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Castleman Disease

Rare Lymphoproliferative Disorder Spanning Localized Unicentric to Aggressive Multicentric Forms

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Dahiliye (İç Hastalıkları) department. Book Appointment →

What is Castleman Disease?

Castleman disease (CD) is a rare lymphoproliferative disorder with annual incidence approximately 6,500–7,700 cases per year in the US, classified by clinical extent (unicentric vs multicentric) and HHV-8 status.

Unicentric Castleman disease (UCD) involves a single enlarged lymph node region or chain (most often mediastinum, neck, or abdomen) and is typically curable with surgery.

Multicentric Castleman disease (MCD) involves multiple lymph node regions with systemic inflammatory features; subtypes include HHV-8-associated MCD (often in HIV-positive patients), idiopathic MCD (iMCD-NOS, iMCD-TAFRO), and POEMS-associated.

Pathology shows characteristic hyaline-vascular, plasma cell, mixed, or plasmablastic variants with proliferation of lymphoid follicles, sclerotic vessels, and dysplastic mantle zones; HHV-8-MCD shows plasmablasts with HHV-8 (LANA-1) staining.

Symptoms

Unicentric: asymptomatic enlarging mass discovered incidentally or on physical examination; rarely compressive symptoms (cough, dyspnea, dysphagia, abdominal mass)
Multicentric: constitutional symptoms (fever, night sweats, fatigue, weight loss), generalized lymphadenopathy, hepatosplenomegaly
Laboratory findings: anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, hypergammaglobulinemia (often polyclonal), elevated IL-6 and CRP, elevated VEGF
Renal manifestations: proteinuria, AA amyloidosis, membranoproliferative glomerulonephritis
TAFRO syndrome (a variant of iMCD): Thrombocytopenia, Anasarca (severe edema/ascites), Fever, Reticulin myelofibrosis, Organomegaly
POEMS-associated: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes
Skin manifestations: rash, hyperpigmentation, paraneoplastic pemphigus, hemangiomas in HHV-8-MCD

Risk Factors

All ages affected; UCD median age 30–35 years, MCD median age 50–65 years
HHV-8-associated MCD: HIV infection, immunosuppression (transplant), Mediterranean and African origin
Idiopathic MCD: no clear environmental or genetic predisposition identified; possible association with autoimmune disease and infection
TAFRO syndrome more common in Asian populations
Differential considerations: lymphoma (especially Hodgkin and follicular), autoimmune lymphoproliferative syndrome, IgG4-related disease, sarcoidosis, infection (tuberculosis, HIV, EBV), POEMS syndrome
Higher risk of secondary malignancy: lymphoma (Hodgkin and non-Hodgkin), Kaposi sarcoma in HHV-8-MCD

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Persistent unexplained lymphadenopathy with constitutional symptoms or laboratory abnormalities
  • Mediastinal or abdominal mass on imaging requiring tissue diagnosis
  • HIV-positive patient with new lymphadenopathy and systemic symptoms (consider HHV-8-MCD)
  • Established Castleman disease with disease progression, treatment failure, or new organ involvement
  • TAFRO syndrome features (thrombocytopenia, anasarca, fever, organomegaly) requiring rapid evaluation

Treatment Methods

01
Tissue diagnosis: excisional lymph node biopsy preferred for histopathology; subtype confirmation includes immunohistochemistry (CD20, CD138, kappa/lambda, HHV-8 LANA-1, IgG4)
02
HHV-8 testing: serology and HHV-8 PCR in blood and tissue for MCD subtyping
03
HIV testing in all multicentric Castleman disease cases
04
Systemic workup: complete blood count, comprehensive metabolic panel, IL-6 level, CRP, ESR, immunoglobulins, serum and urine immunofixation, lactate dehydrogenase, beta-2 microglobulin, cytomegalovirus and EBV serology
05
Imaging: CT chest/abdomen/pelvis with contrast, PET-CT for staging in MCD, bone marrow biopsy in MCD with cytopenias
06
Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD: required histopathology features, multicentric lymphadenopathy, ≥2 of 11 minor criteria including IL-6, CRP, hypoalbuminemia
07
Unicentric Castleman disease: complete surgical excision is curative in >95%; observation if surgically inaccessible; adjuvant radiotherapy for incomplete resection
08
HHV-8-associated MCD: rituximab 375 mg/m² weekly for 4 doses (with or without etoposide); valganciclovir for HHV-8 suppression; antiretroviral therapy if HIV-positive
09
Idiopathic multicentric Castleman disease (iMCD): siltuximab (anti-IL-6 monoclonal antibody, 11 mg/kg every 3 weeks) is first-line; alternative tocilizumab (anti-IL-6 receptor) where siltuximab unavailable
10
Refractory or severe iMCD: combination chemotherapy (cyclophosphamide-vincristine-prednisone, R-CHOP), bortezomib, thalidomide, sirolimus; consider hematopoietic stem cell transplantation in selected cases
11
TAFRO syndrome: high-dose corticosteroids (methylprednisolone pulse), siltuximab or tocilizumab, cyclosporine, rituximab; intensive supportive care for renal failure, anasarca, and thrombocytopenia
12
Long-term follow-up: serial clinical assessment, imaging every 3–6 months during active treatment then annually, CRP and IL-6 monitoring, surveillance for secondary malignancy and treatment-related complications

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