Bone marrow nonneoplastic

Benign changes

Lymphoid aggregates (benign)

Last author update: 1 October 2013
Last staff update: 1 August 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Lymphoid aggregates bone marrow [title]

Page views in 2022: 4,232
Page views in 2023 to date: 1,847
Cite this page: Zhao X. Lymphoid aggregates (benign). website. Accessed June 3rd, 2023.
Definition / general
  • See also persistent polyclonal lymphocytosis, plasmacytosis, polymorphous reactive lymphoid hyperplasia and systemic polyclonal B immunoblastic proliferation
  • Lymphoid aggregates, whether benign or malignant, are relatively uncommon in bone marrow (BM) biopsy specimens
  • Distinguishing benign and malignant (i.e. lymphoma) aggregates can be challenging, especially when multiple aggregates are identified with no history of lymphoma
  • Distribution of B cells and T cells within lymphoid aggregates may be useful in separating benign and malignant aggregates:
    • Likely benign: predominantly T cells or central core of T cells surrounded by a rim of B cells or a mixed distribution of B and T cells
    • Likely benign: small ( < 600 μm), distinct borders without interstitial infiltrate of lymphoid cells, nonparatrabecular distribution
    • Likely malignant: predominantly B cells or central core of B cells surrounded by a rim of T cells (excluding germinal center formation); must also assess other features suggestive of malignancy (large aggregate size, infiltrative edges, cytologic atypia, paratrabecular localization)
  • Benign lymphoid aggregates seen in only 1 - 2% of bone marrow biopsy specimens
  • More frequently seen in autopsy specimens
Clinical features
  • Usually no history of lymphoma, although a history of lymphoproliferative disorder does not necessarily indicate aggregates are malignant
  • Benign aggregates:
    • Mean age 57 years (12 to 99 years)
    • Incidence increases with age
    • Many cases associated with HIV, hepatitis B or C, mycobacteria, fungal or bacterial infections
    • Often associated with immune mediated disorder or inflammatory condition, most commonly primary immune thrombocytopenia
Prognostic factors
  • Up to 1/3 (all ages) may have subsequent malignant lymphoid aggregates in BM or other evidence of lymphoma / lymphoproliferative disorder; usually original biopsy showed atypical or suspicious lymphoid aggregates with follow up recommended
  • Atypical: due to infiltrative edges, paratrabecular localization or predominance of B cells
Microscopic (histologic) description
  • Bone marrow biopsy shows nonparatrabecular distribution of small ( < 600 μm) lymphoid aggregates, which usually have distinct borders without interstitial infiltrate of lymphoid cells
  • Usually predominance of T cells; also haphazard mixture of T and B cells, centrally located T cells (Hum Pathol 2013;44:512)
  • Germinal centers are nonspecific; may indicate a reactive process but also seen in mantle cell lymphoma and splenic marginal zone lymphoma, where germinal centers are associated with lymphomatous infiltrate
Microscopic (histologic) images

Images hosted on other servers:

Morphologically benign

Morphologically suspicious

Morphologically malignant

Benign lymphoid aggregates


Cytology description
  • Aspirate smears may show lymphocytosis, consisting of small to medium sized, mature appearing lymphocytes
Positive stains
  • Mixed mature B and T cells, often with T cell predominance
  • Occasionally bcl2+
  • Low affinity nerve growth factor receptor highlights fine network of adventitial reticular cells in benign lymphoid aggregates; nodular aggregates of various lymphomas have distortion of adventitial reticular cell network and change in expression of low affinity nerve growth factor receptor (Br J Haematol 2002;117:569)
Negative stains
Molecular / cytogenetics description
  • Molecular:
    • PCR for immunoglobulin (heavy chain +/- kappa light chain) gene rearrangement may distinguish benign from malignant bone marrow lymphoid aggregates by demonstrating the lack of clonality but must correlate with other findings
  • Cytogenetics: normal karyotype and no aberrant FISH signals
Differential diagnosis
  • Malignant lymphoid aggregates: paratrabecular localization, infiltration of fat cells, distribution surrounding large sinuses, variation in aggregate size
Back to top
Image 01 Image 02