Answer: C - Rosai-Dorfman disease, MAP21K mutation

Rosai-Dorfman disease is a form of histiocytosis characterized by nodal or extranodal accumulation of large, S100-positive histiocytes that commonly exhibit emperipolesis.

Lymph nodes show marked expansion of sinuses by characteristic large histiocytes with round nuclei and prominent nucleoli, with abundant pale cytoplasm with ill-defined borders. Emperipolesis, the presence of intact haematopoietic cells, typically lymphocytes but also other cells within the histiocyte cytoplasm, is a characteristic feature of RDD. Cytologic atypia, mitoses, and multinucleation are infrequent. The microenvironment contains small B and T cells and numerous polytypic plasma cells (with increased IgG4+ forms).

Approximately 50% of cases of RDD have gain-of-function mutations in the MAPK/ERK pathway, including KRAS, NRAS, MAPK21, ARAF, CSF1R, and rarely, BRAF p.V600E.