Expression of cell adhesion molecules associated with germinal center in Hodgkin's disease: An immunohistochemical study. The germinal center related complex and histologic subtypes

Abstract

Of the four elements known to be associated with germinal center formation--B-cells, follicular dendritic cells, T-cells, and the cell adhesion molecules--the first three have been well studied in Hodgkin's disease, especially the nodular lymphocytic predominance subtype, established as a tumor of germinal center origin. However, no study has been done on the expression of the cell adhesion molecules associated with germinal center formation in Hodgkin's disease. Using the avidin-biodin peroxidase complex method, we studied the staining patterns for CD11a (lymphocyte function-associated antigen 1), CD54 (intercellular cell adhesion molecule 1), and very late antigen 4 (VLA-4) in frozen sections from 24 cases of Hodgkin's disease, along with those for follicular dendritic cell and cell surface markers for lymphocytes. Reed-Sternberg cells and their variants and histiocytic cells stained for CD54. Lymphocytes stained for CD11a. Lymphocytes either formed patchy aggregates or dispersed without forming aggregates. Aggregating lymphocytes expressed CD20 (L-26), whereas dispersed, nonaggregating lymphocytes expressed CD3/CD4, or CD3/CD8. Extracellular matrices of these CD20+ B-cell aggregates stained for CD54, VLA-4, and follicular dendritic cells. CD54 staining revealed four patterns of reaction products deposits: discretely patchy, confluent, predominantly diffuse, and diffuse only. The discrete-patch predominance pattern was seen in the lymphocytic predominance type, both nodular (n = 3) and diffuse (n = 2), and in classic nodular sclerosis with broad collagen bands (n = 4). The confluent pattern was seen in tumors with features of cellular-phase nodular sclerosis versus mixed cellularity type (n = 3). The predominantly diffuse was observed in the remainder of nodular sclerosis type with infrequent, narrow collagen bands (n = 5), in cellular-phase nodular sclerosis (n = 1), in cellular-phase nodular sclerosis versus mixed cellularity type (n = 2), and in mixed cellularity (n = 2). The diffuse-only pattern occurred in mixed cellularity with abundant fibrohistiocytoid stromal cells (n = 2). The cell adhesion molecules associated with germinal center formation were expressed in the great majority of cases of Hodgkin's disease. The expression was closely associated with the occurrence of distinctive CD20+ B-cell aggregates and follicular dendritic cell networks, forming a germinal center-related complex, and the presence of the complex correlated with nodular sclerosing features.