Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases

Farcas, Mihaela; Gatalica, Zoran; Trpkov, Kiril; Swensen, Jeffrey; Zhou, Ming; Alaghehbandan, Reza; Williamson, Sean R.; Magi‐Galluzzi, Cristina; Gill, Anthony J.; Tretiakova, Maria; López, José I.; Montiel, Delia Pérez; Sperga, Māris; Compérat, Éva; Brimo, Fadi; Yilmaz, Aslı; Siadat, Farshid; Sangoi, Ankur R.; Gao, Yuan; Ptáková, Nikola; Kuthi, Levente; Pivovarčíková, Kristýna; Rogala, Joanna; Agaimy, Abbas; Hartmann, Arndt; Fraune, Cristoph; Rychlý, Boris; Hurník, Pavel; Durcanský, D; Bonert, Michael; Gakis, Georgios; Michal, Michal; Hora, Milan; Hes, Ondřej

doi:10.1038/s41379-021-00923-6

Cited by 48 publications

(63 citation statements)

References 30 publications

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“…The loss of chromosome 1 concurrently with activating MTOR mutations was also documented by others [ 9 , 33 ]. The association of EVT and mTOR pathway abnormalities, including non-overlapping mutations in mTOR , TSC2 , and TSC1 , was confirmed in a recent multi-institutional study [ 35 ]. In one case described by Farcas et al, an mTOR mutation showed a coexistence of RICTOR missense mutation [ 35 ].…”

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 77%

“…Similar to LOT, EVT was initially considered as a sporadic tumor, but, in subsequent studies, an identical tumor was described in TSC patients [ 9 , 25 , 34 ]. Based on the limited clinical data, EVT seems to follow a non-aggressive behavior [ 18 ], with no disease recurrence or progression during relative long follow-up ranging from 12 to 198 months (mean 56.3, median 41.5 months) [ 35 ].…”

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

“…EVTs are usually low-stage solitary tumors. On cross section, they are described as solid, tan to brown, and without necrotic or hemorrhagic areas [ 18 , 32 , 33 , 35 ]. EVT has a readily identifiable morphology that does not fit any of the previously described renal entities.…”

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

“…The tumors are consistently positive for CD117, CD10, antimitochondrial antigen antibody, and cathepsin K. Further, the majority of these tumors are positive for PAX8, AE1/AE3, and CK18 [ 9 , 32 , 35 ]. CK7 is negative or restricted to rare scattered cells [ 33 , 35 ].…”

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

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TSC/mTOR Pathway Mutation Associated Eosinophilic/Oncocytic Renal Neoplasms: A Heterogeneous Group of Tumors with Distinct Morphology, Immunohistochemical Profile, and Similar Genetic Background

et al. 2022

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A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.

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Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 77%

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

Section: Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

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TSC/mTOR Pathway Mutation Associated Eosinophilic/Oncocytic Renal Neoplasms: A Heterogeneous Group of Tumors with Distinct Morphology, Immunohistochemical Profile, and Similar Genetic Background

et al. 2022

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“…Mihaela et al sequenced 19 EVTs (also called high-grade oncocytic tumors) and found nonoverlapping mutations in TSC1 (4), TSC2 (7), and mTOR (8) [40].…”

Section: Tsc1 and Tsc2 Mutations In Eosinophilic Vacuolated Tumor (Evt)mentioning

confidence: 99%

Renal Cell Carcinoma in Tuberous Sclerosis Complex

Henske

Cornejo

2021

Genes

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Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent. There are three major renal lesions in TSC: angiomyolipomas, cysts, and renal cell carcinoma (RCC). Major recent advances have revolutionized our understanding of TSC-associated RCC, including two series that together include more than 100 TSC-RCC cases, demonstrating a mean age at onset of about 36 years, tumors in children as young as 7, and a striking 2:1 female predominance. These series also provide the first detailed understanding of the pathologic features of these distinctive tumors, which include chromophobe-like features and eosinophilia, with some of the tumors unclassified. This pathologic heterogeneity is distinctive and reminiscent of the pathologic heterogeneity in Birt–Hogg–Dube-associated RCC, which also includes chromophobe-like tumors. Additional advances include the identification of sporadic counterpart tumors that carry somatic TSC1/TSC2/mTOR mutations. These include unclassified eosinophilic tumors, eosinophilic solid cystic RCC (ESC-RCC), and RCC with leiomyomatous stroma (RCCLMS). A variety of epithelial renal neoplasms have been identified both in patients with tuberous sclerosis complex (TSC) and in the nonsyndromic setting associated with somatic mutations in the TSC1 and TSC2 genes. Interestingly, whether tumors are related to a germline or somatic TSC1/2 mutation, these tumors often display similar morphologic and immunophenotypic features. Finally, recent work has identified molecular links between TSC and BHD-associated tumors, involving the TFEB/TFE3 transcription factors.

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