How would you treat a young patient with symptomatic Rosai-Dorfman disease who has recurrent, life-threatening pericardial and pleural effusions?
Rosai-Dorfman disease is the most tricky one of the top 3 histiocytosis (ECD, LCH, and RDD). It can behave as benign or as an aggressive disease. Given the rarity of the disease, there are no great prospective studies to guide optimal treatments. First-line treatment includes prednisone or other immunosuppressants/chemotherapeutic agents like oral MTX, cytarabine, cladribine. Lately, we are learning more about the role of MAPK-ERK mutations in the pathogenesis of RDD, similar to ECD and LCH. RDD does not harbor BRAF-V600E mutations but can harbor others like MAP2K1 which can be targeted using MEK-inhibitor such as cobimetinib.
The first step is to absolutely ensure the diagnosis is correct. After that, it is recommended to conduct NGS testing on RDD tissue specimens to look for mutations to guide therapy. However, if the disease is aggressive or involves critical organs, it is reasonable to treat with empiric MEK-inhibitor therapy while awaiting mutation analysis results. If targeted therapy is unavailable/inaccessible, then may consider cladribine or low-dose cytarabine. Lately, rituximab has shown some responses as well especially in immune-related RDD.
Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease
Efficacy of MEK inhibition in patients with histiocytic neoplasms
Management and outcomes of sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman Disease)