Rosai-Dorfman disease of the pancreas: Cytologic analysis of three cases presenting as pancreatic masses

Rosai-Dorfman Disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a rare entity characterized by proliferating S100-positive histiocytes. It is most commonly found in lymph nodes with extranodal involvement usually occurring in the head and neck. Pancreatic involvement is extremely rare. The pathology department archives were searched for fine needle aspirations and pancreatic resections showing evidence of RDD. Clinicopathologic features, cytologic smears, cell blocks, immunocytochemical stains and surgical resections were reviewed. Three cases were identified. They were all females, aged 65, 69 and 75, with involvement of the pancreatic tail or head by solid masses of median size 2.3 cm (range 2.1-4.5 cm). Cytologic findings on smears included multiple histiocyte clusters resembling loosely cohesive epithelioid granulomas, singly dispersed histiocytes with moderate to marked nuclear atypia and characteristic emperipolesis. These atypical histiocytes stained positively for CD68, CD163 and S100. Smear background contained variable mixed inflammatory cells, necrotic debris and stromal fragments. The RDD diagnosis was further confirmed on pancreatic resection in two patients and core biopsy in one. The latter patient required three separate procedures before a definitive diagnosis was made. RDD of pancreas is a rare benign inflammatory condition that is diagnostically challenging on cytology. This can cause delays in cytologic diagnosis and/or misdiagnosis. Identification of characteristic cytologic features, primarily histiocytes with emperipolesis, and matching immunocytochemical profile can ensure accurate diagnosis and distinction from mimics.