title: Do patients with tuberous sclerosis complex have an increased risk for malignancies?
abstract: Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months-74 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 1.6-58). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non-renal 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 2.99-9.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6-44.7, 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 TSC1 when compared to TSC2 and patients with no mutation identified (P = 0.032). 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 TSC1. Further studies are needed to confirm these data. ©2016 Wiley Periodicals, Inc.
authors.affiliation: Child Neurology Unit-Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Peron
authors.affiliation: Child Neurology Unit-Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.affiliation: Child Neurology Unit-Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: La Briola
authors.affiliation: Nephrology Unit, San Paolo Hospital, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Volpi
authors.affiliation: Urology Unit, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montanari
authors.affiliation: Biostatististics Unit, Istituto Clinico Humanitas, Rozzano, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morenghi
authors.affiliation: DAMA Unit (Disabled Advanced Medical Assistance), San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ghelma
authors.affiliation: Human Pathology Unit, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bulfamante
authors.affiliation: Pediatrics Department, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Cefalo
authors.affiliation: Child Neurology Unit-Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D010641:Phenotype; D011159:Population Surveillance; D012189:Retrospective Studies; D012306:Risk; D018426:SEER Program; D014402:Tuberous Sclerosis / Q000150:complications* / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy; D055815:Young Adult
keywords: TSC; TSC1; TSC2; cancer; malignancy; neoplasia; tuberous sclerosis complex; tumor