Non-Hodgkin lymphoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[5]

Overview

Non-Hodgkin lymphoma must be differentiated from Hodgkin's disease, viral infections, metastatic carcinoma, and autoimmune diseases.

Differential Diagnosis

Non-Hodgkin lymphoma must be differentiated from common disorders with localized or generalized lymphadenopathy like:

Diseases Clinical manifestations Para-clinical findings Pathogonomic finding
Symptoms
Lab Findings Biopsy
Lymphadenopathy Fever Weight loss Night Sweats Rash Other symptoms Immunochemistry Blood work
Non-Hodgkins lymphoma
  • Painless
+ + + +
  • Coombs test may be positive
  • Hypogammaglobulinemia
  • HIV serology
  • Elevated lactate dehydrogenase
  • Abnormal liver function test
  • Hypercalcemia
  • Anemia
  • Thrombocytopenia
  • Leukopenia
  • Lymphocytosis
Monomorphic medium to large sized lymphocytes seen
INFECTIONS Bacteria Syphilis[1][2][3][4]
  • 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

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[5][6][7][8][9]
  • Painful
+ - - +
  • Abdominal pain
  • hepatosplenomegaly
  • Arthritis
  • Brucella is most commonly isolated from blood cultures
Night sweats, often with characteristic smell, likened to wet hay
Viral Infectious mononucleosis[10]
  • Painful
+ - - +
  • A positive reaction to a mono spot test
  • Direct detection of EBV in blood or lymphoid tissues
Presence of atypical lymphocytes (a type of mononuclear cell) on the peripheral blood smear.
CMV[11][12]
  • Painful
+ - - + Owl Eye inclusion bodies.
HIV[13][14][15][16]
  • Painful or painless
- + - -
  • ELISA
  • Dot blot
  • Latex agglutination assays
  • Western blot assays
  • P24 antigen assays
  • CD4 T-cell count (CD4 count)
  • Plasma HIV RNA viral load
  • Anaemia
  • Thrombocytopenia
  • Leukopenia
Plasma HIV RNA viral load
Cat scratch disease[17][18][19][20]
  • Painful
+ - - +
  • Indirect immunofluorescence or enzymatic immunoassay with titration of IgG or IgM antibodies to detect serum antibody to B henselae.
  • Polymerase chain reaction (PCR) is the most sensitive test
Painful buboes
Mycobacteria Tuberculosis[21][22][23][24][25]
  • Painful
+ + + + Gohn's focus
Parasite Toxoplasmosis[26][27][28][29]
  • Painless
+ - + -
  • IgG, IgM, IgA antibodies against toxoplasmosis seen by ELISA
  • PCR
Multiple ring enhancing lesion on CT Brain.
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy

Histopathology

Pathogonomical

findings

AUTOIMMUNE Systemic lupus erythematosus

(SLE)[30][31][32][33]

  • Painless
+ +/- - + On microscopic histopathological analysis, lupus erythematosus (LE) cells can be seen in SLE. LE cells are neutrophils that have engulfed an intact nucleus. LE cells are also known as LE bodies. Malar rash and photosensitivity
Sjögren's syndrome[34][35][36][37]
  • Painless
- - - +
  • Anti-Ro/SSA
  • Anti-La/SSB
  • Presence of rheumatoid factor (RF)
  • Presence of anti–alpha-fodrin antibody (diagnostic marker of juvenile Sjögren's syndrome)
Sarcoidosis[38][39][40]
  • Painless
- - - -
  • Can involve all organ systems to varying extent and degree.
  • serum ACE level
Biopsy of lung shows non-caseatinggranuloma Non-caseatinggranuloma
Diseases Lymphadenopathy Fever Weight loss Night sweats Rash Other symptoms Immunochemistry Blood work Biopsy

Histopathology

Pathogonomical

findings

NEOPLASIA Hodgkin's disease[41][42][43][44]
  • Painless
+ + + +
  • Presents with "B" symptoms
    • Lactate dehydrogenase (LDH) may be increased.
    • ESR elevated
    • Serum creatinine elevated in nephrotic syndrome.
    • Alkaline phosphatase (ALP) increased
    • Hypercalcemia, hypernatremia, and hypoglycemia.

Fine-needle aspiration

  • Mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells
Reed-Sternberg cells on microscopic pathology.
Chronic lymphocytic leukemia[45][46][47][48]
  • Painless
+ + + -
  • Monoclonality of kappa and lambda producing B cells
  • Presence of smudge cells

CBC

Small cell carcinoma of the lung[49][50][51][52][53]
  • Painless
- - - -

Nearly all SCLC are immunoreactive for

Neuroendocrine and neural differentiation result in the expression of molecules like

  • The tumor cells are small and round, but they can sometimes be ovoid or spindle shaped. They have a scantycytoplasm with a high mitotic count and a hyperchromatic nuclei.
Melanoma[54][55][56]
  • Painless
- - - -
  • Positive for CD133+
  • Positive for CD34+
  • 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[57][58][59][60][61][62][63]
  • Painless
+ + - + -

CBC

- On chest CT scan, Halo sign is seen due to the angioinvasive nature of the disease
Angioimmunoblastic lymphadenopathy[64][65][66][67]
  • Painless
+ + + +
  • 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)[68]
  • Painless
+ + - - - -
  • Hypersecretion of the cytokine IL-6.

References

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