Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness

Abstract

The TOSCA registry highlights the burden of renal angiomyolipoma in patients with TSC and shows that renal manifestations are initially asymptomatic and are influenced by gender and genotype. Furthermore, the occurrence of significant problems from angiomyolipoma in a minority of younger patients suggests that surveillance should begin in infancy or at initial diagnosis.

Renal manifestation of tuberous sclerosis complex

“…Angiomyolipomata are the most prevalent renal lesion in TSC. Their frequency of detection progressive increases from 8.8% in those aged <2 years to 78.9% in those >40 years (Kingswood et al, ). The number who need intervention also rises with age from 1% in the under 2 year olds up to 48.6% in those over 40 (Kingswood et al, ).…”

“…Their frequency of detection progressive increases from 8.8% in those aged <2 years to 78.9% in those >40 years (Kingswood et al, ). The number who need intervention also rises with age from 1% in the under 2 year olds up to 48.6% in those over 40 (Kingswood et al, ). The cell of origin for the angiomyolipomata, categorized a perivascular epithelial cell tumor (PEComa), is unknown (Hornick & Fletcher, ).…”

“…Renal cell carcinoma in patients with TSC has been long described (Bjornsson, Short, Kwiatkowski, & Henske, ), but the frequency for TSC is likely much lower and inflated estimates of 2% are difficult to substantiate because the data are really in collected series (Guo et al, ). In the largest retrospective study of 2,216 subjects, renal malignancy (of all types) was reported in 1.1% (Kingswood et al, ). This is different than for inherited renal cancer predisposition syndromes that have a much more elevated risk, such as Birt‐Hogg‐Dubé with an estimated frequency for renal malignancy about 25% (Maher, ).…”

“…It is hoped that amelioration of renal angiomyolipomata using mTOR inhibitor therapy will improve long‐term outcome of renal function, provided the mTOR inhibitors do not themselves adversely affect clearance. Preliminary evidence of a very low complication rate—including low levels of renal impairment—in the TOSCA cohort suggest that this is a useful strategy (Kingswood et al, ). In that cohort, there has been a switch from historical use of embolization for preemptive treatment of renal angiomyolipomata to mTOR inhibitors.…”

“…Angiomyolipomata are detectable at a younger mean age in patients with TSC2 mutations compared to TSC1 (13 years vs. 24 years), and more often need intervention in TSC2 compared to TSC1 (27% vs. 13%) (Kingswood et al, ). Female gender has been postulated to be associated with an increased incidence of adverse outcome from angiomyolipomata based on data from a case series (Rakowski et al, ) and due to the fact that two thirds of subjects entered into the Exist‐2 study were women (Bissler et al, ).…”