Generalized Lymphatic Anomaly

Generalized lymphatic anomaly (GLA) — also called lymphangiomatosis — is a rare condition involving the abnormal overgrowth of lymphatic vessels in the lungs, pleura (membranes around the lungs), bones, and soft tissue.

Lymphatic vessels are part of the body’s lymphatic system, which transports a clear fluid containing white blood cells called lymph around the body to help clear toxins and waste.

The overgrowth of these vessels leads to lymphatic malformations, small or large cysts, formerly called lymphangiomas. Though benign (non-cancerous), these cysts can lead to serious problems.

There are many synonyms for GLA. Other names include:

• Diffuse pulmonary lymphangiomatosis, or DPL
• Pulmonary lymphangiomatosis

GLA is closely related to Gorham-Stout disease, a condition involving abnormal growth of lymphatic vessels that affects bone.

Generalized lymphatic anomaly (GLA) may affect any area of the body except the brain, where there are no lymphatic vessels. It most commonly affects the lungs and surrounding cavities and tissues of the chest (mediastinum), but it can affect other organs such as the spleen, liver, and bone. GLA can also be associated with problems of the lymphatic central collecting system. This is simply a “plumbing problem” of the lymphatic system, which can cause lymphatic fluid to leak in the chest (pleural effusions) or heart (pericardial effusion), abdomen (ascites), or other organs.

There are no telltale signs of GLA. Diagnosis can be difficult because its symptoms can vary widely or be mild, leading to the disease going undetected into adulthood. In others, physicians may incorrectly identify the symptoms as asthma.

Symptoms of GLA in or around the lungs include:

• Chest pain
• Wheezing
• Shortness of breath
• Chronic cough or coughing up blood
• Repeated respiratory infections

Symptoms of GLA in other areas of the body include:

• Pelvic or abdominal pain
• Swelling
• Fever
• Internal bleeding
• Skin lesions
• Bone pain

The exact cause of GLA is not known. Experts believe GLA is a congenital disorder (present at birth). It affects both males and females and patients of all ages, even infants. Most cases of GLA are diagnosed in childhood, but GLA has been diagnosed in adults as well.

Researchers are studying whether a protein in the body — called vascular endothelial growth factor receptor 3 (VEGFR-3) — may be a factor. Researchers have found high levels of VEFGR-3 in tissues affected by GLA. Other biomarkers (proteins in the blood) are also being tested.

During your initial evaluation, your physician will conduct a thorough medical exam and ask questions about your child to create a detailed medical history.

Tests your physician may recommend include one or more of the following:

• MRI
• CT scan
• Pulmonary function tests
• Lymphangiogram: An imaging test that uses a contrast dye and an X-ray or MRI to visualize the body’s lymphatic system.

If necessary, a biopsy, a procedure in which a tissue sample is taken for further testing in the laboratory, may be taken. However, a biopsy can also present risks, so it is only performed if needed.

There is no one test that can positively diagnose GLA. Because this condition is easily missed or misdiagnosed as asthma, it may go undetected until a patient undergoes an imaging study.

The goal during diagnosis is to pinpoint the location and severity of GLA and use that information to develop a customized, targeted treatment plan.

Your child’s specific treatment plan depends on several factors, including the part of the body affected, severity of the disease, and related complications.

Treatment options may include:

• Medication/drug therapy
• Surgery
• Pleural or pericardial drainage
• Radiotherapy

Drug therapy for GLA

Many types of medications have proven effective for slowing the progression of generalized lymphatic anomaly and relieving symptoms. These include:

• immunosuppressants that target the lymphatic vessels that grow abnormally and disrupt the body’s normal bone regeneration process, including sirolimus (also known as rapamycin) or interferon alfa-2b
• VEGFR-3 inhibitors that slow or halt production of vascular endothelial growth factor receptor 3 (VEGFR-3), a protein researchers believe is linked to the cause of GLA. These inhibitors include propranolol and bevacizumab

Surgery for GLA

Surgical resection (removal) is possible when the disease has not spread throughout lymphatic tissue. When possible, this approach can cure patients if all of the abnormal lymphatic tissue is removed.

In most cases, however, it is too difficult for surgeons to differentiate healthy tissue from the abnormal lymphatic tissue.

The most effective treatment for GLA includes a comprehensive team approach that involves multiple specialists working together to develop customized treatment plans.

As part of the Boston Children’s Vascular Anomalies Center, our experts treating GLA include:

• Hematologists who use the most advanced medical therapies today to target the abnormal growth of lymphatic vessels
• Pulmonologists who specialize in lung conditions and complications
• Surgeons who may remove affected tissues, when possible
• Medical specialists from cardiologists to interventional radiologists who treat the full spectrum of complications related to GLA
• Researchers studying the latest investigational therapies and possible genetic links of the disease
• Dedicated social worker to help coordinate services to treat the emotional needs of your child and arrange support services

At Boston Children’s Hospital, we treat patients with GLA in our Vascular Anomalies Center, considered a premier center in the world for vascular anomalies. Families of children around the globe with GLA seek care at Boston Children’s because we offer highly specialized care, access to leading clinical trials, a comprehensive multidisciplinary team approach, and expert consults for national and international patients.

At Boston Children’s, our team is world renown for its expertise in vascular anomalies, including GLA. Our experts at the Vascular Anomalies Center are actively involved in the latest research on this disease, including participation in leading clinical trials.

Boston Children’s is currently studying the use of immunosuppressant medications to relieve symptoms and slow the progression of GLA. Results have already shown significant success in patients.

These include:

• Sirolimus (also known as rapamycin)
• Interferon alfa-2b
• VEGFR-3 inhibitors

We are also very active in the collection of patient data related to GLA to further improve our understanding of GLA, including what complications to expect, which therapies are more effective than others, predictors of disease stability and/or recurrence, and inheritance patterns. Through this registry, we are studying causes of mortality, effusions, infections, and other challenges in GLA. For more information or to participate, please visit our Lymphatic Anomalies Registry.