March 2021 — Hematopathology Case 2

A 47-year-old presented with a right arm lesion that was gradually increasing in size. There is no significant past medical history. Punch biopsy of the lesion was performed. Representative images are shown in Figures 1 and 2.

Figure 1: HE
Figure 2: OCT2

What is your diagnosis?

  • Reactive fibrohistiocytic infiltrate 
  • Rosai-Dorfman disease
  • IgG4 disease
  • Erdheim-Chester disease

The correct answer is ...

The diagnosis in this case is: Rosai-Dorfman disease.

  • Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis also known as sinus histiocytosis with massive lymphadenopathy. The classic sporadic RDD typically involves the lymph nodes, however, extranodal sites have been reported including skin, bone, nasal cavity, and soft tissue.1 Morphologically, RDD is characterized by emperipolesis (engulfment of lymphocytes by large histiocytes) with expression of CD68, CD163, S100, and negative for CD1a and langerin. Recently, we described a new marker, OCT2, which is a transcription factor that  is expressed in the lesional histiocytes of RDD in >95% of cases (Figure 2, inset shows lesional RDD histiocytes).2 OCT2 expression is usually negative in other histiocytic neoplasms (e.g. Erdheim Chester disease, Langerhans cell histiocytosis).2
  • Erdheim-Chester disease is a non-Langerhans cell histiocytosis and a clonal systemic process with multiorgan involvement and variable clinical outcomes.Typical clinical presentation of ECD includes central diabetes insipidus, perinephric fibrosis, and sclerotic bone lesions. The lesional histiocytes strongly express CD68, CD163, Factor 13A. BRAF V600E is positive in a subset of cases.
  • IgG4 disease: The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance, including dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis and increased numbers of IgG4+ plasma cells (varies among affected organs, ranging from 10 to 200 cells/HPF).3
  • Reactive fibrohistiocytic infiltrate: A reactive fibrosis with mixed inflammatory infiltrate, although in the differential, the presence of emperiopolesis and strong OCT2 expression rules out this possibility. The reactive histiocytes are negative for OCT2.2


  1. Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 2016 Jun 2; 127(22): 2672-2681.
  2. Ravindran A, Goyal G, Go RS and Rech, KL. Rosai-Dorfman Disease Displays a Unique Monocyte-Macrophage Phenotype Characterized by Expression of OCT2. Am J Surg Pathol. 2021 Jan;45(1):35-44
  3. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181-1192.
Photo of Aishwarya Ravindran, M.B.B.S.

Aishwarya Ravindran, M.B.B.S.
Resident, Anatomic and Clinical Pathology
Mayo Clinic

Photo of Karen Rech, M.D.

Karen Rech, M.D.
Consultant, Hematopathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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