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We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months\u201374 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.25%); median age at diagnosis was 37.5 years (range of 1.6\u201358). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non\u2010renal malignancy (3.3%), but we did not find a more prevalent type of cancer. No patient developed more than one malignancy. The prevalence of all malignant tumors was compatible with the prevalence in the general population (5.6%, 95%CI 2.99\u22129.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6\u221244.7, vs. 66.0 years). Two patients (13.3%) died of their cancer, while outcome was favorable in the remaining individuals. Malignant tumors were more frequently diagnosed in patients with mutations in<jats:italic>TSC1<\/jats:italic>when compared to<jats:italic>TSC2<\/jats:italic>and patients with no mutation identified (<jats:italic>P<\/jats:italic>\u2009=\u20090.032). Our study demonstrated that TSC patients do not seem to have an increased risk for malignancies besides renal cell carcinoma. However, when cancer develops, age at diagnosis is lower than in the general population, and malignant tumors are more frequently diagnosed in patients with mutations in<jats:italic>TSC1<\/jats:italic>. Further studies are needed to confirm these data. \u00a92016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37644","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T17:42:56Z","timestamp":1460310176000},"page":"1538-1544","source":"Crossref","is-referenced-by-count":32,"title":["Do patients with tuberous sclerosis complex have an increased risk for malignancies?"],"prefix":"10.1002","volume":"170","author":[{"given":"Angela","family":"Peron","sequence":"first","affiliation":[{"name":"Child Neurology Unit\u2014Epilepsy Center San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Child Neurology Unit\u2014Epilepsy Center San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"La Briola","sequence":"additional","affiliation":[{"name":"Child Neurology Unit\u2014Epilepsy Center San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Volpi","sequence":"additional","affiliation":[{"name":"Nephrology Unit San Paolo Hospital Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Montanari","sequence":"additional","affiliation":[{"name":"Urology Unit San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Morenghi","sequence":"additional","affiliation":[{"name":"Biostatististics Unit Istituto Clinico Humanitas Rozzano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Ghelma","sequence":"additional","affiliation":[{"name":"DAMA Unit (Disabled Advanced Medical Assistance) San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Bulfamante","sequence":"additional","affiliation":[{"name":"Human Pathology Unit San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Cefalo","sequence":"additional","affiliation":[{"name":"Pediatrics Department San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Canevini","sequence":"additional","affiliation":[{"name":"Child Neurology Unit\u2014Epilepsy Center San Paolo Hospital Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.18295\/2075-0528.2766","article-title":"Gasdtric adenocarcinoma in association with tuberous sclerosis: Case report","volume":"9","author":"Ahmed S","year":"2009","journal-title":"Sultan Qaboos Univ Med J"},{"key":"e_1_2_7_3_1","first-page":"1","article-title":"Prevalence and cure of cancer in Italy","volume":"38","year":"2014","journal-title":"Epidemiol Prev"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981115)83:10<2208::AID-CNCR21>3.0.CO;2-K"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00838.x"},{"key":"e_1_2_7_6_1","first-page":"1201","article-title":"Tuberous sclerosis\u2010associated renal cell carcinoma. 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