Localized Rosai-Dorfman disease: Case report of an uncommon tumor and a brief review of the literature

Rosai-Dorfman Disease (RDD) is a rare histiocytic disorder that is usually marked by enormous lymphadenopathy, with or without extranodal disease. We report a diagnostically challenging case of localized RDD in a 51-year-old male who first presented to be evaluated for progressive, painless bilateral cervical lymphadenopathy and a slowly growing subcutaneous lump over the left supraclavicular region. The lack of constitutional symptoms and the slow progression of disease at the beginning contributed to the wide range of differential diagnoses, including lymphoma, soft tissue sarcoma, Erdheim-Chester disease (ECD), Rosai-Dorfman Disease (RDD), and Langerhans cell histiocytosis (LCH). Imaging studies showed bilateral cervical and supraclavicular lymphadenopathy and a well-defined mass in the left supraclavicular region with no visceral or skeletal lesions. Histologic examination of the excision tissue of a lymph node and fine-needle aspiration (FNA) of the supraclavicular mass showed classic RDD findings with large histiocytes displaying emperipolesis and a mixed inflammatory background.  
The immunohistochemistry (IHC) studies were positive for S100, CD68, CD163, OCT2, and cyclin D1 but negative with CD1a and BRAF V600E. A precision oncology approach was possible due to the identification of a MAP2K1 mutation by molecular profiling. After the surgical removal of the lesion in the supraclavicular region, the patient was put on the treatment course with the MEK inhibitor cobimetinib, which caused a significant reduction in lymphadenopathy. Side effects were not significant. 
The patient is still functional and without disease at the three-year follow-up. This case illustrates the significance of tissue diagnosis and molecular profiling of atypical lymphadenopathy and soft tissue lesions. Identification of mutations in the MAPK pathway presents an opportunity for effective treatment in RDD, reflecting the move toward precision treatment in histiocytic and many other conditions.