Hodgkin's lymphoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Hodgkin's lymphoma must be differentiated from sarcoidosis, lymphocytic lymphoma, miliary tuberculosis, infectious mononucleosis, thoracic aortic aneurysm, substernal goiter, thymoma, actinomycosis, chronic lymphocytic leukemia, superior vena cava syndrome, unicentric castleman disease, adult still disease, small cell lung carcinoma, and malignant histiocytosis.

Differentiating Hodgkin's Lymphoma From Other Diseases

Differentiating diagnosis of Lymphoma Symptoms Signs Diagnosis Additional Findings
Fever Rash Diarrhea Abdominal pain Weight loss Painful lymphadenopathy Hepatosplenomegaly Arthritis Lab Findings
Lymphoma ✔ ✘ ✘ ✔ ✔ ✘ ✔ ✘ Increase ESR, increased LDH Night sweats, constant fatigue
Brucellosis ✔ ✔ ✘ ✔ ✔ ✔ ✔ ✔ Relative lymphocytosis Night sweats, often with characteristic smell, likened to wet hay
Typhoid fever ✔ ✔ ✘ ✔ ✘ ✘ ✔ ✔ Decreased hemoglobin Incremental increase in temperature initially and than sustained fever as high as 40°C (104°F)
Malaria ✔ ✘ ✔ ✔ ✘ ✘ ✔ ✔ Microcytosis,

elevated LDH

"Tertian" fever: paroxysms occur every second day
Tuberculosis ✔ ✔ ✘ ✔ ✔ ✔ ✘ ✔ Mild normocytic anemia, hyponatremia, and

hypercalcemia

Night sweats, constant fatigue
Mumps ✔ ✘ ✘ ✘ ✘ ✔ ✘ ✘ Relative lymphocytosis, serum amylaseelevated Parotidswelling/tenderness
Rheumatoid arthritis ✘ ✔ ✘ ✘ ✘ ✘ ✘ ✔ ESR and CRP elevated, positive rheumatoid factor Morning stiffness
SLE ✘ ✔ ✘ ✔ ✔ ✘ ✘ ✔ ESR and CRP elevated, positive ANA Fatigue
HIV ✘ ✘ ✘ ✔ ✔ ✔ ✘ ✔ Constant fatigue

Other Differentials

The differentials include the following:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]

Category of Disease Diseases Signs and symptoms Laboratory findings
Fever Fatigue Arthralgia Myalgia Soft tissue swelling/serositis Skin rash Weight loss Dyspnea Sore throat Lymphadenopathy Complete blood count (CBC) Liver function tests (LFTs)

Inflammatory markers

Autoantibodies

Diagnostic tests

Erythrocyte sedimentation rate (ESR) C- reactive protein (CRP) Anti-nuclear antibodies (ANA) Rheumatoid factor (RF) Anti- glomerular basement membrane (anti-GBM) Anti-dsDNA Anti-Jo1/ Anti Mi2 ANCA

Infections

  HIV + + + + +/- - + +/- + /- + ↑ ↑ - - - - - -
 Herpesviridae + + + + + - - +/- + - ↑ ↑ - - - - - -
 Measles + + + + - - - + + - ↑ ↑ - - - - - -
 Viral hepatitis + + - +/- - - +/- - - +/- ↑ ↑ - - - - - -
 Parvovirus B19 + + + +/- -
  • Slapped cheek rash
 - - - + ↑ ↑ - - - - - -
Infective endocarditis + + + +/- - +/- + - + - ↑ ↑ - - - - - - Blood cultures, ultrasonography
Borreliosis, Brucellosis, Yersiniosis + + + + - - - - + ↑ ↑ - - - - - - Serology, PCR
Syphilis and Jarisch-Herxheimer reaction + + + + - - - + +
  • ALT↑ (Uncommon)
  • AST↑ (Uncommon)
 ↑ ↑ - - - - - - Serology, PCR
Toxoplasmosis + + - + - - - + + - - - - - - Serology, PCR

Neoplasia

 Malignant lymphoma + + - +/- +/- + + - + ↑ ↑ - - - - - - CT, PET/CT, Bone marrow examination, lymph node biopsy
Multicentric Castleman disease + + - - + - + + - + - ↑ ↑ - - - - - - Lymph node biopsy
Angioimmunoblastic T cell lymphoma + + - - - + - - + ↑ ↑ - - - - - - Lymph node biopsy

Drug hypersensitivity

 Drug reaction with eosinophilia and systemic symptoms + + + + +/- - + - - - ↑ ↑ - - - - - - Eosinophil count, skin biopsy
Autoimmune conditions Systemic lupus erythematosus + + + +/- + + + - +/- ↑ ↑ + + - + - - Antinuclear autoantibodies
Inflammatory myositis + + - + (weakness > pain) -
  • Macular red rash over the back of the fingers, elbows or knees (Grotton's sign)
  • Macular purpish or reddish rash on the upper chest or back  (Shawl-like, heliotrope rash)
 - - - +/- - ↑ ↑ +/- +/- - - + - Idem, muscle biopsy
Rheumatoid arthritis + + + - + - + - + - ↑ ↑ +/- +/- - - - - Anti-citrullinated peptids autoantibodies, rheumatoid factor
Systemic vasculitides + + + - + - +/- - +/- - ↑ ↑ - - +/- - - + ANCA, tissue biopsy, arteriography
Familial Mediterranean fever + + + + + + + (due to pain) - +/- - ↑ ↑ - - - - - - Familial history, MEFV gene analysis
Mevalonate kinase deficiency + + + + - + - + + - ↑ ↑ - - - - - - Urinary mevalonic acid, mevalonate kinase analysis
Reactive arthritis + + + - - - + (Aortic insufficiency) - + - ↑ ↑ - - - - - - HLA B27, magnetic resonance imaging

Miscellaneous

 Sarcoidosis + + + - + + + - +
  • Normal ALT, AST
  • ALP ↑ (infiltrative pattern)
 ↑ ↑ - - - - - -
  • Lymph node/Lung biopsy
  • ACE levels
  • FDG-PET

References

  1. ↑ Ejilemele AA, Nwauche CA, Ejele OA (December 2007). "Pattern of abnormal liver enzymes in HIV patients presenting at a Nigerian Tertiary Hospital". Niger Postgrad Med J. 14 (4): 306–9. PMID 18163139.
  2. ↑ Gøransson LG, Omdal R, Husby G (March 1992). "[Adult-onset Still's disease. Diagnosis, differential diagnosis and treatment]". Tidsskr. Nor. Laegeforen. (in Norwegian). 112 (9): 1155–5. PMID 1579936.
  3. ↑ Hatakka A, Klein J, He R, Piper J, Tam E, Walkty A (September 2011). "Acute hepatitis as a manifestation of parvovirus B19 infection". J. Clin. Microbiol. 49 (9): 3422–4. doi:10.1128/JCM.00575-11. PMC 3165617. PMID 21734024.
  4. ↑ Yaguchi D, Marui N, Matsuo M (2015). "Three Adult Cases of HPV-B19 Infection with Concomitant Leukopenia and Low Platelet Counts". Clin Med Insights Case Rep. 8: 19–22. doi:10.4137/CCRep.S18085. PMC 4345940. PMID 25780346.
  5. ↑ Díaz F, Collazos J (March 2000). "Hepatic dysfunction due to parvovirus B19 infection". J. Infect. Chemother. 6 (1): 63–4. doi:10.1007/s101560000023. PMID 11810534.
  6. ↑ "watermark.silverchair.com" (PDF).
  7. ↑ Shetty RK, Vivek G, Naha K, Bekkam S (January 2013). "Right-sided infective endocarditis presenting with purpuric skin rash and cardiac failure in a patient without fever". BMJ Case Rep. 2013. doi:10.1136/bcr-2012-007841. PMC 3603787. PMID 23355575.
  8. ↑ Aucott JN, Crowder LA, Yedlin V, Kortte KB (2012). "Bull's-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of Identification of Erythema Migrans". Dermatol Res Pract. 2012: 451727. doi:10.1155/2012/451727. PMC 3485866. PMID 23133445.
  9. ↑ Karaali Z, Baysal B, Poturoglu S, Kendir M (May 2011). "Cutaneous manifestations in brucellosis". Indian J Dermatol. 56 (3): 339–40. doi:10.4103/0019-5154.82505. PMC 3132922. PMID 21772606.
  10. ↑ La Spada E, Micalizzi A, La Spada M, Quartarano P, Nugara G, Soresi M, Affronti M, Montalto G (September 2008). "[Abnormal liver function in brucellosis]". Infez Med (in Italian). 16 (3): 148–53. PMID 18843212.
  11. ↑ French P (January 2007). "Syphilis". BMJ. 334 (7585): 143–7. doi:10.1136/bmj.39085.518148.BE. PMC 1779891. PMID 17235095.
  12. ↑ "Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features".
  13. ↑ Baveja S, Garg S, Rajdeo A (March 2014). "Syphilitic hepatitis: an uncommon manifestation of a common disease". Indian J Dermatol. 59 (2): 209. doi:10.4103/0019-5154.127711. PMC 3969699. PMID 24700957.
  14. ↑ Mawhorter SD, Effron D, Blinkhorn R, Spagnuolo PJ (May 1992). "Cutaneous manifestations of toxoplasmosis". Clin. Infect. Dis. 14 (5): 1084–8. PMID 1600010.
  15. ↑ Flegr J, Prandota J, Sovičková M, Israili ZH (2014). "Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries". PLoS ONE. 9 (3): e90203. doi:10.1371/journal.pone.0090203. PMC 3963851. PMID 24662942.
  16. ↑ Furtado JM, Smith JR, Belfort R, Gattey D, Winthrop KL (July 2011). "Toxoplasmosis: a global threat". J Glob Infect Dis. 3 (3): 281–4. doi:10.4103/0974-777X.83536. PMC 3162817. PMID 21887062.
  17. ↑ Ripert C (March 2000). "[Reactive hypereosinophilia in parasitic diseases]". Rev Prat (in French). 50 (6): 602–7. PMID 10808314.
  18. ↑ Alvarado-Esquivel C, Torres-Berumen JL, Estrada-Martínez S, Liesenfeld O, Mercado-Suarez MF (May 2011). "Toxoplasma gondii infection and liver disease: a case-control study in a northern Mexican population". Parasit Vectors. 4: 75. doi:10.1186/1756-3305-4-75. PMC 3105944. PMID 21569516.
  19. ↑ Han T, Stutzman L (July 1967). "Mode of spread in patients with localized malignant lymphoma". Arch. Intern. Med. 120 (1): 1–7. PMID 5339237.
  20. ↑ Saeed-Abdul-Rahman I, Al-Amri AM (September 2012). "Castleman disease". Korean J Hematol. 47 (3): 163–77. doi:10.5045/kjh.2012.47.3.163. PMC 3464333. PMID 23071471.
  21. ↑ Saeed-Abdul-Rahman I, Al-Amri AM (September 2012). "Castleman disease". Korean J Hematol. 47 (3): 163–77. doi:10.5045/kjh.2012.47.3.163. PMC 3464333. PMID 23071471.
  22. ↑ Papadavid E, Panayiotides I, Dalamaga M, Katoulis A, Economopoulos T, Stavrianeas N (2010). "Cutaneous involvement in angioimmunoblastic T-cell lymphoma". Indian J Dermatol. 55 (3): 279–80. doi:10.4103/0019-5154.70704. PMC 2965920. PMID 21063526.
  23. ↑ Brockow K, Przybilla B, Aberer W, Bircher AJ, Brehler R, Dickel H, Fuchs T, Jakob T, Lange L, Pfützner W, Mockenhaupt M, Ott H, Pfaar O, Ring J, Sachs B, Sitter H, Trautmann A, Treudler R, Wedi B, Worm M, Wurpts G, Zuberbier T, Merk HF (2015). "Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM)". Allergo J Int. 24 (3): 94–105. doi:10.1007/s40629-015-0052-6. PMC 4479479. PMID 26120552.
  24. ↑ Medlej-Hashim M, Loiselet J, Lefranc G, Mégarbané A (2004). "[Familial Mediterranean Fever (FMF): from diagnosis to treatment]". Sante (in French). 14 (4): 261–6. PMID 15745878.
  25. ↑ Zhang S (May 2016). "Natural history of mevalonate kinase deficiency: a literature review". Pediatr Rheumatol Online J. 14 (1): 30. doi:10.1186/s12969-016-0091-7. PMC 4855321. PMID 27142780.
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