This case is that of a 60-year-old woman with a medical history significant for progressively worsening ventricular function (ejection fraction of 26%), complete heart block, sick sinus rhythm with syncopal episodes, and status post-intracardiac defibrillator placement two years ago. Unfortunately, she was found deceased in bed by her partner, who states she was feeling well and had no acute complaints in the preceding days. The following photos show what was found at autopsy.
The correct answer is ...
This patient’s gross evaluation shows a short axis cross-section of the left and right ventricles. There is near-circumferential and well-demarcated tan-white fibrosis of the left ventricle and interventricular septum that predominately involves the epicardium and extends to involve the mid-myocardium. There is relative sparing of the endomyocardium, although focal areas show transmural involvement. Upon histologic evaluation, there is extensive involvement by non-necrotizing granulomas with prominent lymphohistiocytic inflammation. These findings, along with the clinical history of arrhythmia and progressively worsening cardiac function, are consistent with a diagnosis of cardiac sarcoidosis (CS).
CS is a challenging diagnostic entity, as it may be asymptomatic in a large portion of the affected population. When symptomatic, the presentation may include arrhythmias, conduction system abnormalities, palpitations, chest pain, dyspnea, syncope, heart failure, or sudden death. Clinicians must have a low threshold for considering and evaluating for CS, as imaging can be nonspecific and endomyocardial biopsy can have a low sensitivity given the patchy nature of myocardial involvement. When there is suspicion for CS at the time of explantation or autopsy, especially in the setting of a sudden death, it is important to sample the conduction system well. CS has a predilection for the atrioventricular node and right and left bundle branches, which accounts for the development of conduction system abnormalities and arrhythmias.
The sparing of the endomyocardium lessens the likelihood that this disease process occurred as the result of an ischemic event (i.e., myocardial infarct), which first affect the endomyocardial surface as a watershed area and extend outward. Furthermore, the distribution of the fibrosis does not follow a pattern one would expect after an ischemic event in one of the three major coronary arteries, as there are patchy affected areas even within the distribution of the individual coronary arteries.
While giant cell myocarditis (GCM) is in the differential for an individual with giant cell inflammation in the myocardium, there are several features that decrease the likelihood of the diagnosis in this case. Clinically, it would be uncommon for GCM to occur in someone who was asymptomatic or had slowly progressive cardiac dysfunction over a several year period. The clinical progression for someone with GCM is profoundly rapid and the prognosis is poor. The histologic presentation tends to have an abundance of eosinophils, which are thought to be the main etiology of the widespread myocardial injury and subsequent cardiac dysfunction. While there are some eosinophils in the inflammatory infiltrate in this case, they make up a small percentage of the overall inflammation.
Lastly, given the clinical history of arrhythmia and the presentation with sudden death, arrhythmogenic cardiomyopathy (AC) is also a reasonable differential diagnosis. The gross and histologic findings for AC, however, differ from CS in that one will typically expect to find a dilated right ventricle with fibrofatty replacement of the ventricular wall. The fibrofatty replacement may be patchy or diffuse, and left ventricular involvement is subepicardial. The interventricular septum is typically spared. Of note, while this was previously referred to as arrhythmogenic right ventricular cardiomyopathy, newer data shows that the involvement often is equally represented between both ventricles or may involve the left ventricle alone.
Philip Hurst, M.D.
Fellow, Anatomic & Clinical Pathology
Melanie Bois, M.D.
Consultant, Anatomic Pathology
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science