Cristiana M. Pineda MD, PhD, Adnan Majid MD, Daniel B. Costa MD, PhD, Paul A. VanderLaan MD, PhD
Background
Lung cancer complicated by malignant pleural effusions (MPEs) is associated with significantly increased morbidity and mortality, yet the mechanisms of MPE development remain poorly understood. This study sought to elucidate whether there were specific genomic alterations and/or immunologic biomarkers associated with the presence of MPEs.
Methods
Analysis of comprehensive genomic and immunologic profiling for 275 locally advanced (stage III) or advanced (stage IV) lung adenocarcinomas was subcategorized into cytology-confirmed MPE-positive (MPE+; n = 139 stage IV) and MPE-negative (MPE−; n = 30 stage III + n = 106 stage IV) groups.
Results
Smoking frequency (p = .0001) and tumor mutational burden (p < .001) were demonstrated to be lower in the MPE+ group compared to the MPE− group. Median overall survival in the MPE+ group was shorter than in the MPE− group across all data (2.0 vs. 5.5 years; p < .0001) and for smokers (1.2 vs. 6.4 years; p < .0001). There were a number of differences at the genomic level across all cases and when stratifying by smoking status, including a higher frequency of EGFR mutations and a lower frequency of STK11 mutations in the MPE+ cohort. Finally, investigation of the comutational profiles of tumors by MPE status revealed differences in TP53- and STK11-mutant tumors between the two groups.
Conclusions
Overall, these findings imply that there are both clinical and genetic factors associated with advanced lung adenocarcinoma MPEs. Future studies of these alterations may prove important both for understanding the pathophysiology of MPE development in advanced cancer and for the earlier detection of at-risk patients.
{"title":"Comparative genomic and immunopathologic analysis of lung adenocarcinomas with and without cytology-proven malignant pleural effusions","authors":"Cristiana M. Pineda MD, PhD, Adnan Majid MD, Daniel B. Costa MD, PhD, Paul A. VanderLaan MD, PhD","doi":"10.1002/cncy.22900","DOIUrl":"10.1002/cncy.22900","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer complicated by malignant pleural effusions (MPEs) is associated with significantly increased morbidity and mortality, yet the mechanisms of MPE development remain poorly understood. This study sought to elucidate whether there were specific genomic alterations and/or immunologic biomarkers associated with the presence of MPEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Analysis of comprehensive genomic and immunologic profiling for 275 locally advanced (stage III) or advanced (stage IV) lung adenocarcinomas was subcategorized into cytology-confirmed MPE-positive (MPE+; <i>n</i> = 139 stage IV) and MPE-negative (MPE−; <i>n</i> = 30 stage III + <i>n</i> = 106 stage IV) groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Smoking frequency (<i>p</i> = .0001) and tumor mutational burden (<i>p</i> < .001) were demonstrated to be lower in the MPE+ group compared to the MPE− group. Median overall survival in the MPE+ group was shorter than in the MPE− group across all data (2.0 vs. 5.5 years; <i>p</i> < .0001) and for smokers (1.2 vs. 6.4 years; <i>p</i> < .0001). There were a number of differences at the genomic level across all cases and when stratifying by smoking status, including a higher frequency of <i>EGFR</i> mutations and a lower frequency of <i>STK11</i> mutations in the MPE+ cohort. Finally, investigation of the comutational profiles of tumors by MPE status revealed differences in <i>TP53</i>- and <i>STK11</i>-mutant tumors between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, these findings imply that there are both clinical and genetic factors associated with advanced lung adenocarcinoma MPEs. Future studies of these alterations may prove important both for understanding the pathophysiology of MPE development in advanced cancer and for the earlier detection of at-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"788-798"},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neil B. Marya MD, Patrick D. Powers, Melanie C. Bois MD, Christopher Hartley MD, Sarah E. Kerr MD, Judith Jebastin Thangaiah MBBS, MD, Daniel Norton BA, Barham K. Abu Dayyeh MD, MPH, Richard Cantley MD, Vinay Chandrasekhara MD, Gregory Gores MD, Ferga C. Gleeson MB, BCh, Ryan J. Law DO, Zahra Maleki MD, John A. Martin MD, Liron Pantanowitz MB, BCh, Bret Petersen MD, Andrew C. Storm MD, Michael J. Levy MD, Rondell P. Graham MBBS
Background
The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool.
Methods
Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being “positive,” “negative,” or “indeterminate.” The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared.
Results
Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622–0.859), CADe (0.807; 95% CI, 0.750–0.856), and OCI (0.807; 95% CI, 0.671–0.900) were similar.
Conclusions
This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.
背景：作者之前开发了一种人工智能（AI），用于协助细胞学专家评估从胆管刷洗标本中生成的数字全切片图像（WSI）。本试验旨在评估细胞学专家使用该人工智能工具的新型应用的效率和准确性：方法：连续获取来自不确定狭窄的胆管刷洗 WSI。一个多学科小组审查了所有相关信息，并对每份 WSI 提供了 "阳性"、"阴性 "或 "不确定 "的集中解释。然后将 WSI 上传到人工智能应用程序。人工智能将每个 WSI 打分为恶性肿瘤阳性或阴性（即计算机辅助诊断 [CADx]）。对于每个 WSI，人工智能会根据片段中出现恶性物质的可能性对细胞学片段进行优先排序。通过人工智能，盲法细胞学专家对所有 WSI 进行审查并提供解释（即计算机辅助检测 [CADe]）。通过 CADx、CADe 和原始临床细胞学解释（官方细胞学解释 [OCI]）对 WSI 评估的诊断准确率进行了比较：在 84 例 WSI 中，15 例为阳性，42 例为阴性，27 例经中央审查后为不确定。每项 WSI 平均产生 141,950 张纸片。使用人工智能的细胞学专家在做出解释前对每个 WSI 评估了 10.5 张纸片。此外，细胞学专家对 WSI 的总评估时间平均为 84.1 秒。CADx（0.754；95% CI，0.622-0.859）、CADe（0.807；95% CI，0.750-0.856）和OCI（0.807；95% CI，0.671-0.900）的WSI判读准确率相似：这项试验表明，人工智能应用允许细胞学专家对 WSI 进行分流审查，同时保持准确性。
{"title":"Utilization of an artificial intelligence–enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study","authors":"Neil B. Marya MD, Patrick D. Powers, Melanie C. Bois MD, Christopher Hartley MD, Sarah E. Kerr MD, Judith Jebastin Thangaiah MBBS, MD, Daniel Norton BA, Barham K. Abu Dayyeh MD, MPH, Richard Cantley MD, Vinay Chandrasekhara MD, Gregory Gores MD, Ferga C. Gleeson MB, BCh, Ryan J. Law DO, Zahra Maleki MD, John A. Martin MD, Liron Pantanowitz MB, BCh, Bret Petersen MD, Andrew C. Storm MD, Michael J. Levy MD, Rondell P. Graham MBBS","doi":"10.1002/cncy.22898","DOIUrl":"10.1002/cncy.22898","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being “positive,” “negative,” or “indeterminate.” The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622–0.859), CADe (0.807; 95% CI, 0.750–0.856), and OCI (0.807; 95% CI, 0.671–0.900) were similar.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"779-787"},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianxu Zeng MD, PhD, David Starr MD, Juan Li MD, Xuejie Bi MD, Chun Wang MD, Xinru Bai MD, Yanxue Yin MD, Xue Wu MD, Jingjing Wei MD, Hui Du MD, PhD, Wenkui Dai PhD, Changzhong Li MS, Xiangchen Wu PhD, Ruifang Wu MD, Chengquan Zhao MD
Background
AICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis.
Methods
The authors used the Ruiqian WSI-2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results.
Results
In 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low-grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low-grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow-up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy.
Conclusions
For pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening.
{"title":"AICyte-alone capabilities as an independent screener for triaging cervical cytology using a 50% negative cutoff value","authors":"Xianxu Zeng MD, PhD, David Starr MD, Juan Li MD, Xuejie Bi MD, Chun Wang MD, Xinru Bai MD, Yanxue Yin MD, Xue Wu MD, Jingjing Wei MD, Hui Du MD, PhD, Wenkui Dai PhD, Changzhong Li MS, Xiangchen Wu PhD, Ruifang Wu MD, Chengquan Zhao MD","doi":"10.1002/cncy.22896","DOIUrl":"10.1002/cncy.22896","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>AICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors used the Ruiqian WSI-2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low-grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low-grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow-up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>For pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 11","pages":"723-730"},"PeriodicalIF":2.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rosario Granados MD, PhD, FIAC, Joanny A. Duarte MD, David R. Luján MD, Ana M. Gutierrez-Pecharromán MD, FIAC, Isabel Solís MD, Lourdes Molpeceres MD, Paloma Bajo CT, Elsa Palencia RN, Nuria Martín RN
Background
There is a need for additional longitudinal studies with the Aptima messenger RNA human papillomavirus test (AHPV) to support the safety of extended screening intervals. RNA-based extended interventional nucleic acid (REINA) provides relevant information on the clinical performance of AHPV.
Methods
This is a longitudinal prospective analysis of 1538 participants after AHPV and liquid-based cytology (LBC) co-test complemented with REINA interventional protocol with a second co-test 4 years after negative screening on 2000 women. Diagnostic accuracy and cumulative risks for CIN2+ up to 9 years were calculated for all test combinations.
Results
Sensitivity and specificity for CIN2+ were 96.9% and 88.0% for AHPV and 72.3% and 92.0% for LBC. Negative predictive value (NPV) and positive predictive value (PPV) of AHPV were 99.9% and 23.6%. The 5- and 9-year risks of AHPV-negative women were 0.4% and 1.0% (CIN2+) and 0.3% and 0.7% (CIN3+), a 73% and 64% lower risk than with negative LBC (p ≤ .002). REINA participants with an AHPV-positive result at second co-test after a negative AHPV in first round had a significantly lower 5-year risk of CIN2+ (11.1%) than AHPV-positive women with unknown HPV history (29.5%).
Conclusions
Currently, this constitutes the longest European longitudinal study with AHPV testing in screening population. It reveals 99.9% NPV and a significant protective effect of a previous negative test 5 years after a new HPV infection. These findings support the safety of Aptima for screening intervals beyond 5 years. The risk of disease is lower 9 years after a negative AHPV test than 3 years after a negative LBC. High specificity and PPV of Aptima may benefit controlling overtreatment and colposcopy referrals.
{"title":"RNA extended interventional nucleic acid longitudinal study: Clinical performance of Aptima messenger RNA HPV testing in cervical cancer screening with a 9-year follow-up","authors":"Rosario Granados MD, PhD, FIAC, Joanny A. Duarte MD, David R. Luján MD, Ana M. Gutierrez-Pecharromán MD, FIAC, Isabel Solís MD, Lourdes Molpeceres MD, Paloma Bajo CT, Elsa Palencia RN, Nuria Martín RN","doi":"10.1002/cncy.22895","DOIUrl":"10.1002/cncy.22895","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a need for additional longitudinal studies with the Aptima messenger RNA human papillomavirus test (AHPV) to support the safety of extended screening intervals. RNA-based extended interventional nucleic acid (REINA) provides relevant information on the clinical performance of AHPV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a longitudinal prospective analysis of 1538 participants after AHPV and liquid-based cytology (LBC) co-test complemented with REINA interventional protocol with a second co-test 4 years after negative screening on 2000 women. Diagnostic accuracy and cumulative risks for CIN2+ up to 9 years were calculated for all test combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sensitivity and specificity for CIN2+ were 96.9% and 88.0% for AHPV and 72.3% and 92.0% for LBC. Negative predictive value (NPV) and positive predictive value (PPV) of AHPV were 99.9% and 23.6%. The 5- and 9-year risks of AHPV-negative women were 0.4% and 1.0% (CIN2+) and 0.3% and 0.7% (CIN3+), a 73% and 64% lower risk than with negative LBC (<i>p</i> ≤ .002). REINA participants with an AHPV-positive result at second co-test after a negative AHPV in first round had a significantly lower 5-year risk of CIN2+ (11.1%) than AHPV-positive women with unknown HPV history (29.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Currently, this constitutes the longest European longitudinal study with AHPV testing in screening population. It reveals 99.9% NPV and a significant protective effect of a previous negative test 5 years after a new HPV infection. These findings support the safety of Aptima for screening intervals beyond 5 years. The risk of disease is lower 9 years after a negative AHPV test than 3 years after a negative LBC. High specificity and PPV of Aptima may benefit controlling overtreatment and colposcopy referrals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"757-767"},"PeriodicalIF":2.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22895","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharron Liang MB, BS, FRCPA, Immacolata Cozzolino MD, Pio Zeppa MD, Andrew S. Field MB, BS(Hons), FRCPA, FIAC
Background
The Sydney system for fine-needle aspiration biopsy of lymph nodes has five categories, stressing the role of correlation of cytopathology with clinical, ultrasound, and ancillary findings to achieve diagnosis. The five categories constitute a hierarchical system with increasing risk of malignancy from benign to atypical, suspicious, and malignant categories, which informs recommendations for further workup to achieve a final diagnosis as possible. This article analyzes 10 publications using the Sydney system and a meta-analysis of nine of these studies. The primary goal of the analysis is to ascertain the causes of the large ranges in risk of malignancy for the “atypical” and “inadequate” compared to “benign,” “suspicious,” and “malignant” categories, which were comparable to well-established reporting systems. Research protocols are proposed to improve future studies.
Methods
PubMed literature search from January 2021 to December 2023 identified studies evaluating performance of the Sydney system.
Results
Ten studies showed heterogeneity with clinical setting, study design, ultrasound use and rapid on-site evaluation, operator, cutoff points for “positive” cases, with inherent partial verification biases, resulting in a wide range of risk of malignancy, specificity, and sensitivity values.
Conclusion
Analysis shows the large range is due to heterogeneity of the studies, which suffer from biases and variable statistical analysis that are ultimately included in any meta-analysis, detracting from the usefulness of the risk of malignancy derived by the meta-analysis. Components for ideal analyses of reporting systems are presented.
{"title":"The Sydney system for lymph node FNA biopsy cytopathology: A detailed analysis of recent publications and meta-analysis and a proposal for the components of an ideal prospective study of a cytopathology reporting system","authors":"Sharron Liang MB, BS, FRCPA, Immacolata Cozzolino MD, Pio Zeppa MD, Andrew S. Field MB, BS(Hons), FRCPA, FIAC","doi":"10.1002/cncy.22890","DOIUrl":"10.1002/cncy.22890","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Sydney system for fine-needle aspiration biopsy of lymph nodes has five categories, stressing the role of correlation of cytopathology with clinical, ultrasound, and ancillary findings to achieve diagnosis. The five categories constitute a hierarchical system with increasing risk of malignancy from benign to atypical, suspicious, and malignant categories, which informs recommendations for further workup to achieve a final diagnosis as possible. This article analyzes 10 publications using the Sydney system and a meta-analysis of nine of these studies. The primary goal of the analysis is to ascertain the causes of the large ranges in risk of malignancy for the “atypical” and “inadequate” compared to “benign,” “suspicious,” and “malignant” categories, which were comparable to well-established reporting systems. Research protocols are proposed to improve future studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed literature search from January 2021 to December 2023 identified studies evaluating performance of the Sydney system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten studies showed heterogeneity with clinical setting, study design, ultrasound use and rapid on-site evaluation, operator, cutoff points for “positive” cases, with inherent partial verification biases, resulting in a wide range of risk of malignancy, specificity, and sensitivity values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Analysis shows the large range is due to heterogeneity of the studies, which suffer from biases and variable statistical analysis that are ultimately included in any meta-analysis, detracting from the usefulness of the risk of malignancy derived by the meta-analysis. Components for ideal analyses of reporting systems are presented.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"745-756"},"PeriodicalIF":2.6,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fine-needle aspiration (FNA) biopsy is increasingly used for the diagnosis of hepatocellular masses. Because distinguishing well differentiated hepatocellular carcinoma (HCC) from other well differentiated hepatocellular lesions (e.g., large regenerative nodules or focal nodular hyperplasia) requires an assessment of architectural features, this may be challenging on FNA when intact tissue fragments are not sampled. Poorly differentiated HCC and intrahepatic cholangiocarcinoma (ICC) may exhibit overlapping pathologic features. Molecular testing can be helpful, because mutations in TERT promoter and CTNNB1 (β-catenin) are characteristic of HCC, whereas mutations in BAP1, IDH1/IDH2, and PBRM1 may favor ICC. The goal of this study was to assess the role of next-generation sequencing (NGS) in further subclassifying indeterminate liver lesions sampled by FNA.
Methods
A retrospective review of liver cytology cases with NGS on cell block material was performed. Age, radiologic features, background hepatic disease and treatment, outcome, and NGS data were obtained from the electronic medical record.
Results
Twelve FNA biopsies that had cell blocks from clinically suspected primary hepatic masses were identified. The presence of a TERT promoter mutation supported a diagnosis of HCC for one well differentiated neoplasm. For three patients, the presence of mutations, such as IDH1, CDKN2A/CDKN2B, and BRAF, supported a diagnosis of ICC. Of the eight poorly differentiated carcinomas, NGS helped refine the diagnosis in six of eight cases, with one HCC, three ICCs, and two that had combined HCC-ICC, with two cases remaining unclassified.
Conclusions
Molecular diagnostics can be helpful to distinguish HCC and ICC on FNA specimens, although a subset of primary hepatic tumors may remain unclassifiable.
{"title":"The utility of next-generation sequencing in challenging liver FNA biopsies","authors":"Dana J. Balitzer MD, Nancy Y. Greenland MD, PhD","doi":"10.1002/cncy.22893","DOIUrl":"10.1002/cncy.22893","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fine-needle aspiration (FNA) biopsy is increasingly used for the diagnosis of hepatocellular masses. Because distinguishing well differentiated hepatocellular carcinoma (HCC) from other well differentiated hepatocellular lesions (e.g., large regenerative nodules or focal nodular hyperplasia) requires an assessment of architectural features, this may be challenging on FNA when intact tissue fragments are not sampled. Poorly differentiated HCC and intrahepatic cholangiocarcinoma (ICC) may exhibit overlapping pathologic features. Molecular testing can be helpful, because mutations in <i>TERT</i> promoter and <i>CTNNB1</i> (β-catenin) are characteristic of HCC, whereas mutations in <i>BAP1</i>, <i>IDH1/IDH2</i>, and <i>PBRM1</i> may favor ICC. The goal of this study was to assess the role of next-generation sequencing (NGS) in further subclassifying indeterminate liver lesions sampled by FNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review of liver cytology cases with NGS on cell block material was performed. Age, radiologic features, background hepatic disease and treatment, outcome, and NGS data were obtained from the electronic medical record.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve FNA biopsies that had cell blocks from clinically suspected primary hepatic masses were identified. The presence of a <i>TERT</i> promoter mutation supported a diagnosis of HCC for one well differentiated neoplasm. For three patients, the presence of mutations, such as <i>IDH1</i>, <i>CDKN2A/CDKN2B</i>, and <i>BRAF</i>, supported a diagnosis of ICC. Of the eight poorly differentiated carcinomas, NGS helped refine the diagnosis in six of eight cases, with one HCC, three ICCs, and two that had combined HCC-ICC, with two cases remaining unclassified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Molecular diagnostics can be helpful to distinguish HCC and ICC on FNA specimens, although a subset of primary hepatic tumors may remain unclassifiable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 11","pages":"714-722"},"PeriodicalIF":2.6,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spotlight: Rising stars in cytology","authors":"Bonnie Choy MD","doi":"10.1002/cncy.22891","DOIUrl":"10.1002/cncy.22891","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 11","pages":"673-674"},"PeriodicalIF":2.6,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaitlyn R. Muscarella MD, Paul T. Eberts MD, Laura D. Craig-Owens MD, Elizabeth Kean Groark MD, Dustin R. Osborne PhD, Teresa Osborne RT(R)(VI), Gregg Tracy BSN, Cristopher D. Stephens MD, Laurentia M. Nodit MD
{"title":"Mucinous-appearing contamination of serous effusions by sodium carboxymethyl cellulose from suction canister lids","authors":"Kaitlyn R. Muscarella MD, Paul T. Eberts MD, Laura D. Craig-Owens MD, Elizabeth Kean Groark MD, Dustin R. Osborne PhD, Teresa Osborne RT(R)(VI), Gregg Tracy BSN, Cristopher D. Stephens MD, Laurentia M. Nodit MD","doi":"10.1002/cncy.22892","DOIUrl":"10.1002/cncy.22892","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other.
Methods
A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared.
Results
Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (p < .05). HRAS mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in NRAS/KRAS and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively.
Conclusions
These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.
{"title":"Follicular neoplasms with nuclear atypia versus other types of atypia: Should follicular neoplasms be stratified according to the presence of nuclear atypia?","authors":"Youley Tjendra MD, Yiqin Zuo MD, PhD, Jaylou M. Velez Torres MD","doi":"10.1002/cncy.22889","DOIUrl":"10.1002/cncy.22889","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (<i>p</i> < .05). <i>HRAS</i> mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in <i>NRAS</i>/<i>KRAS</i> and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 11","pages":"707-713"},"PeriodicalIF":2.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>For Vera Gorbunova, PhD, professor of biology and medicine at the University of Rochester in New York, the moment of serendipity initially seemed like a nuisance. Dr Gorbunova’s laboratory studies why certain animals, such as the extremely long-lived, hairless, and so-ugly-they’re-cute subterranean dwellers known as naked mole-rats, are extraordinarily resistant to cancer. The unusual rodents from eastern Africa have a eusocial colony structure reminiscent of honeybees and can live more than 40 years in captivity, roughly 10-fold longer than mice.</p><p>As part of its research, Dr Gorbunova’s laboratory grew naked mole-rat fibroblast cells, which make and secrete collagen and other components of the framework for connective tissues. Graduate students noticed that the cells also were secreting a viscous substance into the cell culture dish. The substance was so thick and gooey that it clogged the vacuum pump used to suck up the growing medium from the dishes. “When people complained about it, we all thought, ‘Well, there must be something interesting,’” Dr Gorbunova recalls.</p><p>After initial tests suggested that the viscous substance was not an overabundant protein, a Google search hinted at hyaluronic acid, a natural lubricant and cushion for skin and other sensitive body parts in humans and other animals. Sure enough, confirmatory tests revealed that the secretions were a very long form of hyaluronic acid made by the <i>HAS2</i> gene.<span><sup>1</sup></span></p><p>From additional experiments, the laboratory found that this version of hyaluronic acid binds to a specific cell receptor and appears to trigger an anticancer response by arresting cell growth and division. “Basically, when there is a lot of high-molecular weight hyaluronic acid in the tissue, it reduces cell proliferation and it also slows down premalignant hyperplastic cells,” Dr Gorbunova says. In transgenic mice, the introduced <i>HAS2</i> gene granted the animals more longevity and resistance to both spontaneous and induced tumors.<span><sup>2</sup></span> “They didn’t become completely resistant like naked mole-rats, which means there are additional mechanisms that are different in the mole-rat, but the incidence was reduced significantly,” she says.</p><p>From an evolutionary perspective, Dr Gorbunova doubts that anticancer activity was the original purpose of the naked mole-rats’ hyaluronic acid production. In a wide range of other tunnel-dwelling species, the researchers recently reported that all produced the same high-molecular-weight compound.<span><sup>3</sup></span> “What we proposed is that it really becomes upregulated with adaptation to subterranean life,” she says. One possibility is that because underground animals are constantly rubbing against tunnel walls, the acid helps to reinforce their skin.</p><p>When the laboratory ramped up hyaluronic acid production in mice, the animals likewise acquired “very stretchy, elastic skin,” she says. “But then once it’s ov
{"title":"Exposing the naked truth about how mole-rats evade cancer","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.22887","DOIUrl":"10.1002/cncy.22887","url":null,"abstract":"<p>For Vera Gorbunova, PhD, professor of biology and medicine at the University of Rochester in New York, the moment of serendipity initially seemed like a nuisance. Dr Gorbunova’s laboratory studies why certain animals, such as the extremely long-lived, hairless, and so-ugly-they’re-cute subterranean dwellers known as naked mole-rats, are extraordinarily resistant to cancer. The unusual rodents from eastern Africa have a eusocial colony structure reminiscent of honeybees and can live more than 40 years in captivity, roughly 10-fold longer than mice.</p><p>As part of its research, Dr Gorbunova’s laboratory grew naked mole-rat fibroblast cells, which make and secrete collagen and other components of the framework for connective tissues. Graduate students noticed that the cells also were secreting a viscous substance into the cell culture dish. The substance was so thick and gooey that it clogged the vacuum pump used to suck up the growing medium from the dishes. “When people complained about it, we all thought, ‘Well, there must be something interesting,’” Dr Gorbunova recalls.</p><p>After initial tests suggested that the viscous substance was not an overabundant protein, a Google search hinted at hyaluronic acid, a natural lubricant and cushion for skin and other sensitive body parts in humans and other animals. Sure enough, confirmatory tests revealed that the secretions were a very long form of hyaluronic acid made by the <i>HAS2</i> gene.<span><sup>1</sup></span></p><p>From additional experiments, the laboratory found that this version of hyaluronic acid binds to a specific cell receptor and appears to trigger an anticancer response by arresting cell growth and division. “Basically, when there is a lot of high-molecular weight hyaluronic acid in the tissue, it reduces cell proliferation and it also slows down premalignant hyperplastic cells,” Dr Gorbunova says. In transgenic mice, the introduced <i>HAS2</i> gene granted the animals more longevity and resistance to both spontaneous and induced tumors.<span><sup>2</sup></span> “They didn’t become completely resistant like naked mole-rats, which means there are additional mechanisms that are different in the mole-rat, but the incidence was reduced significantly,” she says.</p><p>From an evolutionary perspective, Dr Gorbunova doubts that anticancer activity was the original purpose of the naked mole-rats’ hyaluronic acid production. In a wide range of other tunnel-dwelling species, the researchers recently reported that all produced the same high-molecular-weight compound.<span><sup>3</sup></span> “What we proposed is that it really becomes upregulated with adaptation to subterranean life,” she says. One possibility is that because underground animals are constantly rubbing against tunnel walls, the acid helps to reinforce their skin.</p><p>When the laboratory ramped up hyaluronic acid production in mice, the animals likewise acquired “very stretchy, elastic skin,” she says. “But then once it’s ov","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 8","pages":"463-464"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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