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Prognostic Implications of the Bethesda System in Fine-Needle Aspiration for Follicular Thyroid Carcinoma. Bethesda系统细针穿刺治疗滤泡性甲状腺癌的预后意义。
Pub Date : 2024-12-30 DOI: 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。
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引用次数: 0
Clinical Molecular Testing for Clonal Relatedness of Second Melanoma Tumors. 第二代黑色素瘤克隆相关性的临床分子检测。
Pub Date : 2024-12-26 DOI: 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.

上下文。-:黑色素瘤患者可以发展第二肿瘤,代表转移或新的原发性黑色素瘤。这种区别对管理有着深远的影响。虽然临床病理特征往往是足够的,分子分析可以支持克隆相关性的存在或不存在的挑战的情况下。然而,在这种情况下假阳性和假阴性结果的可能性并没有得到很好的描述。-:评价用于确定黑色素瘤肿瘤是否代表原发转移对或不相关肿瘤的临床分子分析。-:我们确定了我们机构的临床病例,其中配对黑色素细胞肿瘤通过分子测定分析克隆相关性。将结果与数据集和/或对照进行比较,以确定配对肿瘤具有克隆相关性的可能性。-:通过单核苷酸多态性(SNP)阵列、靶向下一代测序(NGS)或两者同时评估12对。SNP阵列预测9例中有5例有相关性,4例无相关性。在SNP比较中,全染色体和臂水平的变化通常是非特异性的(巧合的是,不相关的肿瘤之间相似)。靶向NGS预测4例中2例有相关性,1例无相关性,1例不明确或无贡献。对于靶向NGS,非特异性(巧合相似)结果与复发性致癌驱动因子或缺乏检测到的癌基因突变对有关。-: SNP阵列提供的全基因组分析是评估克隆性的最佳方法。有针对性的NGS可以提供信息,但在某些情况下可能模棱两可。测定方法的选择可能取决于考虑因素,包括DNA的数量,独特突变的可能性,以及治疗目标识别的需要。
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引用次数: 0
Online Portal Use of Pathology Reports in Patients With Solid Tumors. 实体肿瘤患者病理报告的在线门户使用。
Pub Date : 2024-12-26 DOI: 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.

上下文。-:患者现在可以通过在线健康门户网站立即查看病理报告。-:更好地描述患者对病理报告有用性的看法,以及通过患者门户访问病理报告的偏好。-:对患有乳腺、内分泌、胃肠道、泌尿生殖系统和胸部恶性肿瘤的肿瘤患者进行半结构化访谈。对患者人口统计信息、癌症类型、问题回答和主题分组评论进行统计分析。-: 230例患者中,性别分布均匀(230例中116例,女性50.4%;230人中114人(49.6%男性)。查看或有支持成员在门户网站查看他们的报告的患者(230人中有172人;74.8%)与没有(230人中有58人;25.2%)仅在报告的“乐于助人”感知上(P < 0.001)。在发现报告有帮助的两个人中,理解医学术语困难是最常提到的挑战(160人中有30人;18.75%)和无帮助(46人中有31人;67.4%)。大多数患者(196 / 230;85.2%的受访者表示,即使是坏消息,也希望立即公布结果。14.7%)会因为害怕误解而选择不立即释放(34人中有11人;32.4%)或从阅读报告中获得令人不安的信息(34人中有23人;67.6%) .Conclusions。-:门户灵活性选项(即患者选择立即释放部分结果,但不是全部结果),以患者为中心的病理报告,教育材料,临床医生对患者的准备以及量身定制的患者支持是可以帮助更多患者从审查病理报告信息中受益的策略。
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引用次数: 0
Technical Competency Assessment of Peripheral Blood Smears: Tools and Trends Learned From 2 College of American Pathologists Q-Probes Studies. 外周血涂片的技术能力评估:从美国病理学家q探针研究学会的工具和趋势。
Pub Date : 2024-12-24 DOI: 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.

上下文。目的:外周血涂片的形态学评价为各种血液病的诊断和治疗提供有价值的信息。-:衡量技术人员在外周血涂片形态学评估方面的能力,并提供绩效趋势。-:参与研究的技术人员通过基于网络的成像工具在两项独立的研究中获取了10张完整的外周血涂片。参与者对每张幻灯片图像进行了100个细胞的差异和形态学评估。评分标准由3名血液病理学家根据其临床意义进行加权(评分范围为0-100)。每个机构和参与者都回答了一份问卷,以评估当前实践和教育计划对能力得分的影响。-:共有来自92间机构的776名技术人员参与研究一,而来自179间机构的1495名技术人员参与研究二。在研究1和研究2中,机构的平均表现得分分别为78.9和87.6,包括一系列血液系统疾病。根据研究1的问卷调查结果,当机构每年通过代理机构要求特定数量的继续教育学分时,表现得分更高(P = 0.005)。在研究2中,在失效胜任力后采取补救措施的机构表现出更高的绩效得分(P = .03)。-:医学技术人员外周血涂片的能力随着经验水平的提高而提高,并通过参加教育项目而受到积极影响。整个幻灯片图像提供了一种方便的评估技术能力的手段,并提供数据,使机构能够适当地集中其程序和教育工作。
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引用次数: 0
The Significance of Detecting an Unusual Myeloblast Immunophenotype in a Presumptive Clinical Diagnosis of Myelodysplastic Syndromes. 检测异常成髓细胞免疫表型在骨髓增生异常综合征推定临床诊断中的意义。
Pub Date : 2024-12-23 DOI: 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.

上下文。-:骨髓增生异常综合征(mds)中的母细胞通常具有原始骨髓免疫表型(CD34+CD117+CD13+CD33+HLA-DR+)。在极少数情况下,在假定的mds中发现CD34阴性或最低表达。-:调查这些病例的发生情况,并检查任何独特的分子遗传特征及其临床相关性。-:回顾性回顾了5年期间进行的2000多项MDS流式细胞术免疫分型试验。排除慢性髓细胞白血病和急性髓细胞白血病(AML)(≥20%原细胞)。-:约800例患者存在与髓系肿瘤相符的异常成髓细胞;96%的病例表现为典型的原始表型,但31例(4%)患者具有不寻常的原细胞,CD34完全或部分阴性。在后者中,13例(42%)发现复发性遗传异常,包括10例核磷蛋白1 (NPM1)突变,1例赖氨酸甲基转移酶2A (KMT2A)重排,2例t(3;5)(q25.3;q35.1)/NPM1::髓系白血病因子1 (MLF1)。这些病例在2022年分类之前被归类为MDS,但根据世界卫生组织第5版分类和国际共识分类,13例中有9例(69%)和13例中有7例(52%)将分别被重新归类为AML。8例(26%)发生多打肿瘤蛋白p53 (TP53)突变,其中6例最终诊断为或迅速发展为纯红细胞白血病。在其余10例中,4例异常地没有可检测到的分子遗传异常。-:我们的数据显示,如果假定的MDS表现为非原始母细胞表型,则需要谨慎排除具有复发性遗传异常并具有少母细胞表现的AML,具有双击TP53突变并异常红细胞增殖的高危髓系肿瘤,以及具有更类似于AML的分子遗传学和临床特征的MDS。
{"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}
引用次数: 0
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. 在真实世界队列中部署机器学习算法,用于乳腺癌中人类表皮生长因子-2染色临床标本的质量控制监测。
Pub Date : 2024-12-18 DOI: 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.

上下文。-:生物标志物状态的精确测定对于临床试验入组和终点分析,以及在现实实践中确定最佳治疗是必要的。然而,由于不同实验室对临床标本的处理和不同病理学家的评估,可能会在这一过程中引入变数。机器学习工具有可能将不一致性降到最低,尽管它们的使用目前还没有得到广泛应用。为了评估机器学习在肿瘤生物标志物评分质量控制过程中的适用性,我们开发并验证了一个自动机器学习模型,该模型将被用作监测人类表皮生长因子-2 (HER2)评估的质量控制工具。-:使用来自多个来源的整张幻灯片图像对模型进行训练,以量化HER2表达,并测量免疫组织化学染色强度、肿瘤面积以及各种乳腺癌表型中伪影或导管原位癌的存在。质量控制工具应用于从常规诊断实践中收集的HER2染色乳腺癌样本图像的真实队列中,以评估HER2检测质量指标和病理实验室之间的趋势。-:使用该算法进行HER2评分的自动图像分析是一致和可靠的。在3个临床实验室中部署HER2质量控制工具,揭示了HER2评分在实验室间的差异和数据报告的不一致性。-:这些结果支持未来将质量控制算法纳入临床实验室的实时监测,有助于肿瘤学临床试验和当地临床实验室和医院的HER2免疫组织化学测试的现实环境。
{"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}
引用次数: 0
Pulmonary Adenocarcinoma Updates: Histology, Cytology, and Grading. 肺腺癌最新进展:组织学、细胞学和分级。
Pub Date : 2024-12-13 DOI: 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.

上下文。-:腺癌是肺癌最常见的组织学亚型,存在于广泛不同的临床、放射学、分子和组织学谱中。组织学模式和预后之间有很强的联系,这是最近描述的分级系统的基础。随着分子病理学研究的快速发展,到目前为止,所有可靶向的突变都在腺癌中被发现,因此需要准确的诊断和分类,以便对分子改变进行分类和适当的治疗。-:讨论2021年世界卫生组织第5版中腺癌分类的基本原理,重点是非黏液性肿瘤,包括肿瘤分级和活检/细胞学诊断。数据源。-: PubMed检索。结论。-:腺癌分级系统提高了肺腺癌分级对预后的影响。小活检材料中腺癌的准确诊断对于分子研究的组织分诊以及最终的患者管理和治疗是重要的。
{"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}
引用次数: 0
The Development and Evaluation of a Convolutional Neural Network for Cutaneous Melanoma Detection in Whole Slide Images. 基于卷积神经网络的全幻灯片皮肤黑色素瘤检测方法的开发与评价。
Pub Date : 2024-12-12 DOI: 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.

上下文。-:目前的黑色素瘤分期系统不能解释黑色素瘤特异性生存变异的26%,因此我们预测患者预后的能力尚未完全阐明。形态学可能比其他实体瘤更重要,尽管观察者之间存在很大差异,但布雷斯洛厚度仍然是最强的预后指标。卷积神经网络在整个幻灯片图像上的应用提供了客观的形态学指标,这可能为患者预后提供新的见解。-:开发和评估一种卷积神经网络,用于在整个幻灯片图像中检测侵入性皮肤黑色素瘤,从而基于肿瘤形态生成客观的预后生物标志物。-:来自5个数据集的包含皮肤黑色素瘤的168张完整幻灯片图像已用于卷积神经网络的初步开发和评估。利用稀疏标注训练了具有全卷积结构的2类肿瘤分割网络。与手动注释相比,该网络在每个像素和每个肿瘤水平上进行评估,以及在3个扫描平台上的变化。-:卷积神经网络定位常规皮肤浸润性黑色素瘤组织,5个测试集的平均每像素灵敏度和特异性分别为97.59%和99.86%。与手工标注相比,该模型生成的肿瘤尺寸之间,以及该模型跨3个扫描平台生成的肿瘤尺寸之间,具有高度的一致性。-:我们开发了一种卷积神经网络,可以准确地检测来自多个数据源的整个幻灯片图像中的侵袭性皮肤常规黑色素瘤。未来的工作应该评估该网络的使用,以生成生存预测的指标。
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引用次数: 0
A Simple Morphometric Analysis of Preoperative Therapy Response for Esophageal Adenocarcinoma. 食管腺癌术前治疗反应的简单形态学分析。
Pub Date : 2024-12-12 DOI: 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.

上下文。-:食管胃切除术标本新辅助治疗后肿瘤消退等级(TRG)的组织学评估是食管腺癌局部复发率和长期生存率的良好预测指标。虽然全球存在多种分级制度,但北美地区广泛采用的是美国病理学家学会(CAP)提出的改良Ryan分级制度。大多数系统依赖于残留肿瘤的定量百分比估计,有或没有额外的定性描述符,这是相对主观的,观察者之间的一致性很差。-:测试一种基于形态计量学的方法,使用显微物镜来估计残余肿瘤的最大焦点的大小。-:对新辅助治疗后的69例食管标本进行评估。使用Olympus显微镜和×10/×22目镜,通过显微镜视野形态测定肿瘤大小。剩余活肿瘤分为4组,使用×2, ×4和×10目标值:小于或等于×10;大于×10字段但小于或等于×4字段的;大于×4字段但小于×2字段;并且大于或等于×2字段。-:形态计量学测量值与CAP治疗效果评分显著相关。大于等于×2组和×2 ~ ×4组的总生存率无显著差异;而三层系统(TRG1:≤×10, TRG2: > ×10和≤×4, TRG3: > ×4)的生存差异有统计学意义(P = 0.01)。三组患者淋巴血管及神经周围浸润率、TNM晚期分期及淋巴结转移率差异均有统计学意义。-:提出的基于显微视野大小的3层形态测量法是一种简单易行的方法,可以根据不同的组织病理特征和总生存期将患者分为3组。
{"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}
引用次数: 0
Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma? 形态学和免疫浸润能预测新诊断的高级别浆液性卵巢癌的同源重组缺失状态吗?
Pub Date : 2024-12-09 DOI: 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.

背景卵巢高级别浆液性癌(HGSOCs)的形态与BRCA基因突变之间存在相关性:除 BRCA 外,研究 HGSOC 形态与同源重组缺陷(HRD)之间的关系:我们回顾了 PAOLA-1 临床试验的 806 例 HGSOC 中的 522 例,包括 163 例有肿瘤 BRCA 基因突变的病例、345 例无肿瘤 BRCA 基因突变的病例和 14 例 BRCA 检测结果不确定的病例。关于 HRD 状态(myChoice HRD Plus 检测法),269 例(52%)为阳性(HRD+),198 例(38%)为阴性(HRD-),55 例(10%)为不确定。形态学分析包括肿瘤结构(超过25%的实性、假性子宫内膜样和过渡形态定义为SET结构)、肿瘤浸润上皮内淋巴细胞(ieTILs)和肿瘤基质淋巴细胞(sTILs):结果:SET结构(51%对40%,P = .02)、大量ieTILs(16%对8%,P = .007)和超过10%的sTILs(27%对18%,P = .02)与肿瘤BRCA突变有关,主要是BRCA1突变的肿瘤。这些标准也与 HRD 状态有关:SET结构为54%对33%(P < .001),ieTIL数量多为14%对6%(P = .008),sTIL数量超过10%为27%对15%(P = .003)。与HRD-肿瘤相比,SET结构也与无肿瘤BRCA突变的HRD+肿瘤明显相关(P < .001)。这 3 项标准的组合显示出较高的特异性(0.99;95% CI,0.97-0.99),但敏感性较低(0.07;95% CI,0.04-0.10):HGSOC的形态与HRD状态和BRCA状态相关,但在日常实践中不能替代分子分析。
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引用次数: 0
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Archives of pathology & laboratory medicine
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