Lymph Vessel Proliferation on Cardiac Biopsy May Help in the Diagnosis of Cardiac Sarcoidosis

BACKGROUND: The diagnosis of cardiac sarcoidosis (CS) is challenging because endomyocardial biopsy has only a 20% to 30% sensitivity rate for diagnosis and it presents with similar clinical features of idiopathic dilated cardiomyopathy (DCM). Lymphatic vessel proliferation in pulmonary sarcoidosis has been previously demonstrated. In this study, we compared endomyocardial biopsy samples obtained from patients with CS and DCM to determine whether lymph vessel counts using D2‐40 immunostaining can be utilized as a complementary tool to distinguish CS from DCM. METHODS AND RESULTS: Endomyocardial biopsy tissues were obtained from 62 patients with CS (30 patients with a diagnosis made histologically, 32 patients with a diagnosis made clinically), and hematoxylin/eosin, Masson trichrome, and D2‐40 immunostaining were performed. Their results were compared with those from 53 patients with DCM. The histological CS group showed significantly increased lymphatic vessels (12.0 [4.0–40.0] versus 2.6 [1.9–3.4], P<0.0001) and more severe mosaic fibrosis (P<0.0001) compared with the DCM group. The optimal threshold was 7.5 lymphatic vessels, and this resulted in a sensitivity of 0.67 and specificity of 0.96. The clinical CS group diagnosed according to Japanese Circulation Society 2016 criteria showed increased lymphatic vessels (4.0 [3.3–9.0] versus 2.6 [1.9–3.4], P<0.0001), more severe mosaic fibrosis (P<0.0001), more inflammatory cell infiltration (53% versus 0%, P<0.0001), and fatty infiltration within fibroblasts (50% versus 17%, P=0.0012) compared with the DCM group. The optimal threshold of lymphatic vessels was 3.5, which resulted in a sensitivity of 0.75 and specificity of 0.68. CONCLUSIONS: Lymphatic vessel counts using D2‐40 immunostaining may help to distinguish clinical CS without granuloma from DCM.