Lymphadenopathy pathophysiology On the Web
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S.  Delband Yekta Moazami, M.D. Ogechukwu Hannah Nnabude, MD
Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as lymphadenitis.
Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as lymphadenitis.The pathogenesis of lymphadenopathy is characterized by the inflammation of lymph nodes. This process is primarily due to an elevated rate of trafficking of lymphocytes into the node from the blood, exceeding the rate of outflow from the node.
- The immune response between the antigen and lymphocyte that leads to cellular proliferation and enlargement of the lymph nodes.
- Lymph nodes may also be enlarged secondarily as a result of the activation and proliferation of antigen-specific T and B cells (clonal expansion).
- On gross pathology, characteristic findings of lymphadenopathy, include:
- Enlarged lymph node
- Soft greasy yellow areas within the capsule
Lymph nodes are a part of the reticuloendothelial (RES) system, which includes lymphatic vessels, the lymphatic fluid found in interstitial fluid, monocytes of the blood, macrophages of the connective tissue, bone marrow, thymus, spleen, bone, and mucosa-associated lymphoid tissue (MALT) of visceral organs 
Lymphatic fluid moves throughout the lymphatic system and enters lymph nodes for filtration of foreign antigen. Foreign antigens are presented to the lymphoid cells, which lead to cellular proliferation and enlargement. Under microscopy, cellular proliferation in lymphoid follicles may be identified as several mitotic figures. Increased activity leads to stretching of the lymphatic capsule and this may cause localized tenderness.
The development of B-cells originates from pluripotent stem cells from the bone marrow. B cells that successfully build their immunoglobulin heavy chains migrate to the germinal centers to allow for antibody diversification by somatic hypermutation. The current school of thought is that B-cell lymphomas occur as a result of alternations in chromosomal translocations and somatic hypermutation.
T-cell development also begins from pluripotent stem cells, which mature within the thymic cortex.  While they are in the thymic cortex, specific rearrangements occur at the T-cell receptor. It is understood that chromosomal translocations at the level of T-cell receptors lead to T-cell lymphomagenesis.
Lymph nodes follicle necrosis may occur due to inflammatory, infectious, or malignant conditions. The neutrophil-rich infiltrates suggests bacterial infection, while lymphocyte-rich predominance may suggest viral infection. However, clinicians must remember that etiologies may vary; lymphomas, leukemias, tuberculosis, or even systemic lupus erythematosus (SLE) may be more appropriate diagnoses in the appropriate clinical context 
- On microscopic histopathological analysis, characteristic findings of lymphadenopathy will depend on the etiology.Common findings, include:
Non-specific reactive follicular hyperplasia (NSRFH)
- Large spaced cortical follicles
- Tingible body macrophages, normal dark/light GC pattern
- Foreign cell population (usually in subcapsular sinuses)
- +/-nuclear atypia
- +/-malignant architecture
- Large follicles
- Epithelioid cells perifollicular & intrafollicular
- Reactive GCs
- Monocytoid cell clusters
- PMNs in necrotic area
- "Stellate" (or serpentine) shaped micro-abscesses
- Presence of granulomas
- Melanin-laden histiocytes
Systemic lupus erythematosus lymphadenopathy
- Blue hematoxylin bodies
- No PMNs
Histology can provide more information regarding the cause of lymphadenopathy when etiology is not clear during initial history taking, physical examination, and laboratory evaluation.
Common causes of lymphadenopathy with their associated histological findings include:
- Bacterial lymphadenitis: Neutrophil-rich infiltrate can be found within the sinus and medullary cords. Follicular hyperplasia can be seen as well.  
- Viral lymphadenopathy: Macrophage infiltration and lymphoid hyperplasia. Necrosis can be seen in those who are immunocompromised.
- Sarcoidosis: non-caseating granulomas that replace the normal architecture of the lymph node
- Non-Hodgkin lymphoma: There is partial or widespread loss of the lymph node by a single cell lineage. Lymphoid cells can either proliferate in a disorderly manner or as those that mimic follicular center structures.
- Hodgkin lymphoma: Can be classified by the histological appearance (from most common to least):
- Mixed cellularity
- ↑ 1.0 1.1 1.2 Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (2014). "Peripheral lymphadenopathy: approach and diagnostic tools". Iran J Med Sci. 39 (2 Suppl): 158–70. PMC 3993046. PMID 24753638.
- ↑ Gowing NF (1974). "Tumours of the lymphoreticular system: nomenclature, histogenesis, and behaviour". J Clin Pathol Suppl (R Coll Pathol). 7: 103–7. PMC 1347234. PMID 4598345.
- ↑ Mesin L, Ersching J, Victora GD (2016). "Germinal Center [[B Cell]] Dynamics". Immunity. 45 (3): 471–482. doi:10.1016/j.immuni.2016.09.001. PMC 5123673. PMID 27653600. URL–wikilink conflict (help)
- ↑ Kumar BV, Connors TJ, Farber DL (2018) Human T Cell Development, Localization, and Function throughout Life. Immunity 48 (2):202-213. DOI:10.1016/j.immuni.2018.01.007 PMID: 29466753
- ↑ Strickler JG, Warnke RA, Weiss LM (1987). "Necrosis in lymph nodes". Pathol Annu. 22 Pt 2: 253–82. PMID 3317224.
- ↑ Fend F, Cabecadas J, Gaulard P, Jaffe ES, Kluin P, Kuzu I; et al. (2012). "Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden". J Hematop. 5 (3). doi:10.1007/s12308-012-0148-6. PMC 3845020. PMID 24307917.
- ↑ Elmore SA (2006) Histopathology of the lymph nodes. Toxicol Pathol 34 (5):425-54. DOI:10.1080/01926230600964722 PMID: 17067938
- ↑ Lucia HL, Griffith BP, Hsiung GD (1985) Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs. Arch Pathol Lab Med 109 (11):1019-23. PMID: 2996461
- ↑ Eberle FC, Mani H, Jaffe ES (2009). "Histopathology of Hodgkin's lymphoma". Cancer J. 15 (2): 129–37. doi:10.1097/PPO.0b013e31819e31cf. PMID 19390308.