Rheumatic Aschoff nodules revisited: an immunohistological reappraisal of the cellular component

Rheumatic fever is still the leading cause of acquired heart disease in children and young adults in developing countries. Recent reports have documented a rising incidence of rheumatic fever in both the USA and Europe. The disease is characterized by specific lesions in the heart muscle and valves called Aschoff nodules. The Aschoff nodule has been neglected in the last few decades as most of the studies were conducted in the 1960s on autopsy tissues. This study examines Aschoff nodules using heart valve material obtained at valve surgery with updated commercially available immunohistochemical antibodies to determine the phenotypic characteristics of the cells involved in the formation of these lesions. Fifteen cases of rheumatic valvulitis, as indicated by the presence of Aschoff nodules, were examined. The Anitschkow and Aschoff cells stained prominently with macrophage markers. Three stages of nodules with Aschoff and Anitschkow cells were identified: stage 1, central fibrinoid necrosis without lymphocytes, stage 2 with occasional T lymphocytes (< 10) and stage 3 with lymphoid aggregates containing both T- and B-lymphocytes (with occasional admixed macrophages). We propose that the stage 1 lesion is the earliest granulomatous stage with the lymphoid aggregates being a later stage in the development of Aschoff nodules. The Aschoff and Anitschkow cells demonstrated mitotic activity and stained with antibodies to the proliferation cell nuclear antigen (PCNA) suggesting that the multinucleated giant cells may be formed, at least partially, by nuclear division rather than fusion.