Bone marrow nonneoplastic
Benign changes
Lymphoid aggregates (benign)
Last author update: 1 October 2013
Last staff update: 1 August 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Lymphoid aggregates bone marrow [title]
Table of Contents
Definition / general | Epidemiology | Etiology | Clinical features | Prognostic factors | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Zhao X. Lymphoid aggregates (benign). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowlymphoidaggregates.html. 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)
Epidemiology
- Benign lymphoid aggregates seen in only 1 - 2% of bone marrow biopsy specimens
- More frequently seen in autopsy specimens
Etiology
- Associated with aging (up to 13%), autoimmune disease, inflammatory conditions, infectious disorders (J Clin Pathol 1999;52:294)
- Benign aggregates also seen in patients with chronic myeloid neoplasms, especially primary myelofibrosis (Virchows Arch A Pathol Anat Histopathol 1991;419:261, Leuk Res 1991;15:525)
- Also lymphoma patients treated with rituximab (Am J Clin Pathol 1999;112:844; Hum Pathol 2008;39:194)
- Occasionally reported in association with tobacco use and certain medications
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
Malignant
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)
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
- Lymphoma may have false negative PCR (Arch Pathol Lab Med 2000;124:511)
- PCR and DNA sequence analysis may have false positives in patients with immune mediated disorders (Hum Pathol 2007;38:1402)
- 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
Additional references
