{"title":"Bridging the global diversity gap in cancer genomics","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70087","DOIUrl":"10.1002/cncy.70087","url":null,"abstract":"<p>Major cancer data-generating efforts, such as The Cancer Genome Atlas (TCGA), have shown how detailed genomic information can provide a crucial base for precision medicine and discovery research. Even so, patients of European ancestry are overrepresented in TCGA and similar databases, and this sample bias limits their generalizability and clinical relevance to real-world populations.<span><sup>1</sup></span> Three major projects collecting cancer data from Africa, Latin America, and India, respectively, demonstrate how that diversity gap might be narrowed through collaborative database building.</p><p>Yaw Bediako, PhD, chief executive officer of Yemaachi Biotech in Accra, Ghana, initially focused his research on infectious disease and on malaria in particular. After losing his father to cancer, he thought more about the less well-documented but rapidly growing burden of cancer on the African continent and began to shift his focus. “Cancer already kills more people in Africa than malaria does,” he points out, noting that cancer rates are rising faster in Africa than nearly any other region in the world.</p><p>In 2021, he cofounded Yemaachi Biotech to help to develop the continent’s biotechnology industry. “The idea to focus on cancer was driven by this realization that cancer is very much a global health disease now,” Dr Bediako says. Less than 3% of genomic data have come from people of African descent, however. “That is a huge problem when you’re in an age of precision medicine and we’re trying to make treatments and diagnostics tailored to an individual, especially now in this AI revolution where everything is based on training sets,” he says. “If you’re not in the training data, you’re not in the solution, right? And most African people find themselves outside the training data.”</p><p>The company’s first signature project, The African Cancer Atlas (TACA), offers a way to help to address the imbalance.<span><sup>2</sup></span> Given the constraints on publicly funded research in Africa, Dr Bediako has sought partnerships with Roche and other pharmaceutical companies to help to fund TACA in exchange for a trove of highly diverse genomic data. “Healthcare solutions that historically have been based upon genomes from predominantly European-origin individuals are less and less effective even in the US, where you have growing black and Hispanic communities,” he says.</p><p>In that regard, the African continent offers a decided strength as home to the world’s most genetically diverse population. “Pretty much every genetic variant present on the planet can be found in Africa, so it’s also a really unique opportunity to move the needle when it comes to the understanding of health in people, regardless of where they’re from,” Dr Bediako says.</p><p>Over the next 5 years, if all goes well, TACA will sequence 15,000 cancer genomes drawn from 7500 individuals in more than 15 African countries. The sequences, representing breast, lung, colorectal, and f","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627485","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}
Min Dai MD, Francis Anthony San Lucas PhD, Hector Alvarez MD, Leomar Ballester MD, PhD, Hui Chen MD, PhD, Keyur P. Patel MD, PhD, Asif Rashid MD, Shun Rao MS, Mark J. Routbort MD, PhD, Gloria Sura MD, Keith Sweeney MD, Gokce Toruner MD, PhD, Peng Wei PhD, Richard Yang MD, PhD, Hyvan Dang BA, Rajyalakshmi Luthra PhD, Sinchita Roy-Chowdhuri MD, PhD
{"title":"Unraveling the nexus: Tumor mutational burden, PD-L1 expression, and oncogenic alterations in non–small cell lung cancer cytology specimens","authors":"Min Dai MD, Francis Anthony San Lucas PhD, Hector Alvarez MD, Leomar Ballester MD, PhD, Hui Chen MD, PhD, Keyur P. Patel MD, PhD, Asif Rashid MD, Shun Rao MS, Mark J. Routbort MD, PhD, Gloria Sura MD, Keith Sweeney MD, Gokce Toruner MD, PhD, Peng Wei PhD, Richard Yang MD, PhD, Hyvan Dang BA, Rajyalakshmi Luthra PhD, Sinchita Roy-Chowdhuri MD, PhD","doi":"10.1002/cncy.70090","DOIUrl":"10.1002/cncy.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non–small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 312 cases evaluated, 192 harbored NSCLC-specific oncogenic alterations. Relative to <i>EGFR</i>-mutated tumors, TMB was significantly higher in <i>KRAS</i> (<i>p</i><sub>adj</sub> = 2.7 × 10<sup>−4</sup>), <i>ERBB2</i> (<i>p</i><sub>adj</sub> = .023), and <i>BRAF</i> (<i>p</i><sub>adj</sub> = .023) -mutated tumors but lower in <i>ALK</i>-rearranged tumors (<i>p</i><sub>adj</sub> = .005). Significantly higher PD-L1 expression was seen in tumors with <i>KRAS</i> (<i>p</i><sub>adj</sub> = .002) and <i>MET</i> exon 14 (<i>p</i><sub>adj</sub> = 1.06 × 10<sup>−4</sup>) when compared to <i>EGFR</i>-mutated tumors. Strong positive correlations between TMB and PD-L1 were observed in <i>ERBB2</i>-, <i>KRAS</i>-, and <i>BRAF</i>-mutated tumors when evaluated as continuous variables. <i>TP53</i> mutations further enhanced immunogenicity when co-occurring with <i>KRAS</i>, <i>ERBB2</i>, or <i>BRAF</i> mutations but this effect was not observed in <i>EGFR</i>-mutated tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate distinct TMB and PD-L1 profiles that may identify patients who will benefit from ICI therapy. Cytology specimens provide adequate material for biomarker testing, which underscores their value in guiding immunotherapy decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527046","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":"Spindle cell lesions in cytology: Risks of malignancy and application of the upcoming World Health Organization Reporting System for Soft Tissue Cytopathology","authors":"Natalie A. H. Ellis MD, Wen-Chi Foo MD","doi":"10.1002/cncy.70089","DOIUrl":"10.1002/cncy.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spindle cell lesions can be challenging to diagnose on cytology alone. The World Health Organization (WHO) is publishing a new WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). The authors examined the performance characteristics of spindle cell lesion diagnoses at their institution when reclassifying according to the WHORSSTC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Spindle cell fine-needle aspirations or fine-needle core biopsies diagnosed on cytology were collected from August 2021 through July 2024. Clinical information, procedural data, cytologic diagnoses, and surgical pathology diagnoses were obtained from the electronic medical records. Cases were reclassified according to the WHORSSTC, and relevant metrics were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 296 cases were identified from 164 women, 131 men, and one transgender female. The average age was 60 years. Biopsies were obtained as fine-needle core biopsies (<i>n</i> = 152), fine-needle aspirations (<i>n</i> = 130), or both (<i>n</i> = 12); and 127 patients (43%) had subsequent surgical pathology follow-up. Most lesions (<i>n</i> = 94; 74%) were mesenchymal on resection. These were initially diagnosed as negative (<i>n</i> = 3; 2%), atypical (<i>n</i> = 14; 11%), suspicious (<i>n</i> = 5; 4%), malignant (<i>n</i> = 35; 28%), and descriptive (<i>n</i> = 70; 55%), with absolute risks of malignancy of 0%, 43%, 80%, 100%, and 44%, respectively. To align with the WHORSSTC, these cases were recategorized as insufficient/nondiagnostic (<i>n</i> = 7; 6%), benign (<i>n</i> = 13; 10%), atypical (<i>n</i> = 12; 9%), soft tissue neoplasm of uncertain malignant potential (<i>n</i> = 54; 43%), suspicious for malignancy (<i>n</i> = 5; 4%), and malignant (<i>n</i> = 36; 28%), with absolute risks of malignancy of 0%, 0%, 42%, 57%, 80%, and 100%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although not all spindle cell lesions prove to be mesenchymal, they can be effectively categorized by the upcoming WHORSSTC with increasing risks of malignancy that better predict biologic potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509667","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}
Tsandmaa Byambadorj MD, Mohammad Rizwan Alam PhD, Yosep Chong MD, PhD
{"title":"Artificial intelligence in nongynecologic cytology: A systematic review of current research and commercial tools","authors":"Tsandmaa Byambadorj MD, Mohammad Rizwan Alam PhD, Yosep Chong MD, PhD","doi":"10.1002/cncy.70092","DOIUrl":"10.1002/cncy.70092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nongynecologic (non-GYN) cytology plays an important role in cellular and molecular cancer diagnosis, although its use is limited by variability and interobserver discrepancies. Recent studies suggest that artificial intelligence (AI) may improve diagnostic consistency and performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This systematic review evaluated contemporary AI research in non-GYN cytology and examined commercially available systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MEDLINE, Embase, and the Cochrane Library were searched for English-language studies published from January 2010 to September 2024. Of ∼24,000 records screened, 71 met inclusion criteria. Commercial platforms (KFBIO, Landing Med, VitaDx/VisioCyt, AIxMED, and CellsVision) were assessed using publicly available regulatory documents, technical specifications, and vendor-reported validation data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Many studies reported high internal diagnostic performance, often exceeding 90% accuracy. Patch-level performance often reached ∼94%, exceeding whole slide image-level metrics. Reduced interobserver variability was frequently observed, with accuracies of 95.9% for senior and 94.4% for junior pathologists. Several studies documented shorter diagnostic time. Thyroid (37%) and urinary bladder (30%) cytology were most frequently studied. AI applications included categorization, segmentation, and atypia detection, with recent work exploring immunocytochemistry support, mutation-associated pattern recognition, and indirect prediction of histologic features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AI in non-GYN cytology shows promise but remains limited by data set quality, weak external validation, and regulatory barriers. At present, AI tools function primarily as decision-support systems. Advancing clinical adoption will require multicenter validation, standardized data sets, and careful integration with expert interpretation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490712","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}
Asma Arshia MBBS, David Kalfert MD, PhD, Ivana Kholová MD, PhD, MIAC
{"title":"Navigating the International System for Reporting Serous Fluid Cytopathology in pericardial effusion: A meta-analysis","authors":"Asma Arshia MBBS, David Kalfert MD, PhD, Ivana Kholová MD, PhD, MIAC","doi":"10.1002/cncy.70091","DOIUrl":"10.1002/cncy.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The International System for Reporting Serous Fluid Cytopathology (TIS) provides a standardized framework for classifying serous fluid cytology into five diagnostic categories: nondiagnostic, negative for malignancy, atypical, suspicious for malignancy, and malignant. Although TIS has been widely adopted for pleural and peritoneal fluids, its application in pericardial effusion cytology remains limited. The objective of this study was to evaluate the use of TIS in pericardial effusion samples and estimate the associated risk of malignancy for each category.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies published between 2013 and 2023 were identified through a comprehensive PubMed search. Eligible studies applied TIS to pericardial effusion cytology. The analysis excluded case reports, case reviews, abstracts, comparative studies, and non-English publications. Furthermore, the authors omitted studies that did not explicitly categorize pericardial fluid samples using the TIS categorization. Ten studies met inclusion criteria, comprising 2976 pericardial fluid samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pooled distribution across TIS categories were: nondiagnostic (2.9%), negative for malignancy (60.2%), atypical (5.4%), suspicious for malignancy (2.4%), and malignant (23.4%). Risk of malignancy estimates based on histologic confirmation were: 10.8% for nondiagnostic, 8.7% for negative for malignancy, 34.0% for atypical, 64.1% for suspicious for malignancy, and 78.6% for malignant categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TIS effectively stratifies pericardial effusion cytology samples by malignancy risk. The progressive increase in the risk of malignancy across categories supports its diagnostic utility. However, substantial heterogeneity, particularly in the negative for malignancy and malignant categories, highlights the need for standardized reporting and further prospective validation of TIS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484719","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}
Cheng-Chieh Chen MSc, Ke-Yu Hsiao MSc, Hsiu-Ling Lin BS, RN
{"title":"Clinical utility of oral cytology for detecting oral epithelial dysplasia or worse: A diagnostic meta-analysis","authors":"Cheng-Chieh Chen MSc, Ke-Yu Hsiao MSc, Hsiu-Ling Lin BS, RN","doi":"10.1002/cncy.70088","DOIUrl":"10.1002/cncy.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The majority of oral cancers are diagnosed at an advanced stage. It has been demonstrated that the implementation of screening programs reduces mortality rates. Oral cytology is a technique that is used in these programs. However, the accuracy of oral cytology remains controversial. Therefore, the objective of this meta-analysis was to validate the accuracy of oral cytology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature search was conducted in the PubMed, Embase, and Cochrane Library databases to identify eligible studies. The inclusion criteria were as follows: studies that evaluated the diagnostic accuracy of oral cytology for low-grade squamous intraepithelial lesion or worse. The article incorporated peer-reviewed articles. In addition, studies that provided sufficient data for conducting a meta-analysis were assessed. The meta-analysis was conducted using a bivariate random-effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 26 articles comprising 8397 specimens were included in the study. The meta-analysis yielded a pooled sensitivity of 93.8% and a pooled specificity of 87.7% of oral cytology for identifying oral epithelia dysplasia or worse. A subgroup analysis of studies that evaluated oral cytology with Papanicolaou staining demonstrated a pooled sensitivity of 94.8%. The accuracy of oral cytology in detecting high-grade squamous intraepithelial lesion or worse was examined, resulting in a pooled sensitivity of 95.7%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This meta-analysis indicated that oral cytology exhibited high sensitivity and specificity in detecting oral epithelia dysplasia or worse, with slightly higher sensitivity for high-grade squamous intraepithelial lesion or worse. A notable advantage of using oral cytology with Papanicolaou staining is the potential for enhanced sensitivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472380","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":"A growing brain drain: US policies are spurring medical researchers to pursue other options","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70081","DOIUrl":"10.1002/cncy.70081","url":null,"abstract":"<p>In March 2025, after weeks of upheaval at the National Institutes of Health (NIH), brewing fights over academic freedom, and increasingly restrictive immigration policies, many researchers in the United States were starting to eye the exits. More than 75% of scientists who responded to a <i>Nature</i> poll said that they were “considering leaving the country following the disruptions to science prompted by the Trump administration.”<span><sup>1</sup></span> Early-career researchers were particularly apt to consider departing. Their top choices were Europe and Canada.</p><p>Other researchers are not even getting in the door or are opting for another entrance to a different career. The disruptions have affected many, including undergraduates who are not receiving internships, graduate students who are encountering closed programs and discontinued fellowships, and postdoctoral fellows and international scholars who are unable to access grants or work visas. “Literally at every single stage of the training spectrum, we have now disincentivized people to pursue these professional trajectories. It’s brain drain by a thousand paper cuts,” says Rachael Sirianni, PhD, a professor of neurological surgery at the University of Massachusetts Chan Medical School in Worcester.</p><p>The rest of the world has taken notice. A growing number of recruitment drives are vying to entice disgruntled or displaced researchers to Canada, China, the United Kingdom, France, Germany, and other countries. Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, says that a LinkedIn feed for scientists has been filled with recruitment offers from foreign countries and institutions. “If I’m seeing it, thousands of others are seeing it as well,” she says. Ironically, many of these efforts have been patterned after the past successes of the leader in medical research: the United States itself.</p><p>The United States, observers say, has long been a magnet for research talent from around the world because of its deep investments in research and its reputation as an attractive destination for immigrants. Both of those advantages are now in jeopardy, creating new openings for other countries. “The pullback on support of science, the rise of pseudoscience and that move away from experts and expertise, it’s got people worried; it’s got people thinking about other places,” says Brad Wouters, PhD, executive vice president of science and research at the University Health Network (UHN) in Toronto, Canada.</p><p>In April, UHN launched a program called Canada Leads, which aims to reverse the Toronto region’s own brain drain by recruiting 100 early-career medical researchers to UHN’s institutions, including Toronto General Hospital, Toronto Western Hospital, and the Princess Margaret Cancer Centre. The $30 million initiative is providing money for supplemental salaries as well as laboratory space, mentorship, and partnerships with academic and industry collaborators. ","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347335","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}
Giuseppe D’Abbronzo MD, Stefano Lucà MD, Immacolata Cozzolino MD, PhD, Marina Accardo MD, Carminia Della Corte MD, PhD, Francesco Iovino MD, PhD, Simona Parisi MD, Ilaria Tedesco BD, Francesco Ingallinella MD, Francesca Grasso MD, Renato Franco MD, PhD, Marco Montella MD, PhD
{"title":"High accuracy in detecting HER2-low status in FNA of primary and metastatic breast cancer","authors":"Giuseppe D’Abbronzo MD, Stefano Lucà MD, Immacolata Cozzolino MD, PhD, Marina Accardo MD, Carminia Della Corte MD, PhD, Francesco Iovino MD, PhD, Simona Parisi MD, Ilaria Tedesco BD, Francesco Ingallinella MD, Francesca Grasso MD, Renato Franco MD, PhD, Marco Montella MD, PhD","doi":"10.1002/cncy.70085","DOIUrl":"10.1002/cncy.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>HER2-positive invasive breast carcinomas (IBCs) account for 15% of breast cancers and are driven by ERBB2 gene amplification. Although historically associated with aggressive behavior, HER2-targeted therapies have significantly improved outcomes. HER2 status is routinely assessed by immunohistochemistry (IHC) and in situ hybridization (ISH). Recently, tumors with low HER2 expression (IHC 1+ or 2+ without amplification), previously classified as HER2-negative, have emerged as a clinically relevant subgroup. Fine-needle aspiration cytology (FNAC) is a minimally invasive alternative to core needle biopsy, particularly useful in inoperable or metastatic settings. FNAC-derived cell blocks (CBs) allow immunocytochemical (ICC) evaluation of biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 46 FNAC-derived CBs from breast cancers (34 primary tumors and 12 metastases) collected at Vanvitelli University Hospital. ICC evaluation of HER2, estrogen receptor (ER), and progesterone receptor (PR) was independently performed by two expert pathologists and compared with corresponding histological assessments. Diagnostic performance was evaluated using sensitivity, specificity, predictive values, concordance rates, and receiver operating characteristic (ROC) curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ICC on FNAC-derived CBs showed good diagnostic performance for HER2-low tumors. Sensitivity ranged from 56.3% to 59.4%, whereas specificity was high (85.7%–92.9%). Positive predictive values reached 90.0%–95.0%, whereas negative predictive values were lower (46.2%–50.0%). Concordance between cytological and histological HER2-low assessment exceeded 90%, with ROC area under the curve values of 0.71–0.76. ER showed excellent concordance, whereas PR demonstrated moderate agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FNAC-derived CBs are a reliable tool for identifying HER2-low breast carcinomas when histological samples are unavailable or limited, emphasizing the need for standardized evaluation criteria.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302680","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}
Di Ai MD, PhD, Youjie Zhang MD, PhD, Kartik Viswanathan MD, PhD, Jilun Zhang BS, Kelly R. Magliocca MD, Scott Steward-Tharp MD, Wen-Yu Hsiao MD, PhD, Qiuying Shi MD, MS
{"title":"Testing insulin-like growth factor messenger RNA–binding protein 3 as a surrogate immunohistochemical marker for indeterminate thyroid nodules with THADA fusion in both cytologic and surgical specimens","authors":"Di Ai MD, PhD, Youjie Zhang MD, PhD, Kartik Viswanathan MD, PhD, Jilun Zhang BS, Kelly R. Magliocca MD, Scott Steward-Tharp MD, Wen-Yu Hsiao MD, PhD, Qiuying Shi MD, MS","doi":"10.1002/cncy.70076","DOIUrl":"10.1002/cncy.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Thyroid adenoma-associated (<i>THADA</i>) gene fusions are recurrent alterations in thyroid nodules that lead to the overexpression of insulin-like growth factor messenger RNA–binding protein 3 (IMP3). Although IMP3 immunohistochemistry has been studied in thyroid tumors, its utility for detecting <i>THADA</i> fusion–positive thyroid specimens remain unassessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors evaluated IMP3 expression in cytologic and surgical specimens from 20 indeterminate thyroid nodules. Eleven cases harbored <i>THADA</i> fusions, including <i>THADA::IGF2BP3</i> (<i>n</i> = 9) and <i>THADA::TRA2A</i> (<i>n</i> = 2), whereas nine control cases lacked detectable <i>THADA</i> fusions. Hematoxylin-and-eosin staining and immunohistochemistry for IMP3 and NRAS Q61R were performed on available cell blocks and surgical specimens. Staining was scored based on extent and intensity, with a composite score >2 considered positive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All nodules with <i>THADA</i> fusions exhibited strong, diffuse, cytoplasmic IMP3 staining in lesional follicular cells, with no staining in adjacent normal thyroid tissue. All control cases were negative for IMP3. NRAS Q61R immunostaining was negative across all cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current findings in a limited cohort demonstrate that IMP3 is a promising surrogate marker for indeterminate thyroid nodules with <i>THADA</i> fusions in both cytologic and surgical specimens. In addition, IMP3 staining may aid in detecting subtle capsular or vascular invasion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302633","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":"Comment on reevaluation of malignancy risk in nondiagnostic thyroid nodules with long-term follow-up via surgical resection or core needle biopsy thyroidology","authors":"Ilker Sengul MD, Demet Sengul MD","doi":"10.1002/cncy.70084","DOIUrl":"10.1002/cncy.70084","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282752","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}