What it takes to diagnose the disease

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Diagnosing iMCD

iMCD can mimic the characteristics of malignant, infectious, and autoimmune disorders1

iMCD’s clinical heterogeneity, as well as its overlap with other disorders and lack of specific biomarkers, can make it challenging to diagnose and manage patients with iMCD. People experiencing lymphadenopathy with no alternative diagnosis should be evaluated for iMCD with an excisional biopsy.

Adapted from Fajgenbaum et al. Blood. 2017.
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Guidelines that can help diagnose iMCD

The Castleman Disease Collaborative Network (CDCN) convened a working group of 34 international experts that established the first evidence-based consensus treatment guidelines for iMCD, based on a review of 244 cases and 88 tissue samples. Below are some highlights from the CDCN guidelines that can help achieve an accurate diagnosis.1

Major Criteria
(need both)

Histology consistent with Castelman disease (CD)

≥2 enlarged lymph node groups

Minor Criteria (need ≥2, with ≥1 laboratory criterion)

Clinical abnormality

  • Constitutional symptoms
  • Large spleen and/or liver
  • Fluid accumulation


  • Violaceous papules
  • Lymphocytic Interstitial pneumonitis

Laboratory abnormality

  • Elevated CRP
  • Anemia
  • Thrombocytopenia
  • Hypergammaglobulinemia


  • Hypoalbuminemia
  • Renal dysfunction

Exclusion Criteria

Exclude diseases that iMCD can mimic, such as autoimmune, malignant and infectious diseases.

In order to diagnose a patient with iMCD, you must ensure they meet both Major Criteria and at least 2 of the 11 Minor Criteria, including ≥1 laboratory abnormality, and rule out diseases in the Exclusion Criteria1

You can download a detailed, print-ready version of the CDCN Diagnostic Criteria, which includes a checklist that can help you during the diagnostic process.


Identification of key laboratory and clinical parameters and the inclusion of an excisional biopsy are ideal for the differential diagnosis of iMCD.1,2

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Key workup to facilitate the differential diagnosis of iMCD


Clinical Examination

Clinical examination should evaluate the presence of constitutional symptoms, enlarged liver or spleen, fluid accumulation, and skin lesions.


Laboratory Workup

Laboratory workup should include blood tests to evaluate the following1:

  • CRP
  • Erythrocyte sedimentation rate (ESR)
  • Hemoglobin
  • Platelets
  • Albumin
  • Creatinine
  • Total proteins
  • Total gamma globulin
  • Immunoglobulin G (IgG)

Imaging Tests

Imaging tests should be performed to confirm the presence of multiple groups of enlarged lymph nodes throughout the body.1

Additionally, tests must be performed to exclude diseases that can mimic iMCD, HHV-8, or human immunodeficiency virus (HIV) infection.1 

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Excisional biopsy ensures pathologic confirmation of iMCD

Fine-needle aspiration or core biopsy is unlikely to capture the affected tissue within the lymph node and may be inadequate to get an accurate diagnosis of iMCD.2-4

An excisional biopsy enables a pathologist to conduct the complete examination of the total lymph node architecture.2,5

Pull down to reveal core biopsy
Graphic showing needle core biopsy, also known as incisional biopsy, may not be enough to confirm idiopathic multicentric Castleman disease.
Graphic showing needle core biopsy, also known as incisional biopsy, may not be enough to confirm idiopathic multicentric Castleman disease.
biopsy details
Regressed Germinal Center
biopsy details
Regressed Germinal Center
biopsy details
Regressed Germinal Center

Collaborate with a pathologist to confirm a diagnosis of iMCD.1

If you have a patient who has unexplained lymphadenopathy, unexplained constitutional symptoms, and they can’t seem to get to a diagnosis, I would recommend an excisional biopsy [to] get a complete look at the lymph node.

Jadee L. Neff, MD, PhD
  1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.

  2. Allin D, David S, Jacob A, Mir N, Giles A, Gibbins N. Use of core biopsy in diagnosing cervical lymphadenopathy: a viable alternative to surgical excisional biopsy of lymph nodes? Ann R Coll Surg Engl. 2017;99(3):242-244.

  3. Gaurin GE, da Costa Dourado CM. Castleman disease. Medscape. https://emedicine.medscape.com/article/2219018-overview. Updated November 24, 2021. Accessed April 21, 2022.

  4. Early detection, diagnosis, and staging of Castleman disease. American Cancer Society. https://www.cancer.org/content/dam/CRC/PDF/Public/8596.00.pdf. Revised February 8, 2018. Accessed May 11, 2022.

  5. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124.

  6. Mahmud SA, Binstadt BA. Autoantibodies in the pathogenesis, diagnosis, and prognosis of juvenile idiopathic arthritis. Front Immunol. 2019;9:3168.

  7. Autoimmune condition. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/autoimmune-condition. Accessed June 9, 2022.

  8. Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132.

  9. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-3067.

  10. Fugl A, Andersen CL. Epstein-Barr virus and its association with disease - a review of relevance to general practice. BMC Fam Pract. 2019;20(1):62.

  11. Mononucleosis: symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/mononucleosis/symptoms-causes/syc-20350328. Published December 22, 2020. Accessed June 9, 2022.

  12. HIV/AIDS: symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/hiv-aids/symptoms-causes/syc-20373524. Published February 13, 2020. Accessed June 9, 2022.