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.

Hereditary renal cell carcinoma syndromes: diagnosis, surveillance and management

“…There has been increasing recognition of a significant risk of RCC in patients with Cowden/PTEN hamartoma tumour syndrome, but germline PTEN mutations are very rare in patients with non-syndromic inherited RCC [36]. Tuberose sclerosis may be associated with early-onset RCC, but RCC is rare in this condition and renal lesions are most commonly angiomyolipomas [37]. Germline VHL, SDHx and FH mutations may predispose to phaeochromocytoma/paraganglioma and RCC, and on rare occasions renal tumours have been reported in association with mutations in the phaeochromocytoma genes TMEM127 and MAX [38, 39].…”

The cutaneous manifestations of tuberous sclerosis complex

“…Sun protection is especially important in patients with TSC. The skin lesions tend to increase in size and incidence over time, although there is no significant risk of malignant transformation (Peron, Vignoli, La Briola, et al, 2016). Subsequent annual exams are also recommended (Teng et al, 2014).…”

“…Subsequent annual exams are also recommended (Teng et al, 2014). The skin lesions tend to increase in size and incidence over time, although there is no significant risk of malignant transformation (Peron, Vignoli, La Briola, et al, 2016). Intervention may be warranted if these are noted to be causing functional difficulties, pain, bleeding, and becoming secondarily infected or inhibiting social interactions.…”

Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond

“…These particular lesions have unique characteristics compared with classic angiomyolipomas, including minimal or no fat, possible increased risk of hemorrhage, and more-aggressive behavior (increased risk of local invasion and distant metastasis) (51). Renal cell carcinoma has rarely been reported in TSC and may have unique clinical-pathologic features (Fig 15) (52,53).…”