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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.
*'''By size''', where [[lymphadenopathy]] in adults is often defined as a short axis of one or more [[lymph nodes]] is greater than 10mm.
==Pathophysiology==
==Pathophysiology==
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.<ref name="pmid24753638">{{cite journal |vauthors=Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A |title=Peripheral lymphadenopathy: approach and diagnostic tools |journal=Iran J Med Sci |volume=39 |issue=2 Suppl |pages=158–70 |year=2014 |pmid=24753638 |pmc=3993046 |doi= |url=}}</ref>
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.  
*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).  
*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:  
*On gross pathology, characteristic findings of [[lymphadenopathy]], include:  
:*Enlarged [[lymph node]]
:*Enlarged [[lymph node]]
:*Soft greasy yellow areas within the capsule
:*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 <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>
[[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]].


[[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]].
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]].


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]].
[[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]].


[[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]].
[[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
 
[[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>


==Causes==
==Causes==
The most common causes of [[lymphadenopathy]] include infections, [[cancers]], and [[connective tissue]] disorders.
The most common causes of [[lymphadenopathy]] include infections, [[cancers]], and [[connective tissue]] disorders.
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>
[[Lymph node]] enlargement can be of [[viral]], [[bacterial]], [[malignant]], [[protozoan]] origin and can even be caused by live [[vaccines]]  
Examples of infections that can cause lymph node enlargement include:
Examples of infections that can cause [[lymph node]] enlargement include:
*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>
*[[Viral]] infections such as [[Epstein-Barr]] [[Virus]] and [[cytomegalovirus]] which cause [[infectious mononucleosis]], and [[CMV mononucleosis]] respectively.
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>
as well HHV8 and [[HIV]].
*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>
*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]].
*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>
*Other [[bacterial]] infections such as [[cat-scratch disease]], [[cutaneous anthrax]], and [[tuberculous]] [[lymphadenitis]]
*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>
*[[Protozoal]] infections including [[African sleeping sickness]], [[Chagas' Disease]],  and [[toxoplasmosis]].


Examples of malignancies that cause lymphadenopathy are:  
Examples of [[malignancies]] that cause lymphadenopathy are:  
* 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>
* Primary: [[Hodgkin lymphoma]] and [[non-Hodgkin]] lymphoma give lymphadenopathy in all or a few lymph nodes.
* 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>
* Secondary: [[metastasis]], [[Virchow's Node]], [[neuroblastoma]], and [[chronic lymphocytic leukemia]].
 
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/>


[[Autoimmune]] causes include: [[systemic lupus erythematosus]] and [[rheumatoid arthritis]] may have generalized [[lymphadenopathy]].
===Benign lymphadenopathy===
===Benign lymphadenopathy===
Examples include:
Examples include:
* 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>
* Reactive Follicular [[hyperplasia]]
* 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>
* Atypical Follicular [[Hyperplasia]]
* 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>
* [[IgG4]]-related sclerosing disease-associated lymphadenopathy  
* 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>
* [[Paracortical hyperplasia]]/[[Interfollicular hyperplasia]]: It is seen in [[viral]] infections, skin diseases, and nonspecific reactions.  
* 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>
* [[Sinus histiocytosis]]: It is seen in lymph nodes draining limbs, inflammatory lesions, and [[malignancies]].  
* 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>
* [[Benign lymphadenopathy]] with extensive [[necrosis]]
 
[[Axillary]] lymphadenopathy can be defined as solid nodes measuring more than 15&nbsp; mm without fatty hilum. [[Axillary]] lymph nodes may be normal up to 30&nbsp; mm if consisting largely of fat.
 
Axillary lymphadenopathy can be defined as solid nodes measuring more than 15&nbsp;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&nbsp;mm if consisting largely of fat.<ref name=dahnert2011/>


In children, a short axis of 8&nbsp;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&nbsp;mm and cervical lymph nodes of up to 20&nbsp;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>
In children, a short axis of 8&nbsp; mm can be used. However, [[inguinal]] lymph nodes of up to 15&nbsp; mm and [[cervical]] lymph nodes of up to 20&nbsp; mm are generally normal in children up to age 8–12.


Lymphadenopathy of more than 1.5&nbsp;cm - 2&nbsp;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>
[[Lymphadenopathy]] of more than 1.5&nbsp; cm - 2&nbsp; cm increases the risk of [[cancer]] or [[granulomatous]] disease as the cause rather than only inflammation or infection. Still, increasing size and persistence over time are more indicative of [[cancer]].


==Differentiating Lymphadenopathy from Other Diseases==
==Differentiating Lymphadenopathy from Other Diseases==
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'''Diagnostic''': wherein 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''': wherein 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]].
The [[lymphadenopathy]] pattern history and physical examination can be suggestive an example would be mononucleosis wearing the practitioner has a strong clinic index of suspicion can perform a confirmatory test which if positive he can go on and treat the patient.
The [[lymphadenopathy]] pattern history and physical examination can be suggestive an example would be [[mononucleosis]] wearing the practitioner has a strong clinic index of suspicion can perform a confirmatory test which if positive he can go on and treat the patient.


'''Unexplained lymphadenopathy'''.
'''Unexplained lymphadenopathy'''.
Unexplained [[lymphadenopathy]] can be generalized into localized or generalized [[lymphadenopathy]].
Unexplained [[lymphadenopathy]] can be generalized into localized or generalized [[lymphadenopathy]].
Unexplained localized [[lymphadenopathy]] is further divided into patterns at no risk for [[malignancy]] or severe illness in which case the patient can be observed for 3 to 4 weeks and if a 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
Unexplained localized [[lymphadenopathy]] is further divided into patterns at no risk for [[malignancy]] or severe illness in which case the patient can be observed for 3 to 4 weeks and if a 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


Unexplained generalized [[lymphadenopathy]] can be approached after a 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 of the illness. If the results of the testing are still not clear, proceed to [[biopsy]] of the most abnormal of 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]].
Unexplained generalized [[lymphadenopathy]] can be approached after a 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 of the illness. If the results of the testing are still not clear, proceed to [[biopsy]] of the most abnormal of 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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==Epidemiology and Demographics==
==Epidemiology and Demographics==
The estimated incidence of [[lymphadenopathy]] in children in the United States ranges from 35%- 45%. It is more common in the [[pediatric]] population. Race and gender have no predilection in [[lymphadenopathy]] [[incidence]].
The estimated incidence of [[lymphadenopathy]] in children in the United States ranges from 35%- 45%. It is more common in the [[pediatric]] population. Race and gender have no predilection in [[lymphadenopathy]] [[incidence]].
Generalities can safely be made about the epidemiology of lymphadenopathy. First, both generalized and localized lymphadenopathies are fairly equally distributed without regard to gender.  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.  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 than 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.  Exposure to blood and blood-borne products either through transfusion, unsafe sexual practices, intravenous drug abuse, or vocation Exposure to infectious disease whether it be travel, in the workplace, or the home Medication exposure-prescription, nonprescription, or supplements Exposure to animal-borne illness either via pets or the workplace Exposure to arthropod bites
Generalities can safely be made about the [[epidemiology]] of [[lymphadenopathy]]. First, both generalized and [[localized lymphadenopathies]] are fairly equally distributed without regard to gender.  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.  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]] than 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.  Exposure to blood and [[blood-borne]] products either through transfusion, unsafe sexual practices, intravenous [[drug abuse]], or vocation Exposure to infectious disease whether it be travel, in the workplace, or the home Medication exposure-prescription, nonprescription, or supplements Exposure to animal-borne illness either via pets or the workplace Exposure to arthropod bites


==Risk Factors==
==Risk Factors==
Line 100: Line 96:
==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==


The natural course of [[lymphadenopathy]] depends on the underlying cause. [[Lymphadenopathy]] due to infectious causes subsides once the infection is controlled. Common complications of lymphadenopathy depend on the site of involvement, e.g. mediastinal lymphadenopathy include compression symptoms like[[Tracheal]] and [[bronchial]] obstruction and [[Dysphagia]] in [[Superior vena cava syndrome]]. Prognosis is generally excellent for infectious causes. Prompt treatment with antibiotics usually leads to a complete recovery. However, it may take weeks, or even months, for swelling to disappear. The amount of time to recovery depends on the cause. Prognosis is poor for [[malignant]] tumors.
The natural course of [[lymphadenopathy]] depends on the underlying cause. [[Lymphadenopathy]] due to [[infectious]] causes subsides once the infection is controlled. Common complications of [[lymphadenopathy]] depend on the site of involvement, e.g. [[mediastinal]] [[lymphadenopathy]] include compression symptoms like[[Tracheal]] and [[bronchial]] obstruction and [[Dysphagia]] in [[Superior vena cava syndrome]]. Prognosis is generally excellent for infectious causes. Prompt treatment with [[antibiotics]] usually leads to a complete recovery. However, it may take weeks, or even months, for swelling to disappear. The amount of time to recovery depends on the cause. Prognosis is poor for [[malignant]] [[tumors]].


==Diagnosis==
==Diagnosis==
Line 106: Line 102:
====Malignant Lymphadenopathy====  
====Malignant Lymphadenopathy====  
:*Node > 2 cm
:*Node > 2 cm
:*Node that is draining, hard, or fixed to underlying tissue
:*[[Node]] that is draining, hard, or fixed to underlying tissue
:*Atypical location (e.g. [[supraclavicular]] node)  
:*Atypical location (e.g. [[supraclavicular]] node)  
:*Risk factors (e.g. [[HIV AIDS|HIV]] or [[TB]])
:*Risk factors (e.g. [[HIV AIDS|HIV]] or [[TB]])
:*[[Fever]] and/or weight loss
:*[[Fever]] and/or [[weight loss]]
:*[[Splenomegaly]]
:*[[Splenomegaly]]


====Benign Lymphadenopathy====  
====Benign Lymphadenopathy====  
:*Node < 1 cm
:*Node < 1 cm
:*Node that is mobile, soft-or tender, and is not fixed to underlying tissue
:*Node that is mobile, [[soft-or tender]], and is not fixed to underlying tissue
:*Common location (e.g. [[supraclavicular]] node)  
:*Common location (e.g. [[supraclavicular]] node)  
:*No associated risk factors  
:*No associated risk factors  
Line 120: Line 116:


===History and Symptoms===
===History and Symptoms===
The hallmark of lymphadenopathy is swollen lymph node. A positive history of a lump in the neck, red, tender skin over lymph node, and swollen, tender, or hard lymph nodes is suggestive of lymphadenopathy. The most common symptoms of lymphadenopathy include a lump in neck or affected part and constitutional symptoms like [[fatigue]], [[fever]], [[malaise]], [[flu]]- like illness, [[nausea]] and [[vomiting]], [[night sweats]], [[weight loss]], and [[cachexia]].
The hallmark of [[lymphadenopathy]] is swollen lymph node. A positive history of a lump in the neck, red, tender skin over [[lymph node]], and swollen, tender, or hard lymph nodes is suggestive of [[lymphadenopathy]]. The most common symptoms of [[lymphadenopathy]] include a lump in neck or affected part and constitutional symptoms like [[fatigue]], [[fever]], [[malaise]], [[flu]]- like illness, [[nausea]] and [[vomiting]], [[night sweats]], [[weight loss]], and [[cachexia]].


===Physical Examination===
===Physical Examination===
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===Laboratory Findings===
===Laboratory Findings===


*'''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
*'''[[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]]


*'''EBV serology''': Epstein-Barr viral mono is present causing regionalized lymphadenopathy
*'''[[EBV serology]]''': [[Epstein-Barr]] [[viral]] mono is present causing regionalized [[lymphadenopathy]]
*Sedimentation rate: A measure of inflammation though not diagnostic, can contribute to diagnostic reasoning
*Sedimentation rate: A measure of [[inflammation]] though not diagnostic, can contribute to diagnostic reasoning


*'''Cytomegalovirus titers''': This viral serology is indicative of possible CMV mononucleosis
*'''[[Cytomegalovirus]] titers''': This [[viral]] [[serology]] is indicative of possible [[CMV]] [[mononucleosis]]


*'''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.  
*'''[[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.  


*'''Bartonella henselae serology''': used for the diagnosis of cat-scratch lymphadenopathy
*'''[[Bartonella]] henselae serology''': used for the diagnosis of [[cat-scratch]] [[lymphadenopathy]]


*'''FTA\RPR''': These tests can diagnose syphilis as the cause of lymphadenopathy
*'''[[FTA\RPR]]''': These tests can diagnose [[syphilis]] as the cause of lymphadenopathy


*'''Herpes simplex serology''': can determine if the lymphadenopathy is herpes-related. Herpes simplex can produce symptoms that are similar to mononucleosis.
*'''[[Herpes simplex]] serology''': can determine if the [[lymphadenopathy]] is herpes-related. [[Herpes simplex]] can produce symptoms that are similar to [[mononucleosis]].


*'''Toxoplasmosis serology''': can be used to diagnose toxoplasmosis
*'''[[Toxoplasmosis]] serology''': can be used to diagnose [[toxoplasmosis]]


*'''Hepatitis B serology''': Serological tests for hepatitis B to establish it as a contributing factor for lymphadenopathy
*'''[[Hepatitis B]] serology''': Serological tests for [[hepatitis B]] to establish it as a contributing factor for [[lymphadenopathy]]


*'''ANA''': this is a screening test for SLE that can help establish it as a cause for generalized lymphadenopathy
*'''[[ANA]]''': this is a screening test for [[SLE]] that can help establish it as a cause for generalized [[lymphadenopathy]]


===Electrocardiogram===
===Electrocardiogram===
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===CT scan===
===CT scan===
A Chest CT scan may be helpful in the diagnosis of hilar [[adenopathy]]. Findings on CT scan suggestive of/diagnostic of [[tuberculosis]], [[sarcoidosis]], [[lymphoma]], and other [[malignancies]]. [[Abdominal]] and [[pelvic CT]] scan in combination with chest CT scan can be revealed in cases of [[supraclavicular]] adenopathy and the diagnosis of [[secondary neoplasm]].
A [[Chest]] [[CT]] scan may be helpful in the diagnosis of [[hilar]] [[adenopathy]]. Findings on [[CT]] scan suggestive of/diagnostic of [[tuberculosis]], [[sarcoidosis]], [[lymphoma]], and other [[malignancies]]. [[Abdominal]] and [[pelvic]] [[CT]] scan in combination with chest [[CT]] scan can be revealed in cases of [[supraclavicular]] [[adenopathy]] and the diagnosis of [[secondary neoplasm]].


===MRI===
===MRI===
[[MRI]] may be helpful in the diagnosis of [[lymphadenopathy]]. Findings on [[MRI]] suggestive of/diagnostic of [[lymphadenopathy]] include negative enhancement that is showed as decreased T1 and T2 signal intensity.
[[MRI]] may be helpful in the diagnosis of [[lymphadenopathy]]. Findings on [[MRI]] suggestive of/diagnostic of [[lymphadenopathy]] include negative enhancement that is showed as decreased [[T1]] and [[T2]] signal intensity.


===Other Imaging Findings===
===Other Imaging Findings===
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==Treatment==
==Treatment==
Treatment of lymphadenopathy is based on the etiology. Generally, treatment of lymphadenopathy is as follows:
Treatment of [[lymphadenopathy]] is based on the etiology. Generally, treatment of [[lymphadenopathy]] is as follows:


*Infectious causes of lymphadenopathy can be treated with antibiotic therapy, antiviral therapy, or antifungal therapy.
*Infectious causes of [[lymphadenopathy]] can be treated with antibiotic therapy, [[antiviral]] therapy, or [[antifungal]] therapy.


*Immune therapy, systemic glucocorticoids can be used for autoimmune causes of lymphadenopathy
*[[Immune]] therapy, systemic [[glucocorticoids]] can be used for [[autoimmune]] causes of [[lymphadenopathy]]


*For malignancies, any combination of surgery, chemotherapy, and radiation therapy can be used.
*For [[malignancies]], any combination of surgery, [[chemotherapy]], and [[radiation]] therapy can be used.


*If medication is the suspected cause, discontinue the medication if possible.
*If medication is the suspected cause, discontinue the medication if possible.
===Medical Therapy===
===Medical Therapy===
The medical therapy depends upon the underlying cause. Appropriate [[antibiotics]] are given for infective causes. [[Glucocorticoids]] for [[autoimmune]] conditions like [[sarcoidosis]], and [[chemotherapy]] and radiation for [[malignant]] causes.
The medical therapy depends upon the underlying cause. Appropriate [[antibiotics]] are given for infective causes. [[Glucocorticoids]] for [[autoimmune]] conditions like [[sarcoidosis]], and [[chemotherapy]] and [[radiation]] for [[malignant]] causes.


===Surgery===
===Surgery===
Surgery is not the first-line treatment option for patients with lymphadenopathy. Surgery is usually reserved for patients with either malignancy and an indication of biopsy. It involves the removal or aspiration of lymph nodes. They are dissected when the cancer is in an advanced stage.
Surgery is not the first-line treatment option for patients with [[lymphadenopathy]]. Surgery is usually reserved for patients with either [[malignancy]] and an indication of [[biopsy]]. It involves the removal or aspiration of [[lymph nodes]]. They are dissected when [[cancer]] is in an advanced stage.
 
===Primary Prevention===
===Primary Prevention===
Good general health and hygiene are helpful in the prevention of any infection.
Good general health and [[hygiene]] are helpful in the prevention of any [[infection]].
 
===Secondary Prevention===
===Secondary Prevention===
Effective measures for the secondary prevention of lymphadenopathy include sentinel lymph node biopsy and early treatment if metastasis is detected.
Effective measures for the [[secondary prevention]] of [[lymphadenopathy]] include sentinel [[lymph node]] [[biopsy]] and early treatment if [[metastasis]] is detected.


==References==
==References==

Latest revision as of 19:36, 4 February 2021

Lymphadenopathy


Lymphadenopathy Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lymphadenopathy from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

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CT scan

MRI

Ultrasound

Other Imaging Findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2],, Raviteja Guddeti, M.B.B.S. [3]Delband Yekta Moazami, M.D.[4]

Overview

Lymphadenopathy (also known as "enlarged lymph nodes") refers to lymph nodes which are abnormal in size, number, or consistency. Common causes of lymphadenopathy are infection, autoimmune disease, or malignancy. Lymphadenopathy may be classified according to distribution into 2 groups: generalized lymphadenopathy and localized lymphadenopathy. 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. Lymph nodes may also be enlarged secondarily as a result of the activation and proliferation of antigen-specific T and B cells (clonal expansion). Lymphadenopathy is very common, the estimated incidence of lymphadenopathy among children in the United States ranges from 35%- 45%. Patients of all age groups may develop lymphadenopathy. Lymphadenopathy is more commonly observed among children. Common complications of lymphadenopathy, may include: abscess formation, superior vena cava syndrome, and intestinal obstruction. Diagnostic criteria for malignant lymphadenopathy, may include: node > 2 cm, node that is draining, hard, or fixed to underlying tissue, atypical location (e.g. supraclavicular node), associated risk factors (e.g. HIV or TB), fever and/or weight loss, and splenomegaly. On the other hand, diagnostic criteria for benign lymphadenopathy, may include: node < 1 cm, node that is mobile, soft-or tender, and is not fixed to underlying tissue, typical location (e.g. supraclavicular node), no associated risk factors, and palpable and painful enlargement. Laboratory findings consistent with the diagnosis of lymphadenopathy may include elevated lactate dehydrogenase (LDH), mild neutropenia, and leukocytosis. There is no treatment for lymphadenopathy; the mainstay of therapy is treating the underlying condition.

Historical Perspective

Classification

Lymphadenopathy may be classified according to distribution into 2 groups localized lymphadenopathy and generalized lymphadenopathy. Lymphadenopathy may be classified as follows:

Pathophysiology

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

Causes

The most common causes of lymphadenopathy include infections, cancers, and connective tissue disorders. Lymph node enlargement can be of viral, bacterial, malignant, protozoan origin and can even be caused by live vaccines Examples of infections that can cause lymph node enlargement include:

as well HHV8 and HIV.

Examples of malignancies that cause lymphadenopathy are:

Autoimmune causes include: systemic lupus erythematosus and rheumatoid arthritis may have generalized lymphadenopathy.

Benign lymphadenopathy

Examples include:

Axillary lymphadenopathy can be defined as solid nodes measuring more than 15  mm without fatty hilum. Axillary lymph nodes may be normal up to 30  mm if consisting largely of fat.

In children, a short axis of 8  mm can be used. 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.

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, increasing size and persistence over time are more indicative of cancer.

Differentiating Lymphadenopathy from Other Diseases

Lymphadenopathy must be differentiated from syphilis, which may present as fever, myalgias, weight loss, and lymph node enlargement. After a thorough history and physical examination, lymphadenopathy can be initially categorized as:

Diagnostic: wherein 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. The lymphadenopathy pattern history and physical examination can be suggestive an example would be mononucleosis wearing the practitioner has a strong clinic index of suspicion can perform a confirmatory test which if positive he can go on and treat the patient.

Unexplained lymphadenopathy. Unexplained lymphadenopathy can be generalized into localized or generalized lymphadenopathy. Unexplained localized lymphadenopathy is further divided into patterns at no risk for malignancy or severe illness in which case the patient can be observed for 3 to 4 weeks and if a response or improvement can be followed. The other alternative is if the patient is found to have a risk formalignancy or serious illness biopsy is indicated

Unexplained generalized lymphadenopathy can be approached after a 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 of the illness. If the results of the testing are still not clear, proceed to biopsy of the most abnormal of 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.

Epidemiology and Demographics

The estimated incidence of lymphadenopathy in children in the United States ranges from 35%- 45%. It is more common in the pediatric population. Race and gender have no predilection in lymphadenopathy incidence. Generalities can safely be made about the epidemiology of lymphadenopathy. First, both generalized and localized lymphadenopathies are fairly equally distributed without regard to gender. 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. 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 than 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. Exposure to blood and blood-borne products either through transfusion, unsafe sexual practices, intravenous drug abuse, or vocation Exposure to infectious disease whether it be travel, in the workplace, or the home Medication exposure-prescription, nonprescription, or supplements Exposure to animal-borne illness either via pets or the workplace Exposure to arthropod bites

Risk Factors

Common risk factors in the development of lymphadenopathy may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for lymphadenopathy

Natural History, Complications, and Prognosis

The natural course of lymphadenopathy depends on the underlying cause. Lymphadenopathy due to infectious causes subsides once the infection is controlled. Common complications of lymphadenopathy depend on the site of involvement, e.g. mediastinal lymphadenopathy include compression symptoms likeTracheal and bronchial obstruction and Dysphagia in Superior vena cava syndrome. Prognosis is generally excellent for infectious causes. Prompt treatment with antibiotics usually leads to a complete recovery. However, it may take weeks, or even months, for swelling to disappear. The amount of time to recovery depends on the cause. Prognosis is poor for malignant tumors.

Diagnosis

Diagnostic Criteria

Malignant Lymphadenopathy

Benign Lymphadenopathy

  • Node < 1 cm
  • Node that is mobile, soft-or tender, and is not fixed to underlying tissue
  • Common location (e.g. supraclavicular node)
  • No associated risk factors
  • Palpable and painful enlargement

History and Symptoms

The hallmark of lymphadenopathy is swollen lymph node. A positive history of a lump in the neck, red, tender skin over lymph node, and swollen, tender, or hard lymph nodes is suggestive of lymphadenopathy. The most common symptoms of lymphadenopathy include a lump in neck or affected part and constitutional symptoms like fatigue, fever, malaise, flu- like illness, nausea and vomiting, night sweats, weight loss, and cachexia.

Physical Examination

Common physical examination findings of lymphadenopathy include fever and tachycardia in infectious causes. There is an enlargement of different groups of lymph node chains depending upon the site of involvement and underlying causes.

Laboratory Findings

  • ANA: this is a screening test for SLE that can help establish it as a cause for generalized lymphadenopathy

Electrocardiogram

X-ray

Chest X-ray can reveal tuberculosis, pulmonary sarcoidosis, and pulmonary neoplasm.

Echocardiography and Ultrasound

Ultrasound can help in the diagnosis of lymphadenopathy to define the presence and extent of a lymph node abscess, to differentiate malignant lymph nodes from lymph node enlargement due to infections. On ultrasound, characteristic findings of lymphadenopathy, include increased lymph node size. In the assessment of number, size, form, marginal description, and internal structures in patients with lymphadenopathy, this imaging modality can be used. Furthermore, color Doppler ultrasonography is used to differentiate between older pre-existing lymphadenopathy and newly active lymphadenopathy in the vascular pattern.

CT scan

A Chest CT scan may be helpful in the diagnosis of hilar adenopathy. Findings on CT scan suggestive of/diagnostic of tuberculosis, sarcoidosis, lymphoma, and other malignancies. Abdominal and pelvic CT scan in combination with chest CT scan can be revealed in cases of supraclavicular adenopathy and the diagnosis of secondary neoplasm.

MRI

MRI may be helpful in the diagnosis of lymphadenopathy. Findings on MRI suggestive of/diagnostic of lymphadenopathy include negative enhancement that is showed as decreased T1 and T2 signal intensity.

Other Imaging Findings

Other Diagnostic Studies

Treatment

Treatment of lymphadenopathy is based on the etiology. Generally, treatment of lymphadenopathy is as follows:

  • If medication is the suspected cause, discontinue the medication if possible.

Medical Therapy

The medical therapy depends upon the underlying cause. Appropriate antibiotics are given for infective causes. Glucocorticoids for autoimmune conditions like sarcoidosis, and chemotherapy and radiation for malignant causes.

Surgery

Surgery is not the first-line treatment option for patients with lymphadenopathy. Surgery is usually reserved for patients with either malignancy and an indication of biopsy. It involves the removal or aspiration of lymph nodes. They are dissected when cancer is in an advanced stage.

Primary Prevention

Good general health and hygiene are helpful in the prevention of any infection.

Secondary Prevention

Effective measures for the secondary prevention of lymphadenopathy include sentinel lymph node biopsy and early treatment if metastasis is detected.

References

References

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