Clinical phenotypes, autoimmunity and outcomes in Rosai–Dorfman disease: An international multicentre cohort study

Summary Rosai–Dorfman disease (RDD) is a rare histiocytic neoplasm with diverse clinical behaviour and immune abnormalities with unknown clinical significance. We performed a retrospective cohort study of 162 patients with RDD from 2003 to 2025 at five international referral centres. Median age was 48 years and 64.8% were female. Multisystem disease occurred in 87 patients (53.7%), commonly involving skin/subcutaneous tissue (49.4%), lymph nodes (39.5%) and bones (34%). Molecular testing was available for 102 patients; 40 (39.2%) were mitogen‐activated protein kinase/rat sarcoma virus oncogene homolog signaling pathway (MAPK/RAS)‐altered, commonly with kirsten rat sarcoma viral oncogene homolog ( KRAS ) or mitogen‐activated protein kinase 1 ( MAP2K/MEK ) alterations. MAPK/RAS alterations were associated with multisystem disease ( p = 0.0034). Autoimmune disease (AID) was documented in 29 patients (17.9%), usually preceding RDD, and 45/95 patients (47.4%) with available autoantibody status had at least one positive autoantibody. Among 153 patients with response data, objective response occurred in 94 (61.4%). Response distribution differed by disease extent; single‐system disease was associated with more complete responses and less progression than multisystem disease. At a median follow‐up of 2.49 years, eight deaths occurred; 5‐year overall survival was 93.4%. AID and autoantibody positivity were not associated with response or overall survival. These findings support disease extent and molecular status as clinically relevant dimensions of RDD assessment, while autoimmune and serological abnormalities should be interpreted in clinical context.