Update and new approaches in the treatment of Castleman disease

Abstract

First described 60 years ago, Castleman disease comprises a rare and heterogeneous cluster of disorders, characterized by lymphadenopathy with unique histological features and associated with cytokine-driven constitutional symptoms and biochemical disturbances. Although unicentric Castleman disease is curable with complete surgical excision, its multicentric counterpart is a considerable therapeutic challenge. The recent development of biological agents, particularly monoclonal antibodies to interleukin-6 and its receptor, allow for more targeted disease-specific intervention that promises improved response rates and more durable disease control; however, further work is required to fill knowledge gaps in terms of underlying pathophysiology and to facilitate alternative treatment options for refractory cases.

Keywords: Castleman disease; angiofollicular lymph node hyperplasia; biologics; rituximab; siltuximab; tocilizumab.

Figure 1

The hyaline vascular variant of CD. Notes: Hematoxylin and eosin–stained sections (panel A, 200× magnification) demonstrate a vascular, atrophic germinal center with surrounding concentric “onion skin” layers of lymphocytes. Immunohistochemical staining for CD23 (panel B, 200× magnification) highlights several follicular dendritic cell clusters within an expanded mantle zone of CD23-positive cells. CD34 (panel C, 200× magnification) identifies a positively staining blood vessel within an atrophic follicle. Abbreviation: CD, Castleman disease.

Figure 2

The plasma cell variant of CD. Notes: Hematoxylin and eosin–stained sections (panel A, 200× magnification) demonstrate preservation of the lymph node germinal center, with associated paracortical plasmacytosis. Immunohistochemical staining for CD21 (panel B, 100× magnification) highlights the follicular dendritic cells within the germinal centers, while CD20 (panel C, 100× magnification) identifies the normal background B-cell population. Immunoperoxidase staining for HHV-8 (panel D, 100× magnification) reveals HHV-8-positive plasma cells within the expanded mantle zones, which play a key role in the pathogenesis of this CD variant. Abbreviations: CD, Castleman disease; HHV-8, human herpesvirus-8.