Multicentric Castleman disease and the evolution of the concept

Pathologica. 2021 Oct;113(5):339-353. doi: 10.32074/1591-951X-351.


The term multicentric Castleman disease (MCD) encompasses a spectrum of conditions that share some overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, causing systemic inflammatory symptoms as well as lymphadenopathy. Some of the histological changes in lymph nodes resemble the histology of unicentric Castleman disease (UCD). However, based on current knowledge, the use of this shared nomenclature is unfortunate, since these disorders differ in pathogenesis and prognosis. In Kaposi sarcoma-associated herpesvirus (KSHV)-associated MCD, cytokine overactivity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. The authors review the evolving concepts and definitions of the various conditions under the eponym of multicentric Castleman disease.

Keywords: Castleman disease; Kaposi sarcoma-associated herpesvirus; TAFRO syndrome; human herpesvirus type 8; interleukin-6.

Publication types

  • Review

MeSH terms

  • Castleman Disease* / diagnosis
  • Herpesvirus 8, Human*
  • Humans
  • Lymph Nodes