.110190
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