Archives of pathology & laboratory medicine最新文献

{"title":"Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma.","authors":"Hao Wu, Madina Sukhanova, Haiming Tang, Xinyan Lu, Minghao Zhong, Hari Deshpande, Seth M Pollack, William B Laskin, Borislav A Alexiev","doi":"10.5858/arpa.2024-0098-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0098-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate.</p><p><strong>Objective.—: </strong>To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas.</p><p><strong>Design.—: </strong>Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model.</p><p><strong>Results.—: </strong>In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes.</p><p><strong>Conclusions.—: </strong>Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010096","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":"Use of Low-Dose Platelets in Actively Bleeding Patients: A Retrospective Analysis of a Cardiac Surgery Cohort.","authors":"Caitlin Raymond, Ashlie Atchison, Sri Bharathi Kavuri, Colby Elder, Scott Lick, David Guerra, Justin B L Halls, Stephen Cheney, Christoper J Zahner, Robert L Kruse","doi":"10.5858/arpa.2024-0102-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0102-OA","url":null,"abstract":"<p><strong>Context.—: </strong>During platelet shortages, many hospitals produce low-dose platelets by splitting a standard platelet unit (>3 × 1011 platelets in the United States) in 2, then providing these low-dose units to patients. While low-dose units were previously found to be effective for prophylactic purposes in patients undergoing chemotherapy in the Prophylactic Platelet Dose (PLADO) trial, their use in actively bleeding patients has not yet been assessed.</p><p><strong>Objective.—: </strong>To assess the use and safety of low-dose platelets in actively bleeding patients.</p><p><strong>Design.—: </strong>We performed a retrospective review of cardiac surgery cases receiving platelet units for 18 months at 1 hospital. Two cohorts, those receiving only whole-dose platelets (37 cases) and those receiving only low-dose platelets (38 cases), were compared during the intraoperative and the 24-hour perioperative period. Mean number of platelet transfusions, dose of other blood products, estimated blood loss, bleeding complications in index cases, and all-cause mortality within 30 days of discharge were compared.</p><p><strong>Results.—: </strong>There was no significant difference in mean number of intraoperative platelet transfusions between the cohorts (1.61 versus 1.53, P = .57). There was no significant increase in the transfusion of other blood products, estimated blood loss, bleeding complications in index cases, or all-cause mortality within 30 days of discharge in the low-dose platelet cohort, apart from a small increase in requirement for fresh frozen plasma in the perioperative period.</p><p><strong>Conclusions.—: </strong>These results suggest that low-dose platelets are tentatively equivalent to whole-dose platelets in cardiac surgery during shortages, with similar transfusion requirements and clinical outcomes between groups. Future multicenter studies are needed to confirm these findings.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001566","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":"Effects of the Paris System on the Unsatisfactory Category in a Cytohistologic Correlation Study of Patients With Urothelial Carcinoma.","authors":"Karina Munhoz de Paula Alves Coelho, Hercilio Fronza, Paula de Carvalho, Giordano Barzotto Tagliari, Lara Cristina Carvalho de Tavares, Jaqueline Stall, Hortência Gomes da Silveira, Paulo Henrique Condeixa de França","doi":"10.5858/arpa.2023-0506-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0506-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The main objectives of the Paris System are to detect high-grade urothelial carcinoma, to standardize morphologic criteria and the cytopathologic report, to reduce the prevalence of the atypia category, and to improve the malignancy risk stratification.</p><p><strong>Objective.—: </strong>To compare the results and sensitivity of cytologic classification before and after reclassification by the Paris System.</p><p><strong>Design.—: </strong>Urinary cytology samples from patients with a histologic diagnosis of urothelial carcinoma were reclassified on the basis of the Paris System categories. The diagnoses before reclassification were divided into 5 categories (A, B, C, D, E) and compared with the Paris System (I, II, III, IV, V). Sensitivity was calculated considering cytohistologic agreement in relation to high-grade urothelial carcinoma.</p><p><strong>Results.—: </strong>A total of 111 urinary cytology samples from patients were analyzed, corresponding to 40 histologic samples; of these, 12 (30%) were high grade and the remaining were low grade. Comparison of the correlated categories showed an increase from 3 (3 of 111; 2.7%) (A) to 31 (31 of 111; 27.9%) (I) in unsatisfactory cases and a decrease from 67 (67 of 111; 60,0%) to 30 (30 of 111; 27.0%) in negative cases, while the atypia category remained unchanged (15 cases [15 of 111; 13.5%]) (C and III). Suspicious cases increased from 5 (5 of 111; 4.5%) (D) to 14 (14 of 111; 12.6%) (IV) and cases of urothelial carcinoma were unchanged (21 cases [21 of 111; 18.9%]) (E and V). Sensitivity was 69% for the previous classification and 90% for the Paris System.</p><p><strong>Conclusions.—: </strong>The Paris System improved the sensitivity of urinary cytology and the standardization of the unsatisfactory criteria, with an increase of cases in this category and a decrease of cases previously classified as negative among patients with a subsequent histologic diagnosis of urothelial carcinoma.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984154","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":"Global Study on the Accuracy of Human Epidermal Growth Factor Receptor 2-Low Diagnosis in Breast Cancer.","authors":"Josef Rüschoff, Alexander Penner, Ian O Ellis, M Elizabeth Hale Hammond, Annette Lebeau, Robert Y Osamura, Fréderique Penault-Llorca, Federico Rojo, Chirag Desai, Akira Moh, Neil Atkey, Gudrun Baenfer, Andreas H Scheel, Corrado D'Arrigo, Hans-Ulrich Schildhaus, Giuseppe Viale","doi":"10.5858/arpa.2024-0052-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0052-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+/2+ with no gene amplification.</p><p><strong>Objective.—: </strong>To assess pathologists' accuracy and training efficacy in the diagnosis of HER2-low.</p><p><strong>Design.—: </strong>Agreement rates of HER2-low scoring in breast cancer tissue were assessed between expert consensus and real-world pathologists (n = 77 from 14 countries) before and after a specific 4-hour training for HER2-low detection. Two assays were evaluated, the Ventana Pathway 4B5 CDx and the Dako HercepTest (polyclonal). Concordance of the pathologists with consensus score and efficacy of training were measured by Cohen κ, overall rater agreement, and receiver operating characteristic (ROC) curve statistics.</p><p><strong>Results.—: </strong>In the Ventana 4B5 HER2-low category, baseline agreement rates were >80% but <90%. Negative percentage agreement was improved from 80.6% to 91.1% by training. In the HER2-0 category, positive percentage agreement (74.6%) was the only parameter below the 80% benchmark but was significantly improved to 89.2% after training. Training efficacy was confirmed by ROC curve analysis, which shows improvement for the identification of HER2-0 and HER2-low cases. Finally, in-depth examination of cases with discordant HER2 status disclosed specific issues of HER2-low underscoring and overscoring.</p><p><strong>Conclusions.—: </strong>The ability of pathologists to achieve acceptable diagnostic accuracy in identifying patients with HER2-low breast cancer could be enhanced by short-term training. Potential routes to improve the quality of HER2-low scoring in clinical practice have been identified.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903869","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 Prevalence of Multistep Algorithms in Diagnostic Clostridioides difficile Laboratory Testing.","authors":"Kaede V Sullivan, Rhona J Souers, Erica Hillesland, Dylan Pillai, Daniel D Rhoads, Robin Rolf, Patricia J Simner, Christina M Wojewoda, Carol A Rauch","doi":"10.5858/arpa.2023-0434-CP","DOIUrl":"https://doi.org/10.5858/arpa.2023-0434-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Laboratory testing practices for diagnosis of Clostridioides difficile infection (CDI) have evolved in response to published guidelines, availability of highly sensitive nucleic acid amplification tests (NAATs), perceived problems with the specificity of NAATs, and CDI reporting requirements.</p><p><strong>Objective.—: </strong>To assess the current state of laboratory practice for diagnostic CDI testing.</p><p><strong>Design.—: </strong>An optional 8-item supplemental questionnaire was distributed in December 2019 to the 1374 laboratories participating in the College of American Pathologists C difficile Detection (CDF) proficiency testing program challenge CDF-C.</p><p><strong>Results.—: </strong>Of 1374 CDF-C participants, 1160 (84.4%) responded, predominantly representing laboratories based in the United States (1077 of 1160; 92.8%). The majority reported using a multistep testing algorithm (684 of 1159; 59.0%). Initial testing with a glutamate dehydrogenase and toxin A/B combination test followed by NAAT for discrepant results was the most common testing method (360 of 1146; 31.4%). NAAT alone (299 of 1146; 26.1%) was next, then NAAT followed by an assay that included toxin A/B enzyme immunoassay if NAAT is positive (258 of 1146; 22.5%). Only 5.4% (62 of 1146) reported using toxin A/B immunoassay alone. Most respondents (1093 of 1131; 96.6%) reported rejecting CDI tests on formed stool, but rejection of CDI testing in pediatric patients was uncommon (211 of 1131; 18.7%). Rejection of CDI testing in patients using laxatives was reported more often by US-based respondents (379 of 1054 [36.0%] versus 9 of 77 [11.7%], P < .001).</p><p><strong>Conclusions.—: </strong>Multistep algorithms for CDI diagnosis are widely used in line with published recommendations. Most respondents reported rejection of formed stool for CDI testing, but few reported rejection of testing in infants and patients taking laxatives, suggesting these may be areas of opportunity for laboratories to pursue in improving CDI testing practices.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891249","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":"Pathologic and Molecular Features of Perihilar Cholangiocarcinoma Based on U-P Point Division.","authors":"Ying Xiao, Qijia Zhang, Canhong Xiang, Jianghui Yang, Bowen Li, Hongfang Yin","doi":"10.5858/arpa.2023-0547-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0547-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines propose a classification scheme that differs from the Union for International Cancer Control (UICC) system, in which the anatomic U-P point is the boundary between intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma (PCC).</p><p><strong>Objective.—: </strong>To investigate whether this classification system improves clinicopathologic and genomic differentiation.</p><p><strong>Design.—: </strong>Fifty-eight PCC cases defined by the UICC system were collected and classified into intrahepatic PCC (IPCC) and extrahepatic PCC (EPCC) categories using U-P point division. They were analyzed by next-generation sequencing using a panel that targeted 425 cancer-related genes.</p><p><strong>Results.—: </strong>The IPCC group exhibited a significant larger tumor size compared with the EPCC group (4.67 ± 2.44 cm versus 2.50 ± 0.91 cm, P = .002). The mutation frequency of KRAS proto-oncogene, GTPase (KRAS) Q61 was also significantly higher in the IPCC group than in the EPCC group (16.7% versus 0.0%, P = .03). There were no statistically significant differences in other pathologic features or genomic characteristics, including tumor mutation burden and microsatellite instability. Significant differences in gene mutation rates, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA; 0.0% versus 15.8%, P = .01) and tumor protein p53 (TP53; 34.5% versus 63.2%, P = .04), were observed between PCC and adjacent biliary tract cancers.</p><p><strong>Conclusions.—: </strong>This study offers valuable insight into the clinicopathologic and genomic features of PCC. It is proposed that the U-P point division may have limited potential to refine the characterization of PCC regarding these features, and that the UICC classification system can readily demonstrate the molecular specificity of PCC.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876947","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":"T-Cell-Rich Hodgkin Lymphoma With Features of Classic Hodgkin Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic and Immunophenotypic Features.","authors":"Siba El Hussein, Hong Fang, Fatima Zahra Jelloul, Wei Wang, Sanam Loghavi, Roberto N Miranda, Jonathan W Friedberg, W Richard Burack, Andrew G Evans, Jie Xu, L Jeffrey Medeiros","doi":"10.5858/arpa.2023-0133-OA","DOIUrl":"10.5858/arpa.2023-0133-OA","url":null,"abstract":"<p><strong>Context.—: </strong>It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies.</p><p><strong>Objective.—: </strong>To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation.</p><p><strong>Design.—: </strong>The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated.</p><p><strong>Results.—: </strong>These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Tiftein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later.</p><p><strong>Conclusions.—: </strong>These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"914-920"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500465","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":"Digital and Computational Pathology Are Pathologists' Physician Extenders.","authors":"Casey P Schukow, Timothy Craig Allen","doi":"10.5858/arpa.2023-0537-ED","DOIUrl":"10.5858/arpa.2023-0537-ED","url":null,"abstract":"","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"866-870"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295543","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":"Real-World Evidence of Intra-institutional Performance Variation in Indefinite Diagnosis of Pleural Effusion Cytology.","authors":"Kuang-Hua Chen, Chien-Yi Kuo, Tai-Di Chen","doi":"10.5858/arpa.2023-0002-OA","DOIUrl":"10.5858/arpa.2023-0002-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Pleural effusion cytology has been widely used in the investigation of pathologic fluid accumulation in pleural spaces. However, up to one-tenth of the cases were not given a definitive diagnosis. These cases have largely been neglected in the bulk of the literature.</p><p><strong>Objective.—: </strong>To provide real-world data on indefinite diagnoses including \"atypia of uncertain significance\" (AUS) and \"suspicious for malignancy\" (SFM) in pleural effusion cytology and to investigate pathologists' practice patterns on using these diagnostic categories.</p><p><strong>Design.—: </strong>We reported the diagnoses of 51 675 cases. Descriptive statistics and correlation coefficients were used to analyze the relationships between different diagnostic categories and pathologists' practice patterns and possible explanatory variables.</p><p><strong>Results.—: </strong>The diagnoses AUS and SFM were reported in 4060 cases (7.86%) and 1554 cases (3.01%) in the cohort, respectively. The mean rates for these indefinite diagnoses varied up to 3-fold between pathologists. Correlations were found between AUS and SFM, as well as between indefinite diagnoses and negative for malignancy (NFM). No correlations were found between pathologists' years of experience or case volume and the rates of indefinite diagnosis or diagnostic certainty.</p><p><strong>Conclusions.—: </strong>A real-world baseline for the rates of indefinite diagnoses in pleural effusion cytology is provided in this large retrospective study. Pathologists show significant variation in their use of indefinite diagnostic categories, and the tendency to use these ambiguous terms was not correlated with individuals' experience or case volume. How to untangle the intertwined relationship between the uncertainty of indefinite diagnoses and that of NFM requires future prospective studies.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"938-944"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464985","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 Droplet Digital Polymerase Chain Reaction-Based Tool to Aid in Melanoma Diagnosis.","authors":"Jason R McFadden, Iman Salem, Mirjana Stevanovic, Rachael E Barney, Advaita S Chaudhari, Meagan Ann Chambers, Keegan O'Hern, Jeffrey M Cloutier, Shaofeng Yan, Alvaro J Ramos-Rodriguez, Darcy Arendt Kerr, Shabnam Momtahen, Robert E LeBlanc, Gregory J Tsongalis, Edward G Hughes, Aravindhan Sriharan","doi":"10.5858/arpa.2024-0027-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0027-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma.</p><p><strong>Objective.—: </strong>To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms.</p><p><strong>Design.—: </strong>One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard.</p><p><strong>Results.—: </strong>ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth.</p><p><strong>Conclusions.—: </strong>With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861913","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}