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General Information

LAM Week

LAM is a rare disorder that affects mostly women, and whose neoplastic nature was recently described. It is thought that LAM occurs in several thousand women in the United States and fewer than 10,000 women worldwide. Mutational inactivation of either tuberous sclerosis complex (TSC) 2 (tuberin) or TSC 1 (hamartin) genes are found in LAM patients. LAM can manifest in the context of tuberous sclerosis (TSC-LAM), or sporadically (S-LAM).

LAM is characterized by impaired breathing. Lung function loss is progressive, pneumothorax is common, and accumulation of lymphatic fluid around the lungs or body cavities as well as hemoptysis (coughing up blood) are observed. With increased diseases severity, patients may require oxygen and lung transplantation. LAM is often misdiagnosed with asthma, emphysema or bronchitis. Therefore, full history, including smoking, use of birth control pills, seizure history and family history of TSC should be obtained to help guide diagnosis.

Histologic analysis has revealed the appearance of multiple cysts in the lung, variable degree of alveolar destruction, formation of nodules containing smooth muscle-like LAM cells in the parenchyma, and in some specimens, the presence of cells positive for HMB-45, a marker of melanocyte lineage. These finding were used in the past for diagnosis in lung specimens. Most recently, a set of studies including high resolution computed tomography (HRCT) that detects pulmonary cysts and nodules, and elevated VEGF-D levels in blood and/or urine are used as valuable biomarkers for diagnosis, prognosis and even response to treatment in the case of VEGF-D.

The origin of the LAM cell in the lung has not been established. The uterus, angiomyolipoma or lymphatics are all proposed as sources of LAM cells. Because of its metastatic behavior, LAM can potentially affect many organs in the body. However, the large filter capacity of lungs and kidneys may explain, at least partially, the prevalence of occurrence of LAM lesions in these tissues. Moreover, studies in animal models have highlighted a prominent role of estrogen and progesterone receptors in LAM pathogenesis, homing, and growth of LAM lesions inside the lung.

TSC gene products function as tumor suppressors and are involved in the control of cell growth, cell migration and cell proliferation. TSC1/2 complex negatively regulate the mammalian target of rapamycin complex 1 (mTORC1), which is a component of the mechanistic target of rapamycin (mTOR) signaling pathway, also known as the mammalian target of rapamycin. Hence, loss of TSC1/2 in LAM induces uncontrolled LAM cell growth and enhances LAM cell viability. Upregulation of STAT1 and STAT3 and autophagy are known mediators of LAM cell viability and survival. Although there is no cure for LAM yet, clinical trials using the rapamycin analog sirolimus demonstrated slow LAM progression. The FDA has approved sirolimus for treatment of LAM in 2015. Since then, few other countries had approved sirolimus to treat LAM patients.

The progress of our understanding of LAM has been remarkable. In about 20 years we went from knowing close to nothing about this disease to having a pharmaceutical intervention to treat these patients.  This has been possible by a tight collaboration among patients, the LAM Foundation, the National Institute of Health, clinicians, and investigators. Together, we will continue generating knowledge and tools to ultimately conquer LAM.

Four Facts About LAM

  1. Lymphangioleiomyomatosis (LAM) is a progressive disease that predominantly affects women, especially during the prime of their lives.  Symptoms may include shortness of breath, collapsed lung, chest pain, cough, fatigue and in 40% of patients one or more benign kidney tumors called angiomyolipomas.

  2. Women with LAM may be misdiagnosed with asthma, emphysema, or bronchitis. The diagnosis of LAM can most often be made without surgical lung biopsy using a combination of high resolution CT imaging of the lungs and abdomen, clinical signs and symptoms, serum VEGF-D levels and sometimes transbronchial biopsy.

  3. In May of 2015, the FDA approved a proven therapy for LAM that can stabilize lung function and improve some measures of quality of life and functional performance. Lung transplant remains the option of last resort for patients with advanced disease.

  4. The discovery of a genetic link between LAM and tuberous sclerosis complex, another rare disease, leads scientists to estimate that more than 250,000 women worldwide are unaware they have LAM.