Histology of Cardiac Sarcoidosis with Novel Considerations Arranged upon a Pathologic Basis

Abstract

Sarcoidosis is a rare disease of isolated or diffuse granulomatous inflammation. Although any organs can be affected by sarcoidosis, cardiac sarcoidosis is a fatal disorder, and it is crucial to accurately diagnose it to prevent sudden death due to dysrhythmia. Although endomyocardial biopsy is invasive and has limited sensitivity for identifying granulomas, it is the only modality that yields a definitive diagnosis of cardiac sarcoidosis. It is imperative to develop novel pathological approaches for the precise diagnosis of cardiac sarcoidosis. Here, we aimed to discuss commonly used diagnostic criteria for cardiac sarcoidosis and to summarize useful and novel histopathologic criteria of cardiac sarcoidosis. While classical histologic observations including noncaseating granulomas and multinucleated giant cells (typically Langhans type) are the most important findings, others such as microgranulomas, CD68+ CD163− pro-inflammatory (M1) macrophage accumulation, CD4/CD8 T-cell ratio, Cutibacterium acnes components, lymphangiogenesis, confluent fibrosis, and fatty infiltration may help to improve the sensitivity of endomyocardial biopsy for detecting cardiac sarcoidosis. These novel histologic findings are based on the pathology of cardiac sarcoidosis. We also discussed the principal histologic differential diagnoses of cardiac sarcoidosis, such as tuberculosis myocarditis, fungal myocarditis, giant cell myocarditis, and dilated cardiomyopathy.

Pathophysiological Gaps, Diagnostic Challenges, and Uncertainties in Cardiac Sarcoidosis

“…Diagnosis of CS in histopathology is currently defined by “myocarditis with non‐necrotizing granulomas with macrophages and multinucleated giant cells, surrounded by fibrosis and a lymphocytic infiltrate.” 36 Although not completely understood, the initiation of the inflammatory process appears to be a combination of genetic predisposition and environmental triggers. The current understanding of pathophysiologic pathway of cardiac granuloma formation is depicted in Figure 3 (according to Drent et al 5 and Kato et al 37 ).…”

Cranial cartilages: Players in the evolution of the cranium during evolution of the chordates in general and of the vertebrates in particular

“…Cartilage is a special type of fibrous connective tissue that is both elastic and stiff. Similar to other connective tissues, cartilage is composed of cells, called cartilage cells, and intercellular substances, called cartilage matrix (Ito, 2005). In humans, there are three types of cartilage: hyaline, elastic, and fibrocartilage.…”

“…In hyaline cartilage, which first forms in place of bone during ontogeny, chondrocytes are spherical or oval in shape, and a few chondrocytes are enclosed in the lacuna cartilaginea (a small cavity in the cartilage matrix). Fibrous connective tissue develops at the margins where fibroblasts are well‐developed (Ito, 2005). Additionally, in hyaline cartilage, the cartilage matrix consists of fibrils (e.g., type II collagen) and amorphous ground substances (e.g., proteoglycan).…”

“…Additionally, in hyaline cartilage, the cartilage matrix consists of fibrils (e.g., type II collagen) and amorphous ground substances (e.g., proteoglycan). Proteoglycans contain mucopolysaccharides, including mucopolysaccharide chondroitin, keratan sulfate, and chondronectin (Ito, 2005). Elastic cartilage is considered to be transformed hyaline cartilage (Ito, 2005).…”

Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis

“…Non-necrotic granulomas per se signify sarcoidosis only if other causes are excluded. 4 , 5 Recently, indirect EMB signs of CS have been suggested, 102 , 103 including small collections of histiocytes (‘microgranulomas’), lymphangiogenesis, and confluent fibrosis with fatty change.…”