Lymphangioleiomyomatosis (LAM): Understanding This Rare Lung Disease

Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that primarily affects women, particularly during their childbearing years. Once considered solely an interstitial lung disease, advancements in understanding have revealed its systemic nature and genetic components. This article provides a comprehensive overview of LAM, covering its causes, symptoms, diagnosis and current treatment options.

What is Lymphangioleiomyomatosis (LAM)?

LAM is characterized by the abnormal growth of smooth muscle-like cells, known as LAM cells, within the lungs, lymphatic system, and sometimes the kidneys. These cells form cysts in the lungs, obstructing airways and damaging lung tissue. It’s now recognized as a low-grade metastatic neoplasm, meaning it behaves like a slow-growing cancer, but with distinct characteristics.¹

Types of LAM

There are two main types of LAM:

• TSC-LAM: This occurs in women with tuberous sclerosis complex (TSC), a rare genetic disorder causing tumors to grow in various organs. Approximately half of women with TSC develop LAM, while it affects only about 10% of men with TSC.²
• Sporadic LAM: This type arises from a genetic mutation that occurs randomly during a person’s lifetime and is not inherited.¹

Who is Affected by LAM?

LAM predominantly affects women of childbearing age, with most diagnoses occurring between the ages of 20, and 40. The estimated prevalence is around three to seven per million women worldwide, though this number is likely underestimated as awareness and diagnostic capabilities improve.² While primarily a disease of women, LAM can occur in men, though it is far less common.³

Symptoms of LAM

The most common symptoms of LAM include:

• Shortness of breath (dyspnea), which can worsen over time
• Spontaneous pneumothorax (collapsed lung)
• Cough
• Chest pain

Beyond pulmonary manifestations, LAM can also present with extra-pulmonary features, such as:

• Abdominal masses, often due to benign kidney tumors called angiomyolipomas (AMLs)
• Lymphatic involvement, leading to lymphadenopathy, pleural effusions, ascites, or lymphangioleiomyomas (lymphatic masses)

Diagnosis of LAM

Diagnosing LAM involves a combination of imaging, pulmonary function tests, and biomarker analysis:

• CT Scan: A CT scan typically reveals round, uniform, thin-walled cysts distributed throughout both lungs, with normal lung tissue in between. However, other conditions can mimic LAM on CT scans.¹
• Spirometry: Pulmonary function tests, like spirometry, assess lung capacity and airflow.
• Vascular Endothelial Growth Factor D (VEGF-D) Level: A blood test measuring VEGF-D levels can be highly indicative of LAM. A level above 800 can often confirm a diagnosis without the need for a biopsy.¹
• Biopsy: In cases with atypical CT findings or absent supporting features, a lung biopsy may be considered, though it’s often avoided if possible.¹

Treatment Options for LAM

Historically, lung transplantation was often the only option for patients with LAM. However, significant advancements in treatment have dramatically improved outcomes.

• mTOR Inhibitors: Medications like sirolimus and everolimus, which inhibit the mTOR pathway, have shown significant promise in slowing disease progression and improving survival rates.¹
• Lung Transplantation: Remains an option for severe cases, but transplant-free survival rates have increased substantially with the utilize of mTOR inhibitors.

The median survival for patients diagnosed with LAM is now estimated to be over 20 years, and the five-year transplant-free survival probability is more than 90%.¹

Looking Ahead

Ongoing research continues to improve our understanding of LAM and develop more effective treatments. Early diagnosis and appropriate management are crucial for maximizing quality of life and extending survival for individuals living with this rare lung disease.