Lymphadenopathy resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]
Synonyms and Keywords: lymphadenopathy management guide, lymph node pathology management guide

Lymphadenopathy resident survival guide microchapters
Overview
Causes
Management
Do's
Don'ts

Overview

Lymphadenopathy (LAD) is used to describe abnormal size, consistency, and the number of lymph nodes. Under normal conditions, lymph nodes may not be palpated. The lymph nodes maybe central or peripheral located deep in the subcutaneous tissue. Common causes of lymphadenopathy include infectious and non-infectious. A thorough physical exam is important to establish a differential diagnosis. The common causes of lymphadenopathy can be remembered using pneumonic CHICAGO (Cancer, Hypersensitivity, Infection, Connective tissue disorders, Atypical lymphoproliferative disorders, Granulomatous, and Others). Excisional biopsy is the gold standard for tissue diagnosis. Infections can be treated with antibiotics while cancers require surgical resection, staging and chemotherapy or radiotherapy.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

The American Academy of Family Physicians (AAFP) and many research articles utilize a pneumonic CHICAGO to include all causes of lymphadenopathy based on etiology.[2][3] The causes may also be remembered based on the location of lymph nodes.

Management

Diagnostic algorithm and management

Abbreviations: UVUltraviolet rays; UTIUrinary tract infection; HEENT: Head, Eyes, Ears. Nose, and Throat exam; IM: Infectious Mononucleosis; L.N: Lymph node;CBC: Complete blood count; ESR: Erythrocyte sedimentation rate; CMP: Comprehensive metabolic panel; LFTs:Liver function tests; URTI: Upper respiratory tract infection; CMV: Cytomegalovirus; IgM: Immuniglobulin M; IgG:Immunoglobuin G; ANA:Antinuclear antibodies; CXR:Chest X-ray; CT: CT scan; VDRL: Venereal disease research laboratory; RPR:Reactive plasma reagen

The algorithm illustrates the approach to management of lymphadenopathy[4][5][6][7][8]. Borrowed from:[9][10][11]

.
 
 
 
 
 
 
 
 
 
History

Patient age (specific demographic characteristics (age) of certain malignancies)
❑ Duration of lymphadenopathy (<2 weeks or >1 year without an increase in size has low malignant potential)
❑ Past medical history of underlying disease, suggestive of immunodeficiency, or recurrent infections
❑ Sexual history suggestive of infection transmission
❑ Family history of certain malignant disorders (breast cancer, or melanoma)
❑ Exposure to communicable infectious diseases/ travel to high-risk areas
❑ Environmental exposure such as UV (skin cancer risk)/ animals/ occupational exposure
❑ Social history such as tobacco use, alcohol use (head and neck cancers risk)
❑ Associated symptoms such as pain, fever, weight loss, anorexia, cough, or recurrent UTIs
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam

Appearance of the patient
Cachexia or surgical scar marks demonstrating previous malignancy treatment

Vital signs

Temperature: High-grade / low-grade fever may demonstrate infection.
Heart rate: Tachycardia with regular pulse may demonstrate infection.
Respiratory rate: Tachypnea may demonstrate respiratory system involvement (infection\ metastasis).
Blood pressure: Chronic hypertension or hypotension (may indicate sepsis as a complication).
Oxygen saturation: may be low if the respiratory system is affected.

❑ HEENT
Cardiovascular examination
Respiratory examination
Gastrointestinal system exam includes oral examination, abdominal examination, and digital rectal exam.

Splenomegaly) may demonstrate IM, hodgkin's/ non-Hodgkin's lymphoma, and sarcoidosis

Extremities exam

❑ Skin exam: Evaluate for the lesions that indicate malignancy such as melanoma/ potential inoculation sites for germ such as traumatic lesions.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Palpable lymph node

❑ Location: (Localized vs generalized)

❑ For nodes involving several groups of nodes; suspect malignancy.
❑ An enlarged node in a lymphatic rich region; suspect local disease.
❑ Associated red streaking, suspect lymphangitis.
❑ Left supraclavicular L.N (Virchow's nodes); suspect gastric carcinoma
❑ Right supraclavicular L.N, suspect intra-thoracic carcinoma

❑ Dimensions
The aforementioned dimensions are abnormal for a palpable lymph node but do not lead to the suspicion of a neoplasm.

supraclavicular, iliac, epitrochlear, and popliteal lymph nodes >0.5cm
Inguinal nodes > 1.5 cm
❑ Other area lymph nodes >1 cm

❑ Tenderness or pain:

❑ Suspect infection.
❑ A neoplastic node may also demonstrate pain due to hemorrhage associated with central necrosis or a brisk growing tumor.

❑ Consistency

❑ Hard on palpation; suspect chronic inflammation
❑ consistent- acute inflammation
❑ Stony-hard and painless nodes-metastatic cancer/ granuloma
❑ Firm and rubbery nodes- lymphoma
❑ Matted L.N suspect mycobacterium / sarcoidosis/ lymphoma / metastatic carcinoma)

❑ Mobility

❑ Freely movable; suspect infections and collagen vascular disease
❑ Fixed L.N to surrounding tissue; suspect malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Labs

CBC with differential
ESR
CMP
Peripheral smaer
LFTs

  • Labs may be required at a later stage pf diagnosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnostic of self-limiting or benign disease
Pharyngitis, URTI, conjunctivitis, cat-scratch disease, etc
 
Suggests infection/ serious infection
 
 
 
Unexplained
 
 
 
Suggests malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
May require specific tests

❑ Throat swab

Sputum exam
 
Perform specific tests
 
 
 
Risk factors for malignancy
Family history, age, exposure, etc
 
 
 
Perform specific tests
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excisional biopsy
 
 
 
 
 
 
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
Positive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat

❑ To read about the treatment of strept throat, click here
❑ Fluctuant L.N: Incision and drainage (avoid if tuberculosis is suspected)
❑ For an untreatable or disease with residual symptoms counsel the patient

❑ Follow up for advancing or persistent LAD
 
 
 
 
 
 
 
 
 
 
 
 
Staging
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat

Surgical resection/ chemotherapy/ radiotherapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low risk
 
 
 
 
High risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specific tests/ biopsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Localized
 
 
 
 
 
Generalized
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review history and clues suggesting malignancy
 
 
 
 
 
Review history and clues suggesting malignancy
 
Positive
 
Treat
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Specific tests
such as CXR, ultrasound, CT, lab workup, biopsy.

❑ The US findings that help differentiate benign LAD from malignant include:

Benign: An isoechoic oviod shaped lesion with variable borders. High long axis/short axis ratio(L/S) of >2. A hilum is present with blood flow. Pulsatility index id <1.5.
Malignant: A hypoechoic round lesion with sharp borders. Low L/S ratio of <2. Hilum is absent with peripheral blood flow distribution.
 
 
 
 
 
 
Observe 3-4 weeks
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Undiagnostic
 
 
Diagnostic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Progress/persists
 
Regress
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No follow-up
 
Biopsy
 
 
Treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Staging
 
Follow-up
 
 
 
 
 
 
 
 
 
Biopsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Staging
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



Differential diagnosis and management[10][11][12][13][9]

Localised lymphadenopathy

  • The table describes possible infectious and oncologic differential diagnoses based upon the location of lymphadenopathy. Please click on the disease name in the management section for a detailed review of the medical therapy utilized in the management of the specific entity. Please click on the disease name in other columns for a detailed review of the disease in general.


Region Lymphadenopathy Infections Malignancies Management (click on disease name to read about the treatment)
Head and neck Preauricular and posterior cervical
  1. Mycobacterial infection
  2. Scalp infections
  3. Kikuchi disease

4. Lymphoma
5. Squamous cell carcinoma (head and neck)
6. Skin cancer

  1. Leprosy, mycobacterium bovis infection, TB
  2. Fungal infections-topical antifungals
  3. Kikuchi disease
  4. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  5. Squamous cell carcinoma
  6. Skin cancer
Submandibular and anterior cervical
  1. URTI
  2. Infectious mononucleosis (IM or mononucleosis)
  3. CMV odontogenic infection
  4. Rubella
  5. Toxoplasmosis
  6. Mycobacterial infection

7. Lymphoma
8. Squamous cell carcinoma (head and neck)
9. Leukemias: AML, ALL, CLL, CML

  1. URTI
  2. Mononucleosis
  3. Odontogenic infection
  4. Rubella
  5. Toxoplasmosis
  6. Leprosy, mycobacterium bovis infection, TB
  7. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  8. Squamous cell carcinoma
  9. Leukemias: AML, ALL, CLL, CML
Supraclavicular
  1. Mycobacterial infection
  2. Mycosis

3. Breast cancer
4. Lung cancer
5. Esophageal cancer
6. mediastinal cancer
7. Stomach cancer (Virchow's node)
8. Laryngeal cancer
9. Thyroid cancer (papillary, medullary,follicular, and anaplastic)

  1. Leprosy, mycobacterium bovis infection, TB
  2. Mycosis
  3. Breast cancer
  4. Lung cancer
  5. Esophageal cancer
  6. Mediastinal cancer
  7. Stomach cancer
  8. Laryngeal cancer
  9. Thyroid cancer: papillary thyroid cancer, medullary thyroid cancer, follicular thyroid cancer and anaplastic thyroid cancer
Axillary Infraclavicular Non-Hodgkin's lymphoma Non-Hodgkin lymphoma
Axillary
  1. Secondary syphilis
  2. Sarcoidosis
  3. Cat-scratch disease
  4. Tularemia
  5. Leprosy
  6. Leishmaniasis
  7. Brucellosis
  8. Sporotrichosis
  9. Skin infection/ skin trauma
  10. Breast infections/[[breast abscess]

11. Breast adenocarcinoma
12. Lymphoma
13. Leukemias: AML, ALL, CLL, CML
14. Kaposi sarcoma
15. Skin cancer

  1. Secondary syphilis
  2. Sarcoidosis
  3. Cat scratch disease
  4. Tularemia
  5. Leprosy
  6. Leishmaniasis
  7. Brucellosis
  8. Sporotrichosis
  9. Skin infection/ skin trauma: erysipelas and cellulitis. Trauma may require minor surgery and antibiotics.
  10. Breast abscess, may require surgery
  11. Breast adenocarcinoma
  12. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  13. Leukemias: AML, ALL, CLL, CML
  14. Kaposi's sarcoma
  15. Skin cancer
Epitrochlear
  1. Skin infections (erysipelas/ impetigo of arm and/ or hand)

2. Lymphoma
3. Skin cancer

  1. Erysipelas (in addition to antibiotics, bed rest, leg elevation, and administration of anticoagulants among patients at risk of venous thromboembolism) and cellulitis
  2. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  3. Skin cancer
Superficial inguinal Horizontal and vertical
  1. STDs (chlamydia, HIV, herpes simplex, hepatitis B, and hepatitis C)
  2. Skin infections (such as erysipelas, impetigo, and cellulitis)
  3. Benign reactive lymphadenopathy

4. Lymphoma
5. Squamous cell carcinoma (vulva, vagina, penis, and anus)
6. Skin cancer
7. Kaposi sarcoma

  1. Chlamydia, HIV, herpes simplex, hepatitis B, and hepatitis C
  2. Erysipelas, Impetigo, cellulitis
  3. Benign reactive lymphadenpathy
  4. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  5. Vulvar cancer, vaginal cancer, penile cancer, and anal cancer
  6. Skin cancer
  7. Kaposi's sarcoma


Generalized lymphadenopathy

  • The table describes possible differential diagnoses of generalized lymphadenopathy based upon the cause. Please click on the disease name in the management section for a detailed review of the medical therapy utilized in the management of the specific entity. Please click on the disease name in other columns for a detailed review of the disease in general.


Autoimmune Drug reactions Infections Malignancies Storage disorders Management (click on disease name to read about the treatment)
  1. SLE
  2. Sjögren’s syndrome
  3. Rheumatoid arthritis

4. Drugs such as sulfonamides, allopurinol, carbamazepine, etc.

5. Infectious mononucelosis
6. Sarcoidosis
7. Syphilis
8. HIV
9. Typhoid
10. Plague
11. Miliary tuberculosis

12. Lymphoma
13. Leukemias: AML, ALL, CLL, CML

14. Gaucher's disease
15. Niemann-Pick disease

  1. Mononucleosis
  2. Sarcoidosis
  3. Syphilis
  4. HIV
  5. Typhoid
  6. Plague
  7. Miliary tuberculosis
  8. Lymphoma: Non-Hodgkin lymphoma, Hodgkin's lymphoma
  9. Leukemias: AML, ALL, CLL, CML
  10. Gaucher's disease
  11. Niemann-Pick disease

Staging

  • TNM stands for Tumor, Nodes, and Metastasis. The TNM staging system is widely utilized in staging tumors, especially solid tumors. For a detailed review of the TNM staging system please click here.
  • For a detailed review of the staging systems utilized in cancer management please click here.
  • Ann Arbor staging is utilized to stage lymphomas. Pleaseclick here for a detailed review on the staging system.

Do's

Don'ts

References

  1. Hiraishi Y, Goto Y, Ohishi N, Nagase T (May 2013). "Infectious mediastinal lymphadenopathy after repeated transbronchial needle aspiration". BMJ Case Rep. 2013. doi:10.1136/bcr-2012-007998. PMC 3669807. PMID 23723103.
  2. "Tips From Other Journals - American Family Physician".
  3. Habermann TM, Steensma DP (July 2000). "Lymphadenopathy". Mayo Clin. Proc. 75 (7): 723–32. doi:10.4065/75.7.723. PMID 10907389.
  4. 4.0 4.1 Garg PK, Jain BK, Dubey IB, Sharma AK (2013). "Generalized lymphadenopathy: physical examination revisited". Ann Saudi Med. 33 (3): 298–300. doi:10.5144/0256-4947.2012.01.7.1525. PMC 6078537. PMID 22750769.
  5. Soldes OS, Younger JG, Hirschl RB (October 1999). "Predictors of malignancy in childhood peripheral lymphadenopathy". J. Pediatr. Surg. 34 (10): 1447–52. doi:10.1016/s0022-3468(99)90101-x. PMID 10549745.
  6. Ghirardelli ML, Jemos V, Gobbi PG (March 1999). "Diagnostic approach to lymph node enlargement". Haematologica. 84 (3): 242–7. PMID 10189390.
  7. Ramadas AA, Jose R, Varma B, Chandy ML (2017). "Cervical lymphadenopathy: Unwinding the hidden truth". Dent Res J (Isfahan). 14 (1): 73–78. doi:10.4103/1735-3327.201136. PMC 5356393. PMID 28348622.
  8. Wilson, Adrian (2008). "Pharyngitis": 15–24. doi:10.1007/978-1-60327-034-2_2.
  9. 9.0 9.1 9.2 Mohseni S, Shojaiefard A, Khorgami Z, Alinejad S, Ghorbani A, Ghafouri A (March 2014). "Peripheral lymphadenopathy: approach and diagnostic tools". Iran J Med Sci. 39 (2 Suppl): 158–70. PMC 3993046. PMID 24753638.
  10. 10.0 10.1 Ferrer R (October 1998). "Lymphadenopathy: differential diagnosis and evaluation". Am Fam Physician. 58 (6): 1313–20. PMID 9803196.
  11. 11.0 11.1 11.2 Bazemore AW, Smucker DR (December 2002). "Lymphadenopathy and malignancy". Am Fam Physician. 66 (11): 2103–10. PMID 12484692.
  12. Kiran KU, Krishna Moorthy KV, Meher V, Rao PN (2009). "Relapse of leprosy presenting as nodular lymph node swelling". Indian J Dermatol Venereol Leprol. 75 (2): 177–9. doi:10.4103/0378-6323.48666. PMID 19293508.
  13. Bonnetblanc JM, Bédane C (2003). "Erysipelas: recognition and management". Am J Clin Dermatol. 4 (3): 157–63. doi:10.2165/00128071-200304030-00002. PMID 12627991.
  14. Fijten GH, Blijham GH (October 1988). "Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians' workup". J Fam Pract. 27 (4): 373–6. doi:10.1080/09503158808416945. PMID 3049914.


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