Lymphadenopathy differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[5] Ogechukwu Hannah Nnabude, MD


Lymphadenopathy can be caused by different disease categories include: neoplasms, such as lymphoma; bacterial, viral, and parasite diseases; and inflammatory conditions, such as systemic lupus erythematosus.

Differentiating different causes of Lymphadenopathy

Lymphadenopathy can be caused by different disease categories include: neoplasms such as lymphoma; bacterial, viral, and parasites diseases; and inflammatory conditions, such as systemic lupus erythematosus.

Different causes of Lymphadenopathy can be differentiated from each other based on their different clinical manifestation such as pain, constitutional symptoms; and para clinical symptoms such as blood test and pathology on biopsy.

Diseases Clinical manifestations Para-clinical findings Pathogonomic finding
Lab Findings Biopsy
Painless or painful Lymphadenopathy Generalized or localized Lymphadenopathy Fever Weight loss Night Sweats Rash Other symptoms Immunochemistry Blood work
Non-Hodgkins lymphoma Painless Generalized + + + +
  • N/A
Hodgkin's disease[1][2][3][4] Painless Generalized + + + +
  • N/A

Fine-needle aspiration

Chronic lymphocytic leukemia[5][6][7][8] Painless Generalized + + + -


On microscopic histopathological analysis:
  • N/A
Small cell carcinoma of the lung[9][10][11][12][13] Painless Localized - - - -

Nearly all SCLC are immunoreactive for

Neuroendocrine and neural differentiation result in the expression of molecules like

  • N/A
  • N/A
Melanoma[14][15][16] Painless Localized - - - -
  • N/A
  • An excisional biopsy (either elliptical, punch, or saucerization) of the thickest portion of the lesion with 1-3 mm margins.
  • Epidermal atrophy and flattening and prominent dermal invasion
Lymphomatoid granulomatosis[17][18][19][20][21][22][23] Painless Generalized or localized + + - +
  • N/A


  • N/A
  • On chest CT scan, Halo sign is seen due to the angioinvasive nature of the disease
Angioimmunoblastic lymphadenopathy[24][25][26][27] Painless Generalized + + + +
  • Immunophenotyping
  • Fluorescence in situ hybridization (FISH)
Lymph node or extranodal tissue biopsy is diagnostic of angioimmunoblastic T-cell lymphoma.
  • Epstein–Barr virus (EBV) has been found in both reactive B-cells and the neoplastic T-cells.
  • Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in cases.
Giant lymph node hyperplasia (Castleman disease)[28] Painless Localized + + - -
  • N/A
  • N/A
  • Hypersecretion of the cytokine IL-6.
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy




Bacteria Syphilis[29][30][31][32] Painless Localized + - - + Primary syphilis:
  • Chancer

Secondary syphilis:

Tertiary syphilis

  • Gumma
  • Organ system involvement
  • Darkfield microscopy to detect T. pallidum.
  • Nontreponemal tests (e.g., VDRLand RPR )
  • Treponemal tests (e.g. FTA-ABS, the TP-PA assay
  • N/A

On microscopic histopathological analysis, characteristic findings of syphilis:

  • Mononuclear leukocytic infiltration, macrophages, and lymphocytes.
  • Swelling and proliferation of small blood vessels.
  • Painless clean base chancre.
Brucellosis[33][34][35][36][37] Painful Localized + - - +
  • Brucella is most commonly isolated from blood cultures
  • N/A
  • N/A
  • Night sweats, often with characteristic smell, likened to wet hay
Viral Infectious mononucleosis[38] Painful Localized + - - +
  • A positive reaction to a mono spot test
  • Direct detection of EBV in blood or lymphoid tissues
  • N/A
CMV[39][40] Painful Localized + - - +
  • Owl Eye inclusion bodies.
HIV[41][42][43][44] Painful or painless Generalized or localized - + - -
  • Anaemia
  • Thrombocytopenia
  • Leukopenia
  • N/A
  • Plasma HIV RNA viral load
Cat scratch disease[45][46][47][48] Painful Localized + - - +
  • N/A
Mycobacteria Tuberculosis[49][50][51][52][53] Painful Generalized or localized + + + +
Parasite Toxoplasmosis[54][55][56][57] Painless Generalized or localized + - + -
  • N/A
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy




Systemic lupus erythematosus


Painless Generalized or localized + +/- - +
Sjögren's syndrome[62][63][64][65] Painless Generalized or localized - - - +
  • N/A
Sarcoidosis[66][67][68] Painless Generalized - - - -
  • Serum ACE level
  • N/A
Biopsy of lung


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