Pathology and Diagnosis of Multicentric Castleman’s Disease

Conference Correspondent - ASH 2014 - Castleman's Disease


Ahmet Dogan presented “Castleman Disease Pathology and Diagnosis” at the ASH 2014 Special Program. MCD histopathologic features can be divided into 4 variants, including hyaline-vascular, plasma cell, mixed, and plasmablastic, according to Dogan.

Hyaline-vascular MCD is characterized by widened mantle zones composed of concentric rings of small lymphocytes in an “onion skin” pattern around small atrophic germinal centers with penetrating hyalinized vessels and dysplastic follicular dendritic cells. In plasma-cell MCD, the germinal centers are hyperplastic rather than atrophic, the interfollicular region contains sheets of plasma cells and vascular proliferations, the follicular dendritic-cells network is normal, and there is preserved lymph node architecture. The mixed variant displays features of hyaline-vascular MCD and of plasma-cell MCD. The reliability and significance of these variants are unclear, because there are reports of transitions between hyaline-vascular and plasma-cell variants on subsequent biopsies, as well as the simultaneous presence of both types of MCD at separate sites within the same patient.

Three recent studies reported 17% to 49% of patients with hyaline-vascular MCD, 46% to 77% with plasma-cell MCD, and 4% to 20% with mixed pathology among 198 cases of HIV-negative MCD. Of note, these histopathologic features are nonspecific, reactive to hypercytokinemia from any source in the body, and can be found in several infectious, rheumatologic, and neoplastic diseases, including non-Hodgkin and cutaneous lymphomas, multiple myeloma, giant-cell carcinoma of the lung, and inflammatory myofibroblastic tumor. Thus, iMCD lymph nodes should not be considered tumors.

The new model of pathogenesis for iMCD includes 2 main principles, indicating that (1) iMCD is not a benign tumor but rather a hyperinflammatory disease in which the candidate pathologic cells are B-lymphocytes, monocytes or macrophages, stromal cells, T-lymphocytes, plasma cells, and endothelial cells; and (2) lymph node changes and organ dysfunction are secondary to hypercytokinemia, possibly as a result of autoimmune or paraneoplastic phenomena.