Castleman’s Disease

  • General Information

    • Lymphoproliferative disorder which is histologically characterized by angiofollicular lymph-node hypertrophy.
    • In the differential diagnosis for localized/diffuse lymphadenopathy with or without systemic manifestations.
    • Rare and relatively benign disorder which can mimick lymphoma clinically, but varies from the latter histologically, prognostically and in its treatment options.
  • Types

    • Localized CD:
      • By definition, localized to one site.
      • Features lymphoid hyperplasia associated with excessive angiogenesis.
      • Asymptomatic in over 50% of patients and is often discovered incidentally.
      • Histological diagnosis requires lymph-node biopsy.
    • Multicentric CD:
      • Characterized by a predominantly lymphadenopathic presentation consistently involving peripheral lymph-nodes and manifestations of multisystem involvement.
      • Considered as a systemic B cell lymphoproliferation, probably arising in immunoregulatory deficit, and resulting in the outgrowth of clonal B-cell populations.
      • It is always symptomatic.
      • Symptoms, primarily a consequence of elevated Interleukin-6 (IL-6) production, are:
        • Asthenia(65%)
        • Weight loss(67%)
        • Fever(69%)
        • Polyadenopathy is common with a mean of four sites involved and is often associated with hepatosplenomegaly.
        • Histological diagnosis is made upon biopsy of an excised peripheral lymph-node.
    • Other forms/associations:
      • A POEMS (Peripheral polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy(M-Protein) and Skin signs) syndrome is observed in 24% of patients.
      • Some MCD forms are associated with Kaposi’s sarcoma displaying prominent vascular proliferation and characteristic lesions.
      • MCD associated with human immunodeficiency virus(HIV) infection is very similar to MCD observed in non-HIV-infected patients, except for the high prevalence of pulmonary symptoms and for the stronger association with Kaposi’s sarcoma.
        • Progression to malignant lymphoma in MCD associated with HIV is frequent.
        • Within a prospective cohort study of HIV-infected patients with MCD, 23% developed HHV 8-associated non-Hodgkin lymphoma.
  • Etiology

    • Poorly understood and no genetic or toxic factor has so far been identified.
    • The hypothesis of a viral infection has been raised and several studies have suggested the role of human herpesvirus 8 (HHV-8), already implicated in Kaposi’s sarcoma. There are a couple of theories:
      • (i) the opportunistic presence of HHV-8, favoured by immune pertubations.
      • (ii) the direct pathogenic role of HHV-8, in association with dysregulation of cytokines.
      • Recent studies support the latter hypothesis by demonstrating that HHV-8 is able to produce an IL-6 homologue, the interleukin reponsible for the plasmacytosis and hypergammaglobulinaemia seen in MCD.
  • Diagnosis

    • Tissue is the issue!
    • Histopathology is characterized by distinctive follicles with expanded mantle zones of small lymphocytes forming concentric rings surrounding 1 or more atretic germinal centers.
    • There is prominent vascularity of the germinal centers, often with a single prominent penetrating vessel. Another important feature is vascular proliferation between the follicles, often with perivascular hyalinization.
    • The “onion-skinning” of mantle zone lymphocytes, together with the prominent central vessel, has been likened to the appearance of a lollipop
  • Management

    • Localized CD is treated by surgical excision which allows full recovery without relapse in almost all cases.
    • Multicentric CD:
      • No therapeutic consensus exists for MCD and diverse treatments (surgery/corticotherapy/chemotherapy) are used, often in combination.
      • Anti-interleukin-6 antibody has also been successfully tried in the alleviation of systemic manifestations.
      • The five-year survival rate in MCD is 82% and this prognosis appears to be far better than that encountered with malignant lymphomas.

Journal of Medical Case Reports 2007, 1:78

Advances in Anatomic Pathology 2009, 16: 4

Detailed Guide: Castleman Disease. American Cancer Society. 2011;http://www.cancer.org/Cancer/CastlemanDisease/DetailedGuide/.