Diagnosis

Castleman disease (CD) is a spectrum of lymphoproliferative disorders with a common histopathology.^1-5

The idiopathic Multicentric Castleman Disease (iMCD) subtype is characterised by abnormal lymphoproliferation in multiple lymph node sites.^.1

iMCD is a rare and devasting disease that can cause multiple organ dysfunction which can lead to death - one in three patients die within 5 years of diagnosis.^1,2

Cytokine storms, which often include IL-6, play a central role in the pathophysiology of iMCD and drive symptoms.⁵
Patients experience symptoms of systemic inflammation – such as fever and fatigue - that can significantly interfere with daily-life.¹ Significant organ damage can also occur due to excessive and uncontrolled release of pro-inflammatory cytokines.

iMCD affects all populations, with diagnosis in patients in an age range of 2 – 80 years.¹ There is limited epidemiological data on iMCD. In the United States, approximately 540 – 960 new cases of iMCD are diagnosed each year.¹

iMCD has a serious and significant impact on patient health and survival:

• Severe organ damage: If uncontrolled iMCD can lead to severe organ damage.¹

• Increased risk of developing cancer: The prevalence of cancer is 3-fold higher in people with iMCD compared with people without iMCD. Approximately 9% of iMCD patients develop haematological malignancies, with the majority of cases being lymphomas.²

• Poor survival: 1 in 3 patients die within five years of diagnosis.¹

Prompt and accurate diagnosis of iMCD is important to reduce treatment delays and ultimately improve clinical outcomes and survival.¹ Many patients are initially misdiagnosed.

Correct diagnosis is often delayed due to a combination of factors including:

• the rarity of the disease
• non-specific clinical symptoms
• non-specific histopathologic features
• lack of specific biomarkers.^1,3
  

Because of these disease features, an iMCD diagnosis is based on clinical symptoms, laboratory results, pathology results and excluding other conditions with shared (or similar) symptoms and signs. Close collaboration between treating physicians and colleagues in pathology can support a timely and accurate diagnosis. International guidelines have been published on the diagnosis of iMCD. These guidelines recommend that patients with suspected iMCD should be examined for major and minor diagnostic criteria (covering lymph node pathology, clinical symptoms and laboratory abnormalities), as well as excluding conditions that mimic iMCD.¹

MAJOR CRITERIA: DEFINED LYMPH NODE ABNORMALITIES

For an iMCD diagnosis the patient must have^:1

• Lymph node histopathology: abnormal lymph node pathology consistent with the iMCD spectrum on an excisional lymph node biopsy. See Lymph node histopathology
• Multicentric lymphadenopathy: Enlarged lymph nodes (short axis diameter ≥ 1cm) in 2 or more lymph node stations (determined by imaging such as computed tomography [CT] scan). See Multicentric lymphadenopathy

Both criteria must be met.

MINOR CRITERIA: PRESENCE OF CERTAIN CLINICAL SYMPTOMS AND LABORATORY ABNORMALITIES

For iMCD the patient must present with ≥2 signs, one of which must be a laboratory abnormality.¹

See Clinical symptoms and laboratory abnormalities

EXCLUSION CRITERIA: EXCLUSION OF OTHER DISEASE WITH SIMILAR SYMPTOMS TO iMCD

Due to shared symptoms, a number of diseases must be excluded for an iMCD diagnosis.¹

See Diseases for exclusion