Lymphangioleiomyomatosis (LAM)

What is lymphangioleiomyomatosis (LAM)?

Lymphangioleiomyomatosis (LAM) is a rare lung disease that causes damaging cysts in your lungs. It can also cause growths in your kidneys and lymphatic system. It’s caused by genetic mutations that allow smooth muscle cells to grow uncontrollably.

Lymphangioleiomyomatosis (pronounced “limf-AN-gee-oh-ly-oh-my-oh-muh-TOH-sis”) mostly affects people assigned female at birth (AFAB). Most people are diagnosed between the ages of 20 and 40, or between puberty and menopause. Because of this, experts believe the hormone estrogen or having a uterus may play a role in cyst development.

Types of lymphangioleiomyomatosis

There are two types of LAM:

• TSC-LAM. Some people with the genetic disorder tuberous sclerosis develop LAM (TSC-LAM). 
• Sporadic LAM. A genetic change (mutation) that happens randomly during your life can cause sporadic LAM. You can’t pass sporadic LAM on to your children.

How common is LAM?

LAM is rare. Fewer than 1 in 140,00 people AFAB has sporadic LAM. Anywhere between 30% to 80% of people AFAB with tuberous sclerosis also have LAM.

What are the symptoms of lymphangioleiomyomatosis (LAM)?

Symptoms of LAM include:

• Shortness of breath (dyspnea) or difficulty breathing. This can get worse over time.
• Wheezing.
• Chest pain.
• Cough.
• Coughing up blood or chyle (lymph from your digestive system).

What causes lymphangioleiomyomatosis (LAM)?

Mutations (changes) in two genes (TSC1 and TSC2) can cause LAM. TSC1 and TSC2 are tumor suppressor genes. They keep certain cells from multiplying out of control. When one of them has a mutation, smooth muscle cells multiply when they shouldn’t. This causes:

• Cysts in your lungs (pulmonary lymphangioleiomyomatosis).
• Kidney tumors (angiomyolipomas).
• Tumors in your lymphatic system.

How do you get LAM?

You can either inherit an abnormal copy of TSC1 or TSC2 from a biological parent who has one, or changes to the gene can be spontaneous (we don’t know why it happens). Inherited changes in TSC1 or TSC2 cause tuberous sclerosis. More than 30% of people AFAB with tuberous sclerosis have LAM. Changes to TSC2 that you didn’t inherit cause sporadic LAM, without additional symptoms of tuberous sclerosis.

What are the risk factors for LAM?

LAM almost exclusively affects people AFAB. Only a few people assigned male at birth (AMAB) have ever received a LAM diagnosis. There’s only one known case of someone AMAB with sporadic LAM. LAM often gets worse during pregnancy and while using medications that contain estrogen.

What are the complications of LAM?

A collapsed lung (pneumothorax) is the most common complication of LAM. Over half of all people with LAM will have a collapsed lung at least once, and they often recur. Many people with LAM are diagnosed after experiencing lung collapse.

Other complications include:

• Chyle around your lungs (chylothorax).
• Fluid around your lungs (pleural effusion).
• Blockage in your lymph system.

How is LAM diagnosed?

To diagnose LAM, a healthcare provider will examine you and ask about your symptoms. They’ll order or perform tests and imaging to better understand:

• How well your lungs are working.
• The levels of oxygen in your blood.
• If there are any changes in your lungs.
• Whether you have higher levels of certain proteins in your blood.

Symptoms of lymphangioleiomyomatosis are similar to those of other, more common lung conditions, so it can be hard for healthcare providers to diagnose.

What tests will be done to diagnose LAM?

You may need the following tests and procedures:

• Lung function tests.
• Blood oxygen level tests (pulse oximetry).
• Imaging. This includes CT scans (computed tomography scans), MRI (magnetic resonance imaging) or high-resolution computed tomography (HRCT) scans. HRCT scans get a more detailed picture of a small area of your lungs to look for certain lung diseases.
• VEGF-D test. Your provider can use blood tests to check for infections, how well your organs are working, and your levels of the protein VEGF-D (vascular endothelial growth factor-D). People with LAM usually have higher amounts of VEGF-D in their blood, but not always.
• Lung biopsy. A provider may perform a bronchoscopy or video-assisted thoracic surgery (VATS) to get a sample for a biopsy.

How is lymphangioleiomyomatosis treated?

There’s no cure for LAM. But the medication sirolimus (also known as rapamycin, or by the brand name Rapamune®) can stabilize it and keep it from getting worse. Sirolimus can also shrink kidney growths (angiomyolipomas), shrink lymphatic masses and fluid collection, and reduce your symptoms.

Other treatments might include:

• Oxygen therapy.
• Inhaled bronchodilators.
• Pulmonary rehabilitation.
• Lung transplant.

Complications and side effects of treatment

Sirolimus can cause severe kidney damage and make you more likely to get serious infections. Talk to your provider about the risks and benefits of taking it.

What can I expect if I have LAM?

LAM can get worse over time, and your treatments may change depending on what’s working for you. You’ll work with a pulmonologist (a healthcare provider who specializes in the lungs) to determine the best way to monitor your condition. They’ll test your lung function periodically. Your provider will individualize your treatment based on your:

• Age.
• Menstrual status (whether or not you’re in menopause).
• Rate of lung function decline.
• Whether your kidneys or lymphatic system are affected.

How fast does LAM progress?

How fast LAM progresses can vary from person to person and can depend on many factors, including: 

• What type of LAM you have. People with TSC-LAM tend to have better lung function than those with sporadic LAM, but their lung function’s rate of decline is usually about the same.
• Your age. LAM stops progressing in some people after menopause, when your body has lower amounts of estrogen. 
• How well you respond to treatment. Sirolimus stabilizes the disease for many people. 

When will I need a lung transplant for LAM?

Many people with LAM (64%) can live 20 years or more after their diagnosis before needing a lung transplant. But because LAM cells don’t start in your lungs, cysts can come back, even after a transplant.

What is the life expectancy of a person with LAM?

Your life expectancy with LAM depends on the severity and how fast it’s progressing. But overall, the outlook is more positive than it was in the past. More than 90% of people with LAM are alive 10 years after their diagnosis.

How do I take care of myself?

Talk to your pulmonologist about what to expect and how to make a plan to manage LAM. Keep all of your follow-up appointments and take your medications as directed. Let your provider know about any new or worsening symptoms or if you have concerning side effects from your treatment.

When should I see my healthcare provider?

If you have shortness of breath, a cough or other concerning symptoms that don’t go away or get worse over time, talk to a healthcare provider.

When should I go to the ER?

Go to the emergency room or seek immediate medical attention if you have signs of a collapsed lung or other serious symptoms, such as:

• Difficulty breathing.
• Chest pain.
• Coughing up blood.
• Bluish skin, lips or nails (cyanosis).

What questions should I ask my doctor?

It might be helpful to ask your healthcare provider:

• Do I have sporadic LAM or TSC-LAM?
• What are my treatment options?
• How do I take my medications?
• What new or worsening symptoms should I look out for?
• Will I need a lung transplant?

Is lymphangioleiomyomatosis (LAM) a type of cancer?

LAM isn’t usually considered cancer. In some ways it acts like metastatic cancer — the cells seem to start somewhere else and move through your blood vessels and lymph system to your lungs and kidneys. The way it grows is sometimes called benign cell metastasis.

But scientists aren’t exactly sure where the cells start. And the growths don’t seem to spread widely to organs like your liver and brain like cancer does. Under a microscope, the cells look more like normal cells rather than cancer cells.

A note from Cleveland Clinic

Thanks to new treatments and a better understanding of LAM, people are living longer without a lung transplant. Still, the adjustment to a new way of life will take time. Finding out you have a lifelong condition can be like getting the rug pulled out from under you. But your healthcare team — and your personal support team — can help you find your footing again.