{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:31:12Z","timestamp":1791289872217,"version":"4.3.0"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2013Hogg\u2013Dube-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.<\/jats:p>","DOI":"10.3390\/genes12101585","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"1585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Renal Cell Carcinoma in Tuberous Sclerosis Complex"],"prefix":"10.3390","volume":"12","author":[{"given":"Elizabeth P.","family":"Henske","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine M.","family":"Cornejo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Lee","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","article-title":"Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial","volume":"381","author":"Franz","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMoa1100391","article-title":"Efficacy and safety of sirolimus in lymphangioleiomyomatosis","volume":"364","author":"McCormack","year":"2011","journal-title":"N. 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