In 2022, the United States Food and Drug Administration (FDA) approved cobimetinib (MEK1/2 inhibitor) for the treatment of adult patients with histiocytic neoplasms, including ECD, LCH, and Rosai-Dorfman disease (RDD) based on results from an open-label phase 2 trial (NCT02649972) [77]. Here, MAP2K1 is linked to sinus histiocytosis with massive lymphadenopathy.