Standardized Diagnosis of Lymphocytic Myocarditis at Autopsy: Application of the Seaport Criteria

Background The histological diagnosis of lymphocytic myocarditis at autopsy is challenged by limited reproducibility and the lack of standardized criteria applicable to non-biopsy specimens. This study aimed to assess the feasibility and diagnostic performance of the new Seaport criteria for autopsy in a heterogeneous cohort of clinical autopsies. Methods An autopsy cohort of 50 consecutive cases was retrospectively revaluated, including 10 sudden death cases originally diagnosed as lymphocytic myocarditis and 40 controls (ischemic heart disease, brain diseases, liver diseases, and metastatic neoplasms). Each case was reclassified according to Seaport criteria as myocarditis (focal, multifocal, or diffuse), lymphocytic infiltrate of uncertain significance (LIUS), or no inflammation. Immunohistochemistry (CD3, CD68, C4d) and molecular testing for viral genome were carried out in myocarditis/LIUS cases. Results By applying the Seaport criteria for autopsy, active lymphocytic myocarditis was confirmed in 9 of 10 originally diagnosed cases, either focal (33%) or multifocal (67%) and never diffuse; one case was reclassified as LIUS. Three additional cases among controls showed LIUS, yielding an overall LIUS prevalence of 8% in the entire series. A subepicardial confluent topography was observed in four myocarditis cases. Temporal assessment revealed subacute forms in 55.6% and acute in 44.4%. Immunohistochemistry confirmed the lymphocytic type, and viral genome was identified in 3/9 myocarditis cases. Conclusions The Seaport criteria are a useful tool in the autopsy setting, supporting a standardized approach to the diagnosis of lymphocytic myocarditis. Refinement of these criteria including topographic distribution of inflammation is warranted. The clinical significance of LIUS remains to be assessed in larger series with clinicopathological correlations.