Kaposiform Hemangioendothelioma (KHE)
Kaposiform Hemangioendotheliomas (KHE) and Tufted Angiomas are very complicated vascular lesions. Until recently they were both misdiagnosed as hemangiomas. These lesions are associated with a phenomenon called Kasabach- Merritt Phenomenon. This phenomenon was first described in 1940 by Kasabach and Merritt. These two practitioners reported an infant with a rapidly enlarging capillary hemangioma and thrombocytopenic purpura (a low platelet count and a very purple firm lesion). The features of this “phenomenon” include an enlarging vascular lesion, a very low platelet count (thrombocytopenia), anemia caused by destruction of red blood cells within the lesion (microangiopathic hemolytic anemia) and consumption of proteins necessary for clotting (consumptive coagulopathy). From 1940 on, this phenomenon was classified as a hemangioma with Kasabach Merritt syndrome.
In 1997, two vascular anomaly groups reported independent research studies showing that these were not true hemangiomas as was previously thought but were associated with vascular lesions pathologically diagnosed as kaposiform hemangioendotheliomas(KHE) or tufted angiomas. (Under the microscope, these lesions do not appear like typical hemangiomas). This phenomenon has been a challenge for physicians because it is very serious and has been associated with a mortality rate of 20 – 30%.
These lesions clinically appear different than hemangiomas. KHE lesions are rare locally aggressive vascular tumors of the skin, deep soft tissue and bone in children. They commonly are found in the upper trunk and extremities, thigh, sacrum or retro peritoneum (back of the abdomen). They usually are present at birth but can appear shortly after birth. They affect both sexes equally. The tumors on MRI scans invade tissues such as the skin, and underlying tissues. They are warm, firm, indurated, purple lesions that can be tense and shiny. The majority of KHE lesions are associated with Kasabach-Merritt phenomenon but there are reports of patients with these lesions that do not have this phenomenon. Aggressive treatment is necessary for patients that have this phenomenon. Therapy has also been recommended for patients who do not have this phenomenon because patients who receive earlier more aggressive therapy have a decreased amount of tumor mass left in later years.
A number of therapies have been reported in the treatment of Kasabach-Merritt phenomenon but none have been 100% effective. Steroids are often used as a first line therapy with varying results. If these lesions respond to steroids they do so in the first several weeks of therapy. Steroids have the advantage that they can be given by mouth but do have side effects which include delayed growth, cushingoid appearance, high blood pressure and increased risk of infection, to name a few. Interferon has been used but its effectiveness also is limited. Interferon needs to be given as an injection once a day and is associated with side effects such as flu-like symptoms (fever, chills) and neurological complications. Antifibrinolytic agents (e-aminocaproic acid or tranexamic acid) have been used with mixed response as well as antiplatelet agents such as aspirin or dipyridamole. These drugs are used to improve the coagulopathy (bleeding tendency). Chemotherapy agents such as cyclophosphamide, vincristine, and actinomycin have been used with variable improvement. Vincrisitne is an agent that has well know but limited side effects in young children. It has to be given as an intravenous injection through a special intravenous catheter. Its main complications are constipation and jaw pain but the drug can have some other neurotoxicity. It is given once a week until an improvement is seen and then the interval of administration is increased. Recently the use of Sirolimus or “rapamycin” has been sued in the treatment of KHE lesions a study is being coordinated at Cincinnati Children’s Hospital and is currently enrolling patients. Rapamycin is an agent with known anti-proliferative activity. It has been shown to slow the progression of tumor cells. The purpose of the study is to determine if rapamycin is a safe and effective agent in children and young adults for use in complicated vascular tumors like KHE, Tufted Angioma and Lymphatic Malformations. (Rapamycin Study) Other medical treatments that have been used are radiation therapy, which should be used as a last resort, compression therapy, and embolization therapy.
Care by an experienced group of physicians is of vital importance. A pediatric hematologist/oncologist is also vital in the care of these patients. Not only is this physician important in the management of the drug therapy but also the physician is important in the management of the bleeding tendency of Kasabach-Merritt phenomenon. At times the administration of blood products such as platelets and red blood cells can make these tumors grow in size because of the release of certain factors.
Recently there has been a report of residual lesions (lesions that are still present) after Kasabach-Merritt phenomenon. Clinical data on 41 patients was reviewed as part of an international cooperative study. The findings revealed residual tumors not “scars” being very common in these lesions after the resolution of thrombocytopenia and coagulopathy. Usually these residual lesions do not cause any problems but there have been reports of a second episode of Kasabach-Merritt phenomenon shortly after it had appeared to resolve.
These are very complex lesions that although benign(not cancer, they do not spread to distant areas) can cause mortality and great morbidity with some limited response to therapy. Presently the standard of therapy is to start with steroid therapy and if there is no response to proceed to therapy with chemotherapy drugs such as vincristine or rapamycin. Research is continuing in the treatment of these lesions. It is vital that these lesions are treated by experiences care-givers.
This article was written by Denise Adams, MD Cincinnati Children’s Hospital, Department of Hematology/Oncology and the Director of the Hemangioma and Vascular Malformation Center. Dr. Adams is the Medical Director of NOVA.
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