Related Experiment Videos
Castleman's disease
G Palestro1, F Turrini, M Pagano
1Departement of Biomedical Science and Human Oncology, University of Torino, Torino, I-10126, Italy. palestro@molinette.unito.it
Insights
Castleman's disease is a rare lymphoproliferative disorder with two main types: hyaline vascular and plasma cell. Both types share hallmarks and may represent a single immune dysregulation disorder.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Castleman's disease (CD) is a rare lymphoproliferative disorder.
- CD is histopathologically classified into hyaline vascular (HV) and plasma cell (PC) variants, with intermediate forms.
- The PC variant is often multicentric, presenting with systemic symptoms, autoimmune phenomena, and an aggressive course.
Purpose of the Study:
- To describe the histopathological features and potential pathogenetic mechanisms of Castleman's disease.
- To differentiate between the hyaline vascular and plasma cell variants of CD.
- To explore the role of immune dysregulation and viral factors in CD pathogenesis.
Main Methods:
- Histopathological analysis of lymph node biopsies.
- Immunophenotypic characterization of B cells and other cellular components.
- Review of clinical and laboratory findings associated with CD.
Main Results:
- Common hallmarks include increased follicular dendritic reticulum cells (FDRC), aberrant B cells, and plasma cell proliferation.
- HV variant features include hyalinized germinal centers and sinus effacement.
- PC variant features include hyperplastic germinal centers and prominent paracortical plasma cells.
Conclusions:
- CD may represent a single disorder linked to immune dysregulation.
- Aberrant B cell growth factor production, such as IL-6, is implicated in CD pathogenesis.
- Human herpesvirus 8 (HHV-8) may play a role in multicentric CD, potentially contributing to IL-6 production and oncogenesis.
Abstract:
Castleman's disease (CD) is a rare atypical lymphoproliferative disorder whose morphology, soon after the original presentation of Castleman et al., has been definitely subdivided in a hyaline vascular (HV) and plasma cell (PC) histopathological pattern, with intermediate variants. The former occurs much more frequently than the latter and is usually localized to the mediastinum or pulmonary hilum. The latter involves lymph nodes separately or in aggregations and often displays multicentricity with systemic symptoms including autoimmune phenomena and aggressive course. Infections are the most frequent causes of patient demise in these cases, followed by malignancies such as Kaposi's sarcoma, malignant lymphoma or epithelial neoplasia. Increase of follicular dendritic reticulum cells (FDRC), often dysplastic, in the germinal center (GC) and marginal zone (MZ), broad MZ expansion with prominence of immunophenotypically aberrant B cells (Ki B3-negative, CD5-positive), possible predominance of paracortical plasma cells often with clusters of clonal l-light chain restricted plasma cells, increase of paracortical plasmacytoid monocytes, represent common hallmarks of CD. However, small hyalinized and hypervascular GCs with hypervascular interfollicular stroma and sinus effacement are common features of the HV variant, whereas hyperplastic GCs with plasma cell aggregates in lymph node paracortex and partially spared sinuses are characteristic features of the PC variant. The frequent concomitance of the HV and PC types at separate sites, together with transient morphological patterns from one type to the other and from the localized to multicentric form during the course of the disease, along with B and T cell impaired functions, with frequent development of autoantibodies, have suggested that CD is a single disorder related to immune dysregulation. A key event in the pathogenesis of CD has been recently suggested to be an abnormal production of a B cell growth factor, such as IL-6, leading to lymphoproliferation and plasma cell differentiation and being involved in the oncogenesis of plasmacytoma. In this event, Kaposi's sarcoma associated virus (HHV-8), which has been found in many cases of CD, especially in the multicentric form, could play a crucial role both in producing IL-6 and releasing angiogenic factors. A possible differentiation block may lead to the development of a malignant lymphoma. Kaposi's sarcoma or other malignant neoplasias can be supposed to be consequences of the immunodeficiency typical of CD.