Lymph nodes & spleen, nonlymphoma

Lymph node-nonspecific findings

Reactive lymphadenopathy

Last author update: 1 December 2016
Last staff update: 20 December 2023 (update in progress)

Copyright: 2003-2024,, Inc.

PubMed search: Hyperplasia[TI] lymph nodes[TI]

Jayalakshmi Balakrishna, M.D.
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Cite this page: Balakrishna J. Reactive lymphadenopathy. website. Accessed April 14th, 2024.
Definition / general
  • Lymph node enlargement due to hyperplasia of cellular components reflecting antigenic stimulation
  • Benign and reversible process.
Essential features
  • Clinically manifests as lymph node enlargement
  • No clonal process
  • No cytologic or architectural atypia
  • Reactive lymphoid hyperplasia
  • Reactive follicular hyperplasia
  • Diffuse paracortical hyperplasia
  • Sinus histiocytosis
ICD coding
  • Represents the reaction of lymphoid tissue to intrinsic or environmental antigens
  • Most lymph node enlargements are reactive
  • In children, most lymphadenopathies are benign; in adults, chance of malignancy increases with age
  • Any lymph node group can be affected depending on the stimulation
  • Lymph nodes filter lymph drained from tributary regions
  • Substances carried by lymph reach the nodes; these may be antigenic and cause an immune reaction
  • Bacteria and fungi cause predominantly inflammatory reactions; viruses and drugs cause predominantly immune reactions
  • 4 patterns of reactive hyperplasia have been described, depending on the etiology: follicular, paracortical / diffuse, sinus and mixed
  • Multiple etiologic factors, including:
    • Bacteria
    • Fungi
    • Viruses
    • Chemicals
    • Environmental pollutants
    • Drugs: phenytoin, allopurinol, atenolol, gold, penicillin, quinidine
    • Altered tissue components
    • Other antigens or allergens
  • Definitive identification of etiologic agent is possible only in a small subset of cases
Clinical features
  • Clinical syndrome usually reflects the underlying disorder
  • Generally, of short duration but may be prolonged
  • Enlargement of lymph node(s) may be painful or tender
  • Associated symptoms include fever, weight loss, malaise, loss of appetite
  • Nodes are soft or fluctuant in inflammation and suppuration
  • Histopathology
  • Exclude specific causes by clinical, laboratory and imaging studies
  • Depends on the etiologic agent
Radiology description
  • Enlarged lymph node(s)
Prognostic factors
  • Benign, self limiting process
  • Prognosis depends on the etiology
  • Treatment of the underlying disorder
Gross description
  • Enlarged, soft, lymph node with tan homogenous cut surfaces
Microscopic (histologic) description
  • Reactive follicular hyperplasia
    • B cell response pattern
    • Enlarged follicles, varying in size and shape, may coalesce and display different configurations
    • Prominent germinal center and mantle zone
    • Germinal centers show mixed small and large lymphocytes - centrocytes and centroblasts
    • Centroblasts polarize to the medial pole forming the darker zone and centrocytes accumulate at the peripheral pole forming the lighter zone
    • Centroblasts are 3 - 4 times larger than the inactivated lymphocytes and show narrow rim of basophilic cytoplasm and large, round to oval vesicular nuclei with 1 - 3 prominent peripheral nucleoli
    • Mitotic figures are frequent
    • Centrocytes are smaller lymphocytes with scant cytoplasm, cleaved nuclei, clumped chromatin and small or absent nucleoli
    • Numerous tingible body macrophages are a characteristic feature of follicular hyperplasia
  • Diffuse paracortical hyperplasia
    • T cell response pattern
    • T cell zones, paracortical or interfollicular are expanded with a heterogeneous population of cells, including numerous small lymphocytes and admixed immunoblasts resulting in a starry sky or moth eaten appearance
    • Immunoblasts in some cases may resemble Reed-Sternberg cells
    • Proliferation of high endothelial venules is another characteristic finding
  • Sinus histiocytosis
    • Sinuses are prominent and are lined by hyperplastic sinus histiocytes
  • Mixed
    • Follicular, diffuse and sinus patterns coexist in one lymph node
Microscopic (histologic) images

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Reactive lymphoid hyperplasia

Cytology description
  • Cellular smears with mixed small and large lymphocytes and numerous tingible body macrophages
  • No cytologic atypia
Positive stains
  • B cell zones are positive for pan B cell markers (CD19, CD20) and T cell zones for pan T cell markers (CD3, CD4, CD8)
  • Immunoblasts are positive for CD20 and CD30
Negative stains
Flow cytometry description
  • No aberrant immunophenotype
Molecular / cytogenetics description
  • Gene rearrangement - polyclonal pattern
Differential diagnosis
  • Atypical lymphoid hyperplasia: cellular atypia
  • Follicular lymphoma: effaced architecture, back to back nodules which invade surrounding tissues and capsule; no tingible body macrophages, no mantle zones; germinal center is BCL2+; follicular cells are monoclonal, t(14;18) present
  • Hodgkin lymphoma: Reed-Sternberg cells and variants are present
  • Other non-Hodgkin lymphomas: monotonous population of atypical lymphoid cells, invasion of capsule and surrounding tissues, monoclonal nature and specific surface markers
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