EXTRAPULMONARY LYMPHANGIOLEIOMYOMATOSIS AND LYMPHANGIOMATOUS CYSTS INTUBEROUS SCLEROSIS COMPLEX

Objective: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LA M) in the tuberous sclerosis complex (TSC). Design: We retrospectively reviewed institutional medical records since 1940 to identify patient s with TSC and extrapulmonary LAM. Material and Methods: Of 403 patien ts with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitonea l lymphangiomatous cysts. The clinical, imaging, and histologic featur es of these three patients were summarized, including analysis of biop sy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. Results: The three young wo men had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent histor y of contraceptive use. All three patients had intra-abdominal lymphan giomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and ute rine biopsy specimens demonstrated positive immunostaining for melanom a-related antigens and expression of estrogen and progesterone recepto rs by ligand-binding assay and immunohistology. Cells cultured from LA M tissue of one of the patients exhibited a mitogenic response to estr adiol. Conclusion: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this;disease who als o have pulmonary LAM. The clinical features of these patients confirm the importance of sex Steroids in the development of these lesions. Im munohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.