Somatic MAP2K1 Variant Driver in a Child With Rosai-Dorfman-Destombes Disease And Vascular Anomaly

Somatic activating mutations in oncogenes, particularly of the mitogen-activated protein kinase (MAPK/MEK) pathway, are a common cause of isolated, sporadic arteriovenous malformations. MAPK alterations have also been implicated in Rosai-Dorfman-Destombes disease, a rare non-Langerhans cell histiocytosis characterized most commonly by massive cervical lymphadenopathy with potential for extranodal organ system involvement. The MAPK pathway is known to play a role in maintaining normal cellular activity and alteration of genes along the pathway may result in over-activation and/or loss of tumor suppression. Here, we report the first case of an individual with a vascular malformation and a histiocytic neoplasm with a common MAP2K1 somatic driver. We review the pathogenesis of these conditions, including the common role of the MAPK/ERK pathway and discuss targeted therapeutic approaches as was pursued in this case.