Key Ideas

Castleman disease is not one disease but a polyclonal lymphoproliferative disorder spanning a spectrum from single-lymph-node (unicentric) to widespread (multicentric) involvement, with an emerging "oligocentric" category recognized in between. Diagnosis depends on a combination of major and minor criteria, and pathology review, even among experienced pathologists, can be genuinely difficult and inconsistent.

More Than "Big Lymph Nodes"

Castleman disease is a rare hematologic disorder where patients present with enlarged lymph nodes with a characteristic histologic appearance. Patient registries provide a unique opportunity to understand the real-world experience of the disease and define an otherwise poorly understood disease entity. Our registry benefits from its size, direct patient engagement, and expert adjudication of all diagnoses to provide the most comprehensive and high-quality understanding of the disease. 

Diagnostic Criteria: Major, Minor, and the Role of Histology

The diagnosis of idiopathic multicentric Castleman disease relies on major criteria, involvement of at least one lymph node station with characteristic histology, plus minor criteria drawn from systemic inflammatory features, assessed both clinically and by laboratory testing.

The hypervascular/hyaline vascular histology is defined by the presence of regressed ("atretic") germinal centers, prominent follicular dendritic cells, and increased vascularity. A plasmacytic Castleman histology consists of hyperplastic follicles and polytypic plasmacytosis. Discordant pathologic interpretations, however, are unfortunately common. This underscores the importance of seeking the interpretation of a pathologist with experience making the diagnosis. 

A Spectrum of Disease with Different Treatments

Patients with unicentric Castleman are oftentimes, but not always, asymptomatic and can be cured with complete surgical excision. Patients with more idiopathic multicentric Castleman disease can have a range of severity to their inflammatory symptoms – most commonly drenching night sweats, fatigue, unexplained weight loss, extravascular fluid accumulation, and vascular rashes. The most severe form of idiopathic multicentric Castleman disease, the TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly), can present with multi-organ dysfunction and critical illness. Siltuximab, a monoclonal antibody targeting interleukin-6, is the first-line treatment for idiopathic multicentric Castleman disease though multi-agent chemotherapy is sometimes nec essary for more severe presentations.

The Value of Registries and Multidisciplinary Review

Given how rare and heterogeneous Castleman disease is, individual clinicians and even individual centers see relatively few cases. A monthly, multidisciplinary rare disease expert panel (a kind of "phone a friend" resource, including pathology review) can help clinicians work through uncertain cases. These are run by the Castleman Disease Collaborative Network. We also encourage patients to enroll in dedicated Castleman disease registries to help us to better understand and treat this rare disease.

For Patients

Castleman disease isn't one single condition, but rather a spectrum of related disorders, all involving abnormal, non-cancerous overgrowth of lymph node tissue, ranging from a single affected lymph node area (which can sometimes be cured with surgery alone) to widespread involvement of many lymph node groups throughout the body, which can cause serious, whole-body inflammation and organ dysfunction.

Diagnosing Castleman disease usually requires a lymph node biopsy with a specific pattern of changes, combined with blood tests and symptoms that reflect body-wide inflammation. Because these tissue changes can be subtle and are sometimes interpreted differently by different pathologists, it's important that biopsy samples be reviewed by pathologists experienced specifically with this disease, and getting a second opinion or expert review is often reasonable and worthwhile.

Key Takeaways

  • Castleman disease spans a spectrum from unicentric (single lymph node station) to multicentric (multiple stations) disease, with an "oligocentric" category increasingly recognized in between, generally with a milder course than classic multicentric disease.

  • Idiopathic multicentric Castleman disease, the greatest driver of disease morbidity, requires both major and minor diagnostic: Multi-station lymphadenopathy with a characteristic histology, in addition to clinical and laboratory evidence of systemic inflammation

  • The defining histologic changes (regressed germinal centers, prominent follicular dendritic cells, increased vascularity) often require an experienced pathologist and can be non-specific; malignant, autoimmune, and infectious disorders can present with lymphadenopathy with a Castleman histology 

  • Severity and presentation vary widely; unicentric Castleman disease can be cured with surgery but idiopathic multicentric Castleman disease should be treated with inhibition of interleukin-6 through siltuximab.

  • If you have a patient with multifocal lymphadenopathy and systemic inflammation, we recommend PETCT and lymph node excision of the most FDG-avid, accessible lymph node to 

References

  1. Brandstadter JD, Fajgenbaum DC. How we manage idiopathic multicentric Castleman disease. Clin Adv Hematol. Oncol. 2022.20(9):564-571

  2. Laczko D, Pillai V, Frank D, et al. How I diagnose Castleman disease. Am J Clin Pathol. 2026. 165(3):aqaf147.

  3. 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. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.

  4. Van Rhee F, Voorhees P, Dispenzieri A, et al. Blood. 2018. 132(20):2115-2124.

  5. Van Rhee F, Oksenhendler E, Srkalovic G, et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease. Blood Adv. 2020. 4(23):6039-6050.

  6. Pierson SK, Brandstadter JD, Torigian DA, et al. Characterizing the heterogeneity of Castleman disease and oligocentric subtype: findings from the ACCELERATE registry. Blood Adv. 2025. 9(8):152-1965.