Cancer Cytopathology最新文献

{"title":"Molecular profiling of breast cancer pleural effusions using cytology specimens: Impact of sample source and cytological features on next-generation sequencing performance","authors":"Harpreet Virk MD,&nbsp;Claire Michael MD,&nbsp;Keri Ann Pfeil MS,&nbsp;Navid Sadri MD,&nbsp;Philip Bomeisl DO,&nbsp;Aparna Harbhajanka MD","doi":"10.1002/cncy.70125","DOIUrl":"10.1002/cncy.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant effusions in breast cancer are a minimally invasive source for molecular profiling. Effusion-derived cytology specimens, cell blocks (CB) and post-ThinPrep PreservCyt (PTPC) supernatant, are reliable sources for molecular testing but differ in DNA concentration and turnaround time (TAT). This study evaluates mutational profiles, cytology characteristics, and clinical correlates to assess the utility of effusion-based molecular testing in breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors screened 2400 malignant effusion cases, identifying 22 cases of breast adenocarcinoma effusions that underwent next-generation sequencing (NGS). Both CB and PTPC supernatant were evaluated for tumor cellularity, fluid volume, DNA concentration, TAT, and mutation detection. Associations with clinicopathological features and outcomes were explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NGS was successful in all 22 cases (mean volume, 426.5 mL; mean tumor cellularity, 50%). Successful sequencing was achieved in low volume samples with high tumor cellularity. Higher tumor cellularity (&gt;50%) was associated with bloody effusions (<i>p</i> = .016). PTPC supernatant yielded 5-fold higher DNA (mean 177.4 ng/µL vs. 33.8 ng/µL) and shorter TAT by 9 days (15 vs. 24 days). <i>TP53</i> mutations were more common in estrogen receptor (ER)-negative and triple-negative breast effusions (<i>p</i> = .025). Mutations in <i>PIK3CA</i>, <i>TP53</i>, <i>CCND1</i>, and <i>AKT</i> were reliably detected. Time from diagnosis to effusion development was significantly shorter in ER negative disease (<i>p</i> = .001)</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Effusion cytology using PTPC supernatant, support successful NGS even in low-volume samples. ER-negative and triple-negative effusions demonstrate more aggressive molecular features including enrichment of <i>TP53</i> mutations and earlier effusion development. Effusion-based molecular testing yields clinically relevant genomic information in advanced breast cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350749","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":"Accurate focal-plane selection is crucial for artificial intelligence assessment of three-dimensional urine cytology specimens for bladder cancer screening and surveillance","authors":"Yoseph Sayegh MD,&nbsp;Brody McNutt MS,&nbsp;Minh-Khang Le MD, PhD,&nbsp;I-Chuang Liao MD,&nbsp;Keluo Yao MD,&nbsp;Camille Ng BS,&nbsp;Ahmad Kohsar DO, MS,&nbsp;Daniel Shou MD,&nbsp;Michael Yu BS,&nbsp;YinXian Jin BS,&nbsp;Louis J. Vaickus MD, PhD,&nbsp;Xiaoying Liu MD, MS,&nbsp;Christopher J. VandenBussche MD, PhD,&nbsp;Samuel E. Harvey MD, PhD,&nbsp;Joshua J. Levy PhD","doi":"10.1002/cncy.70117","DOIUrl":"https://doi.org/10.1002/cncy.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bladder cancer is a common and highly recurrent malignancy requiring lifelong surveillance. Urine cytology serves as a noninvasive triage tool to guide cystoscopy but is limited by variable sensitivity and manual review. Although deep learning enables quantitative cell-level assessment, limited work has examined three-dimensional urine cytology preparations (e.g., SurePath) containing residual cellular fragments, where restricting analysis to a single nominal focal plane may obscure diagnostically relevant features. This study aimed to quantify focal-plane heterogeneity, measure degradation of nuclear-to-cytoplasmic (NC) ratio and nuclear area estimates off plane, and evaluate focal-plane selection algorithms for performance recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 325 SurePath whole-slide images scanned as 11-plane Z-stacks were analyzed that spanned negative through high-grade urothelial carcinoma cases. A detection model identified cells and clusters across planes, and 343 clusters (2435 urothelial cells) were reannotated at the optimal nuclear and cytoplasmic focal depths. Classical focus metrics and vision-transformer models were evaluated for focal-plane prediction. A U-Net segmentation model generated NC ratios and nuclear areas, and Spearman correlations compared annotated and predicted measurements across optimal, off-plane, and algorithm-selected conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Focal-plane prediction accuracy ranged from 42% to 88%, with classical focus metrics outperforming deep-learning approaches. NC ratio correlation was 0.774 at optimal focus and declined progressively off plane (∼0.50 at ±5 planes). Algorithm-selected planes partially recovered performance (up to 0.748). Similar trends were observed for nuclear area estimation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Accurate focal-plane selection is critical for artificial intelligence–based assessment of three-dimensional urine cytology. Future work will extend this analysis to cluster- and patient-level outcomes in multi-institutional validation studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324998","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}

{"title":"Application of the International System for Serous Fluid Cytopathology in cerebrospinal fluid cytology: Overall survival analysis associated with diagnostic categories","authors":"Isil Z. Yildiz Aktas MD,&nbsp;Baidarbhi Chakraborty MD,&nbsp;Jia Meng Zhang MD,&nbsp;Yuan Wang MD,&nbsp;Jocelyn Chandler MD,&nbsp;Carlos Mauricio Mejia Arbelaez MD,&nbsp;Maximilian Wegener MD,&nbsp;Travis Blake Fenlon DO,&nbsp;Abdol Aziz Ould Ismail MD,&nbsp;Jonathan D. Marotti MD,&nbsp;Zhihui Zhang MD, PhD,&nbsp;Xiaoying Liu MD,&nbsp;He Wang MD, PhD","doi":"10.1002/cncy.70127","DOIUrl":"10.1002/cncy.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebrospinal fluid (CSF) cytopathology lacks standardized reporting, leading to diagnostic variability and inconsistent clinical management. Although the International System for Reporting Serous Fluid Cytopathology (TIS) has been established for effusions, its utility in CSF remains underexplored. For this study, the authors applied TIS categories to CSF specimens from three academic centers across two continents and evaluated their association with overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review of pathology databases (2019–2022) across three institutions was performed. Data included demographics, cytologic diagnosis, and OS. Diagnoses were reclassified using TIS criteria. OS was analyzed using Kaplan–Meier curves and Cox proportional hazards models, and multivariable analysis was used for predictors of mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 1137 patients underwent CSF cytologic evaluation. Diagnostic distribution was as follows: 3.2% nondiagnostic, 67.1% negative for malignancy, 6.2% atypia of undetermined significance, 2.7% suspicious for malignancy, and 20.8% malignant. Among 579 patients with follow-up, OS differed across categories (<i>p</i> &lt; .001). Mean survival was longest in patients who were diagnosed as negative for malignancy (53.9 months), followed by atypia of undetermined significance (48.4 months), and suspicious for malignancy (40.3 months), and it was shortest in patients who were diagnosed with malignancy (18.7 months).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Leveraging a large, multi-institutional cohort with up to 5 years of follow-up, this study demonstrated that TIS categories effectively stratify CSF specimens into distinct prognostic groups. The authors identified a significant correlation between diagnostic classification and OS, with a clear decline in patient outcomes from those who had diagnoses of negative for malignancy/atypia of undetermined significance to those who had diagnoses of suspicious for malignancy and malignancy. These findings support the TIS system as a standardized, evidence-based framework that enhances risk stratification and clinical decision-making in CSF cytopathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293376","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}

{"title":"The performance of intraoperative peritoneal washings in detecting pancreatic ductal adenocarcinoma","authors":"Sagar D. Patel DO,&nbsp;William R. Burns MD,&nbsp;Christopher J. VandenBussche MD, PhD","doi":"10.1002/cncy.70126","DOIUrl":"https://doi.org/10.1002/cncy.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Accurate peritoneal staging is critical in pancreatic ductal adenocarcinoma (PDAC), as the presence of peritoneal metastases significantly alters prognosis and treatment strategy. In this setting, some centers use peritoneal washings (PWs), which allow the sampling of a large area of the peritoneal surface in the absence of a visible lesion, to improve peritoneal staging and improve selection for curative-intent surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors conducted a retrospective review of 28 patients who underwent cytopathologic evaluation of intraoperative PWs collected between July 2019 to July 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was high concordance between PWs and concomitant biopsy. Six patients had positive PWs. Of these six patients, five of them had concordant findings noted on biopsy. There was one patient who had benign findings on biopsy despite having a malignant PW. In a similar fashion, 22 patients had PWs that were negative. Nineteen of these patients had concordant findings noted on biopsy. The remaining three patients had biopsy-confirmed metastasis despite benign findings noted on PW.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Peritoneal washings can enhance the detection of peritoneal involvement by PDAC while minimizing false-positive diagnoses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282508","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}

{"title":"Supernatant: What’s in a name?","authors":"Claudio Bellevicine MD, PhD,&nbsp;Elena Vigliar MD, PhD,&nbsp;Giancarlo Troncone MD, PhD,&nbsp;Sinchita Roy-Chowdhuri MD, PhD","doi":"10.1002/cncy.70123","DOIUrl":"10.1002/cncy.70123","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249313","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}

{"title":"Application of The International System for Serous Fluid Cytopathology to cerebrospinal fluid and adjunct flow cytometry analysis improves diagnostic accuracy","authors":"Minhua Wang MD, PhD,&nbsp;Guoping Cai MD","doi":"10.1002/cncy.70122","DOIUrl":"10.1002/cncy.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebrospinal fluid (CSF) is an important diagnostic tool for detecting leptomeningeal involvement by malignancy or other etiologies. Currently, there is no standardized reporting system for CSF cytology. This study aims to assess the application of The International System for Serous Fluid Cytopathology (TIS) in categorizing CSF diagnoses and the role of flow cytometry in improving diagnostic performances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CSF cases at our institution between January 1, 2023, and December 31, 2023, were reviewed and selected slides were examined. Based on the retrospective review of cytomorphologic findings and flow cytometry results, cases were reclassified into five diagnostic categories according to TIS: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study cohort included 854 CSF cases from 439 patients. Flow cytometry was performed in 185 (21.7%) cases with a positive result in 23 cases. After applying TIS, final cytological diagnoses included NFM (87.2%), AUS (7.1%), SFM (0.6%), and MAL (5.0%). The calculated risk of malignancy was 0.3% for NFM, 4.5% for AUS, 66.7% for SFM, and 100% for MAL. The diagnostic performance metrics were 95% sensitivity, 100% specificity, and 99% diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The application of TIS to CSF specimens helps standardize reporting terminology, improves diagnostic accuracy, and offers predictive risk stratification. The conjunction with flow cytometry to CSF cytology helps reduce indeterminate diagnosis, especially for those with an uncertain etiology or prior history of hematological malignancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223268","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}

{"title":"TRBC1/CD3 dual color immunohistochemistry: An effective test to support a diagnosis of T-cell lymphoma in cytology specimens","authors":"Sarah J. Wu MD, PhD,&nbsp;Jeffrey K. Mito MD, PhD","doi":"10.1002/cncy.70116","DOIUrl":"10.1002/cncy.70116","url":null,"abstract":"<p>The diagnosis of T-cell lymphoma is challenging, and establishing clonality is an important aspect of the workup. Molecular testing to establish T-cell clonality though T-cell receptor (TCR) gene rearrangement polymerase chain reaction is the most common modality and can detect clonal rearrangements in ∼90% of T-cell lymphomas, but is limited by increased turnaround time and cost and the need for sufficient material for testing. In the maturation of T cells, the TCR locus rearrangement will result in the mutually exclusive expression of either the TCR beta-chain constant domain 1 or 2 (TRBC1, TRBC2). Antibodies to TRBC1 and TRBC2 have been used in the setting of flow cytometry, and more recently immunohistochemistry, to establish T cell clonality. This study evaluates the utility of a TRBC1/CD3 dual stain for the diagnosis of T-cell lymphoma. The laboratory information system was searched from 2019 through 2025 for cytology samples with a diagnosis of T-cell lymphoma. Twelve samples were identified along with controls. Dual color immunohistochemistry for TRBC1 and CD3 was performed using a brown chromogen for TRBC1 and a red chromogen for CD3. The proportion of cells staining for TRBC1 and CD3 was scored. A monoclonal T-cell population was detected in all samples of T-cell lymphoma. All B-cell lymphomas and benign samples showed a polyclonal staining pattern consisting of a mixture of brown and red cells. Using immunohistochemistry for TRBC1 paired with CD3 is a reliable surrogate for T-cell clonality testing in cytology specimens and can support a diagnosis of T-cell lymphoma on limited material.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223192","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}

{"title":"Successful simplified genomic profiling of cytology specimens using Aspyre Clinical Test for Lung (Tissue)","authors":"Caren Gentile BS, MS,&nbsp;Sarah E. Herlihy BS, PhD,&nbsp;Elyse Shapiro BS, PhD,&nbsp;Ryan Thomas Evans MSc, PhD,&nbsp;Amanda Shull Green BS,&nbsp;Candace King BS,&nbsp;Mary Beth Rossi BS,&nbsp;Elizabeth Gillon-Zhang BS,&nbsp;James Schaffernoth BS,&nbsp;Katherine Elizabeth Knudsen PhD,&nbsp;Cory Kiser BS,&nbsp;Tatiana Yuen BS,&nbsp;Ana-Luisa Silva PhD,&nbsp;Eleanor Ruth Gray MSc, MBiochem, PhD,&nbsp;Barnaby William Balmforth MPhys, PhD,&nbsp;Wendy Jo Levin MS, MD,&nbsp;Jeffrey Gregg MD,&nbsp;Vivianna Van Deerlin MS, MD, PhD","doi":"10.1002/cncy.70121","DOIUrl":"https://doi.org/10.1002/cncy.70121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Testing patients with non–small cell lung cancer for actionable variants is essential for guiding treatment decisions in accordance with established cancer care guidelines, though limited quantity and quality of tumor tissue often leaves insufficient material for comprehensive testing. Cytopathology specimens obtained through minimally invasive techniques are a potential source of diagnostic material for genomic profiling, though typically challenging to analyze.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 85 DNA or total nucleic acid non–small cell lung cancer samples derived from 45 fine-needle aspirate rinse or pleural fluid samples from the Hospital of the University of Pennsylvania archive were tested using the Aspyre Clinical Test for Lung (Tissue) in Biofidelity’s CAP/CLIA laboratory. All samples were previously characterized by the Oncomine Precision Assay Genexus assay (the orthogonal reference method).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-four of 85 passed Aspyre Lung quality control, one failed. Twenty-six samples were positive for variants in the Aspyre Lung panel: 17 for single nucleotide variants (<i>KRAS</i>, <i>EGFR</i>), three for <i>EGFR</i> insertions/deletions, two for <i>MET</i> exon 14 skipping, and five for gene fusions. Eighty-two of 85 samples were run at standard input levels; three of 85 were run at low input but passed Aspyre Lung controls and include one <i>EGFR</i> exon 20 insertion variant-positive. All results were concordant between methods. Positive Percent Agreement and Negative Percent Agreement were 100%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Aspyre Clinical Test for Lung performs effectively on samples derived from fine needle aspirate rinses and pleural fluid. Using these cytology-based specimens for biomarker testing enables pathologists to perform simplified genomic profiling while preserving valuable tissue specimens, potentially reducing the need for additional invasive procedures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194078","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":"Cysteine-mapping efforts offer new tools for drug development and discovery","authors":"Bryn Nelson PhD,&nbsp;William Faquin MD, PhD","doi":"10.1002/cncy.70104","DOIUrl":"10.1002/cncy.70104","url":null,"abstract":"&lt;p&gt;The highly reactive amino acid cysteine has long been an attractive target for drug development. Much of that utility derives from cysteine’s critical biological roles and modifiability in different environments, from its sulfur-containing side chain’s ability to form strong disulfide bonds, and from its status as the most nucleophilic amino acid, which means that it readily donates electrons to binding partners. In addition, some cysteines have low p&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;a&lt;/sub&gt; values, which indicate stronger and more reactive acids. “That reactivity is also associated with function and sensitivities to different environments, and so I think there’s somewhat of a marriage between functional importance and then reactivity,” says Balyn Zaro, PhD, an associate professor of pharmaceutical chemistry at the University of California, San Francisco. That “perfect storm” combination makes cysteine an ideal target for drug developers, she says.&lt;/p&gt;&lt;p&gt;The dynamic nature of different cysteines within the same protein or in the same protein position but within different cells, however, has made determining which sites are better drug targets and which ones are more reactive a challenging task. New tools address those knowledge gaps in part by mapping the characteristics of cysteines in proteins within multiple cancer cell types and then making that information freely available to other researchers.&lt;/p&gt;&lt;p&gt;In 2024, researchers at the Mass General Cancer Center in Boston, Massachusetts, expanded on previous efforts by publishing an ambitious new resource named DrugMap.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This comprehensive atlas lists potential cysteine-based drug targets across 25 cancer types based on a systematic mapping of 416 cancer cell lines.&lt;/p&gt;&lt;p&gt;Coauthor Liron Bar-Peled, PhD, a principal investigator at the Krantz Family Center for Cancer Research at Mass General Cancer Center and associate professor of medicine at Harvard Medical School, says that the goal in drug discovery usually comes down to getting a small molecule to bind to a disease-associated protein. For kinases, a class of enzymes that can modify molecules by adding phosphates to them, researchers have figured out how to create anticancer drugs that effectively bind within the proteins’ pockets. For the majority of cancer-linked proteins, however, “we have no good starting places,” he says. “And because we don’t have a starting point, we often refer to 80% of oncogenes as ‘undruggable’ or very challenging.”&lt;/p&gt;&lt;p&gt;The DrugMap effort has suggested that the true “undruggable” percentage may be far less. “Because of its unique chemical properties, cysteine almost acts as Velcro or a chemical handle for us to attach small molecules,” Dr Bar-Peled says. That handhold can provide a key starting point in the molecule-developing stage of the drug discovery process. Other researchers previously developed chemical proteomics, or a suite of technologies that probe protein–molecule interactions and help to identify dr","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142804","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":"Atypical and suspicious diagnoses in solid pancreatic lesions: Cytomorphologic features and interobserver variability in FNA smears and biopsies.","authors":"Mohammad M Al-Attar, Ruhani Sardana, Melissa Zhao, Martha B Pitman, Vanda F Torous, Ivan Chebib, M Lisa Zhang","doi":"10.1002/cncy.70113","DOIUrl":"10.1002/cncy.70113","url":null,"abstract":"<p><strong>Background: </strong>Atypical (ATY) and suspicious (SUS) diagnoses in fine-needle aspiration/biopsy (FNA/B) of solid pancreatic lesions remain challenging to consistently apply. The most relevant cytomorphologic features and reproducibility of these interpretations across direct smears and FNBs are not well characterized.</p><p><strong>Methods: </strong>In total, 124 FNA/B specimens (87 smears, 37 FNBs) from solid pancreatic masses originally diagnosed as ATY or SUS were identified (from 2014 to 2024). Clinical/pathologic follow-up was reviewed, and morphologic features were systematically assessed. Interobserver variability was evaluated using blinded re-interpretation of 40 smears and 20 FNBs by four cytopathologists and three cytopathology fellows.</p><p><strong>Results: </strong>Non-adenocarcinoma malignancies (16 smears and 3 FNBs) were excluded for outcomes and morphologic analysis. The risk of malignancy was high in both categories (smears: ATY, 72.3%; SUS, 90.0%; FNBs: ATY, 80.0%; SUS, 100%). ATY smears more often showed scant cellularity (87.8% vs. 59.1% of SUS smears; p = .011), whereas SUS cases more commonly demonstrated anisonucleosis ≥4:1 (54.5% vs. 20.4%; p = .010). On FNBs, background chronic pancreatitis was significantly more frequent in SUS cases (75.0% vs. 11.5%; p = .001). Interobserver agreement was fair for smears (κ = 0.355) and lower for FNBs (κ = 0.218), with fellows rendering ATY/SUS diagnoses more frequently than staff cytopathologists.</p><p><strong>Conclusions: </strong>Both ATY and SUS interpretations in solid pancreatic lesions carry high malignancy risk. Smears show clearer morphologic features for upgrading from ATY to SUS, whereas FNBs demonstrate fewer discriminating features and lower reproducibility. These findings support continued refinement of specimen-type-specific morphologic criteria and ongoing education to reduce variability in reporting.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 6","pages":"e70113"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962204","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}