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lymphadenopathy

Etiology: 1) systemic infection - scarlet fever (Streptococcus pyogenes) - cat scratch disease (Bartonella henselae & Bartonella quintana) - secondary syphilis (Treponema pallidum) - Herpes simplex I & II - human immunodeficiency virus (HIV) - toxoplasmosis - brucellosis - rubella - rubeola (measles) - histoplasmosis - dengue fever - leptospirosis - leishmaniasis - trypanosomiasis (Trypanosoma rhodesiense & gambiense) - Chagas' disease (Trypanosoma cruzi) - disseminated tuberculosis - Castleman's disease 2) head & neck infection - reactive - diphtheria (Corynebacterium diphtheriae) - Streptococcus pyogenes - Archanobacterium haemolyticus - herpangina (Coxsackie A virus) - oral Herpes (Herpes simplex I & II) - necrobacillosis (Fusobacterium necrophorum) - dental abscess (mixed anaerobes/aerobes) - infectious mononucleosis (EBV) - cytomegalovirus (CMV) - toxoplasmosis - scrofula (Mycobacterium tuberculosis) - Kawasaki disease - Kikuchi's disease - cat-scratch fever 3) axillary infection - tuberculosis - pneumonia - upper extremity cellulitis - sporotrichosis (Sporothrix schenckii) - tularemia (Francisella tularensis) 4) abdominal infection - mesenteric lymphadenitis (Yersinia enterocolitica) - mycobacteriosis (Mycobacterium avium) 5) inguinal infection - chancroid (Haemophilus ducreyi) - syphilis - Herpes simplex (Herpes virus I & II) - lower extremity cellulitis (Streptococcus, Staphylococcus) - plague (Yersinia pestis) - Lyme disease (Borrelia burgdorferi) - tularemia (tick-borne) (Francisella tularensis) - lymphogranuloma venereum 6) immunologic disease - rheumatoid arthritis - systemic lupus erythematosus - dermatomyositis - serum sickness - drug reactions - phenytoin - hydralazine - allopurinol - silicone implants - angioimmunoblastic lymphadenopathy - Sjogren's syndrome - primary biliary cirrhosis - chronic autoimmune hepatitis 7) malignancies - hematologic - Hodgkin's lymphoma - acute leukemias (T-cell, B-cell, myeloid & monocytoid) - chronic leukemias (T-cell, B-cell, myeloid & monocytoid) - lymphomas - malignant histiocytosis - metastatic tumors to lymph nodes - melanoma - seminoma - lung cancer - breast cancer - prostate cancer - kidney cancer - head & neck cancer - gastrointestinal cancer 8) endocrine diseases - hyperthyroidism 9) lipid storage diseases - Gaucher's disease - Niemann-Pick disease 10) miscellaneous & idiopathic diseases - giant follicular lymph node hyperplasia (Castleman's disease) - sinus histiocytosis - dermatopathic lymphadenitis - sarcoidosis - amyloidosis - mucocutaneous lymph node syndrome (Kawasaki disease) - lymphomatoid granulomatosis - multifocal Langerhans cell (eosinophilic) granulomatosis - familial Mediterranean fever - Kikuchi's histiocytic necrotizing lymphadenitis 11) differential by location of adenopathy* - suboccipital - scalp infections - mononucleosis - toxoplasmosis - tick bites - lymphoma - anterior auricular - ocular infections - cat-scratch fever - posterior auricular - rubella - cervical - head or neck cancer - head or neck infection - infectious mononucleosis - Epstein-Barr virus - cytomegalovirus - toxoplasmosis - rubella - tuberculosis - lymphoma - metastatic cancer - submandibular/submental - neoplasms of the larynx or oropharynx - dental disease - thyroid cancer - supraclavicular - lymphoma - breast cancer - lung cancer - gastrointestinal (GI) cancer - infection - lungs - retroperitoneal space - axillary - infection - trauma - insect bites of hand or arm - cat-scratch fever - breast cancer - lymphoma - melanoma - brucellosis - epitrochlear - hand infection - lymphoma - sarcoidosis - tularemia - secondary syphilis - rheumatoid arthritis - mediastinal/hilar/thoracic - lymphoma - lung infection - lung cancer - sarcoidosis - infectious mononucleosis - tuberculosis - histoplasmosis - retroperitoneal - lymphoma - tuberculosis - germ-cell tumors - seminoma - prostate cancer - inguinal - lymphoma - pelvic cancer - sexually transmitted disease - foot & leg infection & trauma - Pasteurella pestis - generalized (> 2 sites) - infection: - Epstein-Barr virus - cytomegalovirus - toxoplasmosis - tuberculosis - hepatitis - syphilis - HIV/AIDS - histoplasmosis - measles - rubella - varicella - malignancy - lymphoma - leukemia 12) uncommon causes - amyloidosis - sarcoidosis - mucocutaneous lymph node syndrome (Kawasaki's syndrome) - lymphomatoid granulomatosis - angioimmunoblastic lymphadenopathy 13) iatrogenic - serum sickness - drug reaction - silicone - graft vs host disease * < 1% of lymphadenopathy in primary care due to malignancy * risk of malignancy increases with age & chronicity * younger persons are more likely to have infectious cause Pathology: 1) lymphocyte proliferation & hyperplasia of non lymphoid cells in response to antigen exposure - size of the lymph node increases - nodal architecture is preserved 2) entrapment of malignant cells* within lymph nodes results in malignant cells taking residence in lymph nodes, proliferating & causing nodal enlargement with destruction of nodal architecture Clinical manifestations: 1) size: a lymph node larger than 1 cm in diameter is considered enlarged. 2) location: see differential diagnosis 3) mobility - freely mobile lymph nodes are generally benign - lymph nodes fixed to underlying tissue are generally malignant 4) consistency - infection - tender - asymmetric - matted - may have inflamed, red overlying skin - lymphoma: - large - symmetric - firm - mobile; - non tender - rubbery - metastatic tumor - fixed - hard - discrete - non tender 5) temporal course - constant - intermittent 6) associated signs/symptoms: - cough - fever suggests infection vs malignancy - weight loss - night sweats - pruritus - fatigue - arthralgia - myalgia - hepatomegaly - splenomegaly - abdominal masses Laboratory: 1) malignancy suspected (fevers, night sweats, weight loss) - excisional lymph node biopsy* - avoid in patients with suspected head & neck cancer - may compromise potential surgery by disrupting tissue planes in the neck [2] - see head & neck cancer - histologic examination - culture - antigenic typing - chromosomal analysis - molecular studies 2) infection suspected - complete blood count (CBC) - peripheral blood smear - markers of inflammation - erythrocyte sedimentation rate (ESR) - serum C-reactive protein (CRP) - tuberculin skin test (PPD) - coccidioidomycosis serology if indicated - serum protein electrophoresis - heterophile antibodies - serum transaminases - antibodies to Toxoplasmosis - HIV testing - Bartonella hensellae serology 3) autoimmune disease or connective tissue disease suspected - see more specific disease * NEJM knowledge+ seems to endorse fine needle aspiration followed by a core biopsy (maybe not) [7] Special laboratory: - direct laryngoscopy initial testing for upper cervical lymph node - see head & neck cancer Radiology: 1) chest X-ray 2) ultrasound 3) computed tomography (CT) Differential diagnosis: 1) cysts 2) abscess Management: 1) malignancy suspected (fevers, night sweats, weight loss) - excisional lymph node biopsy (a 5 cm axillary mass is acceptable) [2] - biopsy should be performed at the lymphadenopathy of greatest PET uptake, assuming it can be safely accessed [2] 2) infection a) empiric treatment with antibiotics for no more than 1-2 weeks b) observation for 15-30 days after appropriate treatment 3) other specifically directed therapy 4) 50% of lymph node biopsies are non diagnostic 5) 25% of patients with non-diagnostic biopsies develop disease in 1 year 6) observation (without laboratory testing or imaging) for - otherwise asymptomatic patients with - cervical or inguinal lymphadenopathy and - small, mobile lymph nodes of short duration (< several months) [2] - small, soft, freely mobile lymph nodes limited to adjacent sites [2]

Related

differential diagnosis of regional lymphadenopathy & acute encephalitis lymph node

Specific

cervical lymphadenopathy hilar lymphadenopathy inguinal lymphadenopathy lymphadenitis mediastinal lymphadenopathy sinus histiocytosis sinus histiocytosis with massive lymphadenopathy; Rosai-Dorfman disease tonsillar hypertrophy

General

lymphoid tissue disease; lymphoid disorder sign/symptom

Properties

ETIOLOGY: infection inflammation malignant neoplasm

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 603-604
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 10. American College of Physicians, Philadelphia 1998, 2012, 2015, 2022 - Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 324
  4. Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol. 1993 Dec;20(6):570-82. PMID: 8296196
  5. Sahai S. Lymphadenopathy. Pediatr Rev. 2013 May;34(5):216-27. PMID: 23637250
  6. Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg. 1999 Oct;34(10):1447-52. PMID: 10549745
  7. NEJM Knowledge+ Complex Medical Care