Lymphangioleiomyomatosis

Abstract

Lymphangioleiomyomatosis (LAM) is a slow albeit progressive rare neoplastic disease featured with diffuse thin-walled cysts in lungs and angiomyolipomas in kidneys. LAM affects almost exclusively women and has one of the strongest gender predispositions of any extragenital human disease. Two forms of LAM present clinically, sporadic (S-LAM) and tuberous sclerosis complex-associated (TSC-LAM). TSC is an autosomal dominant genetic multisystems neoplastic disease. A high prevalence of LAM can be detected in adult female TSC patients. Tremendous progress has been made in our understanding and management of this rare disease. Both LAM and TSC are TSC2 or TSC1 mutated diseases that result in overactivation of the mechanistic target of rapamycin (mTOR) pathway. Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Therapies targeting female sex hormones have shown preclinical efficacy in animal and cell culture-based experiments, but have not been properly investigated clinically. In this review, we summarize current recommendations in the diagnosis and treatment of LAM.

Pregnancy after the diagnosis of lymphangioleiomyomatosis (LAM)

“…LAM is a rare cystic lung disease mainly diagnosed in women of child-bearing age [ 1 ]. Pregnancy is one of their major concerns when patients are diagnosed with LAM.…”

“…Evaluation should include (1) the degree of LAM on high-resolution CT, (2) baseline pulmonary function and pulmonary function decline rate, (3) previous history of pneumothorax or chylothorax, (4) existence and sizes of kidney AML or retroperitoneal lymphangioleiomyomas, (5) TSC, (6) sirolimus treatment, and (7) previous history of pregnancy. A multidisciplinary team including obstetricians, pulmonary physicians, thoracic surgeons, urologists, interventional radiologists, and geneticists is recommended to ensure optimal management during pregnancy [ 1 ].…”

“…Lymphangioleiomyomatosis (LAM) is a rare disease that mostly afflicts women and primarily affects the lung, kidney, and lymphatic system [ 1 ]. The prevalence of LAM varies, ranging from 1 to 9 per million women in the general population and from 30 to 40% in women with tuberous sclerosis complex (TSC) [ 2 – 4 ].…”

Possible Novel Therapeutic Targets in Lymphangioleiomyomatosis Treatment

“…In addition, a recent study found that estrogen increases membrane translocation of glucose transporters and enhances glucose uptake in a PI3K/Akt-dependent way in mTORC1 hyperactive cells ( 64 ). Estrogen promotes glucose metabolism including upregulating the expression of glucose-6-phosphate dehydrogenase (G6PD) and increasing nicotinamide adenine dinucleotide phosphate (NADPH) and ROS production, and thereby promotes cell survival under oxidative stress ( 65 ). A randomized controlled trial of letrozole (a non-steroidal, competitive aromatase inhibitor lowering serum estrone and estradiol) for postmenopausal women with LAM showed that the rate of change for serum VEGF-D between placebo group and letrozole group was −0.024±0.009 pg/ml/month ( P = 0.015), but the rate of change in FEV 1 for all subjects was −3 ± 3 ml/month ( P = 0.4) ( 66 ).…”

Use of Quantitative CT Analysis to Evaluate the Degree of Lung Destruction in Lymphangioleiomyomatosis

“…[5] The clinical manifestations of LAM patients include progressive dyspnea after activities, recurrent spontaneous pneumothorax, refractory chylothorax and finally lead to respiratory failure. [6] Methods used to assess the severity and progression of pulmonary involvement in LAM include arterial blood gas (ABG), St. George's Respiratory Questionnaire (SGRQ), six-minute walk test (6MWT), pulmonary function test (PFT), and highresolution computed tomography (HRCT). [7] Serum levels of vascular endothelial growth factor (VEGF-D) is a diagnostic biomarker of LAM and associated with severity of LAM.…”