Pub Date : 2024-12-30DOI: 10.5858/arpa.2024-0304-OA
Hyunju Park, Young Lyun Oh, Myoung Kyoung Kim, Soo Yeon Hahn, Jun-Ho Choe, Man Ki Chung, Bogyeong Han, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim
Context.—: Fine-needle aspiration is an effective tool for sampling thyroid nodules; its results are classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), whose categories define malignancy risks.
Objective.—: To compare the histologic outcomes and disease-free survival (DFS) with the preceding BSRTC categories, we hypothesized that the initial cytologic categories may reflect long-term outcomes in follicular thyroid carcinoma (FTC), similar to those observed in papillary thyroid carcinoma.
Design.—: This retrospective study enrolled 134 patients with FTC who underwent preoperative cytology between April 2011 and December 2020. Results were classified into 6 categories according to the BSRTC: nondiagnostic, benign, atypia of uncertain significance (AUS), follicular neoplasm (FN), suspicious for malignancy, or malignant.
Results.—: Overall, 8 of 134 patients (6.0%) were categorized as having a nondiagnostic FTC, 35 of 134 (26.1%) as benign, 51 of 134 (38.1%) as AUS, and 40 of 134 (29.9%) as FN. No lesions were classified as suspicious for malignancy or malignant. The nondiagnostic, AUS, and FN categories were associated with a progressively higher risk of vascular invasion, disease recurrence, and high-risk FTC, based on the 2022 World Health Organization classification (P for trend = .01, .01, and .01, respectively). Disease-free survival was lower in the FN group (log-rank P = .01).
Conclusions.—: The initial BSRTC results may reflect not only the risk of malignancy but also the presence of vascular invasion and poor prognosis when the thyroid nodule is diagnosed as FTC. These results may provide prognostic information for therapeutic decision-making and clinical management of FTC.
上下文。-:细针穿刺是甲状腺结节取样的有效工具;其结果根据Bethesda甲状腺细胞病理学报告系统(BSRTC)进行分类,其分类定义了恶性肿瘤风险。为了比较组织学结果和无病生存期(DFS)与之前的BSRTC分类,我们假设初始细胞学分类可能反映滤泡性甲状腺癌(FTC)的长期结果,类似于甲状腺乳头状癌的观察结果。-:这项回顾性研究纳入了134例FTC患者,他们在2011年4月至2020年12月期间接受了术前细胞学检查。结果根据BSRTC分为6类:非诊断性、良性、意义不确定异型(AUS)、滤泡性肿瘤(FN)、可疑恶性、恶性。总体而言,134例患者中有8例(6.0%)被归类为非诊断性FTC, 35例(26.1%)为良性,51例(38.1%)为AUS, 40例(29.9%)为FN。未发现可疑恶性或恶性病变。根据2022年世界卫生组织的分类,非诊断性、AUS和FN分类与血管侵犯、疾病复发和高风险FTC的风险逐渐升高相关(趋势P分别= 0.01、0.01和0.01)。FN组无病生存率较低(log-rank P = 0.01)。-:当甲状腺结节被诊断为FTC时,最初的BSRTC结果可能不仅反映了恶性肿瘤的风险,还反映了存在血管侵犯和预后不良。这些结果可为FTC的治疗决策和临床管理提供预后信息。
{"title":"Prognostic Implications of the Bethesda System in Fine-Needle Aspiration for Follicular Thyroid Carcinoma.","authors":"Hyunju Park, Young Lyun Oh, Myoung Kyoung Kim, Soo Yeon Hahn, Jun-Ho Choe, Man Ki Chung, Bogyeong Han, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim","doi":"10.5858/arpa.2024-0304-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0304-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Fine-needle aspiration is an effective tool for sampling thyroid nodules; its results are classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), whose categories define malignancy risks.</p><p><strong>Objective.—: </strong>To compare the histologic outcomes and disease-free survival (DFS) with the preceding BSRTC categories, we hypothesized that the initial cytologic categories may reflect long-term outcomes in follicular thyroid carcinoma (FTC), similar to those observed in papillary thyroid carcinoma.</p><p><strong>Design.—: </strong>This retrospective study enrolled 134 patients with FTC who underwent preoperative cytology between April 2011 and December 2020. Results were classified into 6 categories according to the BSRTC: nondiagnostic, benign, atypia of uncertain significance (AUS), follicular neoplasm (FN), suspicious for malignancy, or malignant.</p><p><strong>Results.—: </strong>Overall, 8 of 134 patients (6.0%) were categorized as having a nondiagnostic FTC, 35 of 134 (26.1%) as benign, 51 of 134 (38.1%) as AUS, and 40 of 134 (29.9%) as FN. No lesions were classified as suspicious for malignancy or malignant. The nondiagnostic, AUS, and FN categories were associated with a progressively higher risk of vascular invasion, disease recurrence, and high-risk FTC, based on the 2022 World Health Organization classification (P for trend = .01, .01, and .01, respectively). Disease-free survival was lower in the FN group (log-rank P = .01).</p><p><strong>Conclusions.—: </strong>The initial BSRTC results may reflect not only the risk of malignancy but also the presence of vascular invasion and poor prognosis when the thyroid nodule is diagnosed as FTC. These results may provide prognostic information for therapeutic decision-making and clinical management of FTC.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904308","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}
Pub Date : 2024-12-26DOI: 10.5858/arpa.2024-0267-OA
Jaclyn M Plotzke, David Manthei, Douglas R Fullen, May P Chan, Scott C Bresler, Hong Xiao, Aleodor A Andea, Paul W Harms
Context.—: Patients with melanoma can develop second tumors representing either metastases or new primary melanoma. This distinction has profound implications for management. Although clinicopathologic features are often sufficient, molecular assays can support the presence or absence of clonal relatedness in challenging cases. However, the potential for false-positive and false-negative results in this context is not well described.
Objective.—: To evaluate clinical molecular assays used to determine whether melanoma tumors represent primary-metastasis pairs or unrelated tumors.
Design.—: We identified clinical cases at our institution in which paired melanocytic tumors were analyzed for clonal relatedness by molecular assays. Results were compared against data sets and/or controls to establish the likelihood that paired tumors were clonally related.
Results.—: In total, 12 pairs were evaluated by single-nucleotide polymorphism (SNP) array, targeted next-generation sequencing (NGS), or both. SNP array predicted relatedness in 5 of 9 cases and unrelatedness in 4 cases. In SNP comparisons, whole-chromosomal and arm-level changes were often nonspecific (coincidentally similar between unrelated tumors). Targeted NGS predicted relatedness in 2 of 4 cases and unrelatedness in 1 case, and was equivocal/noncontributory in 1 case. For targeted NGS, nonspecific (coincidentally similar) results were related to recurrent oncogenic drivers or pairs lacking detected oncogene mutations.
Conclusions.—: The genome-wide analysis provided by SNP array was optimal for assessment of clonality. Targeted NGS can be informative but may be equivocal in some cases. The choice of assay may rely upon considerations including the amount of DNA, likelihood of distinctive mutations, and need for therapeutic target identification.
{"title":"Clinical Molecular Testing for Clonal Relatedness of Second Melanoma Tumors.","authors":"Jaclyn M Plotzke, David Manthei, Douglas R Fullen, May P Chan, Scott C Bresler, Hong Xiao, Aleodor A Andea, Paul W Harms","doi":"10.5858/arpa.2024-0267-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0267-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Patients with melanoma can develop second tumors representing either metastases or new primary melanoma. This distinction has profound implications for management. Although clinicopathologic features are often sufficient, molecular assays can support the presence or absence of clonal relatedness in challenging cases. However, the potential for false-positive and false-negative results in this context is not well described.</p><p><strong>Objective.—: </strong>To evaluate clinical molecular assays used to determine whether melanoma tumors represent primary-metastasis pairs or unrelated tumors.</p><p><strong>Design.—: </strong>We identified clinical cases at our institution in which paired melanocytic tumors were analyzed for clonal relatedness by molecular assays. Results were compared against data sets and/or controls to establish the likelihood that paired tumors were clonally related.</p><p><strong>Results.—: </strong>In total, 12 pairs were evaluated by single-nucleotide polymorphism (SNP) array, targeted next-generation sequencing (NGS), or both. SNP array predicted relatedness in 5 of 9 cases and unrelatedness in 4 cases. In SNP comparisons, whole-chromosomal and arm-level changes were often nonspecific (coincidentally similar between unrelated tumors). Targeted NGS predicted relatedness in 2 of 4 cases and unrelatedness in 1 case, and was equivocal/noncontributory in 1 case. For targeted NGS, nonspecific (coincidentally similar) results were related to recurrent oncogenic drivers or pairs lacking detected oncogene mutations.</p><p><strong>Conclusions.—: </strong>The genome-wide analysis provided by SNP array was optimal for assessment of clonality. Targeted NGS can be informative but may be equivocal in some cases. The choice of assay may rely upon considerations including the amount of DNA, likelihood of distinctive mutations, and need for therapeutic target identification.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901096","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}
Pub Date : 2024-12-26DOI: 10.5858/arpa.2024-0327-OA
Amber Y Bo, Yee Chung Cheng, Ben George, Deepak Kilari, Jonathan R Thompson, Julie M Jorns
Context.—: Patients can now immediately review pathology reports via online health portals.
Objective.—: To better characterize patient perceptions of pathology report helpfulness and preferences for access of pathology reports via a patient portal.
Design.—: Semistructured interviews were conducted with oncology patients with breast, endocrine, gastrointestinal, genitourinary, and thoracic malignancies. Patient demographic information, cancer type, question responses, and thematically grouped comments were statistically analyzed.
Results.—: Among 230 patients, there was equal sex distribution (116 of 230, 50.4% female; 114 of 230, 49.6% male). Patients who viewed or had a support member view their reports in the portal (172 of 230; 74.8%) differed from those who did not (58 of 230; 25.2%) only in perception of helpfulness (P < .001) of the report. Difficulty understanding medical terminology was the most frequently cited challenge among both those who found the reports helpful (30 of 160; 18.75%) and not helpful (31 of 46; 67.4%). Most patients (196 of 230; 85.2%) preferred immediate release of results, even if the news was bad, whereas some (34 of 230; 14.7%) would opt out of immediate release for fear of misunderstanding (11 of 34; 32.4%) or receiving distressing information from reading the report (23 of 34; 67.6%).
Conclusions.—: Options for portal flexibility (ie, patient choice of opting for immediate release of some, but not all, results), patient-centered pathology reports, educational materials, clinician preparation of patients, and tailored patient support are strategies that can help more patients benefit from reviewing pathology report information.
{"title":"Online Portal Use of Pathology Reports in Patients With Solid Tumors.","authors":"Amber Y Bo, Yee Chung Cheng, Ben George, Deepak Kilari, Jonathan R Thompson, Julie M Jorns","doi":"10.5858/arpa.2024-0327-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0327-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Patients can now immediately review pathology reports via online health portals.</p><p><strong>Objective.—: </strong>To better characterize patient perceptions of pathology report helpfulness and preferences for access of pathology reports via a patient portal.</p><p><strong>Design.—: </strong>Semistructured interviews were conducted with oncology patients with breast, endocrine, gastrointestinal, genitourinary, and thoracic malignancies. Patient demographic information, cancer type, question responses, and thematically grouped comments were statistically analyzed.</p><p><strong>Results.—: </strong>Among 230 patients, there was equal sex distribution (116 of 230, 50.4% female; 114 of 230, 49.6% male). Patients who viewed or had a support member view their reports in the portal (172 of 230; 74.8%) differed from those who did not (58 of 230; 25.2%) only in perception of helpfulness (P < .001) of the report. Difficulty understanding medical terminology was the most frequently cited challenge among both those who found the reports helpful (30 of 160; 18.75%) and not helpful (31 of 46; 67.4%). Most patients (196 of 230; 85.2%) preferred immediate release of results, even if the news was bad, whereas some (34 of 230; 14.7%) would opt out of immediate release for fear of misunderstanding (11 of 34; 32.4%) or receiving distressing information from reading the report (23 of 34; 67.6%).</p><p><strong>Conclusions.—: </strong>Options for portal flexibility (ie, patient choice of opting for immediate release of some, but not all, results), patient-centered pathology reports, educational materials, clinician preparation of patients, and tailored patient support are strategies that can help more patients benefit from reviewing pathology report information.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901097","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}
Pub Date : 2024-12-24DOI: 10.5858/arpa.2024-0259-CP
Jeffrey A Vos, Girish Venkataraman, Liuyan Jennifer Jiang, Barbara J Blond, Suzanne Coulter, Rhona J Souers
Context.—: Morphologic evaluation of peripheral blood smears provides valuable information to diagnose and manage a variety of hematologic disorders.
Objective.—: To measure the competency of the technical staff in the morphologic evaluation of peripheral blood smears and provide performance trends.
Design.—: Participating technologists accessed 10 whole slide-imaged peripheral blood smears through a web-based imaging tool in 2 separate studies. Participants performed a 100-cell differential and morphologic evaluation for each slide image. Grading criteria, determined by 3 hematopathologists, were weighted according to their clinical significance (score range, 0-100 for each case). Each institution and participant answered a questionnaire to assess the impact of current practices and educational programs on competency scores.
Results.—: A total of 776 technologists from 92 institutions participated in study 1 and 1495 technologists from 179 institutions participated in study 2. Median performance scores for institutions were 78.9 and 87.6 for studies 1 and 2, respectively, encompassing a range of hematologic disorders. Based on results of the questionnaire for study 1, higher performance scores were seen when institutions required a specific number of continuing education credits per year through an agency (P = .005). In study 2, institutions with remediation procedures following a failed competency demonstrated higher performance scores (P = .03).
Conclusions.—: Medical technologist competency of peripheral blood smears improves with level of experience and is positively impacted through attending educational programs. Whole slide images offer a convenient means of assessing technical competence and provide data to allow institutions to appropriately focus their procedures and educational efforts.
{"title":"Technical Competency Assessment of Peripheral Blood Smears: Tools and Trends Learned From 2 College of American Pathologists Q-Probes Studies.","authors":"Jeffrey A Vos, Girish Venkataraman, Liuyan Jennifer Jiang, Barbara J Blond, Suzanne Coulter, Rhona J Souers","doi":"10.5858/arpa.2024-0259-CP","DOIUrl":"https://doi.org/10.5858/arpa.2024-0259-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Morphologic evaluation of peripheral blood smears provides valuable information to diagnose and manage a variety of hematologic disorders.</p><p><strong>Objective.—: </strong>To measure the competency of the technical staff in the morphologic evaluation of peripheral blood smears and provide performance trends.</p><p><strong>Design.—: </strong>Participating technologists accessed 10 whole slide-imaged peripheral blood smears through a web-based imaging tool in 2 separate studies. Participants performed a 100-cell differential and morphologic evaluation for each slide image. Grading criteria, determined by 3 hematopathologists, were weighted according to their clinical significance (score range, 0-100 for each case). Each institution and participant answered a questionnaire to assess the impact of current practices and educational programs on competency scores.</p><p><strong>Results.—: </strong>A total of 776 technologists from 92 institutions participated in study 1 and 1495 technologists from 179 institutions participated in study 2. Median performance scores for institutions were 78.9 and 87.6 for studies 1 and 2, respectively, encompassing a range of hematologic disorders. Based on results of the questionnaire for study 1, higher performance scores were seen when institutions required a specific number of continuing education credits per year through an agency (P = .005). In study 2, institutions with remediation procedures following a failed competency demonstrated higher performance scores (P = .03).</p><p><strong>Conclusions.—: </strong>Medical technologist competency of peripheral blood smears improves with level of experience and is positively impacted through attending educational programs. Whole slide images offer a convenient means of assessing technical competence and provide data to allow institutions to appropriately focus their procedures and educational efforts.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883862","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}
Pub Date : 2024-12-23DOI: 10.5858/arpa.2024-0228-OA
Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang
Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.
Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.
Design.—: Over 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.
Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but 31 patients (4%) had unusual blasts that were either completely or partially negative for CD34. Of the latter, recurrent genetic abnormalities were identified in 13 (42%) including 10 with nucleophosmin 1 (NPM1) mutation, 1 with lysine methyltransferase 2A (KMT2A) rearrangement, and 2 with t(3;5)(q25.3;q35.1)/NPM1::myeloid leukemia factor 1 (MLF1). These cases were classified as MDS prior to the 2022 classifications, but 9 of 13 (69%) and 7 of 13 (52%) cases would be reclassified as AML according to the 5th edition of the World Health Organization classification and the International Consensus Classification, respectively. Eight cases (26%) had multihit tumor protein p53 (TP53) mutation, and 6 of them were ultimately diagnosed as or quickly evolved to pure erythroid leukemia. Of the remaining 10 cases, 4 uncharacteristically had no detectable molecular genetic abnormalities.
Conclusions.—: Our data show that, if a presumptive MDS shows a nonprimitive blast phenotype, caution is needed to rule out AML with recurrent genetic abnormality with an oligoblastic presentation, high-risk myeloid neoplasms with double-hit TP53 mutation with abnormal erythroid proliferation, and MDS with molecular-genetic and clinical features more akin to AML.
{"title":"The Significance of Detecting an Unusual Myeloblast Immunophenotype in a Presumptive Clinical Diagnosis of Myelodysplastic Syndromes.","authors":"Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang","doi":"10.5858/arpa.2024-0228-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0228-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.</p><p><strong>Objective.—: </strong>To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.</p><p><strong>Design.—: </strong>Over 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.</p><p><strong>Results.—: </strong>Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but 31 patients (4%) had unusual blasts that were either completely or partially negative for CD34. Of the latter, recurrent genetic abnormalities were identified in 13 (42%) including 10 with nucleophosmin 1 (NPM1) mutation, 1 with lysine methyltransferase 2A (KMT2A) rearrangement, and 2 with t(3;5)(q25.3;q35.1)/NPM1::myeloid leukemia factor 1 (MLF1). These cases were classified as MDS prior to the 2022 classifications, but 9 of 13 (69%) and 7 of 13 (52%) cases would be reclassified as AML according to the 5th edition of the World Health Organization classification and the International Consensus Classification, respectively. Eight cases (26%) had multihit tumor protein p53 (TP53) mutation, and 6 of them were ultimately diagnosed as or quickly evolved to pure erythroid leukemia. Of the remaining 10 cases, 4 uncharacteristically had no detectable molecular genetic abnormalities.</p><p><strong>Conclusions.—: </strong>Our data show that, if a presumptive MDS shows a nonprimitive blast phenotype, caution is needed to rule out AML with recurrent genetic abnormality with an oligoblastic presentation, high-risk myeloid neoplasms with double-hit TP53 mutation with abnormal erythroid proliferation, and MDS with molecular-genetic and clinical features more akin to AML.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878844","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}
Pub Date : 2024-12-18DOI: 10.5858/arpa.2024-0111-OA
Benjamin Glass, Michel E Vandenberghe, Surya Teja Chavali, Syed Ashar Javed, Murray Resnick, Harsha Pokkalla, Hunter Elliott, Sudha Rao, Shamira Sridharan, Jacqueline A Brosnan-Cashman, Ilan Wapinski, Michael Montalto, Andrew H Beck, Craig Barker
Context.—: Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists. Machine learning tools have the potential to minimize inconsistencies, although their use is not presently widespread.
Objective.—: To assess the applicability of machine learning to the quality control process for biomarker scoring in oncology, we developed and validated an automated machine learning model to be applied as a quality control tool for monitoring the assessment of human epidermal growth factor-2 (HER2).
Design.—: The model was trained using whole slide images from multiple sources to quantify HER2 expression and measure immunohistochemistry stain intensity, tumor area, and the presence of artifacts or ductal carcinoma in situ across breast cancer phenotypes. The quality control tool was deployed in a real-world cohort of HER2-stained breast cancer sample images collected from routine diagnostic practice to evaluate trends in HER2 testing quality indicators and between pathology laboratories.
Results.—: Automated image analysis for HER2 scoring is consistent and reliable using this algorithm. Deployment of the HER2 quality control tool across 3 clinical laboratories revealed interlaboratory variability in HER2 scoring and inconsistencies in data reporting.
Conclusions.—: These results support the future incorporation of quality control algorithms for real-time monitoring of clinical laboratories contributing to clinical trials in oncology and in the real-world setting of HER2 immunohistochemistry testing in local clinical laboratories and hospitals.
{"title":"Deployment of a Machine Learning Algorithm in a Real-World Cohort for Quality Control Monitoring of Human Epidermal Growth Factor-2-Stained Clinical Specimens in Breast Cancer.","authors":"Benjamin Glass, Michel E Vandenberghe, Surya Teja Chavali, Syed Ashar Javed, Murray Resnick, Harsha Pokkalla, Hunter Elliott, Sudha Rao, Shamira Sridharan, Jacqueline A Brosnan-Cashman, Ilan Wapinski, Michael Montalto, Andrew H Beck, Craig Barker","doi":"10.5858/arpa.2024-0111-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0111-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists. Machine learning tools have the potential to minimize inconsistencies, although their use is not presently widespread.</p><p><strong>Objective.—: </strong>To assess the applicability of machine learning to the quality control process for biomarker scoring in oncology, we developed and validated an automated machine learning model to be applied as a quality control tool for monitoring the assessment of human epidermal growth factor-2 (HER2).</p><p><strong>Design.—: </strong>The model was trained using whole slide images from multiple sources to quantify HER2 expression and measure immunohistochemistry stain intensity, tumor area, and the presence of artifacts or ductal carcinoma in situ across breast cancer phenotypes. The quality control tool was deployed in a real-world cohort of HER2-stained breast cancer sample images collected from routine diagnostic practice to evaluate trends in HER2 testing quality indicators and between pathology laboratories.</p><p><strong>Results.—: </strong>Automated image analysis for HER2 scoring is consistent and reliable using this algorithm. Deployment of the HER2 quality control tool across 3 clinical laboratories revealed interlaboratory variability in HER2 scoring and inconsistencies in data reporting.</p><p><strong>Conclusions.—: </strong>These results support the future incorporation of quality control algorithms for real-time monitoring of clinical laboratories contributing to clinical trials in oncology and in the real-world setting of HER2 immunohistochemistry testing in local clinical laboratories and hospitals.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848452","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}
Pub Date : 2024-12-13DOI: 10.5858/arpa.2023-0540-RA
Jake Sharma, Fang Zhou, Andre L Moreira
Context.—: Adenocarcinomas are the most common histologic subtype of lung cancer, and exist within a widely divergent clinical, radiologic, molecular, and histologic spectrum. There is a strong association between histologic patterns and prognosis that served as the basis for a recently described grading system. As the study of molecular pathology rapidly evolves, all targetable mutations so far have been found in adenocarcinomas, thus requiring accurate diagnosis and classification for triage of molecular alterations and adequate therapy.
Objective.—: To discuss the rationale for adenocarcinoma classifications within the 2021 5th edition of the World Health Organization, with a focus on nonmucinous tumors, including tumor grading and biopsy/cytology diagnosis.
Data sources.—: PubMed search.
Conclusions.—: A grading system for adenocarcinoma has improved prognostic impact of the classification of pulmonary adenocarcinoma. An accurate diagnosis of adenocarcinoma in small biopsy material is important for tissue triage for molecular studies and ultimately for patient management and treatment.
{"title":"Pulmonary Adenocarcinoma Updates: Histology, Cytology, and Grading.","authors":"Jake Sharma, Fang Zhou, Andre L Moreira","doi":"10.5858/arpa.2023-0540-RA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0540-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Adenocarcinomas are the most common histologic subtype of lung cancer, and exist within a widely divergent clinical, radiologic, molecular, and histologic spectrum. There is a strong association between histologic patterns and prognosis that served as the basis for a recently described grading system. As the study of molecular pathology rapidly evolves, all targetable mutations so far have been found in adenocarcinomas, thus requiring accurate diagnosis and classification for triage of molecular alterations and adequate therapy.</p><p><strong>Objective.—: </strong>To discuss the rationale for adenocarcinoma classifications within the 2021 5th edition of the World Health Organization, with a focus on nonmucinous tumors, including tumor grading and biopsy/cytology diagnosis.</p><p><strong>Data sources.—: </strong>PubMed search.</p><p><strong>Conclusions.—: </strong>A grading system for adenocarcinoma has improved prognostic impact of the classification of pulmonary adenocarcinoma. An accurate diagnosis of adenocarcinoma in small biopsy material is important for tissue triage for molecular studies and ultimately for patient management and treatment.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820246","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}
Pub Date : 2024-12-12DOI: 10.5858/arpa.2024-0094-OA
Emily L Clarke, Derek Magee, Julia Newton-Bishop, William Merchant, Robert Insall, Nigel G Maher, Richard A Scolyer, Grace Farnworth, Anisah Ali, Sally O'Shea, Darren Treanor
Context.—: The current melanoma staging system does not account for 26% of the variance seen in melanoma-specific survival, therefore our ability to predict patient outcome is not fully elucidated. Morphology may be of greater significance than in other solid tumors, with Breslow thickness remaining the strongest prognostic indicator despite being subject to high levels of interobserver variation. The application of convolutional neural networks to whole slide images affords objective morphologic metrics, which may reveal new insights into patient prognosis.
Objective.—: To develop and evaluate a convolutional neural network for invasive cutaneous melanoma detection in whole slide images for the generation of objective prognostic biomarkers based on tumor morphology.
Design.—: One thousand sixty-eight whole slide images containing cutaneous melanoma from 5 data sets have been used in the initial development and evaluation of the convolutional neural network. A 2-class tumor segmentation network with a fully convolutional architecture was trained using sparse annotations. The network was evaluated at per-pixel and per-tumor levels as compared to manual annotation, as well as variation across 3 scanning platforms.
Results.—: The convolutional neural network located conventional cutaneous invasive melanoma tissue with an average per-pixel sensitivity and specificity of 97.59% and 99.86%, respectively, across the 5 test sets. There were high levels of concordance between the tumor dimensions generated by the model as compared to manual annotation, and between the tumor dimensions generated by the model across 3 scanning platforms.
Conclusions.—: We have developed a convolutional neural network that accurately detects invasive cutaneous conventional melanoma in whole slide images from multiple data sources. Future work should assess the use of this network to generate metrics for survival prediction.
{"title":"The Development and Evaluation of a Convolutional Neural Network for Cutaneous Melanoma Detection in Whole Slide Images.","authors":"Emily L Clarke, Derek Magee, Julia Newton-Bishop, William Merchant, Robert Insall, Nigel G Maher, Richard A Scolyer, Grace Farnworth, Anisah Ali, Sally O'Shea, Darren Treanor","doi":"10.5858/arpa.2024-0094-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0094-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The current melanoma staging system does not account for 26% of the variance seen in melanoma-specific survival, therefore our ability to predict patient outcome is not fully elucidated. Morphology may be of greater significance than in other solid tumors, with Breslow thickness remaining the strongest prognostic indicator despite being subject to high levels of interobserver variation. The application of convolutional neural networks to whole slide images affords objective morphologic metrics, which may reveal new insights into patient prognosis.</p><p><strong>Objective.—: </strong>To develop and evaluate a convolutional neural network for invasive cutaneous melanoma detection in whole slide images for the generation of objective prognostic biomarkers based on tumor morphology.</p><p><strong>Design.—: </strong>One thousand sixty-eight whole slide images containing cutaneous melanoma from 5 data sets have been used in the initial development and evaluation of the convolutional neural network. A 2-class tumor segmentation network with a fully convolutional architecture was trained using sparse annotations. The network was evaluated at per-pixel and per-tumor levels as compared to manual annotation, as well as variation across 3 scanning platforms.</p><p><strong>Results.—: </strong>The convolutional neural network located conventional cutaneous invasive melanoma tissue with an average per-pixel sensitivity and specificity of 97.59% and 99.86%, respectively, across the 5 test sets. There were high levels of concordance between the tumor dimensions generated by the model as compared to manual annotation, and between the tumor dimensions generated by the model across 3 scanning platforms.</p><p><strong>Conclusions.—: </strong>We have developed a convolutional neural network that accurately detects invasive cutaneous conventional melanoma in whole slide images from multiple data sources. Future work should assess the use of this network to generate metrics for survival prediction.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815243","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}
Pub Date : 2024-12-12DOI: 10.5858/arpa.2024-0167-OA
Madhurya Ramineni, Rena X Li, Xiaoyan Liao, Yansheng Hao
Context.—: Histologic assessment of tumor regression grade (TRG) on esophagogastrectomy specimens after neoadjuvant therapy is an excellent predictor of local recurrence rate and long-term survival in esophageal adenocarcinomas. Although several grading systems exist globally, the modified Ryan system suggested by the College of American Pathologists (CAP) is widely used in North America. Most systems rely on quantitative percentage estimation of the residual tumor with or without additional qualitative descriptors, which is relatively subjective with poor interobserver agreement.
Objective.—: To test a morphometric-based approach using the microscopic objective lens to estimate the size of the largest focus of the residual tumor.
Design.—: A total of 69 esophageal specimens post neoadjuvant therapy were evaluated. Tumor size was morphometrically determined by the microscopic field, using an Olympus microscope with ×10/×22 eyepieces. Residual viable tumor was categorized into 4 groups, using ×2, ×4, and ×10 objectives: less than or equal to an ×10 field; larger than an ×10 field but less than or equal to an ×4 field; larger than an ×4 field but less than an ×2 field; and larger than or equal to an ×2 field.
Results.—: Morphometric measurements significantly correlated with the CAP treatment effect scores. There was no significant difference in overall survival between larger than or equal to ×2 and ×2 to ×4 groups; however, a 3-tier system (TRG1: ≤ ×10, TRG2: > ×10 and ≤ ×4, and TRG3: > ×4) showed significant survival differences (P = .01). Significant differences in the percentage of lymphovascular and perineural invasion, advanced TNM stage, and lymph node metastasis were identified among the 3 groups.
Conclusions.—: The proposed 3-tier morphometric approach based on microscopic field size is a simple and easy-to-use method, which helps stratify patients into 3 groups with distinct histopathologic features and overall survival.
{"title":"A Simple Morphometric Analysis of Preoperative Therapy Response for Esophageal Adenocarcinoma.","authors":"Madhurya Ramineni, Rena X Li, Xiaoyan Liao, Yansheng Hao","doi":"10.5858/arpa.2024-0167-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0167-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Histologic assessment of tumor regression grade (TRG) on esophagogastrectomy specimens after neoadjuvant therapy is an excellent predictor of local recurrence rate and long-term survival in esophageal adenocarcinomas. Although several grading systems exist globally, the modified Ryan system suggested by the College of American Pathologists (CAP) is widely used in North America. Most systems rely on quantitative percentage estimation of the residual tumor with or without additional qualitative descriptors, which is relatively subjective with poor interobserver agreement.</p><p><strong>Objective.—: </strong>To test a morphometric-based approach using the microscopic objective lens to estimate the size of the largest focus of the residual tumor.</p><p><strong>Design.—: </strong>A total of 69 esophageal specimens post neoadjuvant therapy were evaluated. Tumor size was morphometrically determined by the microscopic field, using an Olympus microscope with ×10/×22 eyepieces. Residual viable tumor was categorized into 4 groups, using ×2, ×4, and ×10 objectives: less than or equal to an ×10 field; larger than an ×10 field but less than or equal to an ×4 field; larger than an ×4 field but less than an ×2 field; and larger than or equal to an ×2 field.</p><p><strong>Results.—: </strong>Morphometric measurements significantly correlated with the CAP treatment effect scores. There was no significant difference in overall survival between larger than or equal to ×2 and ×2 to ×4 groups; however, a 3-tier system (TRG1: ≤ ×10, TRG2: > ×10 and ≤ ×4, and TRG3: > ×4) showed significant survival differences (P = .01). Significant differences in the percentage of lymphovascular and perineural invasion, advanced TNM stage, and lymph node metastasis were identified among the 3 groups.</p><p><strong>Conclusions.—: </strong>The proposed 3-tier morphometric approach based on microscopic field size is a simple and easy-to-use method, which helps stratify patients into 3 groups with distinct histopathologic features and overall survival.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815242","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}
Pub Date : 2024-12-09DOI: 10.5858/arpa.2024-0081-OA
Amel Kime, Guillaume Bataillon, Isabelle Treilleux, Céline Callens, Frédéric Selle, Florian Heitz, Saverio Cinieri, Antonio González-Martin, Christian Schauer, Gabriel Lindahl, Gabriella Parma, Ignace Vergote, Takashi Matsumoto, Cyriac Blonz, Ulrich Canzler, Anna Maria Mosconi, Eva María Guerra Alía, Eric Pujade-Lauraine, Catherine Genestie, Isabelle Ray-Coquard, Pierre-Alexandre Just
Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.
Objective.—: To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD).
Design.—: We reviewed 522 of 806 cases of HGSOC from the PAOLA-1 clinical trial, including 163 cases with tumor BRCA mutation, 345 cases without tumor BRCA mutation, and 14 cases with inconclusive BRCA tests. Regarding HRD status (myChoice HRD Plus assay), 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-), and 55 (10%) inconclusive. Morphologic analysis included tumor architecture (with more than 25% of solid, pseudoendometrioid, and transitional patterns defining a SET architecture), tumor-infiltrating intraepithelial lymphocytes (ieTILs), and tumor stromal lymphocytes (sTILs).
Results.—: SET architecture (51% versus 40%, P = .02), high number of ieTILs (16% versus 8%, P = .007) and more than 10% of sTILs (27% versus 18%, P = .02) were associated with tumor BRCA mutation, mostly for tumors with a BRCA1 mutation. These criteria were also associated with HRD status: 54% versus 33% (P < .001) for SET architecture, 14% versus 6% (P = .008) for high number of ieTILs, and 27% versus 15% (P = .003) for more than 10% of sTILs. SET architecture was also significantly associated with HRD+ tumors without tumor BRCA mutation (P < .001) when compared with HRD- tumors. The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10).
Conclusions.—: The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.
{"title":"Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma?","authors":"Amel Kime, Guillaume Bataillon, Isabelle Treilleux, Céline Callens, Frédéric Selle, Florian Heitz, Saverio Cinieri, Antonio González-Martin, Christian Schauer, Gabriel Lindahl, Gabriella Parma, Ignace Vergote, Takashi Matsumoto, Cyriac Blonz, Ulrich Canzler, Anna Maria Mosconi, Eva María Guerra Alía, Eric Pujade-Lauraine, Catherine Genestie, Isabelle Ray-Coquard, Pierre-Alexandre Just","doi":"10.5858/arpa.2024-0081-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0081-OA","url":null,"abstract":"<p><strong>Context.—: </strong>A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.</p><p><strong>Objective.—: </strong>To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD).</p><p><strong>Design.—: </strong>We reviewed 522 of 806 cases of HGSOC from the PAOLA-1 clinical trial, including 163 cases with tumor BRCA mutation, 345 cases without tumor BRCA mutation, and 14 cases with inconclusive BRCA tests. Regarding HRD status (myChoice HRD Plus assay), 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-), and 55 (10%) inconclusive. Morphologic analysis included tumor architecture (with more than 25% of solid, pseudoendometrioid, and transitional patterns defining a SET architecture), tumor-infiltrating intraepithelial lymphocytes (ieTILs), and tumor stromal lymphocytes (sTILs).</p><p><strong>Results.—: </strong>SET architecture (51% versus 40%, P = .02), high number of ieTILs (16% versus 8%, P = .007) and more than 10% of sTILs (27% versus 18%, P = .02) were associated with tumor BRCA mutation, mostly for tumors with a BRCA1 mutation. These criteria were also associated with HRD status: 54% versus 33% (P < .001) for SET architecture, 14% versus 6% (P = .008) for high number of ieTILs, and 27% versus 15% (P = .003) for more than 10% of sTILs. SET architecture was also significantly associated with HRD+ tumors without tumor BRCA mutation (P < .001) when compared with HRD- tumors. The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10).</p><p><strong>Conclusions.—: </strong>The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796264","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}