Castleman's disease (CD, angiofollicular lymph node hyperplasia) is a heterogenous group of lymphoproliferative disorders associated in a subset of cases with the human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8). CD comprises at least two distinct diseases (unicentric and multicentric) with very different prognoses. It may also be associated with other malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, and POEMS syndrome.
CD was first described in 1956 by Benjamin Castleman and colleagues, who identified a series of patients with solitary hyperplastic mediastinal lymph nodes containing small, hyalinized follicles and a marked interfollicular vascular proliferation (hyaline vascular variant of CD) . The same investigators later identified lymph nodes with a similar vascular proliferation associated with large hyperplastic germinal centers and sheets of interfollicular plasma cells. Hyalinized follicles were present in some, but not all, such cases.
●All of the patients described in these early papers had localized disease, which is now termed unicentric Castleman's disease (UCD). UCD is associated with systemic symptoms in a subset of cases.
●In contrast, multicentric Castleman's disease (MCD) is a systemic disease with generalized peripheral lymphadenopathy, hepatosplenomegaly, frequent fevers, and night sweats that is usually associated with the plasma cell or mixed variant. Unlike UCD, MCD is strongly associated with immunosuppression and HHV-8 infection.
This topic review will discuss the epidemiology, pathogenesis, clinical features, pathologic features, diagnosis and treatment of MCD. UCD and a review of diseases associated with HHV-8 infection and the virology of HHV-8 are presented separately. (See "Disease associations of human herpesvirus 8 infection" and "Virology, epidemiology, and transmission of human herpesvirus 8 infection" and "Unicentric Castleman's disease".)