Lymphoid Aggregates in Bone Marrow

Lymphoid Aggregates in Bone Marrow

Kaaren K. Reichard, MD

This is the typical appearance of a benign lymphoid aggregate in bone marrow; it is nodular, nonparatrabecular, well circumscribed, and composed of predominantly small mature lymphocytes.

Typical immunohistochemical findings in a benign lymphoid aggregate show a slight T-cell predominance (CD3, red) with a central collection of B cells (CD20, brown).



  • Lymphoid aggregate (LA)

  • Bone marrow (BM)


  • Focal collections of nonneoplastic lymphoid cells

  • Usually identified in BM clot and core biopsy sections


Infectious Agents

  • Variety of systemic infections may be associated with benign LAs in bone marrow

    • Viral most common (e.g., HIV, Epstein-Barr virus)

Underlying Immune Disorders

  • Autoimmune disorders

  • Collagen vascular disease



  • Incidence

    • Increases with age

  • Age

    • More common in older individuals

  • Gender

    • Tends to be more common in females


  • Asymptomatic

  • If symptomatic, relates to underlying disorder

Laboratory Tests

  • Performed for work-up of possible underlying etiology

    • Systemic infection

    • Autoimmune disorder

    • Neoplasia


  • No treatment necessary for benign LAs per se

  • Treatment targeted toward underlying disease (e.g., infection, immune dysregulation)


  • Relates to underlying disease


Histologic Features

  • Small, round, well circumscribed, interstitial/nonparatrabecular

  • Morphologic variations

    • Large, polymorphous aggregates (e.g., HIV)

    • Occasional larger atypical or activated cells (e.g., infection, autoimmune disorder)

    • Associated germinal center (occasional)

    • Associated lipogranuloma (especially in elderly)

    • Associated histiocytes

Cytologic Features

  • Round or slightly irregular nuclear contours, mature, clumped chromatin, inconspicuous nucleoli, usually scant cytoplasm

Predominant Pattern/Injury Type

  • Circumscribed

  • Focal, nodular

  • Interstitial

  • Perivascular

Predominant Cell/Compartment Type

  • Lymphocyte

Bone Marrow Aspirate

  • May identify small, discrete collections of lymphocytes on scanning

  • Background marrow generally does not reveal increased, individually dispersed lymphocytes

Bone Marrow Clot Section/Core Biopsy

  • Discrete foci of predominantly small lymphocytes

  • Interstitial/nonparatrabecular distribution, perivascular, adjacent to dilated sinuses, or associated with a small, penetrating vessel

  • Morphologic variations

    • Large, poorly circumscribed, polymorphous infiltrates

      • Typical of human immunodeficiency virus infection

      • Often see admixed larger, atypical cells; may require distinction from lymphoid neoplasia

    • Occasional larger atypical or activated cells

      • Typical of infection or ongoing immune reaction

    • Associated germinal center

      • Uncommon overall

      • More evident in autoimmune disorders

    • Associated with lipogranuloma

    • Associated with small collections of epithelioid histiocytes



  • Cellular composition

    • Predominance of CD3(+) T cells with few admixed CD20(+) B cells or

    • Equal admixture of CD20(+) B cells and CD3(+) T cells

  • Cellular distribution

    • B cells tend to locate centrally surrounded by concentric rim of T cells

  • B-cell antigen expression

    • No aberrant detection of CD5, CD10, CD43

      • Normal germinal center cells may be CD10(+)

Flow Cytometry

  • Polyclonal B cells

  • Normal T-cell antigens and subsets

  • Caveat

    • Lymphoid aggregate cells may not be well represented in flow cytometric BM aspirate samples


  • Nonclonal


Lymphomas/Chronic Leukemias with Nodular Pattern

  • General comments

    • Paratrabecular or intrasinusoidal pattern helps distinguish from benign LAs

    • B-cell disorders show B-cell predominance (CD20/CD19)

    • Reed-Sternberg cells in classical Hodgkin lymphoma

    • Aberrant antigen expression

      • CD5(+) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)

      • CD10(+) in follicular lymphoma

      • Cyclin D1(+) in MCL

      • Light chain restriction by flow cytometry

    • Molecular studies

      • Clonal

      • Recurring genetic abnormalities in certain disorders [e.g., t(11;14)(q13;q32) in MCL]

  • After rituximab (anti-CD20) treatment

    • Post-therapy aggregates are T-cell predominant

    • Useful distinguishing features from benign LAs

      • Often paratrabecular

      • Often poorly circumscribed

    • CD79a and CD19 useful to identify residual neoplastic cells


  • Rarely cluster

  • Characteristic immunophenotypic profile

Metastatic Tumor

  • In addition to nodular collections, also tend to see sinusoidal involvement

  • Cells typically much larger than lymphocytes

  • Lymphoid markers are negative (e.g., CD20, CD3)

  • Express tumor-associated antigens

Erythroid Colonies

  • Foci of erythroid precursors (round, often dark nuclei) may mimic lymphoid aggregates

    • Often result of poor processing, sectioning, staining

  • Cells are negative for lymphoid markers; positive for hemoglobin A

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphoid Aggregates in Bone Marrow
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