Pub Date : 2024-04-23DOI: 10.5858/arpa.2023-0382-OA
Haishen Tang, Yi Xiong, Jiaqi Tang, Xiaohong Wang, Ya Wang, Liping Huang, Runli Wang, Degang Wang
CONTEXT.— Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia. OBJECTIVE.— To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.— The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. RESULTS.— Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. CONCLUSIONS.— Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.
{"title":"Screening and Diagnosis of Rare Thalassemia Variants.","authors":"Haishen Tang, Yi Xiong, Jiaqi Tang, Xiaohong Wang, Ya Wang, Liping Huang, Runli Wang, Degang Wang","doi":"10.5858/arpa.2023-0382-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0382-OA","url":null,"abstract":"CONTEXT.—\u0000Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia.\u0000\u0000\u0000OBJECTIVE.—\u0000To assess a comprehensive approach for the screening and diagnosis of rare thalassemia.\u0000\u0000\u0000DESIGN.—\u0000The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing.\u0000\u0000\u0000RESULTS.—\u0000Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified.\u0000\u0000\u0000CONCLUSIONS.—\u0000Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671844","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 : 2024-04-18DOI: 10.5858/arpa.2022-0384-CP
Daniel D Mais, Alia N Nazarullah, Anthony J Guidi, Suzanne Dintzis, Barbara J Blond, Thomas A Long, Suzanne N Coulter, Richard W Brown
CONTEXT.— Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. OBJECTIVE.— To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. DESIGN.— Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. RESULTS.— A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. CONCLUSIONS.— The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.
{"title":"Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions.","authors":"Daniel D Mais, Alia N Nazarullah, Anthony J Guidi, Suzanne Dintzis, Barbara J Blond, Thomas A Long, Suzanne N Coulter, Richard W Brown","doi":"10.5858/arpa.2022-0384-CP","DOIUrl":"https://doi.org/10.5858/arpa.2022-0384-CP","url":null,"abstract":"CONTEXT.—\u0000Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks.\u0000\u0000\u0000OBJECTIVE.—\u0000To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories.\u0000\u0000\u0000DESIGN.—\u0000Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates.\u0000\u0000\u0000RESULTS.—\u0000A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified.\u0000\u0000\u0000CONCLUSIONS.—\u0000The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140686830","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 : 2024-04-18DOI: 10.5858/arpa.2023-0455-OA
Qianqian Sun, Weiqing Li, Donghua Yang, P. Lin, Lina Zhang, H. Guo
CONTEXT.— Most patients with non-small cell lung cancers (NSCLC) are diagnosed at advanced stages. The 5-year survival rate of patients with advanced lung cancer is less than 20%, which makes lung cancer the leading cause of cancer-related deaths worldwide. OBJECTIVE.— To identify indicators that can predict the prognosis of lung cancer patients. DESIGN.— To determine the correlation between circulating tumor cells (CTCs), circulating tumor-derived endothelial cells (CTECs), and their subtypes and the prognosis of patients with NSCLC, 80 patients with lung cancer were recruited and 48 patients who met the enrollment criteria were selected in this study. Peripheral blood was collected from the enrolled patients before any treatment and analyzed by the subtraction enrichment and immunostaining-fluorescence in situ hybridization technique to determine the correlation between CTCs and CTECs and lung cancer disease progression and to identify prognostic indicators. RESULTS.— In all patients, the positive rate of CTCs was 100% and the positive rate of CTECs was 81.3%. The CTEC positivity rate was higher in late-stage patients than in early-stage patients (P = .03). Patients with advanced or lymph node metastases had a higher rate of small-size CTC positivity than those with early or no lymph node metastases. Large-size CTEC positivity was higher in patients with advanced NSCLC than in early-stage patients. Patients with ≥1 small-size CTC had shorter progression-free survival, and it was an independent prognostic factor. CONCLUSIONS.— Small-size CTCs are a reliable prognostic indicator and a probable predictor of the severity of disease in NSCLC patients.
{"title":"The Presence of Small-Size Circulating Tumor Cells Predicts Worse Prognosis in Non-Small Cell Lung Cancer Patients.","authors":"Qianqian Sun, Weiqing Li, Donghua Yang, P. Lin, Lina Zhang, H. Guo","doi":"10.5858/arpa.2023-0455-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0455-OA","url":null,"abstract":"CONTEXT.—\u0000Most patients with non-small cell lung cancers (NSCLC) are diagnosed at advanced stages. The 5-year survival rate of patients with advanced lung cancer is less than 20%, which makes lung cancer the leading cause of cancer-related deaths worldwide.\u0000\u0000\u0000OBJECTIVE.—\u0000To identify indicators that can predict the prognosis of lung cancer patients.\u0000\u0000\u0000DESIGN.—\u0000To determine the correlation between circulating tumor cells (CTCs), circulating tumor-derived endothelial cells (CTECs), and their subtypes and the prognosis of patients with NSCLC, 80 patients with lung cancer were recruited and 48 patients who met the enrollment criteria were selected in this study. Peripheral blood was collected from the enrolled patients before any treatment and analyzed by the subtraction enrichment and immunostaining-fluorescence in situ hybridization technique to determine the correlation between CTCs and CTECs and lung cancer disease progression and to identify prognostic indicators.\u0000\u0000\u0000RESULTS.—\u0000In all patients, the positive rate of CTCs was 100% and the positive rate of CTECs was 81.3%. The CTEC positivity rate was higher in late-stage patients than in early-stage patients (P = .03). Patients with advanced or lymph node metastases had a higher rate of small-size CTC positivity than those with early or no lymph node metastases. Large-size CTEC positivity was higher in patients with advanced NSCLC than in early-stage patients. Patients with ≥1 small-size CTC had shorter progression-free survival, and it was an independent prognostic factor.\u0000\u0000\u0000CONCLUSIONS.—\u0000Small-size CTCs are a reliable prognostic indicator and a probable predictor of the severity of disease in NSCLC patients.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140689739","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 : 2024-04-11DOI: 10.5858/arpa.2023-0447-OA
Roland Tian, Eric Wang, Priyadharshini Sivasubramaniam, S. U. Baskota, Anurag Sharma, Matthew J Cecchini
CONTEXT.— Social media is a powerful tool in pathology education and professional networking that connects pathologists and pathology trainees from around the world. Twitter (X) appears to be the most popular social media platform pathologists use to share pathology-related content and connect with other pathologists. Although there has been some published research on pathology-related activity on Twitter during short time frames, to date there has not been published research examining pathology-related Twitter activity in totality from its earliest days of activity to recently. OBJECTIVE.— To comprehensively evaluate the use of pathology on Twitter (X) during the last 10 years. DESIGN.— Pathology-related tweets were systematically scraped from Twitter from January 2012 to January 2023 using pathology hashtags as a surrogate measure for all pathology content on Twitter. COVID-related tweets were approximated by tweets containing the term "COVID." RESULTS.— There were 591 812 unique pathology-related tweets identified during the time period, with #pathology being the most common hashtag used and #PathTwitter becoming more popular since 2020. There has been positive annual growth of pathology Twitter, with peaks in use during major pathology conferences. During the initial phases of the COVID-19 pandemic a sustained increase in pathology tweets was observed. CONCLUSIONS.— Pathology Twitter has grown during the last 10 years and has become increasingly popular for pathology education and networking. With the changing landscape of social media platforms this study provides an understanding of how pathology medical education and professional networking uses of social media are used and evolve over time.
{"title":"Ten Years of Pathology on Twitter (X): Landscape and Evolution of Pathology on Twitter From 2012 to 2023.","authors":"Roland Tian, Eric Wang, Priyadharshini Sivasubramaniam, S. U. Baskota, Anurag Sharma, Matthew J Cecchini","doi":"10.5858/arpa.2023-0447-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0447-OA","url":null,"abstract":"CONTEXT.—\u0000Social media is a powerful tool in pathology education and professional networking that connects pathologists and pathology trainees from around the world. Twitter (X) appears to be the most popular social media platform pathologists use to share pathology-related content and connect with other pathologists. Although there has been some published research on pathology-related activity on Twitter during short time frames, to date there has not been published research examining pathology-related Twitter activity in totality from its earliest days of activity to recently.\u0000\u0000\u0000OBJECTIVE.—\u0000To comprehensively evaluate the use of pathology on Twitter (X) during the last 10 years.\u0000\u0000\u0000DESIGN.—\u0000Pathology-related tweets were systematically scraped from Twitter from January 2012 to January 2023 using pathology hashtags as a surrogate measure for all pathology content on Twitter. COVID-related tweets were approximated by tweets containing the term \"COVID.\"\u0000\u0000\u0000RESULTS.—\u0000There were 591 812 unique pathology-related tweets identified during the time period, with #pathology being the most common hashtag used and #PathTwitter becoming more popular since 2020. There has been positive annual growth of pathology Twitter, with peaks in use during major pathology conferences. During the initial phases of the COVID-19 pandemic a sustained increase in pathology tweets was observed.\u0000\u0000\u0000CONCLUSIONS.—\u0000Pathology Twitter has grown during the last 10 years and has become increasingly popular for pathology education and networking. With the changing landscape of social media platforms this study provides an understanding of how pathology medical education and professional networking uses of social media are used and evolve over time.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140712964","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 : 2024-04-11DOI: 10.5858/arpa.2023-0370-OA
Yayuan Zhao, Pramath Kakodkar, Henry Pan, Richard Zhu, Khalid Musa, Abubaker Hassan, A. Shoker, D. Webster, Twyla Pearce, Pouneh Dokouhaki, Fang Wu, Ahmed Mostafa
CONTEXT.— Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti-human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned. OBJECTIVE.— To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile. DESIGN.— A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers. RESULTS.— There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history. CONCLUSIONS.— Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.
{"title":"The Interplay Between Human Leukocyte Antigen Antibody Profile and COVID-19 Vaccination in Waitlisted Renal Transplant Patients.","authors":"Yayuan Zhao, Pramath Kakodkar, Henry Pan, Richard Zhu, Khalid Musa, Abubaker Hassan, A. Shoker, D. Webster, Twyla Pearce, Pouneh Dokouhaki, Fang Wu, Ahmed Mostafa","doi":"10.5858/arpa.2023-0370-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0370-OA","url":null,"abstract":"CONTEXT.—\u0000Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti-human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned.\u0000\u0000\u0000OBJECTIVE.—\u0000To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile.\u0000\u0000\u0000DESIGN.—\u0000A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers.\u0000\u0000\u0000RESULTS.—\u0000There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history.\u0000\u0000\u0000CONCLUSIONS.—\u0000Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714581","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 : 2024-04-08DOI: 10.5858/arpa.2023-0304-RA
A. N. Husain, David B. Chapel, R. Attanoos, M. Beasley, Luka Brcic, K. Butnor, L. Chirieac, Andrew Churg, S. Dacic, Francoise Galateau-Salle, Kenzo Hiroshima, Yin P Hung, Sonja Klebe, Thomas Krausz, A. Khoor, Leslie Litzky, A. Marchevsky, Kazuki Nabeshima, Andrew G. Nicholson, E. Pavlisko, Anja C Roden, Victor L Roggli, Jennifer L Sauter, Jefree J. Schulte, Michael Sheaff, William D. Travis, Ming-Sound Tsao, A. Walts, Thomas V. Colby
CONTEXT.— Mesothelioma is an uncommon tumor that can be difficult to diagnose. OBJECTIVE.— To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma. DATA SOURCES.— Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks. CONCLUSIONS.— There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.
{"title":"Guidelines for Pathologic Diagnosis of Mesothelioma.","authors":"A. N. Husain, David B. Chapel, R. Attanoos, M. Beasley, Luka Brcic, K. Butnor, L. Chirieac, Andrew Churg, S. Dacic, Francoise Galateau-Salle, Kenzo Hiroshima, Yin P Hung, Sonja Klebe, Thomas Krausz, A. Khoor, Leslie Litzky, A. Marchevsky, Kazuki Nabeshima, Andrew G. Nicholson, E. Pavlisko, Anja C Roden, Victor L Roggli, Jennifer L Sauter, Jefree J. Schulte, Michael Sheaff, William D. Travis, Ming-Sound Tsao, A. Walts, Thomas V. Colby","doi":"10.5858/arpa.2023-0304-RA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0304-RA","url":null,"abstract":"CONTEXT.—\u0000Mesothelioma is an uncommon tumor that can be difficult to diagnose.\u0000\u0000\u0000OBJECTIVE.—\u0000To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma.\u0000\u0000\u0000DATA SOURCES.—\u0000Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks.\u0000\u0000\u0000CONCLUSIONS.—\u0000There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727896","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 : 2024-04-05DOI: 10.5858/arpa.2023-0386-OA
Sang-Mi Kim, Won Young Heo, Hyeonju Oh, Eun Yeon Joo, Young-Min Shon, S. Hong, Soo-Youn Lee, Dae-Won Seo
CONTEXT.— New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. OBJECTIVE.— To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. DESIGN.— Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. RESULTS.— The method was linear with limit of detection less than 0.05 μg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs. CONCLUSIONS.— A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.
{"title":"Therapeutic Drug Monitoring of 6 New-Generation Antiseizure Medications Using a Mass Spectrometry Method: Analysis of 2-Year Experience in a Large Cohort of Korean Epilepsy Patients.","authors":"Sang-Mi Kim, Won Young Heo, Hyeonju Oh, Eun Yeon Joo, Young-Min Shon, S. Hong, Soo-Youn Lee, Dae-Won Seo","doi":"10.5858/arpa.2023-0386-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0386-OA","url":null,"abstract":"CONTEXT.—\u0000New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce.\u0000\u0000\u0000OBJECTIVE.—\u0000To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy.\u0000\u0000\u0000DESIGN.—\u0000Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed.\u0000\u0000\u0000RESULTS.—\u0000The method was linear with limit of detection less than 0.05 μg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs.\u0000\u0000\u0000CONCLUSIONS.—\u0000A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737562","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 : 2024-04-05DOI: 10.5858/arpa.2023-0492-OA
Krithika Shenoy, Richard J. Cote, Gayathri Kini, Mary Anthes-Bartlow, Vijayalakshmi Padmanabhan
CONTEXT.— Core biopsies are standard of care for diagnosis and surveillance of prostate cancer. Fragmentation makes numeric assessment of cancer challenging and increases risk of inaccurate staging with direct implications on management. OBJECTIVE.— To determine factors responsible for fragmentation at our institution. DESIGN.— Prostate core biopsies performed at 2 hospital sites during 1 week were prospectively identified. Biopsies were received in multipart formalin jars, either mounted on a nonadherent dressing pad (Telfa, Medtronic Inc) or freely suspended, and grossed by experienced pathologists' assistants. Fragmentation was defined as the difference between number of cores sent by the clinician and number of cores counted by the pathologist on microscopy. RESULTS.— Forty-six cases (15 benign; 31 malignant) with 535 specimen jars were identified of which 309 of 535 (57.8%) had >1 biopsy core per jar; 230 of 535 (43%) were received mounted on Telfa and 185 of 535 (34.6%) had histologic evidence of adenocarcinoma. Overall fragmentation rate was 157 of 535 (29.3%). Lowest fragmentation rate was seen when 1 core was submitted per jar regardless of mounting method (31 of 226; 14% for single versus 126 of 309; 41% for >1 per jar; P < .001). For 1 Telfa-mounted core, rate of fragmentation was 5 of 18 (27.8%) versus 26 of 203 (12.8%) when unmounted (P = .24). Significant increase in fragmentation of Telfa-mounted cores was seen when there were 3 per jar (32 of 70; 46% mounted fragmented versus 9 of 47; 19% unmounted fragmented specimens; P = .01). CONCLUSIONS.— Submission of >1 biopsy core per jar and use of Telfa for mounting are associated with increased fragmentation. We recommend limiting submission to 1 core per jar and avoid mounting on Telfa pads.
{"title":"Is Fragmentation of Prostate Core Biopsies Inevitable? A Quality Improvement Initiative.","authors":"Krithika Shenoy, Richard J. Cote, Gayathri Kini, Mary Anthes-Bartlow, Vijayalakshmi Padmanabhan","doi":"10.5858/arpa.2023-0492-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0492-OA","url":null,"abstract":"CONTEXT.—\u0000Core biopsies are standard of care for diagnosis and surveillance of prostate cancer. Fragmentation makes numeric assessment of cancer challenging and increases risk of inaccurate staging with direct implications on management.\u0000\u0000\u0000OBJECTIVE.—\u0000To determine factors responsible for fragmentation at our institution.\u0000\u0000\u0000DESIGN.—\u0000Prostate core biopsies performed at 2 hospital sites during 1 week were prospectively identified. Biopsies were received in multipart formalin jars, either mounted on a nonadherent dressing pad (Telfa, Medtronic Inc) or freely suspended, and grossed by experienced pathologists' assistants. Fragmentation was defined as the difference between number of cores sent by the clinician and number of cores counted by the pathologist on microscopy.\u0000\u0000\u0000RESULTS.—\u0000Forty-six cases (15 benign; 31 malignant) with 535 specimen jars were identified of which 309 of 535 (57.8%) had >1 biopsy core per jar; 230 of 535 (43%) were received mounted on Telfa and 185 of 535 (34.6%) had histologic evidence of adenocarcinoma. Overall fragmentation rate was 157 of 535 (29.3%). Lowest fragmentation rate was seen when 1 core was submitted per jar regardless of mounting method (31 of 226; 14% for single versus 126 of 309; 41% for >1 per jar; P < .001). For 1 Telfa-mounted core, rate of fragmentation was 5 of 18 (27.8%) versus 26 of 203 (12.8%) when unmounted (P = .24). Significant increase in fragmentation of Telfa-mounted cores was seen when there were 3 per jar (32 of 70; 46% mounted fragmented versus 9 of 47; 19% unmounted fragmented specimens; P = .01).\u0000\u0000\u0000CONCLUSIONS.—\u0000Submission of >1 biopsy core per jar and use of Telfa for mounting are associated with increased fragmentation. We recommend limiting submission to 1 core per jar and avoid mounting on Telfa pads.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740844","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 : 2024-04-05DOI: 10.5858/arpa.2023-0429-OA
Umberto Maccio, Christoph Andreas Meier, Michael Reinehr, Frank Ruschitzka, Reto A. Schüpbach, Holger Moch, Zsuzsanna Varga
CONTEXT.— Autopsies can reveal clinically undiagnosed diseases. However, the frequency of first diagnoses at autopsy and their association with clinically known risk factors are not well understood because of lack of systematic analyses addressing this topic. OBJECTIVE.— To perform a large retrospective cohort analysis on the frequency of clinically undiagnosed postmortem findings and correlate these with patients' risk factors. DESIGN.— Six hundred forty-eight consecutive and complete autopsies of adults (age >18 years), performed in the University Hospital Zurich, Switzerland, during a 3-year time period were retrospectively analyzed. Clinical diagnoses and postmortem findings were compared in order to identify clinically undiagnosed lesions and clarify their correlation with common risk factors. RESULTS.— In 633 of 648 patients (98%), at least one clinically undiagnosed finding was identified at autopsy. The most common nonneoplastic entities were bronchopneumonia (198; 31%), coronary artery disease (155; 24%) and acute or subacute myocardial infarction (94; 15%), and the most common malignancies were prostate cancer in men (14; 2.2%), followed by kidney cancer (10; 1.5%), gastrointestinal stromal tumor (10; 1.5%), and lung carcinoma (9; 1.4%) in both genders. Clinically undiagnosed cardiac amyloidosis was demonstrated in 8% (52 of 648) of patients and was significantly associated with age, hypertension, chronic kidney disease, coronary artery disease, and hypertensive cardiomyopathy. CONCLUSIONS.— Autopsy is a useful investigation for the detection of clinically undiagnosed entities. In our cohort, cardiac amyloidosis showed the highest number of underlying risk factors, but was clinically underdiagnosed. Our findings underline the necessity of improved clinical detection of cardiac amyloidosis, especially in light of emerging therapeutic options. Moreover, we characterize the most common entities prone to clinical underdiagnosis.
{"title":"Clinically Undiagnosed Diseases in Autopsies: Frequency and Risk Factors.","authors":"Umberto Maccio, Christoph Andreas Meier, Michael Reinehr, Frank Ruschitzka, Reto A. Schüpbach, Holger Moch, Zsuzsanna Varga","doi":"10.5858/arpa.2023-0429-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0429-OA","url":null,"abstract":"CONTEXT.—\u0000Autopsies can reveal clinically undiagnosed diseases. However, the frequency of first diagnoses at autopsy and their association with clinically known risk factors are not well understood because of lack of systematic analyses addressing this topic.\u0000\u0000\u0000OBJECTIVE.—\u0000To perform a large retrospective cohort analysis on the frequency of clinically undiagnosed postmortem findings and correlate these with patients' risk factors.\u0000\u0000\u0000DESIGN.—\u0000Six hundred forty-eight consecutive and complete autopsies of adults (age >18 years), performed in the University Hospital Zurich, Switzerland, during a 3-year time period were retrospectively analyzed. Clinical diagnoses and postmortem findings were compared in order to identify clinically undiagnosed lesions and clarify their correlation with common risk factors.\u0000\u0000\u0000RESULTS.—\u0000In 633 of 648 patients (98%), at least one clinically undiagnosed finding was identified at autopsy. The most common nonneoplastic entities were bronchopneumonia (198; 31%), coronary artery disease (155; 24%) and acute or subacute myocardial infarction (94; 15%), and the most common malignancies were prostate cancer in men (14; 2.2%), followed by kidney cancer (10; 1.5%), gastrointestinal stromal tumor (10; 1.5%), and lung carcinoma (9; 1.4%) in both genders. Clinically undiagnosed cardiac amyloidosis was demonstrated in 8% (52 of 648) of patients and was significantly associated with age, hypertension, chronic kidney disease, coronary artery disease, and hypertensive cardiomyopathy.\u0000\u0000\u0000CONCLUSIONS.—\u0000Autopsy is a useful investigation for the detection of clinically undiagnosed entities. In our cohort, cardiac amyloidosis showed the highest number of underlying risk factors, but was clinically underdiagnosed. Our findings underline the necessity of improved clinical detection of cardiac amyloidosis, especially in light of emerging therapeutic options. Moreover, we characterize the most common entities prone to clinical underdiagnosis.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737954","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 : 2024-04-04DOI: 10.5858/arpa.2023-0534-RA
Anuj Verma, Raja R Seethala, He Wang
CONTEXT.— High-grade transformation, previously known as dedifferentiation, in salivary gland carcinoma and carcinosarcoma ex pleomorphic adenoma is a rare phenomenon. It is, however, clinically relevant and affects treatment and prognosis. OBJECTIVE.— To review the existing literature, describe the histologic and immunophenotypic features, and highlight the diagnostic criteria of high-grade transformation in various salivary gland carcinomas and carcinosarcoma; to review its effect on clinical presentation and prognosis; and to review relevant molecular characteristics and recent concepts and advances. DATA SOURCES.— Literature search in PubMed using key words such as "high-grade transformation," "dedifferentiation," and "carcinosarcoma" in salivary gland. Relevant articles were reviewed, and additional articles were curated from the references of these articles. CONCLUSIONS.— High-grade transformation occurs rarely but has a significant impact on prognosis and management. By microscopy, the high-grade area is usually a distinct nodule and shows solid and nested architecture, cellular atypia, high mitotic count, and necrosis. The molecular features are not well established. Carcinosarcoma almost always arises in a pleomorphic adenoma and likely follows an adenoma-carcinoma-sarcoma pathway.
{"title":"High-Grade Transformation and Carcinosarcoma.","authors":"Anuj Verma, Raja R Seethala, He Wang","doi":"10.5858/arpa.2023-0534-RA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0534-RA","url":null,"abstract":"CONTEXT.—\u0000High-grade transformation, previously known as dedifferentiation, in salivary gland carcinoma and carcinosarcoma ex pleomorphic adenoma is a rare phenomenon. It is, however, clinically relevant and affects treatment and prognosis.\u0000\u0000\u0000OBJECTIVE.—\u0000To review the existing literature, describe the histologic and immunophenotypic features, and highlight the diagnostic criteria of high-grade transformation in various salivary gland carcinomas and carcinosarcoma; to review its effect on clinical presentation and prognosis; and to review relevant molecular characteristics and recent concepts and advances.\u0000\u0000\u0000DATA SOURCES.—\u0000Literature search in PubMed using key words such as \"high-grade transformation,\" \"dedifferentiation,\" and \"carcinosarcoma\" in salivary gland. Relevant articles were reviewed, and additional articles were curated from the references of these articles.\u0000\u0000\u0000CONCLUSIONS.—\u0000High-grade transformation occurs rarely but has a significant impact on prognosis and management. By microscopy, the high-grade area is usually a distinct nodule and shows solid and nested architecture, cellular atypia, high mitotic count, and necrosis. The molecular features are not well established. Carcinosarcoma almost always arises in a pleomorphic adenoma and likely follows an adenoma-carcinoma-sarcoma pathway.","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140741715","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}
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