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| ==Overview== | | ==Overview== |
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| '''Lymphadenopathy''', also called '''adenopathy''', refers to any disease process that involves lymph nodes that are abnormal in consistency and size. This condition has multiple causes, the most common of which include [[neoplasia]], [[autoimmune diseases]], and infection. '''Lymphadenitis''' refers to lymphadenopathies that are due to [[inflammatory processes]]. It is characterized by [[nodal swelling]], pain, skin changes, fever, [[edema]], and/or purulent collections. <ref name="pmid16616313">{{cite journal| author=Gosche JR, Vick L| title=Acute, subacute, and chronic cervical lymphadenitis in children. | journal=Semin Pediatr Surg | year= 2006 | volume= 15 | issue= 2 | pages= 99-106 | pmid=16616313 | doi=10.1053/j.sempedsurg.2006.02.007 | pmc=7111159 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16616313 }} </ref>
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| ==[[Lymphadenopathy classification|Classification]]== | | ==[[Lymphadenopathy classification|Classification]]== |
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| [[Lymphadenopathy]] may be classified as follows:
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| *'''By location''':
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| **[[Tracheobronchial]] [[lymph nodes]].
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| **[[Mediastinal]] [[lymphadenopathy]]
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| **Bilateral [[hilar]] [[lymphadenopathy]]
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| *'''[[Dermatopathic]] [[lymphadenopathy]]''': [[lymphadenopathy]] associated with skin disease.
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| *'''By [[malignancy]]''': [[Benign]] [[lymphadenopathy]] is distinguished from malignant types which mainly refer to [[lymphomas]] or lymph node [[metastasis]].
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| *'''By extent''':
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| ** [[Localized lymphadenopathy]]: due to localized spot of [[infection]]
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| ** [[Generalized]] [[lymphadenopathy]]: due to systemic infection of the body. In some cases, it may persist for prolonged periods possibly without an apparent cause
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| *'''By size''', where [[lymphadenopathy]] in adults is often defined as a short axis of one or more [[lymph nodes]] is greater than 10mm.<ref name="GaneshalingamKoh2009"/><ref name="Schmidt JúniorRodrigues2007"/> However, there is regional variation as detailed in this table:
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| {|class="wikitable"
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| |+cutoff (value)|Upper limit of [[lymph node]] sizes in adults
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| | Generally || 10 mm<ref name="GaneshalingamKoh2009">{{cite journal|last1=Ganeshalingam|first1=Skandadas|last2=Koh|first2=Dow-Mu|title=Nodal staging|journal=Cancer Imaging|volume=9|issue=1|pages=104–111|year=2009|issn=1470-7330|doi=10.1102/1470-7330.2009.0017|pmid=20080453|pmc=2821588}}</ref><ref name="Schmidt JúniorRodrigues2007">{{cite journal|last1=Schmidt Júnior|first1=Aurelino Fernandes|last2=Rodrigues|first2=Olavo Ribeiro|last3=Matheus|first3=Roberto Storte|last4=Kim|first4=Jorge Du Ub|last5=Jatene|first5=Fábio Biscegli|title=Distribuição, tamanho e número dos linfonodos mediastinais: definições por meio de estudo anatômico|journal=Jornal Brasileiro de Pneumologia|volume=33|issue=2|year=2007|pages=134–140|issn=1806-3713|doi=10.1590/S1806-37132007000200006|pmid=17724531|doi-access=free}}</ref>
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| | [[Inguinal]] || 10<ref name=Torabi2004>{{cite journal | vauthors = Torabi M, Aquino SL, Harisinghani MG | title = Current concepts in lymph node imaging | journal = Journal of Nuclear Medicine | volume = 45 | issue = 9 | pages = 1509–18 | date = September 2004 | pmid = 15347718 }}</ref> – 20 mm<ref>{{cite web|url=http://bestpractice.bmj.com/best-practice/monograph/838/diagnosis/step-by-step.html|title=Assessment of lymphadenopathy|website=[[BMJ Best Practice]]|accessdate=2017-03-04}} Last updated: Last updated: Feb 16, 2017</ref>
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| | [[Pelvis]] || 10 mm for ovoid lymph nodes, 8 mm for rounded<ref name=Torabi2004/>
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| !colspan=2|Neck
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| | Generally (non-retropharyngeal) || 10 mm<ref name=Torabi2004/><ref name=Saba2016>[https://books.google.com/books?id=q7v1CwAAQBAJ&pg=PA432 Page 432] in: {{cite book|title=Image Principles, Neck, and the Brain|author=Luca Saba|publisher=CRC Press|year=2016|isbn=9781482216202}}</ref>
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| | [[Jugulodigastric]] [[lymph nodes]] || 11mm<ref name=Torabi2004/> or 15 mm<ref name=Saba2016/>
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| | [[Retropharyngeal]] || 8 mm<ref name=Saba2016/>
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| *Lateral [[retropharyngeal]]: 5 mm<ref name=Torabi2004/>
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| !colspan=2|[[Mediastinum]]
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| | [[Mediastinum]], generally || 10 mm<ref name=Torabi2004/>
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| | Superior [[mediastinum]] and high [[paratracheal]] || 7mm<ref name="SharmaFidias2004"/>
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| | Low [[paratracheal]] and [[subcarinal] || 11 mm<ref name="SharmaFidias2004">{{cite journal|last1=Sharma|first1=Amita|last2=Fidias|first2=Panos|last3=Hayman|first3=L. Anne|last4=Loomis|first4=Susanne L.|last5=Taber|first5=Katherine H.|last6=Aquino|first6=Suzanne L.|title=Patterns of Lymphadenopathy in Thoracic Malignancies|journal=RadioGraphics|volume=24|issue=2|year=2004|pages=419–434|issn=0271-5333|doi=10.1148/rg.242035075|pmid=15026591|url=https://semanticscholar.org/paper/145256a2605c552c77534f2a509227902440bf7b}}</ref>
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| !colspan=2| [[Upper abdominal]]
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| | [[Retrocrural space]] || 6 mm<ref name="DorfmanAlpern1991">{{cite journal|last1=Dorfman|first1=R E|last2=Alpern|first2=M B|last3=Gross|first3=B H|last4=Sandler|first4=M A|title=Upper abdominal lymph nodes: criteria for normal size determined with CT.|journal=Radiology|volume=180|issue=2|year=1991|pages=319–322|issn=0033-8419|doi=10.1148/radiology.180.2.2068292|pmid=2068292}}</ref>
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| | [[Paracardiac]] || 8 mm<ref name="DorfmanAlpern1991"/>
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| | [[Gastrohepatic ligament]] || 8 mm<ref name="DorfmanAlpern1991"/>
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| | Upper [[paraaortic]] region || 9 mm<ref name="DorfmanAlpern1991"/>
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| | [[Portacaval]] space || 10 mm<ref name="DorfmanAlpern1991"/>
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| | Porta hepatis || 7 mm<ref name="DorfmanAlpern1991"/>
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| | Lower [[paraaortic]] region || 11 mm<ref name="DorfmanAlpern1991"/>
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| |}
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| ==[[Lymphadenopathy pathophysiology|Pathophysiology]]== | | ==[[Lymphadenopathy pathophysiology|Pathophysiology]]== |
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| Lymph nodes are a part of the reticuloendothelial (RES) system, which includes lymphatic vessels, 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 <ref name="pmid24753638">Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (2014) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=24753638 Peripheral lymphadenopathy: approach and diagnostic tools.] ''Iran J Med Sci'' 39 (2 Suppl):158-70. PMID: [https://pubmed.gov/24753638 24753638]</ref>
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| 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.<ref name="pmid4598345">{{cite journal| author=Gowing NF| title=Tumours of the lymphoreticular system: nomenclature, histogenesis, and behaviour. | journal=J Clin Pathol Suppl (R Coll Pathol) | year= 1974 | volume= 7 | issue= | pages= 103-7 | pmid=4598345 | doi= | pmc=1347234 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4598345 }} </ref> Increased activity leads to stretching of the lymphatic capsule and this may cause localized tenderness.
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| 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.<ref name="pmid27653600">{{cite journal| author=Mesin L, Ersching J, Victora GD| title=Germinal Center B Cell Dynamics. | journal=Immunity | year= 2016 | volume= 45 | issue= 3 | pages= 471-482 | pmid=27653600 | doi=10.1016/j.immuni.2016.09.001 | pmc=5123673 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27653600 }} </ref> The current school of thought is that B-cell lymphomas occur as a result of alternations in chromosomal translocations and somatic hypermutation.
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| T-cell development also begins from pluripotent stem cells, which mature within the thymic cortex. <ref name="pmid29466753">Kumar BV, Connors TJ, Farber DL (2018) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=29466753 Human T Cell Development, Localization, and Function throughout Life.] ''Immunity'' 48 (2):202-213. [http://dx.doi.org/10.1016/j.immuni.2018.01.007 DOI:10.1016/j.immuni.2018.01.007] PMID: [https://pubmed.gov/29466753 29466753]</ref> 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.
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| 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 <ref name="pmid3317224">{{cite journal| author=Strickler JG, Warnke RA, Weiss LM| title=Necrosis in lymph nodes. | journal=Pathol Annu | year= 1987 | volume= 22 Pt 2 | issue= | pages= 253-82 | pmid=3317224 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3317224 }} </ref>
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| ==Histopathology== | | ==Histopathology== |
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| Histology can provide more information regarding the cause of lymphadenopathy when etiology is not clear during initial history taking, physical examination, and laboratory evaluation.
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| Common causes of lymphadenopathy with their associated histological findings include:
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| *Bacterial lymphadenitis: Neutrophil-rich infiltrate can be found within the sinus and medullary cords. Follicular hyperplasia can be seen as well. <ref name="pmid24307917">{{cite journal| author=Fend F, Cabecadas J, Gaulard P, Jaffe ES, Kluin P, Kuzu I | display-authors=etal| title=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. | journal=J Hematop | year= 2012 | volume= 5 | issue= 3 | pages= | pmid=24307917 | doi=10.1007/s12308-012-0148-6 | pmc=3845020 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24307917 }} </ref> <ref name="pmid17067938">Elmore SA (2006) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17067938 Histopathology of the lymph nodes.] ''Toxicol Pathol'' 34 (5):425-54. [http://dx.doi.org/10.1080/01926230600964722 DOI:10.1080/01926230600964722] PMID: [https://pubmed.gov/17067938 17067938]</ref>
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| *Viral lymphadenopathy: Macrophage infiltration and lymphoid hyperplasia. Necrosis can be seen in those who are immunocompromised.<ref name="pmid2996461">Lucia HL, Griffith BP, Hsiung GD (1985) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2996461 Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs.] ''Arch Pathol Lab Med'' 109 (11):1019-23. PMID: [https://pubmed.gov/2996461 2996461]</ref>
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| *Sarcoidosis: Non-caseating granulomas which replace the normal architecture of the lymph node
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| *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.
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| *Hodgkin lymphoma: Can be classified by the histological appearance (from most common to least):<ref name="pmid19390308">{{cite journal| author=Eberle FC, Mani H, Jaffe ES| title=Histopathology of Hodgkin's lymphoma. | journal=Cancer J | year= 2009 | volume= 15 | issue= 2 | pages= 129-37 | pmid=19390308 | doi=10.1097/PPO.0b013e31819e31cf | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19390308 }} </ref>
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| **Nodular-sclerosing
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| **Mixed cellularity
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| **Lymphocyte-rich
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| **Lymphocyte-depleted
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| ==Causes== | | ==Causes== |
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| Lymph node enlargement can be of viral, bacterial, malignant, protozoan origin and can even be caused by live vaccines <ref name="pmid25996397"> (2015) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=25996397 Reorganized text.] ''JAMA Otolaryngol Head Neck Surg'' 141 (5):428. [http://dx.doi.org/10.1001/jamaoto.2015.0540 DOI:10.1001/jamaoto.2015.0540] PMID: [https://pubmed.gov/25996397 25996397]</ref>
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| Examples of infections that can cause lymph node enlargement include:
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| *Viral infections such as Epstein-Barr Virus and cytomegalovirus which cause infectious mononucleosis, <ref name="pmid23281438">{{cite journal| author=Weiss LM, O'Malley D| title=Benign lymphadenopathies. | journal=Mod Pathol | year= 2013 | volume= 26 Suppl 1 | issue= | pages= S88-96 | pmid=23281438 | doi=10.1038/modpathol.2012.176 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23281438 }} </ref> and CMV mononucleosis respectively.<ref name="pmid4317237">{{cite journal| author=Sinha AK, Lovett M, Pillay G| title=Cytomegalovirus infection with Lymphadenopathy. | journal=Br Med J | year= 1970 | volume= 3 | issue= 5715 | pages= 163 | pmid=4317237 | doi=10.1136/bmj.3.5715.163 | pmc=1702272 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4317237 }} </ref>
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| as well HHV8 <ref name="pmid10889905">{{cite journal| author=O'Leary J, Kennedy M, Howells D, Silva I, Uhlmann V, Luttich K | display-authors=etal| title=Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity? | journal=Mol Pathol | year= 2000 | volume= 53 | issue= 2 | pages= 69-76 | pmid=10889905 | doi=10.1136/mp.53.2.69 | pmc=1186908 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10889905 }} </ref> and HIV.<ref name="pmid8924253">{{cite journal| author=Oksenhendler E, Duarte M, Soulier J, Cacoub P, Welker Y, Cadranel J | display-authors=etal| title=Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients. | journal=AIDS | year= 1996 | volume= 10 | issue= 1 | pages= 61-7 | pmid=8924253 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8924253 }} </ref>
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| *Yersinia pestis, which causes the bubonic plague, causes lymph node swelling so large that it can be seen under the skin. These lymph nodes are called buboes and may become necrotic. <ref name="pmid19606935">{{cite journal| author=Butler T| title=Plague into the 21st century. | journal=Clin Infect Dis | year= 2009 | volume= 49 | issue= 5 | pages= 736-42 | pmid=19606935 | doi=10.1086/604718 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19606935 }} </ref>
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| *Other bacterial infections such as cat-scratch disease, <ref name="pmid21243990">{{cite journal| author=Klotz SA, Ianas V, Elliott SP| title=Cat-scratch Disease. | journal=Am Fam Physician | year= 2011 | volume= 83 | issue= 2 | pages= 152-5 | pmid=21243990 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21243990 }} </ref> cutaneous anthrax, <ref name="pmid21852539">{{cite journal| author=Sweeney DA, Hicks CW, Cui X, Li Y, Eichacker PQ| title=Anthrax infection. | journal=Am J Respir Crit Care Med | year= 2011 | volume= 184 | issue= 12 | pages= 1333-41 | pmid=21852539 | doi=10.1164/rccm.201102-0209CI | pmc=3361358 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21852539 }} </ref> and tuberculous lymphadenitis <ref name="pmid21865192">{{cite journal| author=Fontanilla JM, Barnes A, von Reyn CF| title=Current diagnosis and management of peripheral tuberculous lymphadenitis. | journal=Clin Infect Dis | year= 2011 | volume= 53 | issue= 6 | pages= 555-62 | pmid=21865192 | doi=10.1093/cid/cir454 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21865192 }} </ref>
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| *Protozoal infections including African sleeping sickness, <ref name="pmid23260189">Kennedy PG (2013) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=23260189 Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness).] ''Lancet Neurol'' 12 (2):186-94. [http://dx.doi.org/10.1016/S1474-4422(12)70296-X DOI:10.1016/S1474-4422(12)70296-X] PMID: [https://pubmed.gov/23260189 23260189]</ref> Chagas' Disease, <ref name="pmid21412398">{{cite journal| author=Salazar Schettino PM, Bucio Torres M, Cabrera Bravo M, Ruiz Hernández AL| title=[Chagas disease in Mexico. Report of two acute cases]. | journal=Gac Med Mex | year= 2011 | volume= 147 | issue= 1 | pages= 63-9 | pmid=21412398 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21412398 }} </ref> and toxoplasmosis. <ref name="pmid15194258">{{cite journal| author=Montoya JG, Liesenfeld O| title=Toxoplasmosis. | journal=Lancet | year= 2004 | volume= 363 | issue= 9425 | pages= 1965-76 | pmid=15194258 | doi=10.1016/S0140-6736(04)16412-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15194258 }} </ref>
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| Examples of malignancies that cause lymphadenopathy are:
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| * Primary: Hodgkin lymphoma <ref>{{cite journal |last1=Glass |first1=C|title=Role of the Primary Care Physician in Hodgkin Lymphoma|journal=American Family Physician|volume=78 |issue=5 |pages=615–622 |date=September 2008|url=http://www.aafp.org/afp/2008/0901/p615.html |pmid=18788239}}</ref> and non-Hodgkin lymphoma give lymphadenopathy in all or a few lymph nodes.<ref name=Status>Status and anamnesis, Anders Albinsson. Page 12</ref>
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| * Secondary: metastasis, Virchow's Node, neuroblastoma, <ref>{{cite journal |last1=Colon|first1=NC|last2=Chung|first2=DH|title=Neuroblastoma|journal=Advances in Pediatrics|volume=58 |issue=1 |pages=297–311 |year=2011|pmid=21736987|doi=10.1016/j.yapd.2011.03.011 |pmc=3668791}}</ref> and chronic lymphocytic leukemia.<ref>{{cite journal |last1=Sagatys|first1=EM|last2=Zhang|first2=L|title=Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia|journal=Cancer Control|volume=19 |issue=1 |pages=18–25|date=January 2011|pmid=22143059|doi=10.1177/107327481201900103|doi-access=free}}</ref>
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| Autoimmune causes include: systemic lupus erythematosus <ref>{{cite journal |last1=Melikoglu |first1=MA|last2=Melikoglu|first2=M|title=The clinical importance of lymphadenopathy in systemic lupus erythematosus|journal=Acta Reumatologia Portuguesa|volume=33 |issue=4 |pages=402–406 |date=October–December 2008|pmid=19107085|url=http://www.actareumatologica.pt/oldsite/conteudo/pdfs/ARP_2008_4_402_07__AR_-_Lymphadenopathy.pdf}}</ref> and rheumatoid arthritis may have a generalized lymphadenopathy.<ref name=Status/>
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| ===Benign lymphadenopathy===
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| Examples include:
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| * Reactive Follicular hyperplasia <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| * Atypical Follicular Hyperplasia <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| * IgG4-related sclerosing disease-associated lymphadenopathy <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| * Paracortical hyperplasia/Interfollicular hyperplasia: It is seen in viral infections, skin diseases, and nonspecific reactions. <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| * Sinus histiocytosis: It is seen in lymph nodes draining limbs, inflammatory lesions, and malignancies. <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| * Benign lymphadenopathy with extensive necrosis <ref name="Benign lymphadenopathy">{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}</ref>
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| Axillary lymphadenopathy can be defined as solid nodes measuring more than 15 mm without fatty hilum.<ref name=dahnert2011>[https://books.google.com/books?id=uYREa2bKNW8C&pg=PA559 Page 559] in: {{cite book|title=Radiology Review Manual|author=Wolfgang Dähnert|publisher=Lippincott Williams & Wilkins|year=2011|isbn=9781609139438}}</ref> Axillary lymph nodes may be normal up to 30 mm if consisting largely of fat.<ref name=dahnert2011/>
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| In children, a short axis of 8 mm can be used.<ref>[https://books.google.com/books?id=nmpI1bLGCV4C&pg=PA942 Page 942] in: {{cite book|title=High Yield Imaging Gastrointestinal HIGH YIELD in Radiology|author=Richard M. Gore, Marc S. Levine|publisher=Elsevier Health Sciences|year=2010|isbn=9781455711444}}</ref> However, inguinal lymph nodes of up to 15 mm and cervical lymph nodes of up to 20 mm are generally normal in children up to age 8–12.<ref>{{cite web|website=[[Patient UK]]|url=http://patient.info/doctor/generalised-lymphadenopathy|title=Generalised Lymphadenopathy|author=Laurence Knott|accessdate=2017-03-04}} Last checked: 24 March 2014</ref>
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| Lymphadenopathy of more than 1.5 cm - 2 cm increases the risk of cancer or granulomatous disease as the cause rather than only inflammation or infection. Still, an increasing size and persistence over time are more indicative of cancer.<ref name="pmid12484692">{{cite journal | vauthors = Bazemore AW, Smucker DR | title = Lymphadenopathy and malignancy | journal = American Family Physician | volume = 66 | issue = 11 | pages = 2103–10 | date = December 2002 | pmid = 12484692 }}</ref>
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| ==[[Lymphadenopathy differential diagnosis|Differentiating Lymphadenopathy from other Diseases]]== | | ==[[Lymphadenopathy differential diagnosis|Differentiating Lymphadenopathy from other Diseases]]== |
| | ==[[Epidemiology and Demographics]]== |
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| After a thorough history and physical examination, lymphadenopathy can be initially categorized as:
| | ==Laboratory Evaluation of Lymphadenopathy== |
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| '''Diagnostic''': where in the practitioner has a proximal cause for the lymph nodes and can go on to treat them. Examples would be strep pharyngitis or localized cellulitis.
| | ==Diagnostic Radiological Testing== |
| The lymphadenopathy pattern history and physical examination can be suggestive an example would be mononucleosis wearing the practitioner has strong clinic index of suspicion can perform a confirmatory test which if positive he can go on and treat the patient.
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| '''Unexplained lymphadenopathy'''.
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| Unexplained lymphadenopathy can be generalized into localized or generalized lymphadenopathy.
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| Unexplained localized lymphadenopathy is further divided into patterns at no risk for malignancy or serious illness in which case the patient can be observed for 3 to 4 weeks and if response or improvement can be followed. The other alternative is if the patient is found to have a risk for malignancy or serious illness biopsy is indicated
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| Unexplained generalized lymphadenopathy can be approached after review of epidemiological clues and medications with initial testing with a CBC with manual differential and mononucleosis serology if either is positive and diagnostic proceed to treatment. If both are negative, the second workup approach would be a PPD, and RPR, a chest x-ray, and ANA, hepatitis BS antigen serology, and HIV. Additional testing modalities and lab tests may be indicated depending on clinical cues. If the results of this testing are conclusive, the practitioner can proceed on to diagnosis and treatment at the illness. If the results of the testing are still not clear, proceed onto biopsy of the most abnormal if the nodes.The most functional way to investigate the differential diagnosis of lymphadenopathy is to characterize it by node pattern and location, obtained pertinent history including careful evaluation of epidemiology, and place the patient in the appropriate arm of the algorithm to evaluate lymphadenopathy.
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| =Generalized Lymphadenopathy=
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|
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| '''Common Infective Causation'''
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| *Mononucleosis
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| *HIV
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| *Tuberculosis
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| *Typhoid fever
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| *Syphilis
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| *Plague
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| '''Malignancies'''
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| *Acute leukemia
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| *Hodgkin's lymphoma
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| *Non-Hodgkin's lymphoma
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| '''Metabolic Storage Disorders'''
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| *Gaucher disease
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| *Niemann-Pick disease
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| '''Medication Reactions'''
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| *Allopurinol
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| *Atenolol
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| *Captopril
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| *Carbamazepine
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| *Cephalosporin(s)
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| *Gold
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| *Hydralazine
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| *Penicillin
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| *Phenytoin
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| *Primidone
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| *Pyrimethamine
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| *Quinidine
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| *Sulfonamides
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| *Sulidac
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| '''Autoimmune Disease'''
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| *Sjogren syndrome
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| *Sarcoidosis
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| *Rheumatoid arthritis
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| *Systemic lupus erythematosus
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| =Localized Peripheral Lymphadenopathy=
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| '''Head and Neck Lymph Nodes'''
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| '''Viral infection'''
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| *Viral URI
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| *Mononucleosis
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| *Herpes virus
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| *Coxsackievirus
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| *Cytomegalovirus
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| *HIV
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| '''Bacterial infection'''
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| *Staphylococcal aureus
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| *Group A Streptococcus pyogenes
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| *Mycobacterium
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| *Dental abscess
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| *Cat scratch disease
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| '''Malignancy'''
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| *Hodgkin disease
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| *Non-Hodgkin lymphoma
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| *Thyroid cancer
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| *Squamous cell carcinomas of the head and neck
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| '''Inguinal Peripheral Lymphadenopathy'''
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| '''Infection'''
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| *STDs
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| *Cellulitis
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| '''Malignancy'''
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| *Lymphoma
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| *Squamous cell carcinoma of genitalia
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| *Malignant melanoma
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| '''Axillary Lymphadenopathy'''
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| '''Infection'''
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| *Localized Staphylococcal aureus
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| *Cat-scratch disease
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| *Brucellosis
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| '''Malignancy'''
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| *Lymphoma
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| *Breast cancer
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| *Melanoma
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| *Reaction to breast implants
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| '''Supraclavicular Adenopathy'''
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| *Infections
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| *Mycobacteria
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| *Fungi
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| *Malignancy
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| '''Thoracic and abdominal neoplasms'''
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| *Hodgkin disease
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| *Non-Hodgkin lymphoma
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|
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| ==[[Lymphadenopathy epidemiology and demographics|Epidemiology and Demographics]]==
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| Generalities can safely be made about the epidemiology of lymphadenopathy. <ref name="pmid30188316">{{cite journal| author=Siddiqui S, Osher J| title=Assessment of Neck Lumps in Relation to Dentistry. | journal=Prim Dent J | year= 2017 | volume= 6 | issue= 3 | pages= 44-50 | pmid=30188316 | doi=10.1308/205016817821931079 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30188316 }} </ref> <ref name="pmid30290041">{{cite journal| author=Loizos A, Soteriades ES, Pieridou D, Koliou MG| title=Lymphadenitis by non-tuberculous mycobacteria in children. | journal=Pediatr Int | year= 2018 | volume= 60 | issue= 12 | pages= 1062-1067 | pmid=30290041 | doi=10.1111/ped.13708 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30290041 }} </ref> <ref name="pmid29594802">{{cite journal| author=Prudent E, La Scola B, Drancourt M, Angelakis E, Raoult D| title=Molecular strategy for the diagnosis of infectious lymphadenitis. | journal=Eur J Clin Microbiol Infect Dis | year= 2018 | volume= 37 | issue= 6 | pages= 1179-1186 | pmid=29594802 | doi=10.1007/s10096-018-3238-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29594802 }} </ref>
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|
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| First, both generalized and localized lymphadenopathies are fairly equally distributed without regard to gender.
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|
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| Second, lymphadenopathy is more prevalent in the pediatric population than in the adult population secondary to the greater number of viral infections. It would follow that the majority of the time, lymphadenopathy in the pediatric population is of less consequence again secondary to the prevalence of viral and bacterial infections in that age group. Three-quarters of all lymphadenopathy observed are localized, and of those three-quarters, half of these are localized to the head and neck area. All remaining localized lymphadenopathy is found in the inguinal area, and the remaining lymphadenopathy is found in the axilla in the supraclavicular area. Of note, the differential diagnosis of lymphadenopathy changes significantly with the age of the patient.
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| Third, the patient's location and circumstance are very revealing and lymphadenopathy. For example, in the developing world (sub-Saharan Africa, Southeast Asia, Indian subcontinent), exposure to parasites, HIV, and miliary TB are far more likely to be causes of generalized lymphadenopathy then in the United States and Europe. Whereas, Epstein-Barr virus, streptococcal pharyngitis, and some neoplastic processes are more likely candidates to cause lymphadenopathy in the United States and the remainder of the localized industrial world. An exposure history is very important for diagnosis.
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| Exposure to blood and blood-borne products either through transfusion, unsafe sexual practices, intravenous drug abuse, or vocation
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| Exposure to infectious disease whether it be travel, in the workplace, or the home
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| Medication exposure-prescription, nonprescription, or supplements
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| Exposure to animal-borne illness either via pets or the workplace
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| Exposure to arthropod bites
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|
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| ==[[Lymphadenopathy natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
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| The prognosis of lymphadenopathy depends on its etiology. While many are treatable are have a good prognosis, malignancies, HIV, active tuberculosis, have less favorable prognoses. Localized lymphadenopathies often have a better prognosis than the majority of generalized lymphadenopathies secondary to etiologies. Also, earlier detection is a crucial determinant of prognosis
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| ==Diagnosis==
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|
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| =Laboratory Evaluation of Lymphadenopathy=
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|
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| *'''CBC with manual differential''': This is a foundational test in the diagnosis of both generalized and regional lymphadenopathy. The number and differential of the white blood cells can indicate bacterial, viral, or fungal pathology. In addition, characteristic white blood cell (WBC) patterns are observed with several of the hematological neoplasms producing lymphadenopathy
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|
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| *'''EBV serology''': Epstein-Barr viral mono is present causing regionalized lymphadenopathy
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| *Sedimentation rate: A measure of inflammation though not diagnostic, it can contribute to diagnostic reasoning
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|
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| *'''Cytomegalovirus titers''': This viral serology is indicative of possible of CMV mononucleosis
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| *'''HIV serology''': This serology can be used to diagnose acute HIV syndrome-related lymphadenopathy or to infer the diagnosis of secondary HIV-elated pathologies causing lymphadenopathy.
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| *'''Bartonella henselae serology''': used for the diagnosis of cat-scratch lymphadenopathy
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| *'''FTA\RPR''': These tests can diagnose syphilis as the cause of lymphadenopathy
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| *'''Herpes simplex serology''': can determine if the lymphadenopathy is herpes-related. Herpes simplex can produce symptoms that are similar to mononucleosis.
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| *'''Toxoplasmosis serology''': can be used to diagnose toxoplasmosis
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| *'''Hepatitis B serology''': Serological tests for hepatitis B to establish it as a contributing factor for lymphadenopathy
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|
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| *'''ANA''': this is a screening test for SLE that can help establish it as a cause for generalized lymphadenopathy
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|
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| =Diagnostic Radiological Testing=
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|
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| *'''Chest x-ray''': can reveal tuberculosis, pulmonary sarcoidosis, and pulmonary neoplasm.
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|
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| *'''Chest CT scan''': This modality of radiological imaging can define the above processes and reveal hilar adenopathy.
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| *'''Abdominal and pelvic CT scan''': These images, in combination with chest CT scan, can be revealing in cases of supraclavicular adenopathy and the diagnosis of secondary neoplasm.
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|
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| *'''Ultrasonography''': can be used in the assessment of number, size, size, shape, the marginal definition, and internal structures in patients with lymphadenopathy. Color Doppler ultrasonography is of use in distinguishing the vascular pattern between more established, pre-existing lymphadenopathy and acute lymphadenopathy. Studies have indicated that a low long axis to short axis ratio of lymphadenopathy as measured by ultrasound can be a significant indicator of lymphoma and metastatic cancer as a cause of lymphadenopathy.
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| *'''MRI scanning''': useful in the evaluation of thoracic, abdominal, and pelvic masses.
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| *'''PPD''': can be used in diagnosis of tuberculosis
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| *'''Tissue diagnosis of the node''': this is done by incisional biopsy and remains gold standard for diagnosis of lymphadenopathy.
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| ==Treatment== | | ==Treatment== |
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| Treatment of lymphadenopathy is based on the etiology. Generally, treatment of lymphadenopathy is as follows:
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| *Infectious causes of lymphadenopathy can be treated with antibiotic therapy, antiviral therapy, or antifungal therapy.
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| *Immune therapy, systemic glucocorticoids can be used for autoimmune causes of lymphadenopathy
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| *For malignancies, any combination of surgery, chemotherapy, and radiation therapy can be used.
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| *If medication is the suspected cause, discontinue the medication if possible.
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| [[Category:Medical signs]] | | [[Category:Medical signs]] |
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| [[Category:Physical examination]] | | [[Category: Physical examination]] |
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