Pub Date : 2023-09-01DOI: 10.5858/arpa.2022-0131-OA
Sun-Young Jun, Eui-Jin Lee, Sang-Il Kim, Soyeon An
Context.—: The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas. In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted.
Objective.—: To assess TME-based prognostic risk in AC.
Design.—: We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (>5%) in 64 surgically resected ACs. We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS). We also investigated the relationship of TME to MUC5AC expression.
Results.—: TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P = .03), lymphovascular invasion (P = .05), and MUC5AC immunopositivity (P = .02). TME prognostic risk index displayed better predictive ability for both OS (53.9 versus 46.1 versus 42.2) and RFS (24.8 versus 16.9 versus 15.3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = .003) and RFS (P = .03).
Conclusions.—: TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME.
上下文。-:肿瘤微环境中肿瘤-宿主相互作用(tumor-host interaction, TME)影响恶性肿瘤患者的预后。通过肿瘤出芽(BD)和肿瘤浸润淋巴细胞(TIL)评估TME对非壶腹性小肠和结直肠癌患者的预后有影响。在壶腹癌(AC)中,MUC5AC最近被发现是一个重要的预后指标,但关于TME的研究尚未开展。-:评估ac设计中基于tme的预后风险。-:我们基于64例手术切除的癌前浸润性高级别BD (BD3)和间质til高密度(>5%)生成了TME风险指数。我们评估了其对总生存期(OS)和无复发生存期(RFS)的预测价值。我们还研究了TME与MUC5AC表达的关系。-: TME预后风险指数分为低危(BDLow/TILHigh;64人中有26人;41%),中等风险(BDLow/TILLow或BDHigh/TILHigh;23;36%)和高风险(BDHigh/TILLow;15;23%)组。较高的TME预后风险与较高的肿瘤分级(P = .03)、淋巴血管侵犯(P = .05)和MUC5AC免疫阳性(P = .02)相关。TME预后风险指数对OS (53.9 vs 46.1 vs 42.2)和RFS (24.8 vs 16.9 vs 15.3)的预测能力均优于单独使用BD或TIL。在多因素分析中,TME预后风险指数是OS (P = 0.003)和RFS (P = 0.03)的独立预测因子。-:对于AC患者的OS和RFS, TME风险指数联合BD和TIL比单独BD或TIL更能预测预后风险分层。MUC5AC可能调节肿瘤细胞与免疫之间的相互作用,从而增强TME的侵袭性。
{"title":"Tumor Microenvironment Prognostic Risk and Its Association With MUC5AC in Ampullary Carcinoma.","authors":"Sun-Young Jun, Eui-Jin Lee, Sang-Il Kim, Soyeon An","doi":"10.5858/arpa.2022-0131-OA","DOIUrl":"https://doi.org/10.5858/arpa.2022-0131-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas. In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted.</p><p><strong>Objective.—: </strong>To assess TME-based prognostic risk in AC.</p><p><strong>Design.—: </strong>We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (>5%) in 64 surgically resected ACs. We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS). We also investigated the relationship of TME to MUC5AC expression.</p><p><strong>Results.—: </strong>TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P = .03), lymphovascular invasion (P = .05), and MUC5AC immunopositivity (P = .02). TME prognostic risk index displayed better predictive ability for both OS (53.9 versus 46.1 versus 42.2) and RFS (24.8 versus 16.9 versus 15.3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = .003) and RFS (P = .03).</p><p><strong>Conclusions.—: </strong>TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 9","pages":"1060-1074"},"PeriodicalIF":4.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-23DOI: 10.5858/arpa.2022-0410-CP
Allison Cushman-Vokoun, Ryan J Schmidt, Matthew Charles Hiemenz, Mark Fung, Bing Melody Zhang, Georganne Bradshaw, Manish Gandhi, JinJuan Yao, Sophia Yohe, Amy Beckman, Wayne W Grody, Petros Giannikopoulos
Context.—: Gene editing-based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions.
Objective.—: To educate pathologists about gene editing technologies, inform them of potential indications and risks, outline regulatory and practical issues that could affect hospital-based practice and laboratory testing, and advocate that pathologists need to be present at discussions among industry and regulators pertaining to gene editing-based therapies.
Design.—: A Gene Editing Workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop an educational paper to serve as a stimulus to increase pathologist involvement and inquiry in gene editing therapeutic and diagnostic implementation.
Results.—: Through multiple discussions and literature review, the workgroup identified potential gaps in pathologists' knowledge of gene editing. Additional topics that could impact pathology and laboratory medicine were also identified and summarized in order to facilitate pathologists as stakeholders in gene editing therapy administration and monitoring and potential use in diagnostics.
Conclusions.—: Gene editing therapy is a complex but potentially transformative area of medicine. This article serves as an introduction to pathologists to assist them in future discussions with colleagues and potentially identify and alter pathology practices that relate to gene editing.
{"title":"A Primer on Gene Editing: What Does It Mean for Pathologists?","authors":"Allison Cushman-Vokoun, Ryan J Schmidt, Matthew Charles Hiemenz, Mark Fung, Bing Melody Zhang, Georganne Bradshaw, Manish Gandhi, JinJuan Yao, Sophia Yohe, Amy Beckman, Wayne W Grody, Petros Giannikopoulos","doi":"10.5858/arpa.2022-0410-CP","DOIUrl":"https://doi.org/10.5858/arpa.2022-0410-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Gene editing-based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions.</p><p><strong>Objective.—: </strong>To educate pathologists about gene editing technologies, inform them of potential indications and risks, outline regulatory and practical issues that could affect hospital-based practice and laboratory testing, and advocate that pathologists need to be present at discussions among industry and regulators pertaining to gene editing-based therapies.</p><p><strong>Design.—: </strong>A Gene Editing Workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop an educational paper to serve as a stimulus to increase pathologist involvement and inquiry in gene editing therapeutic and diagnostic implementation.</p><p><strong>Results.—: </strong>Through multiple discussions and literature review, the workgroup identified potential gaps in pathologists' knowledge of gene editing. Additional topics that could impact pathology and laboratory medicine were also identified and summarized in order to facilitate pathologists as stakeholders in gene editing therapy administration and monitoring and potential use in diagnostics.</p><p><strong>Conclusions.—: </strong>Gene editing therapy is a complex but potentially transformative area of medicine. This article serves as an introduction to pathologists to assist them in future discussions with colleagues and potentially identify and alter pathology practices that relate to gene editing.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2022-0051-OA
Kris Lami, Andrey Bychkov, Keitaro Matsumoto, Richard Attanoos, Sabina Berezowska, Luka Brcic, Alberto Cavazza, John C English, Alexandre Todorovic Fabro, Kaori Ishida, Yukio Kashima, Brandon T Larsen, Alberto M Marchevsky, Takuro Miyazaki, Shimpei Morimoto, Anja C Roden, Frank Schneider, Mano Soshi, Maxwell L Smith, Kazuhiro Tabata, Angela M Takano, Kei Tanaka, Tomonori Tanaka, Tomoshi Tsuchiya, Takeshi Nagayasu, Junya Fukuoka
Context.—: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability.
Objective.—: To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications.
Design.—: Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes.
Results.—: Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes.
Conclusions.—: Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.
{"title":"Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.","authors":"Kris Lami, Andrey Bychkov, Keitaro Matsumoto, Richard Attanoos, Sabina Berezowska, Luka Brcic, Alberto Cavazza, John C English, Alexandre Todorovic Fabro, Kaori Ishida, Yukio Kashima, Brandon T Larsen, Alberto M Marchevsky, Takuro Miyazaki, Shimpei Morimoto, Anja C Roden, Frank Schneider, Mano Soshi, Maxwell L Smith, Kazuhiro Tabata, Angela M Takano, Kei Tanaka, Tomonori Tanaka, Tomoshi Tsuchiya, Takeshi Nagayasu, Junya Fukuoka","doi":"10.5858/arpa.2022-0051-OA","DOIUrl":"https://doi.org/10.5858/arpa.2022-0051-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability.</p><p><strong>Objective.—: </strong>To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications.</p><p><strong>Design.—: </strong>Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes.</p><p><strong>Results.—: </strong>Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes.</p><p><strong>Conclusions.—: </strong>Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"885-895"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2022-0042-CP
Frederick Inglis Rudolf Eyerer, Georganne Bradshaw, Patricia Vasalos, Jordan Seth Laser, Chung-Che Chang, Annette Sunhi Kim, Damon R Olson, Ronald Joseph Paler, Jason N Rosenbaum, Eric E Walk, Joseph E Willis, Jinjuan Yao, Sophia Louise Yohe
Context.—: Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex, and optimal testing depends on the clinicopathologic scenario.
Objective.—: To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens.
Data sources.—: A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases.
Conclusions.—: As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immunohistochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs.
{"title":"Getting Your Laboratory on Track With Neurotrophic Receptor Tyrosine Kinase.","authors":"Frederick Inglis Rudolf Eyerer, Georganne Bradshaw, Patricia Vasalos, Jordan Seth Laser, Chung-Che Chang, Annette Sunhi Kim, Damon R Olson, Ronald Joseph Paler, Jason N Rosenbaum, Eric E Walk, Joseph E Willis, Jinjuan Yao, Sophia Louise Yohe","doi":"10.5858/arpa.2022-0042-CP","DOIUrl":"https://doi.org/10.5858/arpa.2022-0042-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex, and optimal testing depends on the clinicopathologic scenario.</p><p><strong>Objective.—: </strong>To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens.</p><p><strong>Data sources.—: </strong>A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases.</p><p><strong>Conclusions.—: </strong>As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immunohistochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"872-884"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2022-0158-OA
John Hedgepeth, Cara Randall, Tracie Massey, Christine Bookhout
Context.—: With the adoption of Epic/Beaker at our institution, surgical pathology specimens are assigned a Current Procedural Terminology (CPT) charge code at the time of accessioning, and pathologists have been made responsible for verifying the accuracy of the code before signing out the case.
Objective.—: To determine with what frequency attending pathologists reassigned the correct charge code to a specimen when the code assigned at accessioning was incorrect, as well as to estimate the potential financial impact of missed changes.
Design.—: We reviewed all specimens received for frozen section during a 7-month period, identified specimens where the default charge code that our departmental protocol assigns at frozen section (88305) was incorrect, and assessed the rate of successful code change by pathologists and the potential financial cost of each missed change.
Results.—: Three hundred fifty-two of 2191 frozen section specimens (16%) required a change in the 88305 charge code. The codes for 195 specimens (55%) were correctly changed by the attending pathologist, while 157 (45%) were not changed (149) or were changed to an incorrect charge code (8). Individual pathologist change rates ranged from 0% to 100%, with a mean and median change rate of 43% and 24%, respectively. Using average code reimbursements at our institution, the loss in revenue from the 157 missed and incorrect frozen section changes was estimated at $13 788 ($1970 per month).
Conclusions.—: Pathologists showed highly variable rates of correcting CPT charge codes when the incorrect code had been previously assigned to a case, with associated loss of revenue from missed and incorrect code changes.
{"title":"Pathologist-Verified Billing: Correction Rates of Miscoded Frozen Section Cases.","authors":"John Hedgepeth, Cara Randall, Tracie Massey, Christine Bookhout","doi":"10.5858/arpa.2022-0158-OA","DOIUrl":"https://doi.org/10.5858/arpa.2022-0158-OA","url":null,"abstract":"<p><strong>Context.—: </strong>With the adoption of Epic/Beaker at our institution, surgical pathology specimens are assigned a Current Procedural Terminology (CPT) charge code at the time of accessioning, and pathologists have been made responsible for verifying the accuracy of the code before signing out the case.</p><p><strong>Objective.—: </strong>To determine with what frequency attending pathologists reassigned the correct charge code to a specimen when the code assigned at accessioning was incorrect, as well as to estimate the potential financial impact of missed changes.</p><p><strong>Design.—: </strong>We reviewed all specimens received for frozen section during a 7-month period, identified specimens where the default charge code that our departmental protocol assigns at frozen section (88305) was incorrect, and assessed the rate of successful code change by pathologists and the potential financial cost of each missed change.</p><p><strong>Results.—: </strong>Three hundred fifty-two of 2191 frozen section specimens (16%) required a change in the 88305 charge code. The codes for 195 specimens (55%) were correctly changed by the attending pathologist, while 157 (45%) were not changed (149) or were changed to an incorrect charge code (8). Individual pathologist change rates ranged from 0% to 100%, with a mean and median change rate of 43% and 24%, respectively. Using average code reimbursements at our institution, the loss in revenue from the 157 missed and incorrect frozen section changes was estimated at $13 788 ($1970 per month).</p><p><strong>Conclusions.—: </strong>Pathologists showed highly variable rates of correcting CPT charge codes when the incorrect code had been previously assigned to a case, with associated loss of revenue from missed and incorrect code changes.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"969-973"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9884391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2021-0593-OA
Patrick C Mathias, Sara Khor, Kathryn Harris, Suzanne J Wood, Farhood Farjah
Context.—: Unnecessary laboratory tests are ordered because of factors such as preselected orders on order sets, clinician habits, and trainee concerns. Excessive use of laboratory testing increases patient discomfort via unnecessary phlebotomy, contributes to iatrogenic anemia, increases risk of bloodstream infections, and increases the cost of care.
Objective.—: To address these concerns, we implemented a multilevel laboratory stewardship intervention to decrease unnecessary laboratory testing, measured by laboratory tests per day attributed to service, across 2 surgical divisions with high laboratory use.
Design.—: The multilevel intervention included 5 components: stakeholder engagement, provider education, computerized provider order entry modification, performance feedback, and culture change supported by leadership. The primary outcome of the study was laboratory tests ordered per patient-day. Secondary outcomes included the number of blood draws per patient-day, total lab-associated costs, length of stay, discharge to a nursing facility, 30-day readmissions, and deaths. A difference-in-differences analytic approach assessed the outcome measures in the intervention period, with other surgical services as controls.
Results.—: The primary outcome of laboratory tests per patient-day showed a significant decrease across both thoracic and cardiac surgery services, with between 1.5 and 2 fewer tests ordered per patient-day for both services and an estimated 20 000 fewer tests performed during the intervention period. Blood draws per patient-day were also significantly decreased on the thoracic surgery service but not for cardiac surgery.
Conclusions.—: A multilevel laboratory stewardship intervention targeted to 2 surgical services resulted in a significant decrease in laboratory test use without negatively impacting length of stay, readmissions, or mortality.
{"title":"Evaluation of a Multilevel Laboratory Stewardship Intervention Targeted to Cardiac and Thoracic Surgical Services at an Academic Medical Center.","authors":"Patrick C Mathias, Sara Khor, Kathryn Harris, Suzanne J Wood, Farhood Farjah","doi":"10.5858/arpa.2021-0593-OA","DOIUrl":"https://doi.org/10.5858/arpa.2021-0593-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Unnecessary laboratory tests are ordered because of factors such as preselected orders on order sets, clinician habits, and trainee concerns. Excessive use of laboratory testing increases patient discomfort via unnecessary phlebotomy, contributes to iatrogenic anemia, increases risk of bloodstream infections, and increases the cost of care.</p><p><strong>Objective.—: </strong>To address these concerns, we implemented a multilevel laboratory stewardship intervention to decrease unnecessary laboratory testing, measured by laboratory tests per day attributed to service, across 2 surgical divisions with high laboratory use.</p><p><strong>Design.—: </strong>The multilevel intervention included 5 components: stakeholder engagement, provider education, computerized provider order entry modification, performance feedback, and culture change supported by leadership. The primary outcome of the study was laboratory tests ordered per patient-day. Secondary outcomes included the number of blood draws per patient-day, total lab-associated costs, length of stay, discharge to a nursing facility, 30-day readmissions, and deaths. A difference-in-differences analytic approach assessed the outcome measures in the intervention period, with other surgical services as controls.</p><p><strong>Results.—: </strong>The primary outcome of laboratory tests per patient-day showed a significant decrease across both thoracic and cardiac surgery services, with between 1.5 and 2 fewer tests ordered per patient-day for both services and an estimated 20 000 fewer tests performed during the intervention period. Blood draws per patient-day were also significantly decreased on the thoracic surgery service but not for cardiac surgery.</p><p><strong>Conclusions.—: </strong>A multilevel laboratory stewardship intervention targeted to 2 surgical services resulted in a significant decrease in laboratory test use without negatively impacting length of stay, readmissions, or mortality.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"957-963"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9884392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2022-0193-OA
Arzu Saglam, Kunwar Singh, Jyoti Kumar, Sumanth Gollapudi, Soham Mukherjee, Amol Singh, Alexandra Butzmann, Lawrence Kaplan, Charambalos Andreadis, Weiyun Z Ai, Bita Fakhri, Aleksander Rajkovic, Kwun Wah Wen, Courtney Onodera, Jessica Van Ziffle, Patrick W Devine, Robert S Ohgami
Context.—: Evidence of T-cell clonality is often critical in supporting the diagnosis of a T-cell lymphoma.
Objectives.—: To retrospectively explore the significance of copy number losses at the 14q11.2 T-cell receptor α locus in relation to the presence of a T-cell neoplasm and proportion of T cells by targeted next-generation sequencing.
Design.—: Targeted next-generation sequencing data from 139 tissue biopsies, including T-cell lymphomas, B-cell lymphomas, classic Hodgkin lymphomas, nonhematopoietic malignancies, and normal samples, were reviewed for copy number losses involving the T-cell receptor α gene segments at chr14q11.2.
Results.—: We found that biallelic or homozygous deletion of 14q11.2 was found in most (28 of 33, 84.8%) T-cell lymphomas. The magnitude of 14q11.2 loss showed a statistically significant correlation with the proportion of T cells in lymphoma tissue samples. Copy number losses could also be detected in other lymphomas with high numbers of T cells (8 of 32, 25% of B-cell lymphomas, 4 of 4 classical Hodgkin lymphomas), though biallelic/homozygous deletion of 14q11.2 was not significantly observed outside of T-cell lymphomas. Most nonhematopoietic neoplasms and normal tissues (59 of 64, 92.2%) showed no significant copy number losses involving the T-cell receptor α locus at chr14q11.2.
Conclusions.—: Analysis of copy number losses at the T-cell receptor α locus chr14q11.2 with targeted next-generation sequencing can potentially be used to estimate the proportion of T cells and detect T-cell neoplasms.
{"title":"Copy Number Loss at Chromosome 14q11.2 Correlates With the Proportion of T Cells in Biopsies and Helps Identify T-Cell Neoplasms.","authors":"Arzu Saglam, Kunwar Singh, Jyoti Kumar, Sumanth Gollapudi, Soham Mukherjee, Amol Singh, Alexandra Butzmann, Lawrence Kaplan, Charambalos Andreadis, Weiyun Z Ai, Bita Fakhri, Aleksander Rajkovic, Kwun Wah Wen, Courtney Onodera, Jessica Van Ziffle, Patrick W Devine, Robert S Ohgami","doi":"10.5858/arpa.2022-0193-OA","DOIUrl":"https://doi.org/10.5858/arpa.2022-0193-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Evidence of T-cell clonality is often critical in supporting the diagnosis of a T-cell lymphoma.</p><p><strong>Objectives.—: </strong>To retrospectively explore the significance of copy number losses at the 14q11.2 T-cell receptor α locus in relation to the presence of a T-cell neoplasm and proportion of T cells by targeted next-generation sequencing.</p><p><strong>Design.—: </strong>Targeted next-generation sequencing data from 139 tissue biopsies, including T-cell lymphomas, B-cell lymphomas, classic Hodgkin lymphomas, nonhematopoietic malignancies, and normal samples, were reviewed for copy number losses involving the T-cell receptor α gene segments at chr14q11.2.</p><p><strong>Results.—: </strong>We found that biallelic or homozygous deletion of 14q11.2 was found in most (28 of 33, 84.8%) T-cell lymphomas. The magnitude of 14q11.2 loss showed a statistically significant correlation with the proportion of T cells in lymphoma tissue samples. Copy number losses could also be detected in other lymphomas with high numbers of T cells (8 of 32, 25% of B-cell lymphomas, 4 of 4 classical Hodgkin lymphomas), though biallelic/homozygous deletion of 14q11.2 was not significantly observed outside of T-cell lymphomas. Most nonhematopoietic neoplasms and normal tissues (59 of 64, 92.2%) showed no significant copy number losses involving the T-cell receptor α locus at chr14q11.2.</p><p><strong>Conclusions.—: </strong>Analysis of copy number losses at the T-cell receptor α locus chr14q11.2 with targeted next-generation sequencing can potentially be used to estimate the proportion of T cells and detect T-cell neoplasms.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"940-948"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2021-0517-OA
Gerard Frigola, Marco Bühler, Marta Marginet, Anna Enjuanes, Ferran Nadeu, Natalia Papaleo, Marta Salido, Eugenia Haralambieva, José Alamo, Federico Garcia-Bragado, Ramiro Álvarez, Rafael Ramos, Iban Aldecoa, Elías Campo, Lluis Colomo, Olga Balagué
Context.—: Despite their stromal origin, follicular dendritic cells (FDCs) share many functions with hematopoietic system cells. FDC neoplasms are currently classified by the World Health Organization along with those of a histiocytic nature. However, the molecular alterations driving oncogenesis in FDC sarcomas (FDCSs) are beginning to be unveiled and do not seem to concur with those described in histiocytic neoplasms, namely MAPK pathway activation.
Objective.—: To identify molecular alterations driving tumorigenesis in FDCS.
Design.—: We investigated the role of MYC and TP53 in FDC-derived tumor oncogenesis and assessed comprehensively the status of the MAPK pathway in 16 FDCSs, 6 inflammatory pseudotumor (IPT)-like FDCSs, and 8 IPTs.
Results.—: MYC structural alterations (both amplifications and rearrangements) were identified in 5 of 14 FDCSs (35.7%), all associated with MYC overexpression. TP53 mutations were identified in 4 of 14 FDCSs (28.6%), all of which displayed intense and diffuse p53 expression. None of these alterations were identified in any IPT-like FDCSs or in IPT cases. No MAPK pathway gene alterations were identified in any of the cases studied.
Conclusions.—: The presence of MYC and TP53 alterations and the lack of association with Epstein-Barr virus segregate classical FDCS from IPT-like FDCS, pointing at different oncogenic mechanisms in both entities. Our results suggest a possible oncogenic role of MYC and TP53 alterations in FDCS. The absence of MAPK pathway alterations confirms the lack of a significant role of this pathway in the oncogenesis of FDC-derived neoplasms.
{"title":"MYC and TP53 Alterations but Not MAPK Pathway Mutations Are Common Oncogenic Mechanisms in Follicular Dendritic Cell Sarcomas.","authors":"Gerard Frigola, Marco Bühler, Marta Marginet, Anna Enjuanes, Ferran Nadeu, Natalia Papaleo, Marta Salido, Eugenia Haralambieva, José Alamo, Federico Garcia-Bragado, Ramiro Álvarez, Rafael Ramos, Iban Aldecoa, Elías Campo, Lluis Colomo, Olga Balagué","doi":"10.5858/arpa.2021-0517-OA","DOIUrl":"https://doi.org/10.5858/arpa.2021-0517-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Despite their stromal origin, follicular dendritic cells (FDCs) share many functions with hematopoietic system cells. FDC neoplasms are currently classified by the World Health Organization along with those of a histiocytic nature. However, the molecular alterations driving oncogenesis in FDC sarcomas (FDCSs) are beginning to be unveiled and do not seem to concur with those described in histiocytic neoplasms, namely MAPK pathway activation.</p><p><strong>Objective.—: </strong>To identify molecular alterations driving tumorigenesis in FDCS.</p><p><strong>Design.—: </strong>We investigated the role of MYC and TP53 in FDC-derived tumor oncogenesis and assessed comprehensively the status of the MAPK pathway in 16 FDCSs, 6 inflammatory pseudotumor (IPT)-like FDCSs, and 8 IPTs.</p><p><strong>Results.—: </strong>MYC structural alterations (both amplifications and rearrangements) were identified in 5 of 14 FDCSs (35.7%), all associated with MYC overexpression. TP53 mutations were identified in 4 of 14 FDCSs (28.6%), all of which displayed intense and diffuse p53 expression. None of these alterations were identified in any IPT-like FDCSs or in IPT cases. No MAPK pathway gene alterations were identified in any of the cases studied.</p><p><strong>Conclusions.—: </strong>The presence of MYC and TP53 alterations and the lack of association with Epstein-Barr virus segregate classical FDCS from IPT-like FDCS, pointing at different oncogenic mechanisms in both entities. Our results suggest a possible oncogenic role of MYC and TP53 alterations in FDCS. The absence of MAPK pathway alterations confirms the lack of a significant role of this pathway in the oncogenesis of FDC-derived neoplasms.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"896-906"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2021-0587-OA
Jooyoung Cho, Jong-Han Lee, Sang-Guk Lee
Context.—: The N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) is a major diagnostic biomarker for heart failure.
Objective.—: To compare the analytical and clinical performance of 3 NT-proBNP immunoassays: the Atellica IM NT-proBNP assay (Siemens Healthcare Diagnostics), the Alere NT-proBNP assay (Abbott Laboratories), and the Elecsys proBNP II assay (Roche Diagnostics).
Design.—: For the Atellica IM NT-proBNP assay, analytical performance, including precision, linearity, and carryover, was fully evaluated. Method comparisons among the 3 assays were performed using the Passing-Bablok regression and the κ agreement test. To evaluate the clinical performance of the assays, 160 patient samples were used from patients with (n = 81) or without (n = 79) heart failure.
Results.—: The analytical performance of the Atellica IM NT-proBNP assay was acceptable according to the manufacturer's claims. The Atellica IM NT-proBNP assay showed a positive bias compared with the Elecsys proBNP II assay. The Cohen κ values among the 3 assays were satisfactory (>0.80) and comparable. There were no significant differences in areas under the curve. However, for the diagnosis of heart failure, the Elecsys proBNP II showed a higher specificity and positive likelihood ratio than the other assays.
Conclusions.—: All 3 NT-proBNP assays showed acceptable concordance, and their clinical performance was comparable. However, the Elecsys proBNP II might be a more discriminating NT-proBNP assay to diagnose heart failure.
上下文。脑利钠肽n端原激素(NT-proBNP)是心力衰竭的主要诊断生物标志物。-:比较3种NT-proBNP免疫测定的分析和临床性能:Atellica IM NT-proBNP测定(西门子医疗诊断)、Alere NT-proBNP测定(雅培实验室)和Elecsys proBNP II测定(罗氏诊断)。-:对于Atellica IM NT-proBNP分析,分析性能,包括精度,线性和结转,得到了充分的评估。方法比较采用passingbablok回归和κ一致性检验。为了评估试验的临床表现,160例患者的样本来自(n = 81)或(n = 79)心力衰竭患者。-:根据制造商的声明,Atellica IM NT-proBNP检测的分析性能是可接受的。与Elecsys proBNP II相比,Atellica IM NT-proBNP检测显示出正偏倚。3个试验的Cohen κ值均令人满意(>0.80)且具有可比性。曲线下面积无显著差异。然而,对于心力衰竭的诊断,Elecsys proBNP II比其他检测方法具有更高的特异性和阳性似然比。-:所有3种NT-proBNP检测均显示可接受的一致性,其临床表现具有可比性。然而,Elecsys proBNP II可能是一种更具鉴别性的NT-proBNP检测来诊断心力衰竭。
{"title":"Evaluation of Analytical Performances and Comparison of 3 NT-proBNP Assays for Diagnosing Heart Failure.","authors":"Jooyoung Cho, Jong-Han Lee, Sang-Guk Lee","doi":"10.5858/arpa.2021-0587-OA","DOIUrl":"https://doi.org/10.5858/arpa.2021-0587-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) is a major diagnostic biomarker for heart failure.</p><p><strong>Objective.—: </strong>To compare the analytical and clinical performance of 3 NT-proBNP immunoassays: the Atellica IM NT-proBNP assay (Siemens Healthcare Diagnostics), the Alere NT-proBNP assay (Abbott Laboratories), and the Elecsys proBNP II assay (Roche Diagnostics).</p><p><strong>Design.—: </strong>For the Atellica IM NT-proBNP assay, analytical performance, including precision, linearity, and carryover, was fully evaluated. Method comparisons among the 3 assays were performed using the Passing-Bablok regression and the κ agreement test. To evaluate the clinical performance of the assays, 160 patient samples were used from patients with (n = 81) or without (n = 79) heart failure.</p><p><strong>Results.—: </strong>The analytical performance of the Atellica IM NT-proBNP assay was acceptable according to the manufacturer's claims. The Atellica IM NT-proBNP assay showed a positive bias compared with the Elecsys proBNP II assay. The Cohen κ values among the 3 assays were satisfactory (>0.80) and comparable. There were no significant differences in areas under the curve. However, for the diagnosis of heart failure, the Elecsys proBNP II showed a higher specificity and positive likelihood ratio than the other assays.</p><p><strong>Conclusions.—: </strong>All 3 NT-proBNP assays showed acceptable concordance, and their clinical performance was comparable. However, the Elecsys proBNP II might be a more discriminating NT-proBNP assay to diagnose heart failure.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"949-956"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.5858/arpa.2020-0632-OA
Amanda Wiggett, Gabor Fischer
Context.—: Clear communication between pathologists and surgeons during intraoperative consultations is critical for optimal patient care.
Objective.—: To examine the concordance of intraoperative diagnoses recorded in pathology reports to surgeon-dictated operative notes and assess the impact of an intervention on the discrepancy rates.
Design.—: Discrepancies between the intended communication by pathologists and the interpretation by surgeons were characterized as minor with no crucial clinical impact, and major with the potential of altering patient management. After analysis, a corrective intervention was implemented with education, information sharing, and a change in protocol, and a comparative analysis was conducted.
Results.—: We examined 223 surgical cases with 578 intraoperative consultations. In 23% (51) of the cases, the intraoperative diagnosis was not recorded in the operative reports. We found minor discrepancies in 34% (59) and major discrepancies in 2% (3) of the remaining cases. Deferrals accounted for 24% (14 of 59) of the minor and 33% (1 of 3) of the major discrepancies. Among the discrepant cases, 56% (35 of 62) were multipart cases, including all major discrepancies. Following intervention, no major discrepancies were found in 101 cases with 186 intraoperative interpretations. The cases with no operative documentation reports decreased from 23% to 16% (16 of 101). Minor discrepancies were found in 11% (9 of 85) of the cases, indicating significant improvement (P < .001).
Conclusions.—: Intraoperative diagnoses can be miscommunicated and/or misinterpreted, possibly impacting intraoperative management, particularly in multipart cases and those involving deferrals. This study highlights the importance of auditing intraoperative communications and addressing the findings through a local intervention.
{"title":"Intraoperative Communications Between Pathologists and Surgeons: Do We Understand Each Other?","authors":"Amanda Wiggett, Gabor Fischer","doi":"10.5858/arpa.2020-0632-OA","DOIUrl":"https://doi.org/10.5858/arpa.2020-0632-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Clear communication between pathologists and surgeons during intraoperative consultations is critical for optimal patient care.</p><p><strong>Objective.—: </strong>To examine the concordance of intraoperative diagnoses recorded in pathology reports to surgeon-dictated operative notes and assess the impact of an intervention on the discrepancy rates.</p><p><strong>Design.—: </strong>Discrepancies between the intended communication by pathologists and the interpretation by surgeons were characterized as minor with no crucial clinical impact, and major with the potential of altering patient management. After analysis, a corrective intervention was implemented with education, information sharing, and a change in protocol, and a comparative analysis was conducted.</p><p><strong>Results.—: </strong>We examined 223 surgical cases with 578 intraoperative consultations. In 23% (51) of the cases, the intraoperative diagnosis was not recorded in the operative reports. We found minor discrepancies in 34% (59) and major discrepancies in 2% (3) of the remaining cases. Deferrals accounted for 24% (14 of 59) of the minor and 33% (1 of 3) of the major discrepancies. Among the discrepant cases, 56% (35 of 62) were multipart cases, including all major discrepancies. Following intervention, no major discrepancies were found in 101 cases with 186 intraoperative interpretations. The cases with no operative documentation reports decreased from 23% to 16% (16 of 101). Minor discrepancies were found in 11% (9 of 85) of the cases, indicating significant improvement (P < .001).</p><p><strong>Conclusions.—: </strong>Intraoperative diagnoses can be miscommunicated and/or misinterpreted, possibly impacting intraoperative management, particularly in multipart cases and those involving deferrals. This study highlights the importance of auditing intraoperative communications and addressing the findings through a local intervention.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"147 8","pages":"933-939"},"PeriodicalIF":4.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}