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Diagnosis of Complex Lymphatic Anomalies
Rare diseases are difficult and challenging to diagnose. If symptoms are not visual with the eye, the most common locations of Complex Lymphatic Anomalies (CLAs) are the lungs and bones. An isolated presentation usually carries a better prognosis than does multi-organ involvement; the combination of pleural and peritoneal involvement with chylous effusions and lytic bone lesions carries the least favourable prognosis.
Complex Lymphatic Anomalies may initially appear simple. And it may be that only as the disease progresses a correct and accurate diagnosis can be made. There is always the possibility with new symptoms, review, and evaluation of the patient, that the diagnosis will change further. One aspect of CLAs that is different from simple lymphatic malformations is a more aggressive disease course.Even though this disease is still benign, as the lymph vessels grow, in size and number, they can aggressively invade the adjacent tissue, bone or organs leading to resorption and replacement by lesions filled with lymph tissue.
In many patients the diagnosis can be made from the clinical history, the findings of the physical exam and blood tests. MRI plays an important role in defining the extent of the disease, other diagnostic tools include X-rays, CT scan, ultrasound, lymphangiography, bone scan, and bronchoscopy can further help to fully evaluate the patient.
Sometimes a biopsy (small sample of tissue) may be taken to confirm the diagnosis and check for specific markers and genetic changes that guide treatment. It is less risky to combine taking a biopsy with a surgical intervention. But the risks and benefits of a biopsy need to be carefully weighed by your medical specialist.
Recently, mutations in genes involved in two key signalling pathways important in lymphatic cell growth and function, the PI3K/mTor and RAS/MAPK pathways, have been found in patients with CLAs. However, the genetic background of CLAs is still not well understood. Most of these mutations are somatic, meaning they are not inherited and develop in a subset of cells in the embryo before birth. Somatic (also called mosaic) mutations are not found in all cells in the body and disease is only found in tissues harbouring the gene mutation. The discovery of mutations in CLAs may lead to new specific targeted therapies in the coming years.
Treating Complex Lymphatic Anomalies
There is no standard approach to manage GLA, GSD, KLA and CCLA patients. Consultation and management with a multidisciplinary vascular anomaly team is highly recommended.
Unfortunately, no cure has been found for these diseases yet. Treatment is often aimed at limiting progression of the disease, and reducing and easing the symptoms. Conservative, pharmacological, interventional, and surgical therapies are possible treatments, and most patients will receive one or more of these procedures throughout their life. A multidisciplinary approach is essential and could include vascular specialists, dermatologist, radiologist, surgeons, interventional radiologists, hemato-oncologists and possibly others.
To control the excess production or leakage of chyle, patients may go on a low-fat diet. Nutrition needs may be complex, and feeding may be through feeding tubes or infusion for hydration. Compression garments may help with swelling. Prevention of infections is very important.
Medical treatment can include antibiotics to treat infections, and bisphosphonates to strengthen bones or vincristine. As PIK3CA mutations have been identified in some CLA patients, sirolimus (an mTOR inhibitor) can be tried as a treatment. KLA patients may benefit from other cancer drugs due to their NRAS mutations. In general, some anti-cancer drugs may have positive effects on lymphatic malformations based on specific genetic bases. But these medications also may have severe side effects, which need to be considered.
Interventional therapy can include sclerotherapy.
Surgical therapy can include debulking of the lymphatic malformation, drainage of fluid from around the heart, lungs or stomach. Orthopaedic surgery may be needed to repair bone damage with plates or cement or even transplant.
Need a second opinion?
Sometimes doctors have difficulty in reaching a diagnosis or in deciding on the most effective treatment at the time of presentation. This is not unusual given that there are so many rare diseases, so your doctor will not be up to date with all new developments. This happens with all extremely rare conditions.
The LGD Alliance Europe can help you, or your own doctor, to get in contact with doctors all over Europe who have experience with the Rare and Complex Lymphatic Diseases. The LGD Alliance Europe is part of the VASCERN, a European network of specialized healthcare centres. For more information go to our patient support page and www.vascern.eu.