Advances in the diagnosis and management of pediatric Langerhans cell histiocytosis and Rosai-Dorfman disease: therapies, biomarkers, and response assessment.

Abstract

Histiocytic disorders are characterized by abnormal accumulation of myeloid-derived histiocytes and a shared biology marked by RAS/MAPK/ERK pathway activation, yet the rarity and heterogeneity of these conditions have limited the availability of robust, well-controlled clinical trials to guide therapy. This review highlights Langerhans cell histiocytosis, the most common subtype, and Rosai-Dorfman disease, a less common non-Langerhans cell histiocytosis entity, using them as key examples to illustrate how advancements in molecular diagnostics and targeted MAPK inhibitors are reshaping clinical management in histiocytic disorders. In both disorders, treatment approaches range from active observation in mild cases to more aggressive interventions in high-risk or progressive disease, emphasizing the spectrum of clinical presentations and the need for individualized, biology-driven strategies.