Lymphangioleiomyomatosis

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Lymphangioleiomyomatosis (LAM) is a rare, progressive and systemic disease that typically results in cystic lung destruction. It predominantly affects women, especially during childbearing years. The term sporadic LAM is used for patients with LAM not associated with tuberous sclerosis complex (TSC), while TSC-LAM refers to LAM that is associated with TSC.

The average age of onset is the early to mid 30s.  Exertional dyspnea (shortness of breath) and spontaneous pneumothorax (lung collapse) have been reported as the initial presentation of the disease in 49% and 46% of patients, respectively.

Diagnosis is typically delayed 5 to 6 years.The condition is often misdiagnosed as asthma or chronic obstructive pulmonary disease. The first pneumothorax, or lung collapse, precedes the diagnosis of LAM in 82% of patients.[7][8] The consensus clinical definition of LAM includes multiple symptoms:

Fatigue
Cough
Coughing up blood (rarely massive)
Chest pain
Chylous complications arising from lymphatic obstruction, including
Chylothorax
Chylous ascites
Chylopericardium
 Chyloptysis
Chyluria
Chyle in vaginal discharge
Chyle in stool.

    Angiomyolipomas (fatty kidney tumors) are present in about 30% of patients with sporadic LAM and up to 90% of patients with TSC-LAM. Angiomyolipomas can sometimes spontaneously bleed, causing pain or low blood pressure.

    Cystic lymphangiomas or lymph nodes with hypodense centers, which mimic necrotizing lymphomas, ovarian or renal cancers, or other malignancies can occur in the retroperitoneum, pelvis or mediastinum.

Lung destruction in LAM is a consequence of diffuse infiltration by neoplastic smooth muscle-like cells that invade all lung structures including the lymphatics, airway walls, blood vessels and interstitial spaces. The consequences of vessel and airway obstruction include chylous fluid accumulations, hemoptysis, airflow obstruction and pneumothorax. The typical disease course displays progressive dyspnea on exertion, spaced by recurrent pneumothoraces and in some patients, chylous pleural effusions or ascites.

Most people have dyspnea on exertion with daily activities by 10 years after symptom onset. Many patients require supplemental oxygen over that interval.

LAM occurs in two settings: in the disease tuberous sclerosis complex (TSC-LAM) and in a sporadic form, in women who do not have TSC (sporadic LAM). In both settings, genetic evidence indicates that LAM is caused by inactivating or “loss of function” mutations in the TSC1 or TSC2 genes, which were cloned in 1997 and 1993 respectively.The TSC1 gene is located on the long arm of chromosome 9 (9q34) and the TSC2 gene is located on the short arm of chromosome 16 (16p13). TSC-LAM occurs in women who have germline mutations in either the TSC1 or the TSC2 gene.

Media Contact
John Mathews
Journal Manager
Journal of Phlebology and Lymphology
Email: phlebology@eclinicalsci.com