Consistent with the Knudson’s “two-hit” theory for explaining the tumorigenesis in which usually through a mutation in one allele coupled with loss of the remaining wild-type allele [11,12], S-LAM develops arising from two somatic mutations in TSC1/2 while TSC-LAM have one germline mutation and one acquired mutation [13,14]. Here, TSC1 is linked to lymphangioleiomyomatosis.