KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies.
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.
Department of Pathology, IRCCS, Istituto Nazionale Tumori, Aviano, Italy.
Antonino
A
Carbone
Molecular Virology Unit and Scientific Directorate, IRCCS, Istituto Nazionale Tumori, Aviano, Italy.
Paolo
P
De Paoli
Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Milano, Italy.
Annunziata
A
Gloghini
Department of Medical Oncology Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy.
Emanuela
E
Vaccher
D000818:Animals; D005871:Castleman Disease / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D006678:HIV / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism
D015850:Interleukin-6; D014764:Viral Proteins
Castleman disease; KSHV-associated MCD; multicentric Castleman disease; multitarget treatment; viral IL-6