Abstract

We present the case of a 69-year-old male with multifocal papillary thyroid carcinoma, granulomatous iritis, a left upper extremity soft tissue mass, and a papular, brownish to violaceous skin rash of the face, trunk, and extremities that did not improve with prednisone. Several skin biopsies demonstrated extensive infiltration of the dermis by bland histiocytes and scattered neutrophils, plasma cells, lymphocytes, and eosinophils. By immunohistochemistry, dermal histiocytes expressed CD163, nuclear Bcl-1, and nuclear OCT2 with a subset of cells, including large multinucleated histiocytes with emperipolesis, noted to be positive for S100. Somatic mutational profiling via next-generation sequencing detected a MAP2K1 p.F53I mutation supporting a diagnosis of Rosai-Dorfman disease (RDD). The presence of partial S100 expression and absence of long bone lesions provided no support for Erdheim-Chester disease. RDD is a non-Langerhans cell histiocytosis with cutaneous and/or systemic involvement frequently characterized by NRAS, KRAS, MAP2K1, or ARAF mutation in sporadic cases. There are associations with IgG4-related disease and various immune-related conditions such as systemic lupus erythematosus, idiopathic juvenile arthritis, autoimmune hemolytic anemia, and HIV. Notably, serum IgG subsets did not suggest IgG4-related disease. The presence of MAP2K1 mutation in RDD is associated with a high likelihood of response to MEK-inhibitor therapy, and the patient’s skin lesions dramatically improved after two cycles of cobimetinib. This case highlights the diagnostic and therapeutic relevance of molecular profiling of cutaneous histiocytic neoplasms. Furthermore, this case supports the recent finding of OCT2 expression in most cases of RDD and the usefulness of OCT2 as a diagnostic adjunct.