LYMPHANGIOMYOMATOSIS AND ANGIOMYOLIPOMA - CLOSELY RELATED ENTITIES CHARACTERIZED BY HAMARTOMATOUS PROLIFERATION OF HMB-45-POSITIVE SMOOTH-MUSCLE

Angiomyolipoma is a hamartomatous condition which can occur as a compo nent of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long be en suspected to be related to angiomyolipoma and tuberous sclerosis be cause of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two e ntities. Five cases of lymphangiomyomatosis and 20 case of angiomyolip oma were retrieved for histological review and immunohistochemical stu dies. The antibodies used were anti-muscle specific actin (HHF-35), an ti-desmin (D33) and antimelanoma (HMB-45). Lesions featuring smooth mu scle proliferation were used as controls. The proliferated smooth musc le cells in both lymphangiomyomatosis and angiomyolipoma were much plu mper and paler or even clear, when compared with the deeply eosinophil ic cytoplasm of the normal spindly smooth muscle cells and those of le iomyomas. Their nuclei were round to oval and pale rather than elongat ed and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomy olipoma there were foci indistinguishable from lymphangiomyomatosis, i .e. plump spindle cells arranged in short fascicles around ramifying e ndothelium-lined spaces. All five cases of lymphangiomyomatosis staine d for muscle-specific actin, desmin and HMB-45. For angiomyolipomas, t he positivity rates for these markers were: 20/20, 17/20 and 18/20, re spectively, including one case that was negative for both desmin and H MB-45. The various smooth muscle proliferations and tumours selected a s controls were uniformly HMB-45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all supp ort a close relationship between lymphangiomyomatosis and angiomyolipo ma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB-45-positive smo oth muscle.