J Pathol Transl Med.  2020 Sep;54(5):396-410. 10.4132/jptm.2020.06.10.

Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy

• Cha MJ
• Seo JW
• Oh S
• Park EA
• Lee SH
• Kim MY
• Park JY

• KMID: 2506273
• DOI: http://doi.org/10.4132/jptm.2020.06.10

Abstract

Background
The definitive pathologic diagnosis of cardiac sarcoidosis requires observation of a granuloma in the myocardial tissue. It is common, however, to receive a “negative” report for a clinically probable case. We would like to advise pathologists and clinicians on how to interpret “negative” biopsies.
Methods
Our study samples were 27 endomyocardial biopsies from 25 patients, three cardiac transplantation and an autopsied heart with suspected cardiac sarcoidosis. Pathologic, radiologic, and clinical features were compared.
Results
The presence of micro-granulomas or increased histiocytic infiltration was always (6/6 or 100%) associated with fatty infiltration and confluent fibrosis, and they showed radiological features of sarcoidosis. Three of five cases (60%) with fatty change and confluent fibrosis were probable for cardiac sarcoidosis on radiology. When either confluent fibrosis or fatty change was present, one-third (3/9) were radiologically probable for cardiac sarcoidosis. We interpreted cases with micro-granuloma as positive for cardiac sarcoidosis (five of 25, 20%). Cases with both confluent fibrosis and fatty change were interpreted as probable for cardiac sarcoidosis (seven of 25, 28%). Another 13 cases, including eight cases with either confluent fibrosis or fatty change, were interpreted as low probability based on endomyocardial biopsy.
Conclusions
The presence of micro-granuloma could be an evidence for positive diagnosis of cardiac sarcoidosis. Presence of both confluent fibrosis and fatty change is necessary for probable cardiac sarcoidosis in the absence of granuloma. Either of confluent fibrosis or fatty change may be an indirect pathological evidence but they are interpreted as nonspecific findings.

Keyword

Myocarditis; Arrhythmogenic right ventricular dysplasia; Tachycardia, ventricular; Sarcoidosis; Cardiac muscle

Figure

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  Fig. 1. Micro-granuloma on the endomyocardial biopsy. (A) Endomyocardial biopsy at 2 years prior to the transplantation of case 1-1 shows confluent fibrosis with edematous stroma. Three foci of infiltration of histiocytes and lymphocytes (arrow) are seen at the margin of fibrosis which is the interface between the fibrosis and myocardium. (B) CD68 staining of the same specimen showing histiocytic infiltration at the micro-granulomas (arrow). (C) Endomyocardial biopsy of case 1-3 shows a micro-granuloma (arrow) of 15 cells in the fibrotic zone. (D) CD68 immunostaining of endomyocardial biopsy of case 1-3 shows positive staining (arrow) on histiocytic marker.

• 

  Fig. 2. Micro-granuloma in an explant heart. (A) Magnification of the ventricular myocardium of explant heart in case 1-2 reveals interstitial fibrosis and a few small granulomas. (B) Immunohistochemical staining on CD68 in the same area shows a small nodular collection of histiocytes or zone of scattered histiocytes.

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  Fig. 3. Histiocytic infiltration, confluent fibrosis and fatty change. (A) Confluent fibrosis, associated fatty change within the fibrosis in case 2-1. (B) CD68 staining in the same area shows increased histiocytes (arrows) scattered in the fibrous area. (C) Confluent fibrosis, associated fatty change within the fibrosis in case 3-1. (D) CD68 staining in the same area shows very rare or no increase of histiocytes (arrow) in the fibrous area.

• 

  Fig. 4. Different types of fatty changes in endomyocardial biopsies. (A) Fatty infiltration in the background of confluent fibrosis (case 3-2). (B) Fatty tissue with variable sizes of adipocytes and adjacent myocardium also show post-inflammatory fibrosis (case 1-5). (C) Subendocardial deposition of fatty tissue. Slender fibrotic zone is visible at the margin of fatty area (case 3-5). (D) Fatty infiltration between the myocardial bundles. Adjacent myocardium is normal without fibrosis or inflammation (case 5-4).

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  Fig. 5. Confluent fibrosis without associated fatty tissue. (A) Confluent fibrosis is not evident in a small biopsy but fibrosis bigger than five times the diameter of the myocardial cells was interpreted as a scar related to a granuloma (case 4-2). (B) Broad scar at the endocardial zone. Some adipocyte-like spaces were found but the scattered individual spaces were not interpreted as fatty change (Case 4-3).

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  Fig. 6. A short-axis sectional view of the first transplant heart with sarcoidosis and fibrosis. (A) A short-axis sectional view of the heart shows multifocal confluent fibrosis involving both ventricles. The right ventricular thinning and dilatation are prominent. Coronary arteries and cardiac veins are filled with red and blue silicone rubber cast. (B) Histotopographic mapping of a short-axis plane of the heart by Masson’s trichrome staining reveals prominent fibrosis (in blue color) in the right ventricular free wall and patchy fibrosis in the ventricular septum and left ventricle.

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  Fig. 7. The second transplant heart with sarcoidosis and hypertrophied ventricles. (A) Sectional view of the heart shows multifocal confluent fibrosis involving predominantly left ventricle and the ventricular septum. Epicardial fatty tissue is prominent in the right ventricle but the myocardium is not much involved. (B) Histotopographic mapping of a short-axis plane of the heart by Masson’s trichrome staining reveals prominent fibrosis (in blue color) in the interventricular septum and the left ventricular free wall. Distribution of the fibrosis is prominent but not limited to the subepicardial zone.

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  Fig. 8. The third transplant heart mimicking sarcoidosis on microscopy but not likely of sarcoidosis on macroscopic view. (A) The left ventricle is dilated and hypertrophied. Multifocal and diffuse fibrosis was noted on gross examination. Fatty infiltration was prominent at the anterior part of the ventricular septum and mid-septal fibrosis was evident. (B) Fatty change associated with myocardial fibrosis was seen at the anterior part of the ventricular septum. (C) Low magnification of the mid-septal fibrosis (Masson’s trichrome stain).

Reference

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