Rosai Dorfman's Disease with MAP2K1 Mutation Refractory to Chemotherapy with Complete Response to MEK Inhibitor Therapy: A Case Report

Background:

Rosai Dorfman's Disease (DRD) is a rare primary histiocytosis, usually benign and self-limited, characterized by significant cervical lymphadenopathy. In 23 to 43% of cases it presents extra-lymph node symptoms. Symptomatic patients are often treated with prednisone and chemotherapy, with varying success rates. Although classically considered non-clonal inflammatory pathologies, NRAS, KRAS and MAP2K1 mutations are described in a fraction of patients with histiocytic disorders.

This report will discuss a case of a patient with DRD with MAP2K1 mutation, who responded dramatically to targeted therapy with cobimetinib, after failure in several lines of treatment.

Case presentation:

A 41-year-old woman was evaluated for massive bilateral cervical adenopathy with 2 months of evolution, associated with fatigue, weight loss (7% in 2 months), chest pain and arthralgias of large joints. Cervical lymph node biopsy was performed, with a diagnosis of Rosai-Dorfman disease. Pet-Scan showed bilateral cervical, supraclavicular and mediastinal lymph node enlargement, with a marked increase in metabolism. She was initially submitted to corticosteroid therapy for up to 8 months, with partial response, but with recrudescence of adenopathies and symptoms in the attempts to reduce prednisone to less than 20 mg/day. She was then sequentially submitted to chemotherapy combinations containing Vinblastine, Methotrexate, 6-Mercaptopurine, Cyclophosphamide and Prednisone, presenting a progressive disease characterized by involvement of the nasopharynx. There was also a failure in response with the use of Lenalidomide. After 19 months of diagnosis, she was treated with 6 cycles of Cladribrine, obtaining a partial response, lost 5 months after completion. Investigation with NGS Panel Target One Pan Cancer (52 Genes) detected MAP2K1 c.607G> mutation. The patient started treatment with the MEK inhibitor Cobimetinib (Cotellic ®) with complete response. The medication was used for 12 months, with a dose reduction between the 7th and 12th month due to cutaneous adverse events. A complete response is maintained one month after cobimetinib discontinuation.

Discussion:

Due to the disease being rare there is still no well-defined protocol for DRD treatment. As it has mostly benign and self-limited evolution, observation is indicated in oligosymptomatic cases and corticosteroid therapy is the first line of treatment when necessary.

Cases that are refractory to traditional therapies, such as the one presented in the report, can be treated with targeted therapies when actionable mutations are identified. The present report supports the idea that genomic analysis can be an important tool in the management of cases of refractory or aggressive DRD.

No relevant conflicts of interest to declare.