What is a lymphatic malformation?

Lymphatic malformations are swellings that consist of multiple lymphatic cysts.  In the past they have also been known by the names ‘Cystic Hygroma’ and ‘Lymphangioma’, but ‘Lymphatic malformation’ is now the preferred name.   The cysts consist of many lymphatic vessels which do not connect to the normal lymphatic circulation. (If you don’t know what lymphatic vessels are, please read our description below). There is enormous variation in what lymphatic malformations look like: they vary from small patches in the skin to extensive swellings that can affect a whole limb or more.  The cysts can be very small or very large (up to several centimetres across) depending on how much fluid they contain.  A lymphatic malformation may consist of only a few cysts, or many thousands of small ones.  They are most often found is in the neck but they can occur almost anywhere in the body.  When the cysts are very large, especially in the neck,  doctors used to call them ‘cystic hygromas’, but they are not really different from other lymphatic malformations.

Sometimes lymphatic malformations seem as though they affect multiple different parts of the body, but when we examine more closely with MRI scans, we generally find that the different swellings are all connected as parts of one continuous lesion that may extend over a wide area.  It is unusual to find totally separate lymphatic malformations in different parts of the body.

What causes lymphatic malformations?

In recent years it has become clear that lymphatic malformations and other vascular malformations are due to what are called ‘somatic mutations’ in particular genes.  In most or all lymphatic malformations the involved gene is called PIK3CA.  Somatic mutations are errors in the genetic code that occurs when the code is being copied from one cell to another.  This means that once this error happens it will be present in all cells arising from the mutated cell.   Even though it affects the genes, a somatic mutation is not inherited from one generation to the next because it only affects the part of the body where the lymphatic malformation occurs, not the germ cells that create new life.  Somatic mutations occur completely by chance. We do not believe that anything done by the parents before pregnancy or the mother during pregnancy causes a lymphatic malformation.  New information is coming out from research laboratories about exactly where in the genetic code the mutation occurs. This will help direct research into new treatments in the future.

What problems can a lymphatic malformation cause?

Many lymphatic malformations do not cause any problems.

The most common problem with a lymphatic malformation is that it affects appearance.  Swellings can be quite large, and they can change over time, becoming larger or smaller depending on how much fluid they contain. (Lymphatic malformations often get bigger with an illness such as a viral infection, then slowly go down again afterwards).  Especially around the face and neck, the swelling can be a significant appearance problem.

Less commonly, lymphatic malformations can cause pain.  Sometimes bleeding into a cyst can cause sudden enlargement of a lymphatic malformation.  Although this looks very alarming, the swelling usually goes down over several weeks.

Infection is an uncommon complication with lymphatic malformations.  The area usually becomes red and swollen and the child has a fever.  If infection starts, it can be difficult for the body to eradicate the infection, and a cycle of recurrent infection can develop. This can lead to increase in size of the lymphatic malformation which can be permanent.  For this reason, we usually treat infections in lymphatic malformations with much longer courses of antibiotics than are used for other infections.

Lymphatic malformations in particular locations can cause specific and important problems.  Swellings in the neck, for instance, can cause pressure on the airway which can lead to breathing difficulties.

What treatments are available for lymphatic malformations?

If a lymphatic malformation is not causing specific problems and appearance is not a problem, it may not need any treatment at all.

If treatment is needed, there are two main types of treatment available:

Injection sclerotherapy.  Injection treatment is good for lymphatic malformations which have large cysts. Treatment is performed under anaesthetic by an interventional radiologist trained in vascular anomalies.  Ultrasound is used to guide a needle into the cyst, drain the fluid and inject a sclerosing agent which will strip the lining from the cyst and stop the fluid from recollecting.  Many different agents can be injected, depending on the nature and site of the malformation.

Surgery.  Most lymphatic malformations can be removed by surgery, but surgery must be performed carefully because the lymphatic malformation can spread around nerves and into muscles.  It is generally not possible to remove every last cell of the lymphatic malformation while preserving the nerves and muscles, so it is possible for the malformation to come back.  As a general rule we feel that keeping the nerves and muscles intact is more important than preventing recurrence and would prefer to accept that the malformation might come back in the future and require more treatment, than do unnecessary damage to normal structures.

Drug treatment.  The drug Sirolimus (or Rapamycin) has proven to be an effective treatment for some patients with lymphatic malformations.  It does not help in every case but can help when pain is a significant problem and also tends to reduce swelling and bleb formation on the tongue. It can also significantly improve skin changes.  Blood testing needs to be performed prior to starting treatment, and regular blood tests are usually required in the first few months of treatment.

More recently, a group of drugs called PI3Kinase inhibitors are being used to treat lymphatic malformations.  These drugs were initially developed to treat cancer, but the discovery of PIK3CA mutations as the cause of lymphatic malformations suggests that they should be effective in this condition as well.  There is promising early data to suggest that this may be the case, and it is hoped that clinical trials will start soon in Australia.

The Lymphatic System

The lymphatic system is a normal part of every body.  In a healthy body the arteries carry blood to capillaries where nutrients and oxygen are exchanged between the red blood cells and the tissues. The capillaries then pass the blood to veins which return the blood to the heart. When capillaries exchange oxygen and nutrients some fluid tends to leak out of the capillaries and ends up in the space between the cells. If this fluid, also known as lymph, accumulates and is not cleared it will lead to swelling. The vessels of the lymphatic system absorb the excess fluid that has leaked from the blood capillary and therefore maintain tissue fluid balance. The lymphatic system flows in one direction, from the periphery of our tissues, where it collects lymph, to the venous system near heart where it empties lymph to the blood circulation. If the lymphatic vessels do not function or are obstructed in some way, then fluid accumulates in the tissue and it will lead to localised tissue swelling condition called oedema.  The lymphatic system also plays a big role in our immune defences.