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Castleman disease

Tuesday 27 April 2004


Definition: Castleman disease is a distinct form of lymph node hyperplasia occurring in two morphologic patterns; hyaline vascular and plasma cell type.

Digital cases

- Case on
- HPC:192 : Localized Castleman disease
- HPC:335 : Plasmocytic Castleman disease (associated to Kaposi sarcoma).
- JRC:7320 : Castleman disease.


- plasmacytic Castleman disease

The former usually presents as a single large mass (unicentric Castleman’ s disease) and the later has plasma cell infiltrates and is multicentric. Multicentric form is associated with immune deficiency states, HIV, HHV8 infection, POEMS syndrome and also secondary to increase of cytokine activity (IL-6).

Castleman disease (CD) has been extended to include two entities: the classical hyaline-vascular (HV) type and the rare plasma cell variant.

The disease appears to be polyclonal in origin in the majority of cases, however evidence for clonal expansion was documented in some cases, possibly representing transformation into non Hodgkin’s lymphoma.

In approximately 1/3 of the cases studied a monoclonal IgH rearrangement was documented. A minor T-cell clone, mostly in a polyclonal background, was also documented in some cases.


The disease is very rare.

Clinical synopsis

The disease may present as a solitary mass frequently occurring in the mediastinum or as a systemic disorder (multicentric Castleman disease) with diffuse adenopathies, systemic symptoms and recurrent infections.

Splenomegaly, hepatomegaly and neurologic symptoms may occur frequently as is the case with autoimmune manifestations.

Microscopical types

There are two variants: the hyaline-vascular type and the plasma cell type.

In the hyaline-vascular type, there are shrunken germinal centres with concentric expansion of the mantle zones with eosinophils and hyalinization around the vessels.

In the plasma cell type, an extensive infiltrate by plasma cells is seen in the interfollicular areas. Some patients may be infected by human herpervirus-8 (HHV-8) which may induce interleuchin-6 (IL-6 or IL6) overproduction. IL-6 is believed to play an essential role in the pathogenesis of the disease.

The hyaline-vascular type is usually diagnosed in asymptomatic patients whereas systemic symptoms are present in the majority of patients with the plasma cell subtype. Patients with multicentric Castleman disease show histologic features consistent with the plasma cell subtype.

- HHV8-associated plasmacytic Castleman disease (plasma cell type Castleman disease)
- hyaline–vascular type Castleman disease (or angiofollicular Castleman disease)

  • In the hyaline-vascular type, numerous lymphoid follicles contain small germinal centers, some of which are depleted lymphocytes and composed of concentrically arranged eosinophilic cells penetrated by small capillaries, so-called hyaline-vascular lesions. Vascular proliferation in the interfollicular area is also present.
  • However, the hyaline-vascular type of germinal center is not specific for Castleman disease.

Topographic types

- solitary form of Castleman disease (localized Castleman disease)
- multicentric form of Castleman disease


- lymph nodes (nodal Castleman disease)
- extranodal Castleman disease

  • subcutis of the extremities and trunk (15105643)
  • skeletal muscles of the extremities and trunk (15105643)
  • mediastinal Castleman disease
  • retroperitoneal Castleman disease
  • pulmonary Castleman disease


- hyaline vascular type-Castleman disease (HVCD)
- plasmacytic type-Castleman disease (PCD)
- mixed pattern type-Castleman disease


- POEMS syndrome
- myasthenia gravis
- paraneoplastic pemphigus
- Hodgkin disease
- follicular dendritic cell dysplasia
- follicular dendritic cell sarcoma


- Castleman disease is a morphologically distinct form of lymph node hyperplasia rather than neoplasm or hamartoma.
- The dendritic follicular cells are thought by some authors to be at core of pathogenesis of hyaline vascular type Castleman disease.

Associated tumors

- Neoplastic potential: appears to manifest mainly through development of:

  • lymphoid tumors in plasma cell type
  • dendritic cell tumors/stromal tumors in vascular hyaline type
  • exceptions are isolated cases of dendritic/stromal tumors in vascular hyaline type accompanied or preceded by plasmacytoma, follicular lymphoma, Hodgkin lymphoma

- High-grade spindle cell sarcomas may develop:

  • originally interpreted as probable vascular nature because myoid tumor cells closely apposed to vascular structures
  • not clear whether myoid cells are truly vessel-related or originate from another member of the reticulum/dendritic cell family (so-called fibroblastic reticulum cells, myoid reticulum cells, or dychthyocytes)


- Many of the cases so far studied showed a normal karyotyope.

- Occasional abnormalities were found in a few patients:

  • One case with the hyaline vascular type showed a t(1;6)(p11;p11), a del(7)(q21q22) and a del(8)(q12q22). In this patient no clonal expansion of lymphoid cells was present, suggesting that the clonal proliferation involved dysplastic stromal cells.
  • Another patient was shown to carry a clonal abnormality in CD21-positive follicular dendritic cells.
  • Abnormal chromosomes in this patient were add(1)(q21), der(6)t(6;12)(q23;q15), add(7)(p22), -9, inv(9)p11q13), del(12)(q15).
  • One patient carried a t(7;14)(p22;q22).


The patients can be treated by surgical excision if the mass is localized. Steroid treatment is recommended in cases with disseminated disease and combination chemotherapy utilized for lymphoma must be reserved to unresponsive patients. Some patients with HIV associated Castleman’s disease were successfully treated with the anti CD20 monoclonal antibody or with the antiviral agent ganciclovir targeting the HHV-8.


The prognosis varies greatly depending on the histologic type and disease presentation. If the disease is localized, surgery with or without radiotherapy may be curative. Those patients with multicentric disease who fail to respond to steroid treatment have a serious disease.




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