Archives of pathology & laboratory medicine最新文献

{"title":"A Comparison Between Immunohistochemistry and mRNA Expression to Identify Human Epidermal Growth Factor Receptor 2-Low Breast Cancer.","authors":"Ximena Baez-Navarro, Mieke R van Bockstal, Angelique van der Made, Carolien H M van Deurzen","doi":"10.5858/arpa.2024-0255-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0255-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Breast cancers (BCs) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) have become a targetable subset because of novel antibody-drug conjugates. HER2 immunohistochemistry (IHC) is the recommended assay for HER2 classification but is associated with limited interobserver agreement concerning HER2-low identification.</p><p><strong>Objective.—: </strong>To investigate whether mRNA expression quantified via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) could serve as a valuable complementary and more objective method to identify HER2-low BCs.</p><p><strong>Design.—: </strong>We selected all cases from a previously published interobserver study, which included 105 needle biopsies from HER2 nonamplified BC cases. HER2 IHC was evaluated by 16 pathologists. For the current study, mRNA was extracted from microdissected invasive tumor cells. RT-qPCR was performed for quantitative evaluation of HER2, using the cutoff values of the MammaTyper assay. We compared the mRNA expression levels with the IHC scores of the majority agreement (IHC 0, IHC >0, <1+ [ultralow], 1+, 2+) and the following HER2 subcategories: HER2 0/ultralow and HER2-low (IHC 1+ and 2+/fluorescence in situ hybridization negative).</p><p><strong>Results.—: </strong>In total, 88 nonamplified HER2 cases could be analyzed. Based on IHC, 17 cases were HER2 0/ultralow and 71 were HER2-low. The mean rank HER2 mRNA level was significantly higher in HER2-low cases than in the HER2 0/ultralow group (P < .001). However, 10 of 17 HER2 0/ultralow cases by IHC (58.8%) were classified as HER2-low by MammaTyper, 2 of 71 cases (2.8%) were HER2-low by IHC and HER2 0/ultralow by MammaTyper, and 2 (2.8%) were HER2-low by IHC and HER2-positive by RP-qPCR.</p><p><strong>Conclusions.—: </strong>Our findings indicate a strong agreement between mRNA expression quantified by RT-qPCR and HER2 IHC scores, although there was a substantial proportion of discordant HER2 results between both methods owing to overestimation of HER2 expression by MammaTyper compared to IHC. Future large-scale trials should determine which technique is best associated with clinical outcome.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Assisted Daily Quality Control System for the Histologic Diagnosis of Gastrointestinal Endoscopic Biopsies: A 1-Year Experience.","authors":"Seung-Yeon Yoo, Yuri Hwang, Seokju Yun, Ok Hee Lee, Jiwook Jang, Youngjin Park, Tae Young Cho, Young Sin Ko","doi":"10.5858/arpa.2024-0173-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0173-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Seegene Medical Foundation, one of the major clinical laboratories in South Korea, developed SeeDP, an artificial intelligence (AI)-based postanalytic daily quality control (QC) system that reassesses all gastrointestinal (GI) endoscopic biopsy (EB) slides for incorrect diagnoses.</p><p><strong>Objective.—: </strong>To review the operational records and clinical impact of SeeDP since its launch in March 2022.</p><p><strong>Design.—: </strong>Operational records of SeeDP were retrieved for the period of March 1, 2022, to February 28, 2023. Among cases scanned during 40 working days (March 10, 2022, to May 4, 2022), all discordant cases encountered by 2 pathologists were reviewed. Cases of SeeDP-assisted revised diagnoses were collected and compared with cases recognized using conventional methods.</p><p><strong>Results.—: </strong>Occasional scanner failures and various types of aberrant errors compromised QC coverage, resulting in the scanning of only 67.7% (572 254 of 844 906) of all EB slides submitted and 0.8% of the scanned slides being further excluded from the AI analysis. The AI predictions differed from the pathologists' diagnoses in 42 760 of the 557 672 gastrointestinal EB slides (7.7%) successfully assessed by the AI models; however, a detailed review of discordant slides revealed that true misdiagnosis accounted for only 5.5% (25 of 454) of the disagreements. Compared with conventional error recognition methods, SeeDP detected more misdiagnoses (7 versus 14) within a significantly shorter time (average, 3.6 versus 38.7 days; P < .001), including 1 signet ring cell carcinoma initially diagnosed as gastritis.</p><p><strong>Conclusions.—: </strong>AI-based daily QC systems are plausible solutions to guarantee high-quality pathologic diagnosis by enabling rapid detection and correction of misdiagnosis.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Accreditation Options for Biorepositories.","authors":"Richard C Davis, Joan Rose, Helena J Ellis, Erik Zmuda, Nalin Leelatian, Thomas Summers, Rebecca Obeng, Jim Vaught, Nilsa C Ramirez, Shannon J McCall","doi":"10.5858/arpa.2023-0221-CP","DOIUrl":"https://doi.org/10.5858/arpa.2023-0221-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Biomedical research relies on available biomaterials and associated data, and the quality of this starting material can have a significant impact on the quality of the experimental results. In the 2000s, best-practice documents and guidelines for biorepositories were published, followed in the 2010s by standards documents used to support accreditation. The College of American Pathologists Biorepository Accreditation Program and the International Standards Organization's standard 20387 were launched in 2012 and 2018, respectively.</p><p><strong>Objective.—: </strong>To identify quantitative and qualitative differences between the two aforementioned biorepository accreditation standards for use by the larger biomedical research community; the results will empower biorepositories to select an accreditation program that best fits their goals.</p><p><strong>Design.—: </strong>Individual requirements of both accreditation standards were identified and a bidirectional crosswalk was performed to identify gaps. Requirements were assigned to one of several standardized categories to enable comparison of the relative emphasis of different categories between the standards.</p><p><strong>Results.—: </strong>Quantitatively, the College of American Pathologists program is comprehensive and stands alone, with 523 requirements, whereas the International Standards Organization program contains 167 requirements and is comprehensive through its incorporation and reference to numerous related standards documents. Qualitatively, both programs rely heavily on the implementation of an overarching quality management system and both programs can accommodate different types of biobanks (eg, human and animal).</p><p><strong>Conclusions.—: </strong>The standards differ in number of requirements, distribution of requirements across categories, and amount of reliance on separate standard documents. This information may aid in selection of an appropriate accreditation standard.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Precision Oncology: Whole-Exome Sequencing in Endometrial Cancer Liquid-Based Cytology.","authors":"Reika Takamatsu, Kohei Nakamura, Tatsuyuki Chiyoda, Kosuke Tsuji, Ryutaro Kawano, Naoki Yoshimi, Wataru Yamagami, Hiroshi Nishihara","doi":"10.5858/arpa.2024-0137-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0137-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Diagnostic strategies for endometrial cancer have been evolving, with cytologic analysis being considered a key method in integrated oncologic diagnostics because of its less invasive nature and adaptability to various assessments. Liquid-based cytology (LBC) has emerged as a promising method for intact DNA preservation; it exhibits improved efficiency in advanced sequencing applications such as next-generation sequencing. However, despite the use of LBC in panel assays, its application in whole-exome sequencing (WES) for comprehensive genomic profiling remains underexplored.</p><p><strong>Objective.—: </strong>To investigate whether molecular classification is possible based on WES using DNA derived from LBC specimens.</p><p><strong>Design.—: </strong>We combined WES with targeted gene panel analysis to compare genomic findings of LBC and traditional tissue samples obtained from 7 cases of endometrial cancer. We investigated pathogenic mutations, tumor mutational burden, and microsatellite instability, and achieved molecular classification with high accuracy.</p><p><strong>Results.—: </strong>We found a substantial concordance between LBC and traditional tissue samples in terms of pathogenic mutation detection, with a 95% match in the LBC samples and 94% in the tissue samples. Notably, our results highlight the importance of combining WES with panel-based analysis in identifying the ultramutated status of a case that had been missed during panel analysis.</p><p><strong>Conclusions.—: </strong>Our findings emphasize the potential of LBC samples in the precise and noninvasive genomic analysis of cases of endometrial cancer and offer a new avenue for developing diagnostic and therapeutic strategies in precision oncology.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait.","authors":"Fátima Ramalhosa, Francesca Lunardi, Nicol Bernardinello, Silvia Gori, Federica Pezzuto, Veronica Tauro, Claudia Del Vecchio, Chiara Giraudo, Elisabetta Balestro, Fiorella Calabrese","doi":"10.5858/arpa.2024-0043-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0043-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited.</p><p><strong>Objective.—: </strong>To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised).</p><p><strong>Design.—: </strong>This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data.</p><p><strong>Results.—: </strong>Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients.</p><p><strong>Conclusions.—: </strong>Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Hybridization Assay as First-Line Diagnostic Test for Sarcomas: Clinical Assessment in a Tertiary Referral Center.","authors":"Carmen Salguero-Aranda, Marco Perez, María Victoria Vargas-Padilla, Amparo Beltrán-Povea, Daniel Delgado-Bellido, David Marcilla, Gema Civantos, Enrique de Álava, Juan Díaz-Martín","doi":"10.5858/arpa.2024-0202-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0202-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Sarcomas are rare and highly heterogeneous mesenchymal tumors with deceptive morphologic features that pose a challenge for precise diagnostics. Chromosomal rearrangements generating pathognomonic gene fusions are useful diagnostic markers, traditionally tested using single-plex standard of care assays with limited diagnostic yield. NanoString nCounter technology has emerged as a robust solution with multiplexing capabilities.</p><p><strong>Objective.—: </strong>To optimize NanoString effective coverage of specific entities and conduct a validation study to support its clinical implementation.</p><p><strong>Design.—: </strong>We reconfigured a NanoString's codeset by including a set of probes for detecting gene fusion variants of solitary fibrous tumors, low-grade fibromyxoid sarcomas/sclerosing epithelioid fibrosarcomas, and undifferentiated small round cell sarcomas, totaling 188 probes. A technical validation study was conducted with 96 retrospective samples. Additionally, 76 prospective samples were evaluated to assess the assay's clinical performance.</p><p><strong>Results.—: </strong>Both technical and clinical validation studies showed that NanoString's codeset reached >88% sensitivity and 100% specificity, compared with standard of care methods, and superior diagnostic yield as a first-line test. Our design enabled the detection of almost all fusion variants of NGFI-A binding protein 2 (NAB2) with signal transducer and activator of transcription 6 (STAT6) in solitary fibrous tumors, as well as cAMP responsive element binding protein 3 like 1/2 (CREB3L1/2) rearrangements in all low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma cases. Identification of specific gene fusions of undifferentiated small round cell sarcoma was also improved, but additional strategies are necessary to attain full coverage.</p><p><strong>Conclusions.—: </strong>The NanoString platform demonstrated good sensitivity, specificity, and superior diagnostic yield. It is a cost-effective assay with rapid turnaround time, low sample consumption, streamlined analysis, and easy customization. Therefore, it is a promising alternative first-line diagnostic tool for routine sarcoma testing.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Myelodysplastic Syndrome.","authors":"Zaina Inam, Miao Pan, Yaser Diab, Reuven Schore, Anant Vatsayan, Jinjun Cheng","doi":"10.5858/arpa.2024-0164-RA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0164-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Myelodysplastic syndromes (MDSs) are rare in children and have unique clinical manifestations and implications.</p><p><strong>Objective.—: </strong>To review the clinical features, pathogenesis, and classification of pediatric MDS.</p><p><strong>Data sources.—: </strong>Published literature and personal experience.</p><p><strong>Conclusions.—: </strong>Pediatric MDS vastly differs from adult MDS. Evaluation for the presence of an underlying germline predisposition syndrome is critical for optimal classification and management. Because of the rarity of cases, resources to aid with the recognition, diagnosis, and management of pediatric MDS are limited, and multi-institutional collaborative studies are needed for the future.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Assessment of Gestational Age in Accelerated Maturation, Delayed Maturation, Villous Edema, Chorangiosis, and Intrauterine Fetal Demise.","authors":"Jeffery A Goldstein, Ramin Nateghi, Lee A D Cooper","doi":"10.5858/arpa.2024-0274-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0274-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Assessment of placental villous maturation is among the most common tasks in perinatal pathology. However, the significance of abnormalities in morphology is unclear and interobserver variability is significant.</p><p><strong>Objective.—: </strong>To develop a machine learning model of placental maturation across the second and third trimesters and quantify the impact of different pathologist-diagnosed abnormalities of villous morphology.</p><p><strong>Design.—: </strong>Digitize placental villous slides from more than 2500 placentas at 12.0 to 42.6 weeks. Build whole slide learning models to estimate obstetrician-determined gestational age for cases with appropriate maturation and normal morphology. Define the model output as \"placental age\" and compare it to the chronologic gestational age.</p><p><strong>Results.—: </strong>Our model showed an r2 of 0.864 and mean absolute error of 1.62 weeks for placentas with appropriate maturation in the test set. Pathologist diagnosis of accelerated maturation was associated with a 2.56-week increase in placental age (±2.91 weeks, P < .001), while delayed maturation was associated with a 0.92-week decrease in placental age (±1.82 weeks, P < .001). Intrauterine fetal demise causes diverse changes to placental age, driven by the nature of the demise. We tested the impact of training a model, using all live births. The resulting r2 was 0.874 and mean absolute error was 1.73 weeks. Furthermore, by including cases with abnormal maturation in the training data, the effect size of accelerated maturation was blunted to only 0.56 ± 2.35 weeks (P < .001).</p><p><strong>Conclusions.—: </strong>We show that various abnormalities of villous maturation and morphology correlate with abnormalities in placental age. This \"no pathologist\" model could be useful in situations where pathologists are unavailable or the need for consistency outweighs the utility of expertise.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Generation of Pathologists: Addressing Modern Curriculum and Educational Scholarship for Pathology Educators and Trainees After the End of the COVID-19 Pandemic.","authors":"Casey P Schukow, Timothy Craig Allen","doi":"10.5858/arpa.2024-0114-RA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0114-RA","url":null,"abstract":"<p><strong>Context.—: </strong>The COVID-19 pandemic irreversibly altered the pathology education landscape. It exacerbated workforce shortages, restricted in-person activities, and highlighted critical means in curricula evaluation to limit the expansion of medical knowledge gaps in postpandemic society. Training enacted swift changes toward online learning (e-learning) practices to minimize potential deficiencies in pathology education. Today, a breadth of widely available online pathology curricular tools, including e-learning and digital pathology, are increasingly being used by medical students, trainees, and pathologists worldwide.</p><p><strong>Objective.—: </strong>To critically address the continued role of e-learning and digital pathology in postpandemic pathology education and scholarship, as a current paucity of literature exists and lingering workflow effects of this pandemic affecting many anatomic and clinical pathology departments globally persist.</p><p><strong>Data sources.—: </strong>A qualitative review of relevant literature is synthesized to create a timely, narrative discussion to bridge this literature gap. Peer-reviewed sources and other original or primary documents will be assessed.</p><p><strong>Conclusions.—: </strong>Because of the subjective nature of curricular development and defining what constitutes scholarship, no widely established consensus is present, though it has been touched on in previous literature. It may be years until we better understand how e-learning and digital pathology shape curricular practices, scholarship production, and patient-care delivery, though recent studies support sustained blended curricula beyond the COVID-19 pandemic. The education landscape continues to become increasingly digitalized, and infrastructures may soon be able to support complete digital pathology practice as the education norm. Future and theoretical insight for pathology and laboratory departments globally are provided.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Napsin-A Immunohistochemistry in the Diagnosis of Pulmonary Alveolar Proteinosis.","authors":"Catherine Larose, Charles Leduc, Martin Chevrier","doi":"10.5858/arpa.2024-0136-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0136-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The diagnosis of pulmonary alveolar proteinosis (PAP) relies on a limited set of stains, namely hematoxylin-eosin and periodic acid-Schiff-diastase (PAS-D), demonstrating abundant alveolar material representing mostly surfactant. As cells harboring surfactant also express Napsin-A (pneumocytes and macrophages), we hypothesized that it would also be expressed within alveoli in PAP.</p><p><strong>Objective.—: </strong>To evaluate the sensitivity and specificity of Napsin-A in the diagnosis of PAP.</p><p><strong>Design.—: </strong>A 12-year retrospective case control study was designed to identify cases of PAP and potential histologic mimics (intra-alveolar fibrin, pulmonary edema, diffuse alveolar damage, and alveolar mucinosis). PAS-D staining and Napsin-A immunohistochemistry were performed. Distribution and intensity were evaluated by using a semiquantitative 3-point scale. Positivity was defined as 2+ intensity score, regardless of distribution.</p><p><strong>Results.—: </strong>Eleven cases of PAP and 46 control cases were identified. Napsin-A showed positivity in all PAP cases and 3 of 12 cases of edema. Among positive cases, all those with a 2+ distribution were PAP cases, with heterogeneous (1+) staining in all cases of edema. PAS-D showed positivity in all cases of PAP and most controls, except cases of edema. Sensitivity and specificity of Napsin-A for PAP were 100% and 94%, respectively, and of PAS-D for PAP, 100% and 21%, respectively. Double positivity for Napsin-A and PAS-D was 100% specific and sensitive for PAP.</p><p><strong>Conclusions.—: </strong>This study is the first to demonstrate that Napsin-A is highly specific for the diagnosis of PAP, more so than PAS-D. It also shows that the combined positivity of Napsin-A and PAS-D is 100% specific and sensitive for PAP.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}