Multicentric Castleman disease and the evolution of the concept

Abstract

Summary 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.

Idiopathic plasmacytic lymphadenopathy: A conceptual history along with a translation of the original Japanese article published in 1980

“…The hyaline-vascular unicentric subtype, the prototype Castleman disease originally reported by Benjamin Castleman in the early 1950s ( Figure 1A ), 4 , 5 is now considered a neoplasm of follicular dendritic cells (FDCs), based on the findings that FDC proliferation and dysplastic FDCs can be observed in the lesion, clonal karyotypic and genetic abnormalities are reported, and approximately 7% of FDC sarcomas arise in the background hyaline-vascular Castleman disease. 6 Multicentric Castleman disease (MCD) encompasses a spectrum of disorders with overlapping clinicopathological manifestations, 7 but this name was not widely known until the early 1980s. Although several researchers had reported and suggested a multicentric form of Castleman disease characterized by multiple lymphoid tissue lesions, it had not yet been established as a disease concept.…”

Hyaline Vascular Type of Unicentric Castleman Disease in a Kidney with End-Stage Renal Disease: A Case Report of a Rare Entity at an Unusual Location and a Special Clinical Setting

“…According to the clinical presentation and disease course, CD is further divided into UCD, a localized disease involving a single lymph node or anatomic site, and MCD, a systemic and progressive disease with lymphadenopathy in multiple nodes [ 1 , 2 ]. MCD is further subclassified into Kaposi sarcoma herpesvirus- (KSHV, also called human herpesvirus 8 (HHV8)) associated MCD (KSHV-MCD) and KSHV-independent idiopathic MCD (iMCD) [ 1 , 11 ]. Histologically, this rare disease shares characteristic morphologic features, which can be categorized into HV-CD, PC-CD and mixed-type CD.…”

A Real-world Study on a Large Retrospective Cohort of Castleman Disease from a Single Center

“…In this cohort, eight patients with CD-like pathological features were subsequently diagnosed as FDCSs. Due to the variety of the pathological manifestations of CD, sometimes it is di cult to distinguish CD from thymoma, FDCS, and Hodgkin's lymphoma [9][10][11] . The diagnosis of iMCD requires the exclusion of infections, autoimmune diseases, primary or acquired immunode ciency syndromes, and malignancies, of which the differentiation of PC-MCD and IgG4RD had always been a challenge in clinical practice [12][13][14][15] .…”

“…Due to the variety of the pathological manifestations of CD, sometimes it is di cult to distinguish CD from thymoma, FDCS, and Hodgkin's lymphoma [9][10][11] . The diagnosis of iMCD requires the exclusion of infections, autoimmune diseases, primary or acquired immunode ciency syndromes, and malignancies, of which the differentiation of PC-MCD and IgG4RD had always been a challenge in clinical practice [12][13][14][15] . Both of them have an appearance of generalized lymph node enlargement and extra-nodal involvement, and iMCD patients may have high serum IgG4 levels, whilst some IgG4RD patients may have CD-like pathological changes 16 .…”