Chambers, Meagan

Context.— The Goldman criteria are widely used to categorize diagnostic discrepancies in autopsy reports for hospital quality assurance. Despite their adoption, little is known about how consistently they are applied across institutions. Objective.— To evaluate the interrater reliability among academic pathologists applying the Goldman criteria to classify missed diagnoses in autopsy cases. Design.— Thirty autopsy cases from 2 academic hospitals were reviewed by 5 experienced autopsy pathologists. Each reviewer independently assigned Goldman classification scores (class I–IV) to missed diagnoses based on the original 1983 definitions. Consensus was defined as at least 60% agreement (≥3 of 5 raters). Fleiss κ and Gwet AC1 were calculated to assess interrater reliability. Results.— A total of 196 missed diagnoses were identified by at least 1 rater. Only 26% (51 of 196) achieved a consensus Goldman classification, and just 4% (8 of 196) had unanimous classification agreement. Most diagnoses (65%; 127 of 196) were not identified by at least 3 raters. Among consensus classification ratings, 49% (25 of 51) were class IV. Fleiss κ was 0.176 (slight agreement) while Gwet AC1 was 0.390 (fair agreement). Collapsing major (classes I–II) and minor (classes III–IV) categories modestly improved agreement. Conclusions.— Interrater agreement in applying the Goldman criteria is only fair to moderate, suggesting significant subjectivity in their application. As the criteria are used for institutional comparison and quality metrics, efforts to standardize definitions and provide reviewer training are warranted to improve reproducibility and utility.

Context.— After-death care can be complicated and time-consuming for clinical staff, and frustrating for bereaved families. Delays and errors can have damaging legal and reputational consequences for hospitals. Offices of Decedent Affairs (ODAs) have been proposed as a solution, and their potential benefits have been described in several single institution reports. The literature lacks a contemporary and comprehensive review of existing ODAs and their approaches. Objective.— To describe the process of establishing a new ODA and to provide a snapshot of the spectrum of structure, function, and impact of existing ODAs in the United States. Design.— A survey was administered to 11 established ODAs spread across the continental United States. Programs were identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. Results.— Eleven ODAs returned the survey, representing more than 190 cumulative years of experience in decedent care in the hospital setting (median, 10 years). There was a wide range in staffing (both staff size and background) as well as scope of services offered. The median ratio of hospital deaths to full-time equivalent (FTE) staffing was 360 deaths per FTE. Respondents reported that ODAs unburden clinical providers and facilitate decedent management. Some respondents reported a quicker turnover of hospital beds and shorter intervals between pronouncement of death and autopsy. ODAs increased autopsy rates when the autopsy services were part of the ODA. Conclusions.— This survey provides practical information for hospitals considering establishing a new ODA and useful benchmarks for existing ODA programs.

Context.— Decedent Affairs Offices and Programs can serve as an avenue to assist medical centers in facilitating efficient and comprehensive decedent management, despite a paucity of literature on their roles, establishment, and efficacy. Objective.— To characterize the motivations and rationales for establishing Decedent Affairs Offices. Design.— A survey was administered to 11 established Decedent Affairs Offices/Programs, identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. The questions comprehensively cover establishment, operations, and outcomes data available by institution. Results.— Survey respondents reported the rationale for starting their programs and the benefits such offices can have. Conclusions.— Decedent Affairs Offices and Programs provide a useful option to medical centers to navigate the increasingly complex task of comprehensive decedent management. The present survey helps to delineate the similarities and differences between these programs at 11 institutions, to aid nascent programs in their establishment and growth over time.

Context.— Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. Objective.— To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms. Design.— One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. Results.— ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. Conclusions.— With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.

Abstract Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called “diffuse hemispheric glioma with H3 p.K28M (K27M) mutation” (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27.