Cardiovascular PathologyPub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.carpath.2025.107763
Sarah Parsons, Hans H de Boer
{"title":"The SCVP and AECVP 'Seaport criteria' for lymphocytic myocarditis: Retrospective application to an autopsy cohort.","authors":"Sarah Parsons, Hans H de Boer","doi":"10.1016/j.carpath.2025.107763","DOIUrl":"10.1016/j.carpath.2025.107763","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing lymphocytic myocarditis in non-biopsy specimens remains challenging due to sampling variability, subjective interpretation of histology, and lack of standardized criteria. In 2025, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) proposed the \"Seaport criteria\" to address these limitations.</p><p><strong>Objective: </strong>To assess the practical applicability of the Seaport criteria in a retrospective cohort of forensic autopsy cases with myocardial lymphocytic-predominant inflammation.</p><p><strong>Methods: </strong>Ninety-three autopsy cases with lymphocytic-predominant myocardial inflammation were re-evaluated according to the Seaport criteria. Death in these cases was attributed to myocarditis (n = 45), unascertained causes (n = 34), or drug toxicity (n = 14). We assessed adherence to the recommended technical requirements, reclassified inflammation as diffuse, multifocal, focal myocarditis, or lymphocytic infiltrates of unknown significance (LIUS), and reviewed the original histological descriptions.</p><p><strong>Results: </strong>Most cases (82 %) met the minimum technical sampling standards. Pediatric cases were disproportionately non-compliant with sampling requirements, but not due to insufficient myocardium being sampled. Original histological reporting varied substantially in terminology and detail, with myocyte injury inconsistently reported and a lack of sufficient information for grading under the Seaport criteria. Re-classification resulted in 36 cases of diffuse, 27 multifocal, 2 focal myocarditis, and 28 LIUS. The most common diagnosis in cases given myocarditis as the cause of death was diffuse myocarditis (33/45), whereas LIUS was most frequent in the drug-related and unascertained cohorts. Myocyte injury was sometimes difficult to interpret.</p><p><strong>Conclusions: </strong>The Seaport criteria are feasible to classify lymphocytic myocarditis in autopsy hearts, with potential to standardize histological assessment and therefore improve diagnostic consistency. However, challenges remain in recognizing myocyte injury. Further prospective multicenter validation is recommended.</p>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":" ","pages":"107763"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Greta Verena Freundt, Friedrich Alexander von Samson-Himmelstjerna, Jan-Thorge Nitz, Frederik Stelter, Norbert Frey, Mark Luedde, Michael R Preusch, Hans-Jörg Hippe
{"title":"The orphan receptor GPRC5B promotes macrophage infiltration and an inflammatory plaque phenotype in atherosclerosis.","authors":"Greta Verena Freundt, Friedrich Alexander von Samson-Himmelstjerna, Jan-Thorge Nitz, Frederik Stelter, Norbert Frey, Mark Luedde, Michael R Preusch, Hans-Jörg Hippe","doi":"10.1016/j.carpath.2025.107784","DOIUrl":"https://doi.org/10.1016/j.carpath.2025.107784","url":null,"abstract":"<p><strong>Background and aims: </strong>Atherosclerosis is driven by chronic inflammation of the vascular wall, in which macrophages play a central role. The orphan G protein-coupled receptor GPRC5B is expressed in vascular cells and macrophages and is upregulated during monocyte-to-macrophage differentiation. It has been shown to activate NFκB-dependent inflammatory pathways in adipose tissue and glomeruli. Here, we investigated the impact of GPRC5B on macrophage infiltration and the progression of atherosclerotic plaque development in vivo.</p><p><strong>Methods: </strong>Bone marrow from heterozygous GPRC5B-transgenic C57BL/6 mice and wild-type controls was transplanted into lethally irradiated LDL receptor-deficient mice. Animals were fed a Western-type diet for 16 weeks, after which atherosclerotic lesions in the aortic sinus were analyzed.</p><p><strong>Results: </strong>Mice receiving GPRC5B-transgenic bone marrow showed no significant differences in serum lipids or cardiac mass indices. However, they exhibited significantly increased macrophage infiltration within atherosclerotic plaques and a non-significant trend toward larger and more complex lesions.</p><p><strong>Conclusions: </strong>GPRC5B overexpression in bone marrow-derived monocyte/macrophage lineage cells promotes a more inflammatory plaque phenotype, characterized by enhanced macrophage infiltration. These findings highlight GPRC5B as a potential modulator of plaque progression and suggest it may represent a novel therapeutic target in vascular inflammation and atherosclerosis.</p>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":" ","pages":"107784"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengxue Zhang , Yan Zhou , Chrystalle Katte Carreon , Ann Nguyen , Tiana Riley , Aliya N. Husain , Huihua Li
{"title":"Clinical significance of C4d positivity within the first month after heart transplantation in detecting antibody-mediated rejection on endomyocardial biopsies","authors":"Mengxue Zhang , Yan Zhou , Chrystalle Katte Carreon , Ann Nguyen , Tiana Riley , Aliya N. Husain , Huihua Li","doi":"10.1016/j.carpath.2025.107783","DOIUrl":"10.1016/j.carpath.2025.107783","url":null,"abstract":"<div><h3>Background</h3><div>The pathologic definition for antibody-mediated rejection (AMR) includes both histopathological and immunopathological components. C4d is the most validated diagnostic marker for immunopathologic AMR; however, the clinical significance of early C4d positivity (≤1 month post-transplant) on endomyocardial biopsies (EMBs) is unknown.</div></div><div><h3>Methods</h3><div>Patients who had ≥1 episode of C4d-positive EMB within the first month after heart transplantation were selected, the coexistence with acute cellular rejection (ACR) and the correlations of C4d positivity with histopathologic features of AMR, clinical graft dysfunction, presence of donor specific antibodies (DSAs), and clinical outcomes were examined.</div></div><div><h3>Results</h3><div>112 EMBs from 46 patients were qualified and included in the study. 19 patients had single C4d-positive EMB whereas 27 patients developed multiple (2-4) episodes of C4d positivity within the first month. 40 % of C4d-positive EMBs showed concurrent ACR (26 with G1R, 6 with G2R). The C4d positivity correlated well with the histopathologic AMR, with 73 % of C4d-positive EMBs showing all or partial histologic features of AMR. Only 29 % of the C4d-positive EMBs were associated with clinical graft dysfunction, indicating that most early C4d-positive EMBs were clinically asymptomatic. DSAs were found positive in 28 patients (61 %), with preformed DSAs being more common than de novo DSAs. Although no cardiac allograft vasculopathy was observed in any patient, two pediatric patients died of AMR shortly after transplantation whereas three adult patients passed away mostly because of infection.</div></div><div><h3>Conclusion</h3><div>Heart transplant recipients with C4d-positive EMBs within the first month post-transplant were mainly asymptomatic; combined evaluation including clinical, pathological, and serological testing should be conducted for the best management of AMR.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107783"},"PeriodicalIF":1.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Giovanni Maria Lancisi (1654-1720) and the first historical investigation on pathology of sudden death","authors":"Daniela Marrone , Cristina Basso , Gaetano Thiene","doi":"10.1016/j.carpath.2025.107780","DOIUrl":"10.1016/j.carpath.2025.107780","url":null,"abstract":"<div><div>Between 1705 and 1706, Rome experienced a series of sudden deaths, prompting Pope Clement XI to set up a commission to investigate the causes. Giovanni Maria Lancisi, a prominent physician, oversaw forensic autopsies and wrote “De subitaneis mortibus” (“On Sudden Deaths”, 1708), a groundbreaking treatise that examined death through a mechanistic lens, offering both theoretical and practical insights. Lancisi’s book presented life as a dynamic interaction of bodily fluids and systems, with death defined as the cessation of these movements. He proposed that sudden death is not rare but a natural endpoint when life-sustaining processes abruptly cease. The treatise identified various causes of sudden death, involving heart and vessels, and debunked fears of an ongoing epidemic in Rome. By analyzing cadaveric lesions, Lancisi demonstrated that these deaths were primarily due to pre-existing morbid conditions. His observations advanced the emerging field of pathological anatomy, applying scientific method on the study of sudden death.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107780"},"PeriodicalIF":1.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aortic regurgitation as a cause of sudden cardiac death with aortic and left ventricular remodelling - the role of the bicuspid valve","authors":"Lauren Moran, Joseph Westaby, Mary N. Sheppard","doi":"10.1016/j.carpath.2025.107781","DOIUrl":"10.1016/j.carpath.2025.107781","url":null,"abstract":"<div><h3>Background and objective</h3><div>Aortic regurgitation (AR) results in blood flow from the aorta back into the left ventricle, which leads to left ventricular hypertrophy and dilation which, in a clinical setting, leads to heart failure and death. However, it is not a well-recognised cause of sudden cardiac death (SCD).</div></div><div><h3>Methods</h3><div>We identified 10 cases of AR with no other cause of death from our database of 8,551 cases of SCD. All these cases had a full autopsy with negative toxicology. Diagnosis of AR was based upon the presence of prominent ridges on the edge of the aortic valve (AV) cusps with aortic root dilatation, and no significant calcification within the cusps. We measured heart weight, circumference of aortic annulus and ascending aorta, diameter of left ventricle, and circumferential left ventricle wall thickness prospectively. Cases were age and sex matched 2:1 to individuals with morphologically normal hearts with normal aortic valves.</div></div><div><h3>Results</h3><div>Age was 43±14 years, with 7 males and 3 females in the AR group, and 14 males and 6 females in the control group. Heart weight was significantly higher in individuals with AR compared to controls (642±200g vs 370±75g, p<0.001). All cases showed thick regurgitant ridges on the edges of all valvular leaflets macroscopically. The aortic annulus circumference (73±14mm vs 54±7mm, p<0.001) and the circumference of the ascending aorta (85±27mm vs 56±7mm, p<0.001) were significantly dilated in AR. The left ventricular cavity diameter was significantly larger in AR (52±15mm vs 30±8mm, p<0.001). There was no significant difference seen in maximal wall thickness of the left ventricle (16±6mm vs 14±2mm, p=0.068). 7 out of 10 AR cases had bicuspid aortic valves (70%) while two were rheumatic and one just had a dilated aorta. Microscopically, left ventricular fibrosis was seen in 7 of the AR cases (70%).</div></div><div><h3>Discussion</h3><div>AR is a rare cause of SCD, most commonly associated with bicuspid aortic valve. It can be recognised by prominent ridges on the AV cusps and/or thickening of the cusp free margin with aortic annular dilatation. It is only considered significant as a cause of death when found with increased heart weight, left ventricular dilatation, and/or ventricular fibrosis in the absence of other cardiac pathology. We demonstrate that there is a strong association between BAV, AR and SCD. As BAV is a congenital condition, clinical or surgical intervention could potentially prevent subsequent cardiac enlargement and fibrosis, thereby preventing SCD.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107781"},"PeriodicalIF":1.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan M. Federspiel , Jan-Christian Reil , Peter H. Schmidt , Paul Teping , Frank Ramsthaler , Tanja Schwab , Hans-Joachim Schäfers
{"title":"Aortic valve morphology rather than aortic valve function, aortic dilatation, and age interferes with ascending aortic structural and biomechanical properties","authors":"Jan M. Federspiel , Jan-Christian Reil , Peter H. Schmidt , Paul Teping , Frank Ramsthaler , Tanja Schwab , Hans-Joachim Schäfers","doi":"10.1016/j.carpath.2025.107782","DOIUrl":"10.1016/j.carpath.2025.107782","url":null,"abstract":"<div><div>Aortic valve (AV) malformation and AV malfunction have been linked to aortic wall degeneration. Studies concomitantly assessing AV morphology, AV function, age, ascending aortic dilatation, and aortic biomechanical properties are lacking. This exploratory study aims to close this gap. Surgical samples of the ascending aorta (n=102) were histologically assessed. Based on echocardiographic studies, the elastic modulus (slope stress-strain curve) was calculated. Patient characteristics were collected from the patient charts. Samples obtained during autopsy (n=10) served as reference for the microscopic analysis. The patient characteristics, structural aortic wall changes, and biomechanical wall properties were statistically explored using comparative analyses and a Spearman correlation matrix. Marked medial degeneration was found significantly earlier in life for unicuspid AV morphology compared to bicuspid and tricuspid AV. Significantly fewer lamellar units and thinner aortic walls were found in surgical samples compared to the reference group regardless of AV morphology, AV function, age, and aortic dilatation. Adventitial structural impairment was associated with stiffer aortic walls. Hints were found that AV morphology (rather than AV function, age, and presence/absence of aortic dilatation) affects structural and functional ascending aortic wall properties. Additionally, the observations suggest more advanced aortic degeneration in association with unicuspid AV, underpin the need for non-surgical control samples in surgical pathological studies, and highlight the importance of the adventitial layer for aortic biomechanics.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107782"},"PeriodicalIF":1.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David S. Katzianer , Deborah H. Kwon , Maran Thamilarasan , J. Emanuel Finet , Wael Jaber , Milind Desai , Nicholas Smedira , E. Rene Rodriguez , Carmela D. Tan , Mazen Hanna
{"title":"Prevalence of amyloid deposition in patients undergoing surgical myectomy for presumed hypertrophic cardiomyopathy","authors":"David S. Katzianer , Deborah H. Kwon , Maran Thamilarasan , J. Emanuel Finet , Wael Jaber , Milind Desai , Nicholas Smedira , E. Rene Rodriguez , Carmela D. Tan , Mazen Hanna","doi":"10.1016/j.carpath.2025.107779","DOIUrl":"10.1016/j.carpath.2025.107779","url":null,"abstract":"<div><h3>Background</h3><div>Cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) share the phenotypic characteristic of increased left ventricular wall thickness and, while more common with HCM, both conditions can result in dynamic left ventricular outflow (LVOT) obstruction. We sought to examine the incidence of amyloid deposition in myectomy specimens at a high-volume center for surgical myectomy and describe the pathologic characteristics and patient population.</div></div><div><h3>Methods and Results</h3><div>We reviewed the surgical myectomy database at our institution and found a total of 27 of 3,292 (0.8 %) with cardiac amyloidosis on pathologic examination of myectomy specimens. Many of these had preoperative imaging features consistent with hypertrophic cardiomyopathy with asymmetric hypertrophy and LVOT obstructive physiology.</div></div><div><h3>Conclusion</h3><div>Nearly 1 % of patients referred for surgical myectomy were found to have unexpected amyloid deposits on pathologic examination. Recognition of this finding, although very infrequent, is important for long-term management of these patients.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107779"},"PeriodicalIF":1.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}