Representative samples with sarcoid granulomas.

<p>An autopsy sample (<b>A–C</b>) and an EMB sample (<b>D–F</b>) from patients with sarcoidosis were stained with haematoxylin and eosin and immunostained with anti-<i>P</i>. <i>acnes</i> antibody. Many sarcoid granulomas were observed at the lower magnification (<b>A, D</b>). Small round bodies indicated by the black arrows (<b>C, F</b>) were found in some of epithelioid cells and multinucleated giant cells of these sarcoid granulomas by immunohistochemistry with anti-<i>P</i>. <i>acnes</i> antibody. Original magnification; ×200 (left), ×1000 (middle and right).</p

Immunohistochemical identification of <i>Propionibacterium acnes</i> in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients

<div><p>Background</p><p>Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect <i>Propionibacterium acnes</i>, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients.</p><p>Methods and results</p><p>We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a <i>P</i>. <i>acnes</i>-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. <i>P</i>. <i>acnes</i>-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples.</p><p>Conclusions</p><p>Frequent identification of <i>P</i>. <i>acnes</i> in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of <i>P</i>. <i>acnes</i> in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.</p></div

Clinical profiles of the patients providing EMB samples.

<p>Clinical profiles of the patients providing EMB samples.</p

Patient characteristics.

<p>Patient characteristics.</p

Summary of histologic and immunohistochemical findings.

<p>Summary of histologic and immunohistochemical findings.</p

Representative samples with massive inflammatory foci.

<p>Specimens obtained from autopsy samples in patients with CS (<b>A–C</b>), myocarditis (<b>D–F</b>), or other cardiomyopathy (<b>G-I</b>) were stained by haematoxylin and eosin and immunostained with anti-<i>P</i>. <i>acnes</i> antibody. Massive inflammatory cell infiltration was observed in samples from patients with CS (<b>A, B</b>), myocarditis (<b>D, E</b>), or other cardiomyopathies (<b>G, H</b>). Positive <i>P</i>. <i>acnes</i> immunostaining in macrophages of these inflammatory foci was detected only in samples from patients with CS (<b>C</b>; black arrows), and not in samples from those with myocarditis (<b>F</b>) or other cardiomyopathies (<b>I</b>). Original magnification; ×200 (left), ×1000 (middle and right).</p

Schematic representation of granulomatous inflammation caused by <i>P</i>. <i>acnes</i>.

<p>Granulomas begin as small collections of lymphocytes and macrophages with intracellular <i>P</i>. <i>acnes</i> (early inflammatory foci) as observed in the minimal or massive inflammatory foci of the CS-group samples. Macrophages change to epithelioid cells and become organized into a cluster of cells (immature granuloma). Further progression results in ball-like clusters of cells and fusion of macrophages into giant cells with or without remaining intracellular <i>P</i>. <i>acnes</i> (mature granuloma).</p

Representative samples with minimal inflammatory foci.

<p>Specimens obtained from autopsy samples and EMB samples in patients with CS (<b>A–D</b>), M (<b>E–H</b>), and CM (<b>I–L</b>) were stained by haematoxylin and eosin (<b>A, C, E, G, I,</b> and <b>K</b>) and immunostained with anti-<i>P</i>. <i>acnes</i> antibody (<b>B, D, F, H, J,</b> and <b>L</b>). Black arrows indicate positive <i>P</i>. <i>acnes</i>-immunostaining. Minimal inflammatory cell infiltration was observed in samples from all six patients. Even at the lowest inflammatory cell infiltration, positive <i>P</i>. <i>acnes</i>-immunostaining in macrophages of these inflammatory foci was detected in samples from patients with CS (<b>B, D</b>), but not in samples from those with M (<b>F, H</b>) and CM (<b>J, L</b>), regardless of the sample type. Original magnification; ×1000.</p