KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies

Int J Cancer. 2015 Jul 15;137(2):251-61. doi: 10.1002/ijc.28923. Epub 2014 May 5.

Abstract

Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder presenting with heterogeneous pathological and clinical features. It comprises disease entities with a complex aetiology and overlapping pathogenesis. MCD can be found in association with HIV infection, plasma-cell dyscrasias, Kaposi sarcoma (KS), B-cell lymphomas including primary effusion lymphoma (PEL) and its solid variant, and Hodgkin lymphoma. In KSHV-associated MCD cases, a common association is KS and a specific variant of lymphoma referred to as "plasmablastic lymphoma," also called "large B-cell lymphoma arising in KSHV-associated MCD" lacking EBV infection. MCD is often referred to as human interleukin-6 (hIL-6) syndrome, since an overproduction of IL-6 occurs in MCD-associated diseases as well as in MCD itself. hIL-6 and a viral IL-6 (vIL-6) homolog encoded by KSHV can independently or together lead to flares of KSHV-associated MCD. Recently, a new clinical entity was proposed to describe a severe systemic infection/reactivation of KSHV: KSHV inflammatory syndrome (KICS). KICS may contribute in inducing the inflammatory symptoms seen in some patients with severe KS or PEL. The precise relationship of KICS to KSHV-associated MCD is unclear and it is possible that KICS may be prodromal symptoms to frank KSHV-associated MCD. Options for treatment of KSHV-associated MCD and related diseases include monoclonal antibodies, chemotherapy, immune modulators, virus-activated cytotoxic therapy and antiviral therapies. A comprehensive understanding of the intricacies of the HIV-KSHV coinfection will probably lead to additional advances in therapy and managements for these disorders.

Keywords: Castleman disease; KSHV-associated MCD; multicentric Castleman disease; multitarget treatment; viral IL-6.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Castleman Disease / metabolism
  • Castleman Disease / therapy
  • Castleman Disease / virology*
  • HIV / physiology
  • Herpesvirus 4, Human / physiology
  • Herpesvirus 8, Human / metabolism
  • Herpesvirus 8, Human / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Interleukin-6 / metabolism
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / therapy
  • Sarcoma, Kaposi / virology*
  • Viral Proteins / metabolism

Substances

  • Interleukin-6
  • Viral Proteins

Supplementary concepts

  • Multi-centric Castleman's Disease