Diane M. Libert MD, Yili Zhu PhD, Aihui Wang ScM, Grace M. Allard BS, Alarice Cheng-Yi Lowe MD
Background
Circulating tumor cells (CTCs) shed into blood provide prognostic and/or predictive information. Previously, the authors established an assay to detect carcinoma cells from pleural fluid, termed effusion tumor cells (ETCs), by employing an immunofluorescence-based CTC-identification platform (RareCyte) on air-dried unstained ThinPrep (TP) slides. To facilitate clinical integration, they evaluated different slide processing and storage conditions, hypothesizing that alternative comparable conditions for ETC detection exist.
Methods
The authors enumerated ETCs on RareCyte, using morphology and mean fluorescence intensity (MFI) cutoffs of >100 arbitrary units (a.u.) for epithelial cellular adhesion molecule (EpCAM) and <100 a.u. for CD45. They analyzed malignant pleural fluid from three patients under seven processing and/or staining conditions, three patients after short-term storage under three conditions, and seven samples following long-term storage at –80°C. MFI values of 4′,6-diamidino-2-phenylindol, cytokeratin, CD45, and EpCAM were compared.
Results
ETCs were detected in all conditions. Among the different processing conditions tested, the ethanol-fixed, unstained TP was most similar to the previously established air-dried, unstained TP protocol. All smears and Pap-stained TPs had significantly different marker MFIs from the established condition. After short-term storage, the established condition showed comparable results, but ethanol-fixed and Pap-stained slides showed significant differences. ETCs were detectable after long-term storage at –80°C in comparable numbers to freshly prepared slides, but most marker MFIs were significantly different.
Conclusions
It is possible to detect ETCs under different processing and storage conditions, lending promise to the application of this method in broader settings. Because of decreased immunofluorescence-signature distinctions between cells, morphology may need to play a larger role.
{"title":"Detection of effusion tumor cells under different storage and processing conditions","authors":"Diane M. Libert MD, Yili Zhu PhD, Aihui Wang ScM, Grace M. Allard BS, Alarice Cheng-Yi Lowe MD","doi":"10.1002/cncy.22803","DOIUrl":"10.1002/cncy.22803","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Circulating tumor cells (CTCs) shed into blood provide prognostic and/or predictive information. Previously, the authors established an assay to detect carcinoma cells from pleural fluid, termed effusion tumor cells (ETCs), by employing an immunofluorescence-based CTC-identification platform (RareCyte) on air-dried unstained ThinPrep (TP) slides. To facilitate clinical integration, they evaluated different slide processing and storage conditions, hypothesizing that alternative comparable conditions for ETC detection exist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors enumerated ETCs on RareCyte, using morphology and mean fluorescence intensity (MFI) cutoffs of >100 arbitrary units (a.u.) for epithelial cellular adhesion molecule (EpCAM) and <100 a.u. for CD45. They analyzed malignant pleural fluid from three patients under seven processing and/or staining conditions, three patients after short-term storage under three conditions, and seven samples following long-term storage at –80°C. MFI values of 4′,6-diamidino-2-phenylindol, cytokeratin, CD45, and EpCAM were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ETCs were detected in all conditions. Among the different processing conditions tested, the ethanol-fixed, unstained TP was most similar to the previously established air-dried, unstained TP protocol. All smears and Pap-stained TPs had significantly different marker MFIs from the established condition. After short-term storage, the established condition showed comparable results, but ethanol-fixed and Pap-stained slides showed significant differences. ETCs were detectable after long-term storage at –80°C in comparable numbers to freshly prepared slides, but most marker MFIs were significantly different.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>It is possible to detect ETCs under different processing and storage conditions, lending promise to the application of this method in broader settings. Because of decreased immunofluorescence-signature distinctions between cells, morphology may need to play a larger role.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 5","pages":"297-308"},"PeriodicalIF":3.4,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905077","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}
Stephan E. P. Kops MD, MSC, Lizanne J. W. van der Burgt BSc, CT, Shoko Vos MD, PhD, Lia J. M. van Zuijlen-Manders BSc, CT, Roel L. J. Verhoeven PhD, Erik H. F. M. van der Heijden MD, PhD
Background
Rapid on-site evaluation (ROSE) of cytopathology plays an important role in determining whether representative samples have been taken during navigation bronchoscopy. With touch imprint cytology (TIC), histologic samples can be assessed using ROSE. Although advised by guidelines, there have been almost no studies on the performance of TIC during navigation bronchoscopy. The objective of this study was to evaluate the value of TIC-ROSE (forceps/cryobiopsy) in combination with conventional ROSE (cytology needle/brush).
Methods
In this single-center, prospective cohort study, patients who had pulmonary nodules with an indication for navigation bronchoscopy were consecutively included. The primary outcome of the study was the concordance of ROSE and the procedural outcome. The concordance rates of TIC-ROSE and the combination of TIC-ROSE plus conventional ROSE were compared.
Results
Fifty-eight patients with 66 nodules were included. Conventional ROSE and TIC-ROSE were assessable in 61 nodules (90.9%) each. By combining both ROSE techniques, all sampled lesions were assessable. Combining conventional ROSE with TIC-ROSE showed concordant results in 51 of 66 cases (77.3%) versus 44 of 66 (66.7%) and 48 of 66 (72.8%) concordant results for conventional ROSE and TIC-ROSE alone, respectively, compared with the procedural outcome. There was no indication of tissue depletion as a result of TIC. The combined ROSE approach had a statistically significant higher concordance rate compared with conventional ROSE alone.
Conclusions
TIC-ROSE is a cheap, easily implementable technique that can result in higher concordant ROSE outcomes. This could lead to more efficient procedures and possibly higher diagnostic results. In a monomodality sampling setting with only histologic samples, TIC can provide ROSE.
背景：细胞病理学快速现场评估（ROSE）在确定导航支气管镜检查中是否采集了具有代表性的样本方面发挥着重要作用。通过触摸印迹细胞学（TIC），组织学样本可通过 ROSE 进行评估。尽管有相关指南的建议，但几乎还没有关于导航支气管镜检查期间 TIC 性能的研究。本研究的目的是评估 TIC-ROSE（镊子/干细胞活检）与传统 ROSE（细胞学针/刷）相结合的价值：在这项单中心前瞻性队列研究中，连续纳入了具有导航支气管镜检查指征的肺部结节患者。研究的主要结果是 ROSE 与手术结果的一致性。比较了TIC-ROSE和TIC-ROSE加传统ROSE组合的吻合率：结果：共纳入了 58 名患者，66 个结节。结果：58 名患者共 66 个结节，传统 ROSE 和 TIC-ROSE 分别可评估 61 个结节（90.9%）。结合两种 ROSE 技术，所有取样病灶均可评估。将传统 ROSE 与 TIC-ROSE 结合使用，66 个病例中有 51 个病例（77.3%）的结果是一致的，而单独使用传统 ROSE 和 TIC-ROSE 则分别有 66 个病例中的 44 个病例（66.7%）和 48 个病例（72.8%）的结果是一致的。没有迹象表明 TIC 会导致组织损耗。与单用传统 ROSE 相比，联合 ROSE 方法的吻合率在统计学上有显著提高：结论：TIC-ROSE 是一种廉价、易于实施的技术，可提高 ROSE 结果的一致性。结论：TIC-ROSE 是一种廉价且易于实施的技术，可提高 ROSE 结果的一致性，从而提高手术效率，并可能提高诊断结果。在只有组织学样本的单一模式取样环境中，TIC 可提供 ROSE。
{"title":"Rapid on-site evaluation of touch imprint cytology in navigation bronchoscopy for small peripheral pulmonary nodules","authors":"Stephan E. P. Kops MD, MSC, Lizanne J. W. van der Burgt BSc, CT, Shoko Vos MD, PhD, Lia J. M. van Zuijlen-Manders BSc, CT, Roel L. J. Verhoeven PhD, Erik H. F. M. van der Heijden MD, PhD","doi":"10.1002/cncy.22786","DOIUrl":"10.1002/cncy.22786","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rapid on-site evaluation (ROSE) of cytopathology plays an important role in determining whether representative samples have been taken during navigation bronchoscopy. With touch imprint cytology (TIC), histologic samples can be assessed using ROSE. Although advised by guidelines, there have been almost no studies on the performance of TIC during navigation bronchoscopy. The objective of this study was to evaluate the value of TIC-ROSE (forceps/cryobiopsy) in combination with conventional ROSE (cytology needle/brush).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-center, prospective cohort study, patients who had pulmonary nodules with an indication for navigation bronchoscopy were consecutively included. The primary outcome of the study was the concordance of ROSE and the procedural outcome. The concordance rates of TIC-ROSE and the combination of TIC-ROSE plus conventional ROSE were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-eight patients with 66 nodules were included. Conventional ROSE and TIC-ROSE were assessable in 61 nodules (90.9%) each. By combining both ROSE techniques, all sampled lesions were assessable. Combining conventional ROSE with TIC-ROSE showed concordant results in 51 of 66 cases (77.3%) versus 44 of 66 (66.7%) and 48 of 66 (72.8%) concordant results for conventional ROSE and TIC-ROSE alone, respectively, compared with the procedural outcome. There was no indication of tissue depletion as a result of TIC. The combined ROSE approach had a statistically significant higher concordance rate compared with conventional ROSE alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TIC-ROSE is a cheap, easily implementable technique that can result in higher concordant ROSE outcomes. This could lead to more efficient procedures and possibly higher diagnostic results. In a monomodality sampling setting with only histologic samples, TIC can provide ROSE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 4","pages":"233-241"},"PeriodicalIF":3.4,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721740","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}
Hugo Rimbach, Maximilian Linxweiler MD, Sandrina Körner PhD, Sigrun Smola MD, Barbara Linxweiler, Stefanie Speicher, Johanna Helfrich, Erich-Franz Solomayer MD, Mathias Wagner MD, Bernhard Schick MD, Jan Philipp Kühn MD
Background
Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes.
Methods
Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (N = 93 neck dissections), and the cytological suspension obtained was processed via the liquid-based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data.
Results
Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N− cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (p < .0001) and 0.9658 for the prediction of N+ with ECS (p < .0001).
Conclusions
Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.
{"title":"Prediction of lymph node status in patients with surgically treated head and neck squamous cell carcinoma via neck lavage cytology: A pilot study","authors":"Hugo Rimbach, Maximilian Linxweiler MD, Sandrina Körner PhD, Sigrun Smola MD, Barbara Linxweiler, Stefanie Speicher, Johanna Helfrich, Erich-Franz Solomayer MD, Mathias Wagner MD, Bernhard Schick MD, Jan Philipp Kühn MD","doi":"10.1002/cncy.22800","DOIUrl":"10.1002/cncy.22800","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (<i>N</i> = 93 neck dissections), and the cytological suspension obtained was processed via the liquid-based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N− cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (<i>p</i> < .0001) and 0.9658 for the prediction of N+ with ECS (<i>p</i> < .0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 5","pages":"285-296"},"PeriodicalIF":3.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701928","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}
Joshua J. X. Li, Joanna K. M. Ng, Cheuk-Yin Tang, Bryan C. H. Chan, Sau Yee Chan, Jasmine H. N. Law, Jeremy Y. Teoh, Christopher J. VandenBussche, Gary M. Tse
Introduction
Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas.
Methods
Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses.
Results
There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p < .05). Larger lesion size and higher urine volume did not improve detection rates (p < .05).
Conclusions
The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.
{"title":"Urine cytology in the detection of renal cell carcinomas – a territory-wide multi-institutional retrospective review of more than 2 decades","authors":"Joshua J. X. Li, Joanna K. M. Ng, Cheuk-Yin Tang, Bryan C. H. Chan, Sau Yee Chan, Jasmine H. N. Law, Jeremy Y. Teoh, Christopher J. VandenBussche, Gary M. Tse","doi":"10.1002/cncy.22789","DOIUrl":"10.1002/cncy.22789","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (<i>p</i> < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (<i>p</i> < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (<i>p</i> < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (<i>p</i> < .05). Larger lesion size and higher urine volume did not improve detection rates (<i>p</i> < .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 3","pages":"186-192"},"PeriodicalIF":3.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701929","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}
There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories.
Methods
A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies.
Results
A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected.
Conclusions
There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs.
{"title":"Cell block practices in European cytopathology laboratories","authors":"Irena Srebotnik Kirbis PhD, Ivana Kholova MD, PhD, Heini Huhtala MSc, Massimo Bongiovanni MD, Margareta Strojan Flezar MD, MIAC, PhD, Chantell Hodgson MSc, Beatrix Cochand-Priollet MD, MIAC, PhD","doi":"10.1002/cncy.22793","DOIUrl":"10.1002/cncy.22793","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 4","pages":"250-259"},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697015","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}
The prognosis for patients diagnosed with medullary thyroid carcinoma (MTC) varies significantly with the timing of detection: the earlier the diagnosis, the higher the likelihood of achieving a complete cure (or at least a better outcome). Ogmen et al. show that the routine measurement of calcitonin in serum could lead to an earlier MTC diagnosis.
{"title":"Diagnosing medullary thyroid carcinoma is facilitated by measuring calcitonin in FNA washout fluids: Alea iacta est","authors":"Pierpaolo Trimboli MD, Anna Crescenzi MD","doi":"10.1002/cncy.22797","DOIUrl":"10.1002/cncy.22797","url":null,"abstract":"<p>The prognosis for patients diagnosed with medullary thyroid carcinoma (MTC) varies significantly with the timing of detection: the earlier the diagnosis, the higher the likelihood of achieving a complete cure (or at least a better outcome). Ogmen et al. show that the routine measurement of calcitonin in serum could lead to an earlier MTC diagnosis.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 3","pages":"139"},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697016","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}
Samantha Peiling Yang MBBS, Min En Nga MBBS, Manish Mahadeorao Bundele MBBS, Simion I. Chiosea MD, Sze Hwa Tan MBBS, Jeffrey H. Y. Lum MBBS, Rajeev Parameswaran MBBS, Ming Yann Lim MBBS, Hao Li MBBS, Wei Keat Cheah MBBS, Kathleen Su-Yen Sek MBBS, Andre Teck Huat Tan MBBS, Thomas Kwok Seng Loh MBBS, Kee Yuan Ngiam MBBS, Wee Boon Tan MBBS, Xinyong Huang MBBS, Thomas Wai Thong Ho MBBS, Keng Hua Lim MBBS, Chwee Ming Lim MBBS, Reyaz M. Singaporewalla MBBS, Anil Dinkar Rao MBBS, Nandini C. L. Rao MBBS, Dennis Yu Kim Chua MBBS, David Chao-Wu Chin MBBS, Abigail I. Wald PhD, Virginia A. LiVolsi MD, Yuri E. Nikiforov MD, PhD, E. Shyong Tai MBBS
Background
Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy.
Methods
This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed.
Results
Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III–IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria.
Conclusions
Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III–IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.
{"title":"Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules","authors":"Samantha Peiling Yang MBBS, Min En Nga MBBS, Manish Mahadeorao Bundele MBBS, Simion I. Chiosea MD, Sze Hwa Tan MBBS, Jeffrey H. Y. Lum MBBS, Rajeev Parameswaran MBBS, Ming Yann Lim MBBS, Hao Li MBBS, Wei Keat Cheah MBBS, Kathleen Su-Yen Sek MBBS, Andre Teck Huat Tan MBBS, Thomas Kwok Seng Loh MBBS, Kee Yuan Ngiam MBBS, Wee Boon Tan MBBS, Xinyong Huang MBBS, Thomas Wai Thong Ho MBBS, Keng Hua Lim MBBS, Chwee Ming Lim MBBS, Reyaz M. Singaporewalla MBBS, Anil Dinkar Rao MBBS, Nandini C. L. Rao MBBS, Dennis Yu Kim Chua MBBS, David Chao-Wu Chin MBBS, Abigail I. Wald PhD, Virginia A. LiVolsi MD, Yuri E. Nikiforov MD, PhD, E. Shyong Tai MBBS","doi":"10.1002/cncy.22796","DOIUrl":"10.1002/cncy.22796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III–IV cytology nodules. Most positive samples had <i>RAS</i>-like (41.7%), followed by <i>BRAF</i>-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of <i>RAS</i>-like mutations, specifically <i>NRAS</i>, in Bethesda categories III and IV and more <i>BRAF</i>-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III–IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 5","pages":"309-319"},"PeriodicalIF":3.4,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697017","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>Four years into the coronavirus disease 2019 (COVID-19) pandemic, multiple studies have agreed that patients with cancer are more susceptible to COVID-19 infection and have a higher risk of worse outcomes than the general population. Large cohort studies have revealed plenty of nuances, however, while raising additional questions in need of better answers.</p><p>Some cancer types, such as hematologic malignancies, have been associated with a higher risk of poor COVID-19 outcomes, as have some treatment types, such as recent cytotoxic chemotherapies, as well as a long list of other demographic factors and comorbidities. Researchers are just starting to investigate the added danger of long COVID-19.</p><p>The data, however, have also provided some reassurances, says Noha Sharafeldin, MD, PhD, MSc, an assistant professor of medicine at the University of Alabama at Birmingham and an associate scientist at the university’s O’Neal Comprehensive Cancer Center. One of the most notable findings is that vaccination against the SARS-CoV-2 virus can reduce the risk of severe infection even among those with hematologic malignancies.</p><p>“I think the thing we know for sure, if, God forbid, we’re hit with something similar again, is that this should be a group of people who should be at the forefront of protection efforts because of so many factors working against them,” Dr Sharafeldin says. “But the flip side of it is that vaccines work in those patients. We shouldn’t think that these patients might not benefit from these kinds of interventions.”</p><p>In a study that predated the first COVID-19 vaccines, Dr Sharafeldin and her colleagues found that COVID-19 positivity as significantly associated with an increased risk of all-cause mortality in adult patients with cancer.<span><sup>1</sup></span> Within the subset of patients who had cancer and were positive for COVID-19, multiple comorbidities, male gender, an age of 65 years or older, a hematologic malignancy, multiple tumor sites, and cytotoxic therapy received up to 30 days before the COVID-19 diagnosis were all associated with a higher risk of all-cause mortality. Recently administered immunotherapies or targeted therapies, however, did not increase the risk.</p><p>Dr Sharafeldin says that the assessment provided a kind of early natural history of COVID-19. The study drew on the medical records of nearly 4.4 million patients in the National COVID Cohort Collaborative. At the time, no one was sure of how to account for COVID-19 vulnerability or diagnosed infections in patients with cancer, particularly those in need of a bone marrow transplant. The study allowed the researchers to quantify the overall risk and identify the most vulnerable subset of patients with cancer. As expected, Dr Sharafeldin says, patients with hematologic malignancies had the highest risk of all-cause death, which was explainable by their predisposition for greater immunodeficiency.</p><p>“One thing we solidified is that this g
{"title":"Heightened but variable COVID-19 risks for patients with cancer","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.22791","DOIUrl":"10.1002/cncy.22791","url":null,"abstract":"<p>Four years into the coronavirus disease 2019 (COVID-19) pandemic, multiple studies have agreed that patients with cancer are more susceptible to COVID-19 infection and have a higher risk of worse outcomes than the general population. Large cohort studies have revealed plenty of nuances, however, while raising additional questions in need of better answers.</p><p>Some cancer types, such as hematologic malignancies, have been associated with a higher risk of poor COVID-19 outcomes, as have some treatment types, such as recent cytotoxic chemotherapies, as well as a long list of other demographic factors and comorbidities. Researchers are just starting to investigate the added danger of long COVID-19.</p><p>The data, however, have also provided some reassurances, says Noha Sharafeldin, MD, PhD, MSc, an assistant professor of medicine at the University of Alabama at Birmingham and an associate scientist at the university’s O’Neal Comprehensive Cancer Center. One of the most notable findings is that vaccination against the SARS-CoV-2 virus can reduce the risk of severe infection even among those with hematologic malignancies.</p><p>“I think the thing we know for sure, if, God forbid, we’re hit with something similar again, is that this should be a group of people who should be at the forefront of protection efforts because of so many factors working against them,” Dr Sharafeldin says. “But the flip side of it is that vaccines work in those patients. We shouldn’t think that these patients might not benefit from these kinds of interventions.”</p><p>In a study that predated the first COVID-19 vaccines, Dr Sharafeldin and her colleagues found that COVID-19 positivity as significantly associated with an increased risk of all-cause mortality in adult patients with cancer.<span><sup>1</sup></span> Within the subset of patients who had cancer and were positive for COVID-19, multiple comorbidities, male gender, an age of 65 years or older, a hematologic malignancy, multiple tumor sites, and cytotoxic therapy received up to 30 days before the COVID-19 diagnosis were all associated with a higher risk of all-cause mortality. Recently administered immunotherapies or targeted therapies, however, did not increase the risk.</p><p>Dr Sharafeldin says that the assessment provided a kind of early natural history of COVID-19. The study drew on the medical records of nearly 4.4 million patients in the National COVID Cohort Collaborative. At the time, no one was sure of how to account for COVID-19 vulnerability or diagnosed infections in patients with cancer, particularly those in need of a bone marrow transplant. The study allowed the researchers to quantify the overall risk and identify the most vulnerable subset of patients with cancer. As expected, Dr Sharafeldin says, patients with hematologic malignancies had the highest risk of all-cause death, which was explainable by their predisposition for greater immunodeficiency.</p><p>“One thing we solidified is that this g","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 2","pages":"73-74"},"PeriodicalIF":3.4,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674063","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}
Yara Mansour MD, Mehdi Boubaddi MD, Typhaine Odion, Marion Marty MD, Geneviève Belleannée MD, Arthur Berger MD, Clément Subtil MD, Christophe Laurent MD, PhD, Sandrine Dabernat PhD, Samuel Amintas PharmD, PhD
Background
Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment. The combination of EUS-FNA sample examination and KRAS mutation detection can improve the sensitivity for diagnosis. In this context, the material used for molecular analysis may condition performance.
Methods
The authors prospectively compared the performance of cytologic analysis combined with a KRAS droplet digital polymerase chain reaction (ddPCR) assay for PDAC diagnosis using either conventional formalin-fixed, paraffin-embedded cytologic samples or needle-rinsing fluids.
Results
Molecular testing of formalin-fixed, paraffin-embedded cytologic samples was easier to set up, but the authors observed that the treatment of preanalytic samples, in particular the fixation process, drastically reduced ddPCR sensitivity, increasing the risk of false-negative results. Conversely, the analysis of dedicated, fresh needle-rinsing fluid samples appeared to be ideal for ddPCR analysis; it had greater sensitivity and was easily to implement in clinical use. In particular, fluid collection by the endoscopist, transportation to the laboratory, and subsequent freezing did not affect DNA quantity or quality. Moreover, the addition of KRAS mutation detection to cytologic examination improved diagnosis performance, regardless of the source of the sample.
Conclusions
Considering all of these aspects, the authors propose the use of an integrated flowchart for the KRAS molecular testing of EUS-FNA samples in clinical routine.
{"title":"Droplet digital polymerase chain reaction detection of KRAS mutations in pancreatic FNA samples: Technical and practical aspects for routine clinical implementation","authors":"Yara Mansour MD, Mehdi Boubaddi MD, Typhaine Odion, Marion Marty MD, Geneviève Belleannée MD, Arthur Berger MD, Clément Subtil MD, Christophe Laurent MD, PhD, Sandrine Dabernat PhD, Samuel Amintas PharmD, PhD","doi":"10.1002/cncy.22795","DOIUrl":"10.1002/cncy.22795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment. The combination of EUS-FNA sample examination and <i>KRAS</i> mutation detection can improve the sensitivity for diagnosis. In this context, the material used for molecular analysis may condition performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors prospectively compared the performance of cytologic analysis combined with a <i>KRAS</i> droplet digital polymerase chain reaction (ddPCR) assay for PDAC diagnosis using either conventional formalin-fixed, paraffin-embedded cytologic samples or needle-rinsing fluids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Molecular testing of formalin-fixed, paraffin-embedded cytologic samples was easier to set up, but the authors observed that the treatment of preanalytic samples, in particular the fixation process, drastically reduced ddPCR sensitivity, increasing the risk of false-negative results. Conversely, the analysis of dedicated, fresh needle-rinsing fluid samples appeared to be ideal for ddPCR analysis; it had greater sensitivity and was easily to implement in clinical use. In particular, fluid collection by the endoscopist, transportation to the laboratory, and subsequent freezing did not affect DNA quantity or quality. Moreover, the addition of <i>KRAS</i> mutation detection to cytologic examination improved diagnosis performance, regardless of the source of the sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Considering all of these aspects, the authors propose the use of an integrated flowchart for the <i>KRAS</i> molecular testing of EUS-FNA samples in clinical routine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 5","pages":"274-284"},"PeriodicalIF":3.4,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139677819","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}
Recent efforts to develop a histologic grading system for medullary thyroid carcinoma is gaining broad acceptance. How well do these grading parameters translate to cytology specimens?
{"title":"Cytologic risk stratification of medullary thyroid carcinoma: Does it make the grade?","authors":"Michiya Nishino MD, PhD","doi":"10.1002/cncy.22799","DOIUrl":"10.1002/cncy.22799","url":null,"abstract":"<p>Recent efforts to develop a histologic grading system for medullary thyroid carcinoma is gaining broad acceptance. How well do these grading parameters translate to cytology specimens?</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 4","pages":"209-211"},"PeriodicalIF":3.4,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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