The Many Faces of Cardiac Sarcoidosis

Virian D. Serei, MD, PhD; Billie Fyfe, MD

Disclosures

Am J Clin Pathol. 2020;153(3):294-302. 

In This Article

Cardiac Gross Pathology

Grossly, granulomas may coalesce to form gross irregular infiltrating lesions that are yellow-tan, white-tan, or gray.[8,15] Granulomas may involve any area of the heart. Although studies report variable distribution, the left ventricular free wall is generally most frequently involved, followed by the left basal interventricular septum, and the right ventricle. Atria are less commonly involved.[4,8,15,16] The interventricular septum has been shown to have the highest incidence of grossly recognizable disease involvement when compared to the left ventricular free wall and right ventricle.[10] Pericardial and epicardial inflammation are typically a direct extension of myocardial involvement and may be associated with exudative pericardial effusions.[15,17] The cardiac valves and coronary arteries are not usually involved.[4,16,18] Grossly visible scarring associated with chronic disease is most often subepicardial and can be transmural[18,19] Image 1 and Image 2. Profound scarring is often found in those with chronic disease requiring heart transplantation and in patients who die from sudden cardiac death secondary to cardiac sarcoidosis[16,18,19] (Image 1 and Image 2).

Image 1.

A 23-year-old woman with no significant medical history presented with 2 months of heart failure symptoms following a viral gastrointestinal infection. A cardiac magnetic resonance image showed dilated ischemic cardiomyopathy with diffuse global enhancement and ejection fraction of 12%. An initial endomyocardial biopsy showed one fragment with a dense inflammatory infiltrate composing of lymphocytes and macrophages, without giant cells (A, H&E, x200). Immunophenotypic analysis for lymphoproliferative disorder was negative but lymph node biopsy was recommended due to the clinically noted presence of mediastinal adenopathy. Despite aggressive diuresis and pressor support, she did not improve from a cardiovascular standpoint. She was listed for heart transplantation and implanted with a left ventricular assist device (LVAD). Excisional biopsy of an anterior mediastinal lymph node (B, H&E, x40) at the time of LVAD implantation showed architectural effacement by multiple nonnecrotizing granulomas (arrow) with extensive giant cell formation and multifocal calcification, corresponding to Schaumann bodies (arrowheads). Analysis of the apical core showed multifocal areas of nonnecrotizing granulomatous inflammation (C, H&E, x200). Extensive inflammation with lymphocytes and giant cells with associated fibrosis involving approximately one-third of the submitted tissue was also present (D, H&E, x40). Grocott methenamine silver stain and acid-fast staining were negative for fungi and acid-fast bacilli. The patient began prednisone therapy and the ejection fraction improved to 59% after 12 months. The LVAD was explanted but shortly thereafter severe heart failure recurred. This necessitated cardiac transplantation. The native heart showed extensive concentric ventricular scarring (E). Microscopically, the scarring corresponded to extensive myocardial fibrosis with scattered lymphocytic inflammation with no residual granulomas (F, H&E, x40). Evidence of the previous LVAD placement and explant procedure was present. The apex was repaired using a Cohn felt plug (G), with the surrounding myocardium showing interstitial fibrosis (H, H&E, x20).

Image 2.

A 52-year-old man with a medical history significant for ischemic cardiomyopathy and biopsy-proven cutaneous sarcoidosis with lung involvement presented with congestive heart failure. Ejection fraction was 15% for 8 years. Despite diuresis and pressor treatment, a left ventricular assist device was implanted and he was listed for heart transplant. Endomyocardial biopsy and apical core both showed myocyte hypertrophy and scattered interstitial inflammation (A and B, H&E, x200). Mediastinal lymph node (C, H&E, x200) showed nonnecrotizing granulomatous inflammation (arrows) with negative acid-fast and Grocott methenamine silver staining, consistent with the history of sarcoidosis. Eighteen months later, he underwent successful cardiac transplantation. The explanted heart grossly showed marked biventricular dilatation with focal areas of scarring (D). Microscopically, there was marked interstitial fibrosis, mild diffuse inflammation, and occasional granuloma formation (E, arrow, H&E, x200). One granuloma (F, H&E, x200) contained focal necrosis (asterisk), with Grocott methenamine silver stain and acid-fast stain negative for fungi and acid-fast bacilli, respectively (not shown).

Secondary cardiac structural changes may occur due to cardiac sarcoidosis. While rarely reported, the presence of ventricular hypertrophy may reflect earlier stages of disease and may be due to expansion of granulomatous inflammation and edema[20] (Image 1). More commonly present are dilated cardiomyopathy and aneurysm formation[10,18,20] (Image 2). As a consequence of the cardiac structural changes, conduction disturbances, arrhythmias, right-sided heart failure with associated peripheral edema, and left-sided heart failure with subsequent pulmonary edema and hypertension can occur in these patients.[4]

Patients with systemic sarcoidosis are also at increased risk for cardiovascular disease, including congestive heart failure, coronary artery disease, and atrial fibrillation.[21] Particularly in patients with end-stage pulmonary sarcoidosis, extensive pulmonary fibrosis leading to pulmonary hypertension can lead to right-sided heart failure (cor pulmonale).[3] Additionally, it is postulated that chronic systemic inflammation due to sarcoidosis can precipitate premature atherosclerosis and coronary artery disease.[21]

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