Archives of pathology & laboratory medicine最新文献

Context.—: Anatomic pathology as a subspecialty has been invaluable in understanding emerging and reemerging infectious diseases throughout many outbreaks and pandemics.

Objective.—: To describe the contributions of the Archives of Pathology & Laboratory Medicine to understanding emerging infections.

Data sources.—: Medical literature and periodicals.

Conclusions.—: The Archives has a long tradition of supporting significant anatomic pathology research into these diseases through timely publishing of original research articles, patient cases, histopathology findings, reviews, and commentaries of public health importance. This was highlighted during the 1976 Legionnaires' disease outbreak in Philadelphia, when the Archives published the first description of the pathologic findings of Legionnaires' disease based on an autopsy study of 26 persons who had died from the novel infection. In that article, John Blackmon, Martin Hicklin, and Francis Chandler at the Centers for Disease Control and Prevention described the pathologic findings of severe pneumonia in all patients and were able to visualize the causative bacillus. The Archives continued to address the importance of emerging infections by publishing a special issue in February 1996 entitled "Emerging and Reemerging Global Microbial Threats." With the increasing importance of emerging infections, a second special issue on this topic was published in August 1997 entitled "Emerging and Reemerging Infectious Diseases." In response to the Zika virus outbreak that began in Brazil in 2015, the Archives became the first peer-reviewed journal to devote a special issue to this emerging viral infection that was causing fetal deaths and congenital malformations, entitled "The Zika Virus Global Pandemic: The Latest Emerging Infection." During the global COVID-19 pandemic, the Archives continued to publish timely articles addressing many important issues about SARS-CoV-2 infections.

Context.—: As part of the 100th anniversary of Archives of Pathology & Laboratory Medicine, we revisit a seminal article published by Juan Rosai, MD, and Ronald Dorfman, MBBCh, FRCPath, in this journal in 1969. This is one of the initial series describing the entity now known as Rosai-Dorfman-Destombes disease (RDD), following the case series of the French pathologist Pierre-Paul Louis Lucien Destombes, MD, which describes a striking but enigmatic entity that now bears their names. Rosai and Dorfman described this process using the moniker sinus histiocytosis with massive lymphadenopathy, with presentation in pediatric and young adults, with massive, painless cervical lymphadenopathy and a benign, but potentially protracted course. Histiocytes show characteristic cytomorphologic features (making it one of the most beloved entities by pathologists and board examiners alike), including round, hypochromatic nuclei with prominent nucleoli and abundant pale eosinophilic cytoplasm, with trafficking of inflammatory elements termed emperipolesis.

Objective.—: To review the historical context surrounding the recognition of RDD and key clinicopathologic and molecular features.

Data sources.—: Historical papers as well as more recent studies advancing our understanding of RDD were identified from the literature, using PubMed and other search engines.

Conclusions.—: RDD remains a potentially challenging entity for diagnosis and treatment given variation in presentation, morphologic features, and often a lack of known molecular drivers, which may occur in isolation or in patients with altered immune function, germline disorders, or other neoplastic conditions.

Context.—: Gastric intestinal metaplasia is a recognized precursor and risk factor to gastric cancer, and correct diagnosis is required for clinical decision-making.

Objective.—: To evaluate potential missed intestinal metaplasia diagnoses and develop automated approaches to quantification, we developed an artificial intelligence pipeline for review of both whole slide images and pathology reports.

Design.—: A patch-based classifier was trained and applied to 1935 gastric biopsy specimens. Specimens with disagreement between the artificial intelligence pipeline and the clinical pathology report were reviewed by 3 pathologists who were blinded to the diagnoses.

Results.—: Following review, 30 of 297 apparently "false-positive" artificial intelligence detections were determined to represent undetected intestinal metaplasia. The artificial intelligence quantification of intestinal metaplasia strongly agreed with human scoring (Spearman rank correlation coefficient, 0.90; P < .001). Finally, a large language model-based evaluation of pathology report text showed near perfect ability to categorize reports as positive or negative for intestinal metaplasia (99.3% of specimens) with a few reports evaluated as equivocal (0.7%).

Conclusions.—: An artificial intelligence-based quality assurance pipeline could detect missed intestinal metaplasia in as many as 1.5% of gastric biopsy specimens, highlighting a potentially addressable diagnostic gap. An automated pipeline could additionally provide quantitative information that could be informative for management.

Context.—: Effective pathology report feedback is vital for trainee education but is often limited by information technology systems that lack integrated educational support. Most laboratory information systems do not retain resident draft reports after report finalization and lack workflows for structured feedback, hindering self-assessment and progress tracking.

Objective.—: To develop and implement a feedback system that allows pathology trainees to compare their preliminary diagnostic reports with finalized faculty reports and corresponding digital slides.

Design.—: A custom feedback system was developed, integrating with Cerner Millennium (laboratory information system) and the Paige digital pathology platform. Trainees flagged cases by simulating a report finalization command, which stored their preliminary diagnosis. An automated report compared the resident and faculty diagnoses side by side and included direct links to the relevant digital slides. A total of 3854 cases from 13 trainees were analyzed for diagnostic concordance, categorized as accurate, mostly accurate, partially accurate, or inaccurate.

Results.—: Overall diagnostic accuracy was 68.8% (2650 of 3854), increasing to 86.1% (3317 of 3854) when "mostly accurate" cases were included. Accuracy varied by trainee (range, 55.5% [238 of 429]-78.3% [553 of 706]) and organ system (highest in neuropathology at 83.8% [31 of 37], lowest in placenta at 46% [46 of 100]). System usage also varied, with some trainees reviewing more than 700 cases and others fewer than 10. Report comparison allowed for assessment of both diagnostic accuracy and report quality.

Conclusions.—: This integrated feedback system enables scalable, trainee-centered evaluation of diagnostic performance and report writing, fostering reflective learning in daily practice. The database generated through this system further provides opportunities for deeper data exploration, identification of educational trends, and development of competency-based assessment frameworks.

Context.—: Training the next generation of pathologists is vital for high-quality clinical medicine. Competency-Based Medical Education (CBME) and accumulation of "Entrustable Professional Activities" (EPAs) are being implemented worldwide to standardize medical training in all specialties. However, CBME research specific to pathology is lacking. Surveys of training programs routinely using EPAs highlight challenges with administrative burden, completion rates, and feedback.

Objective.—: To investigate the impact of EPAs on workload and feedback in a pathology program after 5 years of implementation.

Design.—: A cross-sectional survey was administered to residents in the Diagnostic and Molecular (Anatomical) Pathology program at the University of Toronto, which transitioned to an EPA-based CBME system in 2019.

Results.—: The response rate was 83% (n = 25 of 30). More than half of responding residents submitted at least 4 EPAs per week (52%; n = 13), and most residents (76%; n = 19) estimated spending at least a half hour per week submitting and following up on EPAs. Most residents (92%; n = 23) disagreed with the statement that EPAs provided valuable feedback to their learning; however, all residents (100%; n = 25) agreed verbal feedback at sign-out was one of the most useful assessments of their abilities. Only a minority (36%; n = 9) regularly received verbal feedback alongside an EPA. Respondents overwhelmingly felt that EPAs had a negative effect on the rapport between staff and residents, and cited concerns about staff workloads.

Conclusions.—: This study is the first to quantify the workload associated with CBME in a pathology residency program and raises practical considerations for training programs considering implementation of EPAs.

Context.—: The Becton Dickinson BACTEC blood culture media bottle shortage led hospitals to create a mitigation strategy to conserve bottles while ensuring a high quality of care.

Objective.—: To describe how our existing framework of teams was able to quickly pivot to implement conservation strategies without negatively impacting patient care.

Design.—: A team implemented various mitigation measures based on current inventory, which included education, leveraging electronic medical record guidance and alerts with evidence-based information on appropriate ordering, alternative sources of supply, and real-time dashboards to inform next steps.

Results.—: Implementation of educational efforts and alerts resulted in more than 22 000 blood cultures avoided in 6 months, with an increase in blood culture positivity rates by 25%. We did not see any adverse events that impacted the quality of patient care. We observed cost savings of nearly $200 000 in 2024 with these measures.

Conclusions.—: Handling widespread shortages in situations of single suppliers requires rapid assembly of key stakeholders with decision-making authority and support of executive leadership. Existing frameworks of experienced teams quickly assessed the situation, worked on mitigation measures, predicted future challenges, and implemented alternatives to ensure patient care was not disrupted.

Context.—: Drug-induced autoimmune-like hepatitis (DI-ALH) and idiopathic autoimmune hepatitis (iAIH) share similar clinical, biochemical, serologic, and histologic features. Differentiating between them is crucial for treatment and prognosis.

Objective.—: To identify clinical and histologic factors that distinguish DI-ALH from iAIH and develop a predictive scoring algorithm.

Design.—: We evaluated diagnostic laboratory data and histologic features from index liver biopsies of 14 well-characterized DI-ALH cases and compared them with those from 19 age- and sex-matched iAIH cases. Data included age, sex, autoantibodies (anti-nuclear antibody, anti-smooth muscle antibody), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase, immunoglobulin G, and total bilirubin (T. Bili). Histologic evaluation included modified Ishak scores, histologic activity index (HAI), type of portal inflammation, zonality of lobular inflammation, plasma cell clusters, cholestasis, bile duct damage, ballooning degeneration, portal endothelialitis, central venulitis, ceroid macrophages, lobular disarray, polyglucosan inclusions, bile duct loss, and ductular reaction. Fibrosis was assessed by using the Scheuer and Ishak systems.

Results.—: A scoring algorithm with weighted scores for ALT above 289.5 U/L, AST above 303.5 U/L, ALP above 119.5 U/L, T. Bili above 0.65 mg/dL, HAI above 9.5, zone 2 sparing, lobular disarray, ballooning degeneration, ceroid macrophages, central venulitis, and advanced Ishak fibrosis yielded a receiver operating characteristic area under the curve of 0.99, with an optimal cutoff score of 6.5 favoring DI-ALH.

Conclusions.—: A scoring algorithm that incorporates specific liver biopsy findings, HAI, and liver biochemistry profiles effectively distinguishes DI-ALH from iAIH.

Context.—: In silico mutagenesis can be performed to introduce variants into next-generation sequencing data. This method holds potential promise for proficiency testing since rare or novel variants can be modeled that are not found in available proficiency testing materials.

Objective.—: To determine whether in silico mutagenesis could be used as a viable proficiency testing methodology for undiagnosed disorders by exome sequencing.

Design.—: Laboratories performed exome sequencing on reference samples and uploaded raw sequence data files to the College of American Pathologists. These files were then mutagenized in silico to introduce variants, including those deemed to be causative for the clinical scenario provided. The laboratories processed the mutagenized files through their bioinformatic pipelines and performed interpretation to identify pathogenic and likely pathogenic primary and secondary findings. Responses were evaluated for concordance with intended responses.

Results.—: A total of 7 educational (nongraded) proficiency testing challenges were performed between 2018 and 2021. An average of 47 laboratories participated in each program, which each containing between 2 to 5 (average = 3.6) intended response variants. Intended response variant types included substitutions and small insertion/deletion variants. Participating laboratories returned 94.3% of intended response variants across all programs on average (per program range, 91.5%-97.3%). The percentage of laboratories that correctly returned all intended response variants for a program ranged from 70.0% to 96.7%.

Conclusions.—: In silico mutagenesis represents a suitable approach for graded intended response-based proficiency testing for exome sequencing that allows laboratories to assess both analytical and interpretative components of the test.

Context.—: Pathology is essential to global health care, yet disparities remain in access to education and training. The College of American Pathologists (CAP) Foundation addresses these gaps through grants and awards that support trainees, early-career pathologists, and initiatives promoting equity worldwide. Since 2015, total funding has increased from $18,400 to $84,098, an astounding 357%.

Objective.—: To evaluate the CAP Foundation Grants and Awards Program during a 10-year period, assessing financial investment, award distribution, recipient characteristics, and impact.

Design.—: A mixed-methods retrospective study integrated (1) quantitative analysis of program data, (2) qualitative feedback from awardees, and (3) a quantitative award impact survey of past CAP Foundation awardees. Variables included demographics, award type, funding amounts, geographic distribution, and career stage. Surveys assessed professional development, mentorship, and long-term engagement with CAP.

Results.—: From 2015 to 2024, a total of 744 applicants submitted 760 applications, resulting in 355 awards across 14 categories. Applications increased more than 8-fold, peaking in 2023, with surges during the COVID-19 pandemic. Medical student applications grew from 1 in 2020 to 17 in 2024 (76% annual growth); 9 of 12 Medical Student Travel Award recipients (75%) entered pathology residency. Geographic disparities were noted, with smaller residency programs showing higher per capita application rates. Among 174 survey respondents, 129 (74%) reported networking benefits, 127 (73%) learning benefits, and 99 (57%) mentorship benefits, though only 49 (28%) sustained long-term mentoring relationships.

Conclusions.—: The CAP Foundation's awards program has expanded access, supported career development, and fostered future pathologists. Strengthening long-term mentorship and bridging education-to-practice gaps may further enhance its impact.

Context.—: Pancreatobiliary maljunction (PBM) is a congenital malformation characterized by the pancreatic and common bile ducts joining anatomically outside the duodenal wall, resulting in the formation of a long common channel. PBM-associated conditions include choledochal cysts and reflux-associated cholecystopathy. Precursor lesions, such as biliary intraepithelial neoplasias, intraductal papillary neoplasms of the bile duct, intracholecystic papillary neoplasms, and cancers associated with PBM, occur in the gallbladder, bile duct, and pancreas. Most PBM cases, along with their associated conditions, precursor lesions, and cancers, have been reported in Asian countries, including Japan and South Korea. However, recent studies have shown no significant difference in frequency between Eastern and Western populations.

Objective.—: To summarize the current understanding of PBMs, as well as recent developments related to associated precursor lesions and cancers.

Data sources.—: To understand the clinicopathologic characteristics of PBMs and their associated precursor lesions and cancers, reports from PubMed (US National Library of Medicine) were reviewed.

Conclusions.—: PBM is a congenital malformation diagnosed primarily by gastroenterologists and radiologists. Pathologists diagnose PBM-associated conditions, including choledochal cysts and reflux-associated cholecystopathy. PBM-related precursor lesions and cancers can develop in the gallbladder, bile duct, and pancreas. Therefore, understanding PBM-associated conditions is crucial for the early detection and effective treatment of patients with PBM-related cancers.