Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney

Kapur, Payal; Gao, Ming; Zhong, Hua; Chintalapati, Suneetha; Mitui, Midori; Barnes, Spencer; Zhou, Qinbo; Miyata, Jeffrey; Carrillo, Deyssy; Malladi, Venkat S.; Rakheja, Dinesh; Pedrosa, Iván; Xu, Lin; Kinch, Lisa N.; Brugarolas, James

doi:10.1038/s41379-021-00896-6

Cited by 41 publications

(70 citation statements)

References 70 publications

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“…In the initial study by Trpkov et al, LOT was characterized by a typical CD117 negative/CK7 positive immunoprofile and consistent distinct morphology. Subsequently, multiple studies have been conducted across the global pathology community, identifying to date more than 100 LOT cases that were previously classified as renal oncocytoma [ 25 , 26 ], eosinophilic variant of chromophobe RCC [ 25 , 27 ], unclassified RCC, or “low-grade eosinophilic renal neoplasm” [ 25 , 28 ]. Morini et al reported the incidence of LOT to be 3.6% of all chromophobe RCCs [ 27 ].…”

Section: Low-grade Oncocytic Tumor (Lot)mentioning

confidence: 99%

“…The incidence of LOT in tumors previously misclassified as renal oncocytoma is reported at 4.18% by Kravtsov et al [ 26 ]. Based on the current knowledge, LOT seems to be a new distinct entity that can present in both syndromic and non-syndromic settings (tumors with the same morphology were described in patients with TSC [ 25 ]). Most recently, LOT was proposed to be considered as a provisional entity by the Genitourinary Pathology Society (GUPS) [ 18 ].…”

Section: Low-grade Oncocytic Tumor (Lot)mentioning

confidence: 99%

“…LOT is typically a solitary, small tumor that shows low stage, and it is associated with indolent clinical behavior based on the available data. Recent studies have shown that LOT may rarely be multiple and/or bilateral [ 17 , 25 , 29 ]. LOT is typically a tan/brown, solid tumor, which may show edematous or hemorrhagic focal areas on a cut surface [ 24 , 27 , 28 , 30 , 31 ].…”

Section: Low-grade Oncocytic Tumor (Lot)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: Low-grade Oncocytic Tumor (Lot)mentioning

confidence: 99%

Section: Low-grade Oncocytic Tumor (Lot)mentioning

confidence: 99%

Section: Low-grade Oncocytic Tumor (Lot)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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“…One had a TSC1 mutation that was discovered to be a germline mutation. Four had mTOR mutations, and one had a Rheb mutation [41].…”

Section: Tsc1 and Tsc2 Mutations In Sporadic Low-grade Oncocytic Tumor (Lot) Of The Kidneymentioning

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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“…While typically indolent and presenting in adult females, this neoplasm often occurs in children 15 and may rarely present with metastatic disease which in one case has dramatically responded to treatment with MTOR inhibitors. Finally, corresponding to group three, a neoplasm provisionally termed "low-grade oncocytic tumor" (LOT) 16 has been described and in this issue of Modern Pathology demonstrated to be associated with somatic TSC1/2 gene mutations [17][18][19] . These neoplasms resemble the eosinophilic variant of chromophobe RCC in that they are composed of solid areas of low-grade oncocytic cells with perinuclear halos, which label with cytokeratin 7.…”

mentioning

confidence: 99%

Renal cell carcinoma associated with tuberous sclerosis complex (TSC)/mammalian target of rapamycin (MTOR) genetic alterations

Argani

Mehra

2022

Modern Pathology

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Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney

Cited by 41 publications

References 70 publications

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

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

Renal Cell Carcinoma in Tuberous Sclerosis Complex

Renal cell carcinoma associated with tuberous sclerosis complex (TSC)/mammalian target of rapamycin (MTOR) genetic alterations

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