Lymphatic Malformations

Lymphatic malformations are collections of malformed, dilated lymphatic channels that do not function correctly. The lymphatic system consists of organs (spleen, thymus, tonsils and adenoids), lymph nodes and thin tubes called lymphatic vessels which carry clear lymphatic fluid. The lymphatic system is an important part of the immune system and functions to remove excess fluid from the tissues of the body.

In lymphatic malformations, the abnormal lymphatic vessels have impaired or slowed transfer of the lymphatic fluid back into the venous system. This causes excess fluid to accumulate and to dilate the abnormal lymphatic channels, resulting in swelling or enlargement of the affected area.

Lymphatic malformations form prior to birth. Although the exact cause of LMs is unknown, they are thought to be caused by errors in the formation and development of the lymphatic vessels during fetal development. Lymphatic malformations are not caused by any known drug, medication or environmental factor that the baby may have been exposed to during the pregnancy. Most LMs are identified at birth or within 2 years of age but some may not be apparent until adolescence or early adulthood.

Lymphatic malformations most commonly occur in the head and neck area (illustration 1), but may involve any area of the body. Although they usually involve only one area (illustration 3), lymphatic malformations can be diffuse or involve multiple body sites (illustration 4). Symptoms and the severity of complications of LMs vary widely and typically depend on the size and the location(s) of the malformation. Regardless of size, lymphatic malformations may cause organ dysfunction, functional disabilities or deformity.

Lymphatic malformations are also sometimes referred to as lymphangiomas or cystic hygromas. However, these terms are outdated and are not recommended to describe these conditions.

Physical Description Show

Lymphatic malformations have variable appearances. We classify LMs as macrocystic, microcystic or a combination of both.

Macrocystic LMs are composed of large fluid-filled cysts that present as soft, smooth masses under normal or blue-colored skin.

Microcystic malformations are sponge-like and typically appear as an area of swelling or mass-like. Microcystic LMs may also have lymphatic blebs overlying the lesion. Lymphatic blebs are small, raised vesicles containing clear lymphatic fluid and look like blisters. The lymphatic blebs may also become dark red / purple due to bleeding into the vesicle.

Both macrocystic and microcystic malformations may cause enlargement of any body part (the lip, cheek, ear, tongue, limb, finger, toe). Some lymphatic malformations are completely internal and not visible.

Diagnosis Show

Medical history and physical examination are generally sufficient to diagnosis of lymphatic malformation.

A diagnosis may be confirmed by ultrasonography. A magnetic resonance imaging (MRI) or computed tomography (CT) may be performed to evaluate the extent of the malformation and areas of involvement.

Possible Complications Show

Infection of the skin or soft tissues (cellulitis) may occur due to stagnant (non-moving) lymphatic fluid in the malformation or due to bacteria entering the body through open lymphatic vesicles. Cellulitis could potentially lead to a more serious or even life-threatening infection. Immediate treatment with antibiotics is essential to treat these skin and soft tissue infections. Bleeding into the area of the malformation may cause rapid enlargement of the malformation and pain. Bleeding may occur spontaneously or from trauma to the area. There may also be spontaneous leakage of lymphatic fluid from blebs on the skin. These lymphatic vesicles can also bleed. Chronic pain and/or cosmetic disfigurement may occur from the malformation itself or as a result of complications from the malformation.

Additional complications may be possible, depending upon the specific area of the body that is affected by the lesion:

A lesion involving the trachea (windpipe), tongue or chest can cause difficulty breathing.
A lesion in the gastrointestinal tract (stomach and intestines) can cause protein loss.
A lesion in the thorax (chest) can cause chylothorax, which is a leakage of lymphatic fluid into the chest cavity. It can also cause heart and lung complications.
A lesion in the abdomen can cause chylous ascites, which is a leakage of lymphatic fluid into the abdomen.

Although certain complications cannot be prevented, they can sometimes be diminished.

Developing an infection in a lymphatic malformation of the head/neck region is less likely if careful attention is paid to oral hygiene. Regular tooth brushing and visits to the dentist are recommended.

Diffuse Lymphatic Malformations

Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare diffuse lymphatic malformations that involve multiple body sites, most commonly the bones, chest, skin, spleen, liver and gastrointestinal tract. In both GLA and GSD, the lymphatic malformations involve the bones but appear differently on imaging. Gorham-Stout disease, also called “vanishing bone disease,” is characterized by LMs that cause destruction of the bony cortex (outermost layer of the bone) and progressive bone loss. In GLA, the lymphatic malformations appear “punched out” or as holes within the bone. These bony lesions may result in fractures. It is not uncommon that these conditions are not identified until after a bone fracture. If the spine is involved, there is a risk of neurological issues.

Patients with GLA and GSD have an increased risk of developing chylous effusions or leakage of lymphatic fluid into the lungs or abdomen or around the heart, particularly if the ribs are involved. In addition to the potential complications listed above, individuals with GLA and GSD may have other complications depending on locations of the malformation involvement.

Kaposiform lymphangiomatosis (KLA) is a rare disorder characterized by abnormal “kaposiform” lymphatic clusters in multiple body sites and is complicated by effusions, similar to GLA. However, KLA is more aggressive than GLA and is associated with coagulopathy (clotting and bleeding issues). Complications are directly related to the extent of the organ involvement and coagulopathy severity. Because of its aggressive nature and similarities to a vascular tumor called kaposiform hemangioendothelioma (KHE), it is unclear whether KLA is a lymphatic malformation or a vascular tumor.

Treatment and Management Show

All children with lymphatic malformations should undergo a thorough evaluation by a medical professional who has experience in managing and treating patients with LMs. Treatment decisions must be made on an individual basis, with consideration given not only to the physical functioning of the child, but also to the prevention of permanent disfigurement and the emotional and social well-being of the child.

In general, there is no “cure” for lymphatic malformations unless it is localized and can be completely removed, which is usually not possible. Management varies depending on the depth, location and extent of the malformation and the overall treatment strategy may involve multiple treatment approaches. Treatment options include:

Observation. Small malformations with minimal cosmetic or functional issues are often observed over time without treatment.

Compression therapy. This involves wearing a tight-fitting garment which is typically custom-made on the affected body part (if possible) to prevent pain or enlargement of the malformation.

Sclerotherapy. This procedure involves injecting an irritating solution into the malformation in order to shrink the abnormal lymphatic channels. This procedure is typically very successful in treating macrocystic LMs but is generally less effective in treating microcystic LMs.

Drug therapy. Medical therapy may be used for extensive or complicated lymphatic malformations, particularly when surgical procedures are not an option.

Topical sirolimus: This medication is applied directly to the affected skin and is usually used to treat lymphatic blebs.

Oral sirolimus: This medication is taken by mouth. Oral sirolimus has shown to be effective at treating microcystic and macrocystic LMs.

Zoledronic acid (Zometa): This medication is given as an intravenous (IV) medication. Treatment with Zometa is considered in patients with bony disease who develop fractures or have significant symptoms, typically after attempting oral sirolimus alone.

Surgical excision. Some lesions, particularly those that are small and localized, may be completely surgically removed. When extensive or surrounding vital structures, surgical excision may only allow for partial removal or may not be possible at all.

Laser therapy. This procedure uses special light beams to treat the skin component of the lymphatic malformation. Laser therapy may be used to treat bleeding or leaking lymphatic blebs. Laser therapy typically requires multiple treatments that are spaced over several months.

Associated Risks

The mentioned management approaches have certain benefits that improve the functioning and emotional well-being of the child. Despite these benefits, each of these management approaches has drawbacks and limitations:

Sclerotherapy. In rare occurrences, blistering, scarring, infection, numbness or localized tissue loss may occur. In some cases, the malformation may shrink but then reappear or enlarge over time and in others, the malformation may not respond to sclerotherapy treatment at all.

Drug therapy.

Topical sirolimus: There is minimal risk of systemic absorption if used as prescribed. Topical sirolimus may cause skin irritation rarely.

Oral sirolimus: As with any medication, this medication has potential side effects. Prior to starting, your provider will review the common, less common and rare side effects of this medication.

Zoledronic acid (Zometa): As with any medication, this medication has potential side effects. Prior to starting, your provider will review the common, less common and rare side effects of this medication.

Surgical excision. Some degree of scarring will occur with surgical removal of the malformation. Surgical excision may also cause damage to structures involved with the lesion. Residual lesions may regrow.