What it takes to diagnose the disease

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Diagnosing iMCD

Varying clinical presentation makes iMCD challenging to diagnose

Idiopathic multicentric Castleman disease (iMCD) is a condition that shares characteristics with different autoimmune, malignant, and infectious conditions. Swollen lymph nodes and various other symptoms are commonly observed in patients with iMCD.1

Adapted from Fajgenbaum et al. Blood. 2017.
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The importance of diagnosing iMCD early

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The importance of early iMCD diagnosis is emphasized by the high rates of hospitalizations (60%) and emergency department visits (54%) in patients with iMCD within the first year of diagnosis.9

Retrospective studies have found that many patients with iMCD may have life-threatening conditions such as malignancies, renal failure, respiratory failure, or thrombosis. Additionally, the incidence rates of patients with iMCD being diagnosed with cancer was much higher when compared with the general population. Continued observation of these outcomes year after year warrants the importance of early diagnosis.1,9

The prevalence and seriousness of these morbidities in patients diagnosed with iMCD highlights the need for a timely and accurate diagnosis and treatment.9

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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 diagnostic guidelines for iMCD, based on a review of 244 cases and 88 tissue samples. Below are some highlights from the recent CDCN guidelines that can help achieve an accurate diagnosis.1

Major Criteria1

  • Lymph node must have histopathologic features consistent with Castleman disease
  • Patient must have enlarged lymph nodes in ≥2 lymph node stations based on physical/imaging tests

Minor Criteria1

  • Patients must meet ≥2 of 11 minor criteria, such as the presence of constitutional symptoms or the presence of an enlarged liver or spleen
  • ≥1 criteria must be a laboratory abnormality such as elevated C-reactive protein (CRP) or anemia

Exclusion Criteria1

  • “Castleman-like” histopathologic changes and clinical abnormalities may be present in several malignant, infectious, and autoimmune conditions and should be excluded
  • Human herpesvirus-8
    (HHV-8)
    must also be excluded

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.

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Identification of key laboratory and clinical parameters and the inclusion of an excisional biopsy are ideal for the differential diagnosis of iMCD.1,10

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Key workup to facilitate the differential diagnosis of iMCD

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Clinical Examination

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

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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)
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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

An excisional biopsy allows for the complete examination of the total lymph node architecture.1,10

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

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

  3. Autoimmune condition. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/autoimmune-condition. Accessed October 26, 2021.

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

  5. 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.

  6. 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.

  7. Mononucleosis: symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/mononucleosis/symptoms-causes/syc-20350328. Published December 22, 2020. Accessed November 2, 2021.

  8. HIV/AIDS: symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/hiv-aids/symptoms-causes/syc-20373524. Published February 13, 2020. Accessed November 2, 2021.

  9. Mukherjee S, Martin R, Sande B, et al. A longitudinal population level analysis of healthcare resource utilization, comorbidity, and survival in idiopathic multicentric Castleman disease patients. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020; virtual meeting. Oral abstract 2059.

  10. 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.