mTOR inhibitor therapy as a disease modifying therapy for tuberous sclerosis complex.

Between 1993 and 2003, through experiments involving Drosophila sp., cancer biologists identified the protein kinase known as the mammalian target of rapamycin, its pathway, and its relationship to the genes responsible for tuberous sclerosis. Thereafter, clinical research has resulted in regulatory approval of mTOR inhibitors for four distinct manifestations of the disease: giant cell astrocytoma, angiomyolipoma, lymphangioleiomyomatosis, and epilepsy. These developments are summarized and the practical use of mTOR inhibitors to improve the lives of patients with tuberous sclerosis reviewed.

Linfangioleiomiomatosis pulmonar: reporte de un caso

La linfangioleiomiomatosis es una enfermedad rara con menos de 250 casos reportados en la literatura universal, que ocurre únicamente en mujeres, usualmente en edad reproductiva y que se caracteriza por la proliferación de células de musculo liso en tejido pulmonar y en los vasos linfáticos. Presentamos el caso de una mujer de 29 años, con disnea progresiva, tos con escasa espectoración y neumotórax espontáneo bilateral. El diagnóstico se realizó mediante biopsia pulmonar a cielo abierto, donde se encontró proliferación de haces de músculo liso los cuales se disponían preferentemente alrededor de las estructuras vasculares,bronquiales y septo alveolares. Comentamos los principales hallazgos clínicos, radiológicos e histopatológicos.

Pulmonary lymphangioleiomyomatosis in a male.

Pulmonary lymphangioleiomyomatosis has been observed almost exclusively in women, usually in their reproductive years. Exacerbations with pregnancy and after hormonal manipulation have been documented, and it has been suggested that its pathogenesis is due to the influence of hormonal(estrogenic) stimulus. The clinical, roentgenographic, and histopathologic features of this case of pulmonary lymphangioleiomyomatosis in a 22-year-old male are all characteristic of those described in prior reports, except for the patient's sex. With the following case of pulmonary lymphangioleiomyomatosis in a male, we suggest the possibility of the existence of an additional pathogenetic mechanism.

Lymphangiomyomatosis--newer concepts in pathogenesis and management--case reports.

Lymphangiomyomatosis was first reported more than forty years ago. Although its incidence is rare, its occurrence is being increasingly recognized and has been the subject of a growing number of cases reports in recent years. This study adds 2 more cases to the file. Both cases involved young women with the characteristic symptoms of dyspnea, cough, abdominal discomfort and swelling, chest pain, and hemoptysis, with abundant formation of refractory chylous, serous ascites. Although the progression of the disease differed in each case, pulmonary function was affected in a similar way by the presence of obstructive and restrictive defects and a decrease in diffusing capacity. Underlying abnormalities were dilated lymphatics, thickened lymphatic walls, and muscular proliferation of leiomyomatous origin, leading to bronchial restriction. The authors point to the subtlety required in arriving at a differentiated diagnosis of lymphangiomyomatosis lymphangioleiomyomatosis and the difference between the two conditions. They also make particular recommendations in respect to the importance of preliminary hormone receptor tests and to the wisdom to be exercised in ligating a main lymphatic duct in the chest to control the formation of ascites. Pneumothorax, a frequent manifestation of lymphangiomyomatosis, is found to be the result of chronic air trapping due to a combination of narrowing of conducting airways and disruption of normal lung parenchyma.

[Diagnostic reflections on lung lymphangioleiomyomatosis]. / Riflessioni di ordine diagnostico sulla linfangioleiomiomatosi polmonare.

Two cases of histologically proven pulmonary lymphangiomyomatosis were studied by means of an adequate combination of the current imaging modalities. After an anatomical survey of the secondary pulmonary lobule, the authors discuss the pathologic appearance, the pathogenetic factors (mainly hormones), and the diagnostic problems concerning this pathologic condition. Finally, the authors emphasize the decisive role of high-resolution CT (HRCT) in the evaluation of pulmonary lymphangioleiomyomatosis.

Pulmonary lymphangiomyomatosis associated with tuberous sclerosis. Treatment with tamoxifen and tetracycline-pleurodesis.

A 44-year-old woman was seen with the clinical and histologic picture of lymphangiomyomatosis syndrome. She also had dermatologic and neurologic stigmata of tuberous sclerosis. After the development of a recurring chylothorax, she had a downhill course unresponsive to dietary, bronchodilator, corticosteroid and progesterone therapy. In an open lung specimen, the search for steroid receptor for estrogen was positive. The discovery in this case of an estrogen receptor represents important evidence for establishing an association between tuberous sclerosis and lymphangiomyomatosis. Tamoxifen therapy and tetracycline pleurodesis were successful in stopping the progressive course and controlling the chylothorax.