Lymphadenopathy#Causes

File:Retroperitoneal lymphadenopathy of testicular seminoma, 1 50, CT image.svg lymphadenopathies of testicular seminoma embrace the aorta. Computed tomography image.]]

Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include:

• Reactive: acute infection (e.g., bacterial, or viral), or chronic infections (tuberculous lymphadenitis,{{cite journal |last1=Fontanilla |first1=JM|last2=Barnes|first2=A|last3=Von Reyn|first3=CF|title=Current diagnosis and management of peripheral tuberculous lymphadenitis|journal=Clinical Infectious Diseases|volume=53 |issue=6 |pages=555–562 |date=September 2011|pmid=21865192|doi=10.1093/cid/cir454|doi-access=free}} cat-scratch disease{{cite journal |last1=Klotz |first1=SA|last2=Ianas|first2=V|last3=Elliott|first3=SP|title=Cat-scratch Disease|journal=American Family Physician|volume=83 |issue=2 |pages=152–155 |year=2011|pmid=21243990|url=http://www.aafp.org/afp/2011/0115/p152.html}}).
• The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes". The buboes often become necrotic and may even rupture.{{cite journal |last1=Butler |first1=T|title=Plague into the 21st century|journal=Clinical Infectious Diseases|volume=49 |issue=5 |pages=736–742 |year=2009|pmid=19606935|doi=10.1086/604718|doi-access=free}}
• Infectious mononucleosis is an acute viral infection usually caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes.
• It is also a sign of cutaneous anthrax{{cite journal |last1=Sweeney |first1=DA|last2=Hicks|first2=CW|last3=Cui|first3=X|last4=Li|first4=Y|last5=Eichacker|first5=PQ|title=Anthrax infection|journal=American Journal of Respiratory and Critical Care Medicine|volume=184 |issue=12 |pages=1333–1341 |date=December 2011|pmid=21852539|doi=10.1164/rccm.201102-0209CI |pmc=3361358}} and human African trypanosomiasis{{cite journal |last1=Kennedy |first1=PG|title=Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)|journal=Lancet Neurology|volume=12 |issue=2 |pages=186–194 |date=February 2013|pmid=23260189|doi=10.1016/S1474-4422(12)70296-X|s2cid=8688394}}
• Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy).
• Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection{{cite journal |last1=Kim |first1=TU|last2=Kim|first2=S|last3=Lee|first3=JW|last4=Lee|first4=NK|last5=Jeon|first5=UB|last6=Ha|first6=HG|last7=Shin|first7=DH|title=Plasma cell type of Castleman's disease involving renal parenchyma and sinus with cardiac tamponade: case report and literature review|journal=Korean Journal of Radiology|volume=13 |issue=5 |pages=658–663 |date=September–October 2012|pmid=22977337|doi=10.3348/kjr.2012.13.5.658 |pmc=3435867}}{{cite journal |last1=Zhang |first1=H|last2=Wang|first2=R|last3=Wang|first3=H|last4=Xu|first4=Y|last5=Chen|first5=J|title=Membranoproliferative glomerulonephritis in Castleman's disease: a systematic review of the literature and 2 case reports|journal=Internal Medicine (Tokyo, Japan)|volume=51 |issue=12 |pages=1537–1542 |date=June 2012|pmid=22728487|doi=10.2169/internalmedicine.51.6298|doi-access=free}}
• Mesenteric lymphadenitis after viral systemic infection (particularly in the GALT in the appendix) can commonly present like appendicitis.{{cite journal |last1=Bratucu |first1=E|last2=Lazar|first2=A|last3=Marincaş|first3=M|last4=Daha|first4=C|last5=Zurac|first5=S|title=Aseptic mesenteric lymph node abscesses. In search of an answer. A new entity?|journal=Chirurgia (Bucarest, Romania: 1990)|volume=108 |issue=2 |pages=152–160 |date=March–April 2013|pmid=23618562|url=http://revistachirurgia.ro/pdfs/2013-2-152.pdf}}{{cite journal |last1=Leung |first1=A|last2=Sigalet|first2=DL|title=Acute Abdominal Pain in Children|journal=American Family Physician|volume=67 |issue=11 |pages=2321–2327 |date=June 2003|pmid=12800960|url=http://www.aafp.org/afp/2003/0601/p2321.html}}

Infectious causes of lymphadenopathy may include bacterial infections such as cat scratch disease, tularemia, brucellosis, or prevotella, as well as fungal infections such as paracoccidioidomycosis.{{cite journal |last1=Cordova |first1=LA |last2=Torres |first2=J |title=Paracoccidioidomycosis|journal=StatPearls [Internet]. Treasure Island (FL) |date=19 September 2022 |pmid=33085335}}{{cite journal |last1=Marques |first1=Sílvio Alencar |title=Paracoccidioidomycosis |journal=Clinics in Dermatology |date=1 November 2012 |volume=30 |issue=6 |pages=610–615 |doi=10.1016/j.clindermatol.2012.01.006 |pmid=23068148 }}

• Tumoral:
• Primary: Hodgkin lymphoma{{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}} and non-Hodgkin lymphoma give lymphadenopathy in all or a few lymph nodes.Status and anamnesis, Anders Albinsson. Page 12
• Secondary: metastasis, Virchow's node, neuroblastoma,{{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}} and chronic lymphocytic leukemia.{{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}}
• Autoimmune: systemic lupus erythematosus{{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}} and rheumatoid arthritis may have a generalized lymphadenopathy.
• Immunocompromised: AIDS. Generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS).{{cite journal |last1=Lederman |first1=MM|last2=Margolis|first2=L|title=The lymph node in HIV pathogenesis|journal=Seminars in Immunology|volume=20 |issue=3 |pages=187–195 |date=June 2008|pmid=18620868|doi=10.1016/j.smim.2008.06.001 |pmc=2577760}} "Lymphadenopathy syndrome" has been used to describe the first symptomatic stage of HIV progression, preceding a diagnosis of AIDS.
• Bites from certain venomous snakes such as the pit viper{{cite journal |last1=Quan|first1=D|title=North American poisonous bites and stings|journal= Critical Care Clinics |volume=28 |issue=4 |pages=633–659 |date=October 2012|pmid=22998994|doi=10.1016/j.ccc.2012.07.010}}
• Unknown: Kikuchi disease,{{cite journal |last1=Komagamine |first1=T|last2=Nagashima|first2=T|last3=Kojima|first3=M|last4=Kokubun|first4=N|last5=Nakamura|first5=T|last6=Hashimoto|first6=K|last7=Kimoto|first7=K|last8=Hirata|first8=K|title=Recurrent aseptic meningitis in association with Kikuchi-Fujimoto disease: case report and literature review|journal=BMC Neurology|volume=12 |pages=187–195 |date=September 2012|pmid=23020225|doi= 10.1186/1471-2377-12-112 |pmc=3570427|doi-access=free}} progressive transformation of germinal centers, sarcoidosis, hyaline-vascular variant of Castleman's disease, Rosai-Dorfman disease,{{cite journal |last1=Noguchi |first1=S|last2=Yatera|first2=K|last3=Shimajiri|first3=S|last4=Inoue|first4=N|last5=Nagata|first5=S|last6=Nishida|first6=C|last7=Kawanami|first7=T|last8=Ishimoto|first8=H|last9=Sasaguri|first9=Y|last10=Mukae|first10=H|title=Intrathoracic Rosai-Dorfman disease with spontaneous remission: a clinical report and a review of the literature|journal=The Tohoku Journal of Experimental Medicine|volume=227 |issue=3|pages=231–235 |year=2012|pmid=22789970|url=https://www.jstage.jst.go.jp/article/tjem/227/3/227_231/_pdf |doi=10.1620/tjem.227.231|doi-access=free}} Kawasaki disease,{{cite journal |last1=Weiss |first1=PF|title=Pediatric vasculitis|journal=Pediatric Clinics of North America|volume=59 |issue=2|pages=407–423|date=April 2012|pmid=22560577|doi=10.1016/j.pcl.2012.03.013 |pmc=3348547}} Kimura disease{{cite journal |last1=Koh |first1=H|last2=Kamiishi|first2=N|last3=Chiyotani|first3=A|last4=Takahashi|first4=H|last5=Sudo|first5=A|last6=Masuda|first6=Y|last7=Shinden|first7=S|last8=Tajima|first8=A|last9=Kimura|first9=Y|last10=Kimura|first10=T|title=Eosinophilic lung disease complicated by Kimura's disease: a case report and literature review|journal=Internal Medicine (Tokyo, Japan)|volume=51 |issue=22|pages=3163–3167|date=April 2012|pmid=23154725|url=https://www.jstage.jst.go.jp/article/internalmedicine/51/22/51_51.8600/_pdf|doi=10.2169/internalmedicine.51.8600|doi-access=free|url-access=subscription}}

{{visible anchor|Benign}} lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia are easy to diagnose, but some cases may be confused with follicular lymphoma. There are seven distinct patterns of benign lymphadenopathy:

• Follicular hyperplasia: This is the most common type of reactive 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}}
• 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.
• Nodal extensive necrosis
• Nodal granulomatous inflammation
• Nodal extensive fibrosis (Connective tissue framework)
• Nodal deposition of interstitial substance

These morphological patterns are never pure. Thus, reactive follicular hyperplasia can have a component of paracortical hyperplasia. However, this distinction is important for the differential diagnosis of the cause.

File:Ultrasonography of a normal lymph node.jpg of a typical normal lymph node: smooth, gently lobulated oval with a hypoechoic cortex measuring less than 3 mm in thickness with a central echogenic hilum.{{cite journal|last1=Dialani|first1=V.|last2=James|first2=D. F.|last3=Slanetz|first3=P. J.|title=A practical approach to imaging the axilla|journal=Insights into Imaging|volume=6|issue=2|year=2014|pages=217–229|issn=1869-4101|doi=10.1007/s13244-014-0367-8|pmid=25534139|pmc=4376818}} Creative Commons attribution license]]

File:Ultrasonography of a suspected malignant lymph node.jpg that shows hyperaemic blood flow in the hilum and central cortex and/or abnormal (non-hilar cortical) blood flow.]]

In cervical lymphadenopathy (of the neck), it is routine to perform a throat examination including the use of a mirror and an endoscope.{{cite journal|last1=Balm|first1=A. J. M.|last2=van Velthuysen|first2=M. L. F.|last3=Hoebers|first3=F. J. P.|last4=Vogel|first4=W. V.|last5=van den Brekel|first5=M. W. M.|title=Diagnosis and Treatment of a Neck Node Swelling Suspicious for a Malignancy: An Algorithmic Approach|journal=International Journal of Surgical Oncology|volume=2010|year=2010|pages=1–8|issn=2090-1402|doi=10.1155/2010/581540|pmid=22312490|pmc=3265261|doi-access=free}}

On ultrasound, B-mode imaging depicts lymph node morphology, whilst power Doppler can assess the vascular pattern.{{cite journal|last1=Ahuja|first1=A.T.|title=Ultrasound of malignant cervical lymph nodes|journal=Cancer Imaging|volume=8|issue=1|year=2008|pages=48–56|issn=1470-7330|doi=10.1102/1470-7330.2008.0006|pmid=18390388|pmc=2324368}} B-mode imaging features that can distinguish metastasis and lymphoma include size, shape, calcification, loss of hilar architecture, as well as intranodal necrosis. Soft tissue edema and nodal matting on B-mode imaging suggests tuberculous cervical lymphadenitis or previous radiation therapy. Serial monitoring of nodal size and vascularity are useful in assessing treatment response.

Fine-needle aspiration cytology (FNAC) has sensitivity and specificity percentages of 81% and 100%, respectively, in the histopathology of malignant cervical lymphadenopathy. PET-CT has proven to be helpful in identifying occult primary carcinomas of the head and neck, especially when applied as a guiding tool prior to panendoscopy, and may induce treatment related clinical decisions in up to 60% of cases.

Lymphadenopathy may be classified by:

• Size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm.
• By extent:
• Localized lymphadenopathy: due to localized spot of infection; e.g., an infected spot on the scalp will cause lymph nodes in the neck on that same side to swell up

File:স্থানীয় লিম্ফঅ্যাডিনোপ্যাথি.jpg

• Generalized lymphadenopathy: due to a systemic infection of the body; e.g., influenza or secondary syphilis
• Persistent generalized lymphadenopathy (PGL): persisting for a long time, possibly without an apparent cause
• By localization:
• Hilar lymphadenopathy.
• Mediastinal lymphadenopathy
• Bilateral hilar lymphadenopathy
• Dermatopathic lymphadenopathy: lymphadenopathy associated with skin disease.
• By malignancy: Benign lymphadenopathy is distinguished from malignant types which mainly refer to lymphomas or lymph node metastasis.

File:Long and short axis.png

File:Dermatopathic lymphadenopathy - low mag.jpg of dermatopathic lymphadenopathy, a type of lymphadenopathy. H&E stain.]]

• By size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm. However, there is regional variation as detailed in this table:

Lymphadenopathy of the axillary lymph nodes can be defined as solid nodes measuring more than 15 mm without fatty hilum.[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}} 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.[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}} 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.{{cite web|website=Patient UK|url=http://patient.info/doctor/generalised-lymphadenopathy|title=Generalised Lymphadenopathy|author=Laurence Knott|access-date=2017-03-04}} Last checked: 24 March 2014

Lymphadenopathy of more than 1.5–2 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.{{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 }}

• Adenitis
• Lymphovascular invasion

{{Clear}}

{{Reflist}}

• [http://www.humpath.com/spip.php?article13820 HPC:13820] {{Webarchive|url=https://web.archive.org/web/20120602060509/http://www.humpath.com/spip.php?article13820 |date=2012-06-02 }} on humpath.com (Digital slides)

{{Medical resources

| ICD10 = {{ICD10|I|88||i|80}}, {{ICD10|L|04||l|00}}, {{ICD10|R|59|1|r|50}}

| ICD9 = {{ICD9|289.1}}-{{ICD9|289.3}}, {{ICD9|683}}, {{ICD9|785.6}}

| ICDO =

| OMIM =

| MedlinePlus = 001301

| eMedicineSubj = ped

| eMedicineTopic = 1333

| DiseasesDB = 22225

| MeshID = D008206

}}

{{Lymphatic organ disease}}

{{Bacterial cutaneous infections}}

Category:Cytopathology

Category:Inflammations

Category:Diseases of veins, lymphatic vessels and lymph nodes