Abstract

A 55-year-old woman with a past medical history significant for metastatic colon adenocarcinoma secondary to an activating KRAS mutation (c.35G>A, p.G12D), presented to dermatology clinic with new onset skin lesions. Physical exam was significant for grouped, indurated brown-red papules and nodules on the bilateral arms, pannus, and lower right back. There was no cervical, axillary, or inguinal lymphadenopathy. Clinical concern for metastatic carcinoma was present, so a punch biopsy was performed. Unexpectedly, histologic examination revealed a superficial to deep infiltrate of S100-positive histiocytes with emperipolesis within a background of mixed inflammatory cells, including plasma cells, lymphocytes, and neutrophils. The lesional cells were also positive for Oct-2 and cyclinD1 and were negative for CD1a and Langerin. There was no evidence of metastatic colon adenocarcinoma, supported by a negative CDX-2 immunostain. The morphologic and immunohistochemical findings were compatible with cutaneous Rosai-Dorfman disease (RDD), a rare histiocytic proliferative disorder. Interestingly, RDD is known to be driven by activating mitogen-activated protein (MAP) kinase pathway alterations. In the context of a prior colon carcinoma with an activating KRAS mutation, we performed next-generation DNA sequencing to investigate any possible relatedness between the colon cancer and the new onset RDD. The RDD was found to harbor a MAP2K1 mutation (c.362G>C, p.C121S), but did not contain any of the known somatic variants detected in the colon cancer. Therefore, we describe a unique case of a patient with two neoplasms driven by distinct mutations in the MAP kinase pathway.