Characteristics and clinical implications of reactive germinal centers in the bone marrow

Hum Pathol. 2017 Oct:68:7-21. doi: 10.1016/j.humpath.2017.03.024. Epub 2017 Apr 17.

Abstract

Reactive germinal centers (GCs) in the bone marrow (BM) have been described in patients with autoimmune disorders, infections, malignancies, and following certain drug therapies, or as an isolated finding without obvious underlying disease. In this study, we describe the clinical conditions in which reactive GCs occur in BM samples, and their topography and accompanying laboratory and ancillary findings in the setting of a cancer center. We identified 32 BM specimens with reactive GCs with an estimated frequency less than 0.02% over a 12-year period. Fifteen (46.9%) BM specimens had concurrent hematolymphoid neoplasms: most often a variety of small B-cell lymphomas, but also myelodysplastic syndromes. One (3.1%) case was involved by metastatic melanoma. Isolated reactive GCs were observed in 16 (50%) patients. Most BM specimens (n = 25; 78.1%) showed only one reactive GC with a size ranging from 20 to 500 μm, and most GCs (29/32) were nonparatrabecular. GCs were positive for CD10 and BCL6, and were negative for BCL2. CD3 and CD5 demonstrated T cells surrounding the GC and CD21, and CD23 highlighted follicular dendritic cells. Reactive GCs are uncommon and can be seen in association with hematolymphoid and other types of neoplasms or as an isolated finding. Reactive GCs are usually located in a nonparatrabecular distribution. A panel of immunohistochemical stains is useful to confirm the nonneoplastic nature of these GCs to avoid misdiagnosis as lymphoma or as histologic evidence of transformation in a patient with small B-cell lymphoma in the bone marrow.

Keywords: Bone marrow biopsy; Bone marrow metastasis; Low grade B-cell lymphoma; Myelodysplastic syndrome; Reactive germinal centers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Biomarkers, Tumor / analysis
  • Biopsy
  • Bone Marrow / chemistry
  • Bone Marrow / immunology
  • Bone Marrow / pathology*
  • Bone Marrow Examination
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / immunology
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / secondary
  • Diagnosis, Differential
  • Female
  • Germinal Center / chemistry
  • Germinal Center / immunology
  • Germinal Center / pathology*
  • Humans
  • Immunohistochemistry
  • Lymphoma, B-Cell / chemistry
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / pathology*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • BCL2 protein, human
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2