Multicentric Castleman Disease

editPREVIOUS EDITION

This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.

Primary Author(s)*

Sudha Arumugam, MD

Cancer Category/Type

Cancer Sub-Classification/Subtype

None

Definition/Description of Disease

Castleman disease was initially described in 1956 by Castleman et al, who reported on 13 cases of localized mediastinal lymphoid proliferations in asymptomatic patients.^[1] It is now recognized that there are different morphologic variants (hyaline vascular, plasma cell/plasmablastic, and mixed or transitional) as well as clinical forms (unicentric and multicentric) classified under the broad clinicopathologic syndrome termed Castleman disease.^[2] Multicentric Castleman Disease is a rare clinicopathologic entity encompassing a group of systemic polyclonal lymphoproliferative disorders. It belongs to the spectrum of HHV8-associated lymphoproliferative disorders in which there is a proliferation of morphologically benign lymphocytes, plasma cells, and vessels due to excessive production of cytokines, IL6 features prominently amongst these.^[3]Multicentric Castleman disease is idiopathic in HIV-negative and HHV8-negative patients.

Synonyms/Terminology

Angio follicular lymph-node hyperplasia

Giant node hyperplasia

Epidemiology/Prevalence

HHV8 Positive Multicentric Castleman Disease occurs in immunosuppressed patients across all ethnic groups, particularly in association with HIV/AIDS. ^[3] Immunocompetent individuals may be affected with the disease in HHV8 endemic areas such as sub-Saharan Africa and Mediterranean countries. In cases where HIV was acquired via sexual transmission, there is a strong association with the development of HHV8-positive MCD, men are predominantly affected.

Clinical Features

Signs and Symptoms	Progressive lymphadenopathy Splenomegaly or hepatosplenomegaly Fever Night sweats Fatigue Weight loss Respiratory symptoms Coincident Kaposi Sarcoma or HHV8-positive diffuse large B-cell lymphoma Skin rash
Laboratory Findings	Anemia Thrombocytopenia Hypoalbuminemia Hypogammaglobinemia Elevated C-reactive protein

Sites of Involvement

Multicentric Castleman Disease affects multiple lymph node sites, predominantly in the cervical region and commonly involves the spleen.^[4]

Morphologic Features

HHV8-infected plasmablasts are the characteristic features of HHV8 Multicentric Castleman disease.^[4] Plasmablasts are present in the lymph node and spleen.^[2] The B cell follicles of lymph nodes shows varying degree of hyalinization and involution of germinal centers with prominent mantle zones that may intrude and efface the germinal centers.^[3] Follicles may show onion skinning or widened concentric rings of mantle zone lymphocytes along with prominent penetrating venules, these findings are typical of Castleman disease.^[3] Variable numbers of medium to large plasmablasts with amphophilic cytoplasm and eccentrically placed nuclei can be found among the mantle zone cells and adjacent interfollicular regions.^[3] Sheets of mature plasma cells may be seen expanding the interfollicular region, some such cells may display cytoplasmic inclusions (Russell bodies) or crystalline forms.^[3] With disease progression, the plasmablasts increase in number and may coalesce to form clusters.^[3] If the disease proceeds to become HHV8-positive diffuse large B-cell lymphoma, NOS these clusters may expand clonally to form sheets of lymphoma cells that efface the normal follicular architecture.^[3] Plasmablastic aggregates that develop during disease progression may be oligoclonal or monoclonal.