The histopathological spectrum of myocardial inflammation in relation to circumstance of death: a retrospective cohort study in clinical and forensic autopsies

Abstract

Interpreting a myocardial inflammation as causal, contributory or as of no significance at all in the cause of death can be challenging, especially in cases where other pathologic and/or medico-legal findings are also present. To further evaluate the significance of myocardial inflammation as a cause of death we performed a retrospective cohort study of forensic and clinical autopsy cases. We revised the spectrum of histological inflammatory parameters in the myocardium of 79 adult autopsy cases and related these to the reported cause of death. Myocardial slides were reviewed for the distribution and intensity of inflammatory cell infiltrations, the predominant inflammatory cell type, and the presence of inflammation-associated myocyte injury, fibrosis, edema and hemorrhage. Next, the cases were divided over three groups, based on the reported cause of death. Group 1 (n = 27) consisted of all individuals with an obvious unnatural cause of death. Group 2 (n = 29) included all individuals in which myocarditis was interpreted to be one out of more possible causes of death. Group 3 (n = 23) consisted of all individuals in which myocarditis was reported to be the only significant finding at autopsy, and no other cause of death was found. Systematic application of our histological parameters showed that only a diffuse increase of inflammatory cells could discriminate between an incidental presence of inflammation (Group 1) or a potentially significant one (Groups 2 and 3). No other histological parameter showed significant differences between the groups. Our results suggest that generally used histological parameters are often insufficient to differentiate an incidental myocarditis from a (potentially) significant one.

Figure 1.

Micrographs with examples of a various types of myocardial inflammation. (A) A single focus of inflammatory cells with myocyte injury, constituting a focal myocarditis (HE, ×20). (B) Two inflammatory foci with myocyte necrosis, consistent with a diagnosis of multifocal myocarditis (HE, ×10). (C) Extensive diffuse myocardial inflammation with myocyte injury, i.e. an active diffuse myocarditis (HE, ×5).

Figure 2.

Micrographs with examples of myocyte injury. (A) An almost totally disintegrated cardiomyocyte amidst an inflammatory infiltrate consisting of lymphocytes and macrophages (HE, ×20). (B) The necrotic cardiomyocyte is still recognizable as thin, slightly eosinophilic cell remnants, adjacent to normal, vital cardiomyocytes (HE, ×20).

Figure 3.

Micrographs of a case of fulminant eosinophilic myocarditis, to illustrate the application of immunohistochemical staining. (A) The standard haematoxylin and eosin-stained section (HE, ×10) shows abundant inflammation, (B) which consists of CD45-positive lymphocytes (immunohistochemical staining, ×10), (C) CD68-positive macrophages (immunohistochemical staining, ×10) and (D) myeloperoxidase-positive neutrophilic and eosinophilic granulocytes (immunohistochemical staining, ×10).