Oral sildenafil as a treatment option for lymphatic malformations in PIK3CA-related tissue overgrowth syndromes.

ABSTRACT

Patients with extensive lymphatic malformations associated with tissue overgrowth syndromes (such as Klippel-Trenaunay syndrome and CLOVES) often pose a therapeutic challenge for physicians. In recent years, it has been suggested that oral sildenafil therapy might be used to treat congenital lymphatic malformations. However, this possible new therapy has not yet been used in patients with lymphatic malformations associated with tissue overgrowth syndromes. A 30-year-old man with extensive capillary-lymphatic malformations of the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of pain, dyspnea, and functional impairment. Several weeks after the start of the treatment, the patient reported softening of the lymphatic malformation and a significant improvement of his symptoms and physical condition. So far, sildenafil is still considered a last resort in the treatment of complex treatment-resistant lymphatic malformations. With this case report, we demonstrate that sildenafil could also be an alternative treatment option for lymphatic malformations in patients with syndromes belonging to the PIK3CA-related overgrowth spectrum.