Extrapulmonary lymphangioleiomyomatosis (LAM): Clinicopathologic features in 22 cases

Abstract

We describe the lesions of extrapulmonary lymphangioleiomyomatosis (LAM) affecting the lymph nodes of the mediastinum and retroperitoneum in 22 women (mean age +/- SD, 42.4+/-10.5 years). In most of these patients, the diagnosis of extrapulmonary LAM preceded that of pulmonary LAM, usually by 1 to 2 years. Eleven patients had distinct symptoms, including chylous pleural effusion and/or ascites, abdominal pain, and palpable abdominal masses. In the other 11 patients, the masses caused no symptoms. Well-circumscribed, encapsulated masses, measuring up to 20 cm in size, occurred in the mediastinum in 2 patients, the upper retroperitoneum in 15, extensive areas of the retroperitoneum in 2, and the pelvis in 3. The masses exceeding 3 cm in diameter contained large, multiple cysts filled with yellow-tan chylous fluid. Histologically, the masses were characterized by a proliferation of smooth muscle cells (LAM cells) arranged in fascicular, trabecular, and papillary patterns, which were associated with slit-like vascular channels. The LAM cells varied from small, spindle-shaped cells to large epithelioid cells. Immunohistochemical studies showed a strong reactivity of most LAM cells for alpha-smooth muscle actin and smooth muscle myosin heavy chain and a weak to moderate reactivity of a lesser number of cells for desmin and nonmuscle myosin heavy chain II-B. A reaction for HMB-45 and estrogen and progesterone receptors was observed mainly in epithelioid LAM cells. These patterns of reactivity are similar to those observed in pulmonary LAM. However, the chylous cysts are not a feature of pulmonary LAM and are thought to result from obstruction of lymphatics.

Leiomyomatosis-Like Lymphangioleiomyomatosis of the Colon in a Female with Tuberous Sclerosis

“…the occurrence in a female of reproductive age with TSC and the histologic spectrum of changes that embody spindle and epithelioid smooth muscle cells surrounding endothelial-lined spaces in conjunction with a lymphangiomatous component and HMB45 expression. Furthermore, extrapulmonary LAM is a known phenomenon, having been described in mediastinal lymph node, retroperitoneum, and uterus (22,23), and hence a colonic location in this instance does not exclude a diagnosis of LAM.…”

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

“…All three cases reported to date also had renal angiomyolipomas, but in only one of them was an association with pulmonary lymphangioleiomyomatosis observed. 14,20 Based on the recent demonstration that MTOR inhibitors can regulate major functional activities of osteoclasts, including the expression of cathepsin K, and on the demonstration that the expression of cathepsin K in osteoclasts is regulated by MITF, 21 we investigated PEComa lesions of the kidney for the expression of cathepsin K, a papain-like cysteine protease with high matrix-degrading activity, to better understand the molecular mechanisms involved in their pathogenesis and to evaluate its diagnostic usefulness in comparison with other commonly used markers.…”

Serum Vascular Endothelial Growth Factor-D Levels in Patients With Lymphangioleiomyomatosis Reflect Lymphatic Involvement

“…7 LAM lung nodules contain channels lined by lymphatic endothelial cells. 7,8 Extrapulmonary LAM cells in the lymphatics are arranged in fascicular and papillary patterns, and are commonly present in lymph nodes of the mediastinum and retroperitoneum. 8 One third of women with tuberous sclerosis complex (TSC), an autosomal-dominant disorder associated with benign, hamartomatous lesions, present with pulmonary cysts.…”