Abstract
Non-Langerhans cell histiocytosis (NLCH) is a broad disorder encompassing different diseases arising from dermal dendritic histiocytes. Xanthogranuloma (XG) is a cutaneous subtype of NLCH that can be present in isolated or multiple locations. If localized, XGs can be treated with surgical resection or radiation; however, if they present more disseminated, they are poorly responsive to traditional chemotherapeutic agents. This case discusses a 26-year-old male who presented with diffuse light brown/tan papules progressively spreading from the bilateral groin axillae to the trunk, pelvis, and eyelids over the course of six months. Histologic evaluation demonstrated findings consistent with XG with immunostaining strongly positive for neurotrophic tyrosine kinase receptor 1 (NTRK1) gene fusion. He was diagnosed as likely having an early form of XG disseminatum before visceral involvement had developed, but given how rare and complex XG diseases are to classify, he might also be considered to have disseminated adult XG. He was started on larotrectinib, an oral tropomyosin inhibitor used to treat solid tumors associated with NTRK gene fusions. Improvement in the lesions was noticeable as early as six weeks, with a successful partial clinical response by four months of treatment, where he ceased to develop new lesions, and the pre-existing lesions became more macular. He eventually discontinued therapy due to a known side effect of weight gain and has continued to maintain his response since. This report demonstrates a positive clinical response of an NTRK1 inhibitor in an adult with NTRK1-positive XGs, providing further evidence that targeted therapy may be beneficial for these otherwise challenging patients.