Genetically determined cardiomyopathies at autopsy: the pivotal role of the pathologist in establishing the diagnosis and guiding family screening

Abstract

Cardiomyopathies (CMP) comprise a heterogenous group of diseases affecting primarily the myocardium, either genetic and/or acquired in origin. While many classification systems have been proposed in the clinical setting, there is no internationally agreed pathological consensus concerning the diagnostic approach to inherited CMP at autopsy. A document on autopsy diagnosis of CMP is needed because the complexity of the pathologic backgrounds requires proper insight and expertise. In cases presenting with cardiac hypertrophy and/or dilatation/scarring with normal coronary arteries, a suspicion of inherited CMP must be considered, and a histological examination is essential. Establishing the actual cause of the disease may require a number of tissue-based and/or fluid-based investigations, be it histological, ultrastructural, or molecular. A history of illicit drug use must be looked for. Sudden death is frequently the first manifestation of disease in case of CMP, especially in the young. Also, during routine clinical or forensic autopsies, a suspicion of CMP may arise based on clinical data or pathological findings at autopsy. It is thus a challenge to make a diagnosis of a CMP at autopsy. The pathology report should provide the relevant data and a cardiac diagnosis which can help the family in furthering investigations, including genetic testing in case of genetic forms of CMP. With the explosion in molecular testing and the concept of the molecular autopsy, the pathologist should use strict criteria in the diagnosis of CMP, and helpful for clinical geneticists and cardiologists who advise the family as to the possibility of a genetic disease.

Keywords: Autopsy; Cardiomyopathies; Genetic; Sudden cardiac death.

Fig. 1

Diagrammatic representation of the gross phenotype of normal heart and primary inherited cardiomyopathies at short axis cut. Normal heart, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (ACM), and restrictive cardiomyopathy (RCM). Note that in primary RCM, at cross section, the phenotype is usually not distinct from normal heart, and atrial dilatation in the absence valvular and endocardial diseases is the red flag at gross examination

Fig. 2

Hypertrophic cardiomyopathy (HCM) and pitfall (postmortem hypercontraction). A Macroscopic short axis cut with circumferential hypertrophy of the left ventricle. There is also prominent septal hypertrophy with anteroseptal irregular scarring. Note also prominent papillary muscles and trabeculae in the left ventricle. B Microscopic section shows individual myocyte and bundle disarray with hyperchromatic nuclei. There is an increase in interstitial collagen, findings in keeping with HCM (hematoxylin and eosin stain). C Macroscopic short axis cut with circumferential increase in thickening of the left ventricle due to hypercontraction. There is no scarring or prominent septal hypertrophy. Note also the prominent papillary muscles and trabeculae in left ventricle. D Microscopic section shows myocyte hypercontraction with contraction bands in otherwise normal myocytes. There is no increase in interstitial collagen (hematoxylin and eosin stain)

Fig. 3

Arrhythmogenic cardiomyopathy (ACM) and pitfall (fatty heart). A Macroscopic short axis cut with fat infiltration from epicardial surface of the anterior, lateral, and posterior wall of the right ventricle with fat infiltration also of the lateral left ventricle wall. B Microscopic section shows fat admixed with collagen. There is individual myocyte and bundle degeneration (insert) in keeping with ACM (hematoxylin and eosin stain). C Macroscopic short axis cut with circumferential increase in epicardial fat surrounding both right and left ventricle. D Microscopic section shows mature fat admixed with myocyte bundles. There is no myocyte degeneration or increase in collagen (hematoxylin and eosin stain)

Fig. 4

Dilated cardiomyopathy (DCM) and pitfall (postmortem putrefaction). A Macroscopic short axis cut with dilated left ventricle chamber and thinning of the left ventricular free wall. B Microscopic section shows interstitial and replacement collagen admixed with hypertrophied and degenerate myocytes in keeping with DCM (hematoxylin and eosin stain). C Macroscopic short axis cut with dilated left ventricle chamber and thinning of the left ventricular free wall. Note also the dark discoloration of both right and left ventricle. D Microscopic section shows hazy myocytes with separation of individual myocytes and myocyte bundles. There is bacterial proliferation within capillaries. Gas bubble formation is also noted (hematoxylin and eosin stain)