Pathogenesis and new therapeutic agents for intractable lymphatic diseases

<p>Lymphangiomas, also known as lymphatic malformations, lymphangiomatosis, Gorham’s disease, and lymphangiectasia, are challenging lymphatic anomalies marked by abnormal growth and invasion of lymphatic tissue. Cystic lymphangioma presents at birth as a clump of lymphatic cysts of different sizes, leading to a variety of symptoms depending on the anatomical location. Lymphangiomatosis is characterized by widespread infiltration of lymphatic tissue, and can result in a range of complications including chylothorax, pericardial effusion, and bone dissolution, with symptoms dependent on the infiltration site. Gorham’s disease results in gradual erosion of bones throughout the body, whereas lymphangiectasia causes swelling and lymph fluid leakage due to congenital anomalies in lymph vessel structures. These disorders may appear similar clinically, but are distinct in their pathophysiology and radiological signatures.</p><p>Advances have been made in the genetic understanding of these diseases, with PIK3CA/RAS gene mutations identified in the lesions. Sirolimus, an mTOR inhibitor, has been recognized for its efficacy in managing these conditions and was approved in Japan in 2021 after showing good symptom control in national and international studies. In this review, the pathogenesis and diagnosis of lymphatic anomalies and emerging treatments will be introduced for pediatricians and radiologists.</p>