Toolkit Modules:

1. Disease Overview
2. Pathology of Castleman Disease
3. Clinical Manifestations
4. Important Differential Diagnoses
5. Case Studies

To avoid a delay in the accurate diagnosis of suspected Castleman disease, an experienced pathologist is recommended.

Evaluation of a surgically excised lymph node is central to the diagnosis of Castleman, and is also instrumental in ruling out malignancy and other disorders.

Histopathologic interpretation and subtype classification should be performed in concert with several other considerations, including:

  • Clinical presentation
  • Evaluation of lab tests for inflammatory cytokines, especially IL-6
  • Serologic and molecular tests for HHV8, HIV, Epstein-Barr virus, and Cytomegalovirus

In addition, clinical and serologic exclusion should be made of the following conditions:

  • Autoimmune disorders
  • Connective tissue disorders
  • Rheumatoid arthritis
  • Other similar disorders

Hyaline Vascular Variant of Castleman Disease

The Most prominent characteristics of the hyaline vascular variant of Caslteman Disease include the following:

  • Follicles that are regressed, or depleted of germinal center cells
  • Mantle zones that are expanded with small lymphocytes arranged concentrically in an “onion skin” fashion

Additionally, the biopsy should reveal an interfollicular region that is expanded, with the following features:

  • Prominent hyalinized blood vessels
  • Myoid cells
  • Dendritic reticulum cells
  • Predominantly small T‐lymphocytes
  • Focal Aggregates of plasmacytoid dendritic cells

Other histopathologic features of HV-CD include:

  • A“lollipop” appearance (hyalinized blood vessels penetrating the follicles with concentric rimming of mantle zone lymphocytes)
  • Expanded, dysplastic follicular dendritic cell networks
  • Closed sinusoids
  • Vascular proliferation and permeability
  • Follicular mantle cells that may show co-expression of CD5 and CD20

By molecular analysis, HV-CD has shown:

  • Lymphocytes are polyclonal
  • Follicular dendritic cells have moderate to strong expression of EGFR


Plasma Cell Variant of CD (PCCD)

The most prominent characteristics of PC-CD include the following:

  • Lymph nodes that show preserved architecture with hyperplastic follicles
  • Increased interfollicular plasma cells, which are usually polyclonal but may be monotypic
  • Plasma cells that, when monotypic, are usually lambda light chain restricted, IgG Or IgA, especially in PC-CD-associated POEMS syndrome (Polyneuropathy, Organomegaly, Endocrino pathy, Monoclonal protein, and Skin changes)
  • Rare instances of monoclonality, which may lead to lymphoma
  • Follicles that often contain hyperplastic germinal centers, but may also show regressed features

Histopathologic features are not specific to the plasma cell variant of CD, and can be seen in reactive lymphadenopathies including, but not limited to:

  • Infections
  • Autoimmune diseases
  • Collagen Vascular and mixed connective tissue diseases
  • Rheumatoid Arthritis with certain toxins
  • HIV-related lymphadenopathy

These diseases should be excluded before attributing morphologic changes to PC-CD.