Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus

Abstract

International audienceMultifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. Treatments for MLT have been disappointing, and the treatments classically used for infantile hemangioma are often ineffective. We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. The pathogenesis of MLT remains unclear, but lymphatic differentiation is widely acknowledged. Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for ML

Orthotopic liver transplant for multifocal lymphangioendotheliomatosis with thrombocytopenia

“…Propranolol, which has been utilized in the treatment of neonatal hemangiomatosis (12), has been used in the treatment of MLT, with inconsistent results (5,10). Although our patient did receive propranolol as well, it ultimately did not improve her liver failure or her GI bleeding, and she was found to have multiple GI lesions despite prior treatment with propranolol.…”

“…Treatments targeting vascular proliferation, such as thalidomide, however, have not shown sustained improvement , and bevacizumab, an antibody to vascular endothelial growth factor utilized in the treatment of cancers for its inhibition of angiogenesis , has been used with some success in patients with MLT , but unfortunately did not decrease the incidence of bleeding in our patient. Sirolimus, an inhibitor of angiogenesis, including lymphangiogenesis, has also been used in two patients with MLT , but unfortunately our patient developed pancreatitis, a rare but known adverse effect associated with sirolimus in <3% of patients who receive it . It is possible that earlier initiation of bevacizumab and/or sirolimus may have been helpful in the management of her liver disease; however, she had not had any indication of liver disease until her acute development of ascites a month prior to transfer.…”

Multifocal Lymphangioendotheliomatosis with Thrombocytopenia: Presentation of Two Cases Treated with Sirolimus

“…MLT has been described in several publications, although different names have been used (). To our knowledge, our report is the second to describe the treatment of MLT with sirolimus .…”

Peri-articular lymphatic system and "Bi" theory of Chinese medicine in the pathogenesis and treatment of arthritis

“…Lymphatic endothelial cells (LECs) of capillaries present loose overlapping intercellular junctions and anchoring filaments that support fluid drainage. LECs specifically express proteins such as lymphatic endothelial hyaluronan receptor 1 (LYVE-1) (13–16) and podoplanin, (17–19) which have been used as markers for identifying lymphatic vessels in tissue sections. The LEC junctions and permits interstitial fluid uptake when interstitial fluid accumulates within tissues, the extracellular matrix swells and pulls the anchoring filaments.…”