September 2020 — Hematopathology

A 66 year-old previously healthy man presented with hematuria and constitutional symptoms such as night sweats for over 2 years. CT scan of abdomen revealed retroperitoneal soft tissue thickening encasing the left ureter, abdominal aorta and central mesenteric vessels, concerning for IgG4 disease. Serum IgG4 was 50 mg/dL (reference: 2.4-121). Core needle biopsy of retroperitoneum was performed. Representative images are shown in Figure 1-3. Additional immunostains for CD1a and langerin were negative.

Figure 1
Figure 2
Figure 3

What is your diagnosis?

  • Rosai-Dorfman disease
  • Reactive fibrosis
  • IgG4 disease
  • Erdheim-Chester disease

The correct answer is...

The correct answer is Erdheim-Chester disease.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis and a clonal systemic process with multiorgan involvement and variable clinical outcomes.(1) Typical findings of ECD include central diabetes insipidus, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific fibroinflammatory infiltrate.(2) Morphologically, in this case, the core biopsy shows a fibroadipose tissue involved by a subtle histiocytic infiltrate in a background of marked fibrosis, scattered lymphocytes and plasma cells (Figure 1). The histiocytes have oval to spindled nuclei and abundant amphophilic cytoplasm.The lesional histiocytes strongly express CD163, Factor 13a, BRAF V600E (Figure 2).

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.(3) Morphologically, RDD is characterized by emperipolesis (engulfment of lymphocytes by large histiocytes) with expression of CD68, CD163, S100, and negative for CD1a and langerin.

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).(4) In the above case, the core biopsy shows a focal plasma cell infiltrate and IgG4 plasma cells number up to 50 per HPF focally without an increase in IgG4+/IgG+ plasma cell ratio (Figure 3). These findings are not conclusive for IgG4 disease.

Reactive fibrosis: A reactive fibrosis with mixed inflammatory infiltrate, although in the differential, the strong expression of Factor 13a and BRAF V600E in the CD163-positive histiocytes supports a neoplastic process in the above case.

1. Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2017.
2. Goyal G, Heaney ML, Collin M, et al., Erdheim-Chester disease: consensus recommendations for evaluation, diagnosism and treatment in the molecular era. Blood 2020; 135(22): 1929-1945.
3. Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 2016 Jun 2; 127(22): 2672-2681.
4. 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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