Original ArticlesRosai-Dorfman Disease Displays a Unique Monocyte-Macrophage Phenotype Characterized by Expression of OCT2Ravindran, Aishwarya MBBS*; Goyal, Gaurav MD†,‡; Go, Ronald S. MD†; Rech, Karen L. MD*; On Behalf of the Mayo Clinic Histiocytosis Working GroupAuthor Information *Department of Laboratory Medicine and Pathology, Division of Hematopathology †Division of Hematology, Mayo Clinic, Rochester, MN ‡Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL K.L.R., A.R., and G.G.: designed the study. K.L.R. and A.R.: reviewed the pathology reports, collected the data, performed the analysis, and acquired the pathology images. All authors reviewed, edited and contributed to the contents of the manuscript. Presented in part at the 2018 College of American Pathologists Annual Meeting in Chicago, IL. Conflicts of Interest and Source of Funding: Supported by institutional funds from the Department of Laboratory Medicine and Pathology at Mayo Clinic, Rochester, MN. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Karen L. Rech, MD, Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (e-mail: [email protected]). The American Journal of Surgical Pathology: January 2021 - Volume 45 - Issue 1 - p 35-44 doi: 10.1097/PAS.0000000000001617 Buy Metrics Abstract Rosai-Dorfman disease (RDD) is a rare histiocytosis with heterogenous clinical features. In this study, we characterized the histologic and phenotypic features in 33 RDD patients to better define the pathologic diagnosis. Cases included 24 patients with extracutaneous disease (“R” group), and 9 patients with lesions limited to the skin or subcutaneous tissue (“C” group). We identified OCT2 as a novel marker for the monocyte-macrophage phenotype of RDD, expressed in 97% of RDD cases. In contrast, OCT2 expression was seen in 0% of Erdheim-Chester disease cases and 6.7% of Langerhans cell histiocytosis cases. Other markers useful in the diagnosis of RDD included S100 (100%), CD163 (88%), and cyclin D1 (97%). In a subset of cases, RDD showed moderate to strong expression of factor 13a (30%), p16 (64%), and phosphorylated extracellular signal-regulated kinase (45%); RDD was uniformly negative for ZBTB46, CD1a, and langerin. Within the “R group” of RDD, increased expression of factor 13a or phosphorylated extracellular signal-regulated kinase showed a statistically significant association with multifocal disease (P<0.05). Identification of the unique monocyte-macrophage phenotype of RDD with OCT2 expression furthers our understanding of this complex disease and allows for more uniform classification. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.