Renal
angiomyolipomas are highly vascular
tumors that occur sporadically, in women with pulmonary
lymphangiomyomatosis (
LAM), and in
tuberous sclerosis complex (
TSC). The goal of this study was to determine whether the distinctive vessels of
angiomyolipomas are neoplastic or reactive. We studied
angiomyolipomas with loss of heterozygosity (LOH) in the TSC2 region of chromosome 16p13 from patients with
LAM. We found that
angiomyolipomas contain five morphologically distinct vessel types: cellular, collagenous, hemangiopericytic, glomeruloid, and aneurysmatic. Using
laser capture microdissection, we determined that four of the vessel types have TSC2 LOH and are therefore neoplastic. One vessel type, collagenous vessels, did not have LOH, and is presumably reactive. Recently, activation of
S6 Kinase and its target S6
ribosomal protein (S6) was demonstrated in cells lacking TSC2 expression. We found that
angiomyolipoma vessel types in which LOH were detected were immunoreactive with anti-phospho-S6
antibodies.
Angiomyolipoma cells without LOH, including the endothelial component of the vessels, were not immunoreactive. To our knowledge,
angiomyolipomas are the first benign vascular
tumor in which the vascular cells, rather than the stromal cells, have been found to be neoplastic.
Angiomyolipomas appear to reflect novel vascular mechanisms that may be the result of activation of cellular pathways involving
S6 Kinase.