Lymphadenopathy pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(24 intermediate revisions by 7 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Lymphadenopathy}}
{{Lymphadenopathy}}
{{CMG}}; {{AE}} {{RT}}
{{CMG}}; {{AE}} {{RT}} {{DYM}} [[Ogechukwu Hannah Nnabude, MD]]


==Overview==
==Overview==
Lymph nodes are part of the immune system. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as [[lymphadenitis]].
Lymph nodes are part of the [[immune system]]. As such, they are most readily palpable when fighting infections. Infections can either originate from the organs that they drain or primarily within the lymph node itself, referred to as [[lymphadenitis]].


==Pathophysiology==
==Pathophysiology==
* If an [[infection]] remains untreated, the center of the node may become necrotic, resulting in the accumulation of fluid and debris within the structure. This is known as an abscess and feels a bit like a tensely filled balloon or grape (a.k.a. fluctuance). Knowledge of which nodes drain specific areas will help search efficiently. Following infection, lymph nodes occasionally remain permanently enlarged, though they should be non-tender, small (less the 1 cm), have a rubbery consistency.  It is common, for example, to find small, palpable nodes in the submandibular/tonsilar region of otherwise healthy individuals. This likely represents sequelae of past pharyngitis or dental infections.
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>
*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 <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>


* [[Malignancies]] may also involve the lymph nodes, either primarily (e.g. [[lymphoma]]) or as a site of metastasis.  In either case, these nodes are generally firm, non-tender, matted (i.e. stuck to each other), fixed (i.e. not freely mobile but rather stuck down to underlying tissue), and increase in size over time. The location of the lymph node may help to determine the site of malignancy. Diffuse, bilateral involvement suggests a systemic malignancy (e.g. lymphoma) while those limited to a specific anatomic region are more likely associated with a local problem. Enlargement of nodes located only on the right side of the neck in the anterior cervical chain, for example, would be consistent with a [[squamous cell carcinoma]], frequently associated with an intra-oral primary cancer.
[[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]].
* Diffuse upper airway infections (e.g. [[mononucleosis]]), systemic infections (e.g. [[tuberculosis]]) and inflammatory processes (e.g. [[sarcoidosis]]) can also cause lymphadenopathy (i.e. lymph node enlargement). This can be either symmetric or asymmetric.  


===Microscopic pathology===
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]].
===Patterns of Benign (Reactive) Lymphadenopathy===
There are three distinct patterns of benign lymphadenopathy:
*  Follicular hyperplasia. Seen in infections, autoimmune disorders, and nonspecific reactions.
*  Paracortical hyperplasia. Seen in viral infections, skin diseases, and nonspecific reactions.
*  Sinus histiocytosis. Seen in lymph nodes draining limbs, inflammatory lesions, and malignancies.
 
 
 
==References==
{{reflist|2}}


[[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 <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>


==Microscopic findings==
*On microscopic histopathological analysis, characteristic findings of [[lymphadenopathy]] will depend on the etiology.Common findings, include:<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>


'''Non-specific reactive follicular [[hyperplasia]] (NSRFH)'''
:*Large spaced cortical follicles
:*Tingible body [[macrophages]], normal dark/light GC pattern
'''[[Lymph node metastasis]]'''
:*Foreign cell population (usually in [[subcapsular]] sinuses)
:*+/-nuclear [[atypia]]
:* +/-[[malignant]] architecture
'''[[Toxoplasmosis]]'''
:*Large [[follicles]]
:*[[Epithelioid]] cells perifollicular & intrafollicular
:*Reactive GCs
:*[[Monocytoid]] cell clusters
'''[[Cat-scratch disease]]'''
:*[[PMNs]] in [[necrotic]] area
:*"Stellate" (or serpentine) shaped [[micro-abscesses]]
:*Presence of [[granulomas]]
'''[[Dermatopathic lymphadenopathy]]'''
:*[[Melanin]]-laden [[histiocytes]]
:*[[Histiocytosis]]
'''[[Systemic lupus erythematosus]] lymphadenopathy'''
:*Blue hematoxylin bodies
:*[[Necrosis]]
:*No PMNs
Histology can provide more information regarding the cause of [[lymphadenopathy]] when etiology is not clear during initial history taking, physical examination, and laboratory evaluation.


Common causes of [[lymphadenopathy]] with their associated histological findings include:


*[[Bacterial]] [[lymphadenitis]]: [[Neutrophil]]-rich infiltrate can be found within the sinus and [[medullary cords]]. Follicular [[hyperplasia]] can be seen as well. <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>
*[[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>
*[[Sarcoidosis]]: [[non-caseating]] [[granulomas]] that replace the normal architecture of the [[lymph node]]
*[[Non-Hodgkin lymphoma]]: There is partial or widespread loss of the [[lymph nod]]e by a single cell lineage. [[Lymphoid cells]] can either proliferate in a disorderly manner or as those that mimic follicular center structures.
*[[Hodgkin lymphoma]]: Can be classified by the histological appearance (from most common to least):<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>
**[[Nodular-sclerosing]]
**Mixed cellularity
**[[Lymphocyte]]-rich
**[[Lymphocyte]]-depleted


==References==
{{reflist|2}}
{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Inflammations]]
[[Category:Dermatology]]
[[Category:Hematology]]
[[Category:Physical examination]]

Latest revision as of 05:13, 9 December 2021

Lymphadenopathy Microchapters

Home

Patient Information

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

X Ray

CT scan

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Lymphadenopathy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Lymphadenopathy pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Lymphadenopathy pathophysiology

CDC on Lymphadenopathy pathophysiology

Lymphadenopathy pathophysiology in the news

Blogs on Lymphadenopathy pathophysiology

Directions to Hospitals Treating Lymphadenopathy

Risk calculators and risk factors for Lymphadenopathy pathophysiology

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

Overview

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.

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.[1]

  • 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 [1]

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.[2] 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.[3] 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. [4] 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 [5]

Microscopic findings

  • On microscopic histopathological analysis, characteristic findings of lymphadenopathy will depend on the etiology.Common findings, include:[1]

Non-specific reactive follicular hyperplasia (NSRFH)

  • Large spaced cortical follicles
  • Tingible body macrophages, normal dark/light GC pattern

Lymph node metastasis

Toxoplasmosis

Cat-scratch disease

Dermatopathic lymphadenopathy

Systemic lupus erythematosus lymphadenopathy

  • Blue hematoxylin bodies
  • Necrosis
  • No PMNs

Histology can provide more information regarding the cause of lymphadenopathy when etiology is not clear during initial history taking, physical examination, and laboratory evaluation.

Common causes of lymphadenopathy with their associated histological findings include:

References

  1. ↑ 1.0 1.1 1.2 Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (2014). "Peripheral lymphadenopathy: approach and diagnostic tools". Iran J Med Sci. 39 (2 Suppl): 158–70. PMC 3993046. PMID 24753638.
  2. ↑ Gowing NF (1974). "Tumours of the lymphoreticular system: nomenclature, histogenesis, and behaviour". J Clin Pathol Suppl (R Coll Pathol). 7: 103–7. PMC 1347234. PMID 4598345.
  3. ↑ Mesin L, Ersching J, Victora GD (2016). "Germinal Center [[B Cell]] Dynamics". Immunity. 45 (3): 471–482. doi:10.1016/j.immuni.2016.09.001. PMC 5123673. PMID 27653600. URL–wikilink conflict (help)
  4. ↑ Kumar BV, Connors TJ, Farber DL (2018) Human T Cell Development, Localization, and Function throughout Life. Immunity 48 (2):202-213. DOI:10.1016/j.immuni.2018.01.007 PMID: 29466753
  5. ↑ Strickler JG, Warnke RA, Weiss LM (1987). "Necrosis in lymph nodes". Pathol Annu. 22 Pt 2: 253–82. PMID 3317224.
  6. ↑ Fend F, Cabecadas J, Gaulard P, Jaffe ES, Kluin P, Kuzu I; et al. (2012). "Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden". J Hematop. 5 (3). doi:10.1007/s12308-012-0148-6. PMC 3845020. PMID 24307917.
  7. ↑ Elmore SA (2006) Histopathology of the lymph nodes. Toxicol Pathol 34 (5):425-54. DOI:10.1080/01926230600964722 PMID: 17067938
  8. ↑ Lucia HL, Griffith BP, Hsiung GD (1985) Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs. Arch Pathol Lab Med 109 (11):1019-23. PMID: 2996461
  9. ↑ Eberle FC, Mani H, Jaffe ES (2009). "Histopathology of Hodgkin's lymphoma". Cancer J. 15 (2): 129–37. doi:10.1097/PPO.0b013e31819e31cf. PMID 19390308.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Lymphadenopathy_pathophysiology&oldid=1716960"