Castleman Disease

Updated: Jan 21, 2015
  • Author: Neetu Radhakrishnan, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Overview

Background

Castleman disease (CD) is a rare disease of lymph nodes and related tissues. It is a heterogenous group of lymphoproliferative disorders that are sometimes associated with human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8). Although Castleman disease is not cancerous, it may also be associated with malignancies such as Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, and POEMS syndrome. The disease is nonclonal, with no IgH or TCR gene rearrangements.

Castleman disease was first described by Dr. Benjamin Castleman in the 1950s. [1]

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Pathophysiology

Castleman disease (CD) is characterized by nodal expansions that usually leave the structure of the underlying lymph node at least partially intact. B cells and plasma cells are polyclonal, and T cells show no evidence of an aberrant immunophenotype.

Castleman disease can be grouped in numerous ways, as discussed below.

Localized versus multicentric Castleman disease

Localized (unicentric) Castleman disease

This is the more common type of Castleman disease, affecting only a single group of lymph nodes, usually in the chest or abdomen.

Multicentric Castleman disease

Multicentric Castleman disease (MCD) affects more than one group of lymph nodes. It can also affect organs that contain lymphoid tissue. This form is often associated with HIV and HHV-8 and results in systemic symptoms: serious infections, fevers, weight loss, fatigue, night sweats, and nerve damage that can cause weakness and numbness. Anemia and hypergammaglobulinemia are common. In addition, MCD may transform to lymphoma.

Microscopic subtypes of Castleman disease

The hyaline vascular type is most common type of Castleman disease (approximately 90% in some studies). [2]

It is localized and causes few symptoms. The prognosis is typically good, but, in rare cases, it may be multicentric.

The plasma cell type is often symptomatic and multicentric but may be localized. Histologically, there are sheets of mature plasma cells within interfollicular tissues that surround normal to large germinal centers, and the intense capillary proliferation seen in the hyaline vascular subtype is absent. Dysregulation of interleukin-6 (IL-6) has been implicated in the pathogenesis of plasma cell Castleman disease. [3, 4]

In the mixed subtype, there are areas of both hyaline vascular and plasma cell types. This is a rare subtype of Castleman disease.

The plasmablastic type of Castleman disease is usually multicentric and symptomatic. It has a less favorable prognosis.

Subtypes of Castleman disease based on viral infections

Infection with HIV, HHV-8, or Kaposi sarcoma herpesvirus (KSHV) plays a role in at least some cases of Castleman disease.

MCD is more common in people with HIV infection. MCD is often subclassified based on HIV/HHV-8 status.

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Etiology

The exact cause of Castleman disease is unknown. An increased production of IL-6 by lymph nodes appears to have a role in the development of Castleman disease. [4]

HHV-8 and release of IL-6 or related polypeptides also appears to have a role. [5]

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Epidemiology

Castleman disease is rare. It has no apparent sexual predilection and affects people of all ages, although it appears to be rare in children. The plasma cell type has a greater prevalence among young males and females.

The mean age of patients with MCD is 50-65 years. Persons with HIV infection may be younger. Males account for 50%-65% of MCD cases. The incidence of MCD has increased with better antiretroviral therapy (ART) for the management of HIV infection. On multivariate analysis, risk factors for the development of MCD included the following: [6]

  • Nadir CD4 count higher than 200/µL
  • Increased age
  • No previous ART exposure
  • Nonwhite ethnicity
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Prognosis

The prognosis of Castleman disease varies based on the type. The prognosis in unicentric Castleman disease is excellent. MCD has a variable prognosis, from indolent disease to an episodic relapsing form to a rapidly progressive form leading to death within weeks (the last commonly seen in individuals with HIV infection).

A 2011 meta-analysis by Talat et al reported 3-year disease-free survival free survival (DFS) rates based on disease type as follows: [7]

  • Class I (unicentric, hyaline vascular, HIV-negative): 93%
  • Class II (plasma cell unicentric disease, mixed-pathology unicentric disease, or multicentric hyaline vascular [all HIV-negative]): 79%
  • Class III (multicentric, plasma cell, HIV-negative): 46%
  • Class IV (HIV-positive [multicentric]): 28%
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Patient Education

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