CD71 expression in Rosai–Dorfman disease: a useful adjunct marker in the differential diagnosis of histiocytic proliferations

AIMS: Accurate diagnosis of histiocytosis remains challenging due to overlapping morphologic and immunophenotypic features among subtypes, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease/xanthogranuloma (ECD/XG) and Rosai-Dorfman disease (RDD). RDD is a rare disorder characterized by large S100-positive histiocytes with emperipolesis; however, emperipolesis may be difficult to recognize due to abundant admixed inflammatory cells or stromal fibrosis. Moreover, unlike LCH and ECD, RDD does not harbour BRAF V600E mutation, limiting the utility of high-sensitivity molecular analysis and mutant-specific immunohistochemistry for BRAF, which are available in many institutions. We observed the expression of CD71 in histiocytes in RDD. Therefore, we investigated the diagnostic utility of CD71 immunohistochemistry for RDD. METHODS AND RESULTS: We retrospectively reviewed electronic medical records to identify the cases of histiocytosis and reactive histiocytic proliferations. Clinical data and molecular results were also reviewed. The cohort comprised 58 cases, including RDD (n = 22), LCH (n = 6), non-LCH/ECD/XG (n = 14), histiocytic sarcoma (n = 4) and benign reactive cases (n = 12). CD71 demonstrated membranous and cytoplasmic staining in all RDD cases (22/22, 100%). In contrast, lesional cells in LCH were uniformly negative for CD71. Most non-RDD cases lacked CD71 expression, although dim cytoplasmic staining was observed in a subset of cases. Two sarcoidosis cases and one histiocytic sarcoma showed CD71 expression comparable to RDD. CONCLUSIONS: CD71 immunohistochemistry is a sensitive marker for identifying histiocytes in RDD and serves as a useful adjunct in distinguishing RDD from other histiocytic proliferations.