Lymphadenopathy

Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis,<ref>Template:DorlandsDict</ref> producing swollen or enlarged lymph nodes. In clinical practice, the distinction between lymphadenopathy and lymphadenitis is rarely made and the words are usually treated as synonymous. Inflammation of the lymphatic vessels is known as lymphangitis.<ref>Template:DorlandsDict</ref> Infectious lymphadenitis affecting lymph nodes in the neck is often called scrofula.

Lymphadenopathy is a common and nonspecific sign. Common causes include infections (from minor causes such as the common cold and post-vaccination swelling to serious ones such as HIV/AIDS), autoimmune diseases, and cancer. Lymphadenopathy is frequently idiopathic and self-limiting.

Causes

File:Retroperitoneal lymphadenopathy of testicular seminoma, 1 50, CT image.svg

Retroperitoneal 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,<ref>Template:Cite journal</ref> cat-scratch disease<ref>Template:Cite journal</ref>).
  • 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.<ref>Template:Cite journal</ref>
  • 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.<ref name="Benign lymphadenopathy"/>
  • It is also a sign of cutaneous anthrax<ref>Template:Cite journal</ref> and human African trypanosomiasis<ref>Template:Cite journal</ref>
  • Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy).<ref name=Status/>
  • Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
  • Mesenteric lymphadenitis after viral systemic infection (particularly in the GALT in the appendix) can commonly present like appendicitis.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

• Tumoral:
  • Primary: Hodgkin lymphoma<ref>Template:Cite journal</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>
  • Secondary: metastasis, Virchow's node, neuroblastoma,<ref>Template:Cite journal</ref> and chronic lymphocytic leukemia.<ref>Template:Cite journal</ref>
• Autoimmune: systemic lupus erythematosus<ref>Template:Cite journal</ref> and rheumatoid arthritis may have a generalized lymphadenopathy.<ref name=Status/>
• Immunocompromised: AIDS. Generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS).<ref>Template:Cite journal</ref> "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<ref>Template:Cite journal</ref>
• Unknown: Kikuchi disease,<ref>Template:Cite journal</ref> progressive transformation of germinal centers, sarcoidosis, hyaline-vascular variant of Castleman's disease, Rosai-Dorfman disease,<ref>Template:Cite journal</ref> Kawasaki disease,<ref>Template:Cite journal</ref> Kimura disease<ref>Template:Cite journal</ref>

Benign (reactive) lymphadenopathy

Template:Visible anchor 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:<ref name="Benign lymphadenopathy" />

• Follicular hyperplasia: This is the most common type of reactive lymphadenopathy.<ref name="Benign lymphadenopathy">Template:Cite journal</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.
• 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.

Diagnosis

File:Ultrasonography of a normal lymph node.jpg

Medical ultrasonography 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.<ref name=Dialani2014>Template:Cite journal Creative Commons attribution license</ref>

File:Ultrasonography of a suspected malignant lymph node.jpg

Ultrasonography of a suspected malignant lymph node:
- Absence of the fatty hilum
- Increased focal cortical thickness greater than 3 cm
- Doppler ultrasonography that shows hyperaemic blood flow in the hilum and central cortex and/or abnormal (non-hilar cortical) blood flow.<ref name=Dialani2014/>

In cervical lymphadenopathy (of the neck), it is routine to perform a throat examination including the use of a mirror and an endoscope.<ref name="Balmvan Velthuysen2010">Template:Cite journal</ref>

On ultrasound, B-mode imaging depicts lymph node morphology, whilst power Doppler can assess the vascular pattern.<ref name="Ahuja2008">Template:Cite journal</ref> B-mode imaging features that can distinguish metastasis and lymphoma include size, shape, calcification, loss of hilar architecture, as well as intranodal necrosis.<ref name="Ahuja2008"/> Soft tissue edema and nodal matting on B-mode imaging suggests tuberculous cervical lymphadenitis or previous radiation therapy.<ref name="Ahuja2008"/> Serial monitoring of nodal size and vascularity are useful in assessing treatment response.<ref name="Ahuja2008"/>

Fine-needle aspiration cytology (FNAC) has sensitivity and specificity percentages of 81% and 100%, respectively, in the histopathology of malignant cervical lymphadenopathy.<ref name="Balmvan Velthuysen2010"/> 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.<ref name="Balmvan Velthuysen2010"/>

Classification

Lymphadenopathy may be classified by:

• Size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes greater than 10 mm.<ref name="GaneshalingamKoh2009"/>
• 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

    Inflammatory localized lymphadenopathy at right mandibular angle

  • 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
• Localization:
  • Hilar lymphadenopathy.
  • Mediastinal lymphadenopathy
  • Bilateral hilar lymphadenopathy
• Dermatopathic lymphadenopathy: lymphadenopathy associated with skin disease.
• Malignancy: Benign lymphadenopathy is distinguished from malignant types which mainly refer to lymphomas or lymph node metastasis.

Size

File:Long and short axis.png

File:Dermatopathic lymphadenopathy - low mag.jpg

Micrograph of dermatopathic lymphadenopathy, a type of lymphadenopathy. H&E stain.

• Size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes greater than 10 mm.<ref name="GaneshalingamKoh2009"/><ref name="Schmidt JúniorRodrigues2007"/> However, there is regional variation as detailed in this table:

Upper limit of lymph node sizes in adults

Generally	10 mm<ref name="GaneshalingamKoh2009">Template:Cite journal</ref><ref name="Schmidt JúniorRodrigues2007">Template:Cite journal</ref>
Inguinal	10<ref name=Torabi2004>Template:Cite journal</ref> – 20 mm<ref>Template:Cite web Last updated: Last updated: Feb 16, 2017</ref>
Pelvis	10 mm for ovoid lymph nodes, 8 mm for rounded<ref name=Torabi2004/>
Neck
Generally (non-retropharyngeal)	10 mm<ref name=Torabi2004/><ref name=Saba2016>Page 432 in: Template:Cite book</ref>
Jugulodigastric lymph nodes	11 mm<ref name=Torabi2004/> or 15 mm<ref name=Saba2016/>
Retropharyngeal	8 mm<ref name=Saba2016/> Lateral retropharyngeal: 5 mm<ref name=Torabi2004/>
Mediastinum
Mediastinum, generally	10 mm<ref name=Torabi2004/>
Superior mediastinum and high paratracheal	7 mm<ref name="SharmaFidias2004"/>
Low paratracheal and subcarinal	11 mm<ref name="SharmaFidias2004">Template:Cite journal</ref>
Upper abdominal
Retrocrural space	6 mm<ref name="DorfmanAlpern1991">Template:Cite journal</ref>
Paracardiac	8 mm<ref name="DorfmanAlpern1991"/>
Gastrohepatic ligament	8 mm<ref name="DorfmanAlpern1991"/>
Upper paraaortic region	9 mm<ref name="DorfmanAlpern1991"/>
Portacaval space	10 mm<ref name="DorfmanAlpern1991"/>
Porta hepatis	7 mm<ref name="DorfmanAlpern1991"/>
Lower paraaortic region	11 mm<ref name="DorfmanAlpern1991"/>

Lymphadenopathy of the axillary lymph nodes can be defined as solid nodes measuring more than 15 mm without fatty hilum.<ref name=dahnert2011>Page 559 in: Template:Cite book</ref> Axillary lymph nodes may be normal up to 30 mm if consisting largely of fat.<ref name=dahnert2011/>

In children, a short axis of 8 mm can be used.<ref>Page 942 in: Template:Cite book</ref> However, inguinal lymph nodes of up to 15 mm and cervical lymph nodes of up to 20 mm are generally normal in children up to age 8–12.<ref>Template:Cite web Last checked: 24 March 2014</ref>

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.<ref name="pmid12484692">Template:Cite journal</ref>

See also

• Adenitis
• Lymphovascular invasion

External links

• HPC:13820 Template:Webarchive on humpath.com (Digital slides)