Mohammed S. Ahmed MD, Dianna Klippel-Almaraz MS, Sara E. Amin MD, Gloria H. Sura MD, Uma Rani Kundu MD, Wendong Yu MD, PhD, John M. Stewart MD, PhD, Qiong Gan MD, PhD, Savitri Krishnamurthy MD
{"title":"Utility of whole-slide imaging for rapid evaluation of thyroid FNA: A multireader prospective study","authors":"Mohammed S. Ahmed MD, Dianna Klippel-Almaraz MS, Sara E. Amin MD, Gloria H. Sura MD, Uma Rani Kundu MD, Wendong Yu MD, PhD, John M. Stewart MD, PhD, Qiong Gan MD, PhD, Savitri Krishnamurthy MD","doi":"10.1002/cncy.70046","DOIUrl":"10.1002/cncy.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors evaluated 98 ultrasound-guided thyroid FNAB cases. Smears were stained with Papanicolaou and Diff-Quik and were scanned at ×20 magnification using a Leica Aperio CS2 scanner. Five cytopathologists evaluated specimen adequacy and Bethesda categorization using WSI followed by LM assessment after a 2-week washout. Intraobserver and interobserver agreements were calculated using Cohen and Fleiss kappa (κ) statistics. Scan time, interpretation time, and the need for ×40 magnification or z stacking were recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 463 slides were scanned, with mean scan time of 5.48 minutes. WSI quality was acceptable in most cases. Z stacking and ×40 magnification were requested in 23% and 14% of reviews, respectively. Intrareader agreement between WSI and LM examination was excellent (κ = 0.86–0.95). Inter-reader agreement was moderate for both WSI (κ = 0.48) and LM examination (κ = 0.56). Concordance was highest for Bethesda categories I and VI and lowest for categories III–V. Interpretation with WSI took significantly longer than with LM examination (<i>p</i> < .0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>WSI is a feasible alternative to LM examination for ROSE of thyroid FNABs, with high intrareader agreement and comparable inter-reader agreement. The limited need for high magnification and z stacking supports its practical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spotlight: Rising stars in cytology","authors":"David Kim MD","doi":"10.1002/cncy.70043","DOIUrl":"10.1002/cncy.70043","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915078","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}
Adam Kowalewski MD, PhD, MIAC, Jędrzej Borowczak MD, PhD, Olivier Choussy MD, Maria Lesnik MD, Nathalie Badois MD, Jerzy Klijanienko MD, PhD, MIAC
{"title":"Comparative analysis of the World Health Organization Reporting System for Head and Neck Cytopathology and the Milan System for Reporting Salivary Gland Cytopathology","authors":"Adam Kowalewski MD, PhD, MIAC, Jędrzej Borowczak MD, PhD, Olivier Choussy MD, Maria Lesnik MD, Nathalie Badois MD, Jerzy Klijanienko MD, PhD, MIAC","doi":"10.1002/cncy.70041","DOIUrl":"10.1002/cncy.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A comparative analysis of the International Academy of Cytology–International Agency for Research on Cancer–World Health Organization Reporting System for Head and Neck Cytopathology (WHO) and the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 2218 salivary gland fine-needle aspiration samples collected at the Institut Curie, Paris (1954–2022) were evaluated, with 1356 having histological follow-up. Samples were classified according to the MSRSGC (nondiagnostic [ND], nonneoplastic [NN], atypia of undetermined significance [AUS], benign neoplasm [BN], salivary gland neoplasm of uncertain malignant potential [SUMP], suspicious for malignancy [SM], and malignant [M]) and the WHO system (insufficient/inadequate/nondiagnostic, benign, atypical, neoplasm of uncertain malignant potential [NUMP], suspicious for malignancy [SM], and malignant [M]). The risk of malignancy (ROM) was calculated for each category, and diagnostic performance metrics were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the MSRSGC, the ROM was ND, 50% (<i>n</i> = 2); NN, 16.8% (<i>n</i> = 149); AUS (no cases); BN, 4.3% (<i>n</i> = 514); SUMP, 50% (<i>n</i> = 2); SM, 56.1% (<i>n</i> = 66); and M, 98.2% (<i>n</i> = 623). In the WHO system, the ROM was insufficient/inadequate/nondiagnostic, 50% (<i>n</i> = 2); benign, 7.1% (<i>n</i> = 663); atypical (no cases); NUMP, 50% (<i>n</i> = 2); SM, 56.1% (<i>n</i> = 66); and M, 98.2% (<i>n</i> = 623). The WHO’s “benign” category, which combines NN and BN, balanced the NN’s higher ROM (16.8%) and BN’s lower ROM (4.3%) into 7.1%. Excluding the ND and SUMP/NUMP categories, both systems demonstrated high diagnostic performance: sensitivity, 93.3%; specificity, 93.9%; positive predictive value, 94.2%; and negative predictive value, 92.9%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Both systems effectively identify malignancy. The WHO system’s merger of NN and BN into the benign category streamlines reporting and reduces variability, although it may mask clinically significant differences between nonneoplastic and benign neoplastic lesions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897583","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":"The utility of next-generation sequencing in metastatic prostate cancer FNA biopsies","authors":"Deepika Sirohi MD, Chien-Kuang Cornelia Ding MD, PhD, Bradley A. Stohr MD, PhD, Ronald Balassanian MD, Poonam Vohra MD, Rahul Aggarwal MD, Emily Chan MD, PhD, Nancy Y. Greenland MD, PhD","doi":"10.1002/cncy.70038","DOIUrl":"10.1002/cncy.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current American Society of Clinical Oncology guidelines state that patients with metastatic prostate cancer (MPC) should undergo germline and somatic DNA sequencing. The authors examined the utility of next-generation sequencing (NGS) on fine-needle aspiration (FNA) biopsies in which NGS was performed on cell block (CB) and/or smears.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review was performed of cytology cases with diagnosis of MPC either before and/or after NGS on FNA material. Clinical and NGS data were obtained from the medical record. Androgen receptor, NKX3.1, INSM1, synaptophysin, chromogranin, Rb, PTEN, and Ki67 immunohistochemical stains were performed on CB if not originally done.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Slides and NGS data were available for 46 MPC FNA biopsies from 45 patients from 2015 to 2024. Metastatic sites included 20 lymph node, 12 liver, five lung, four soft tissue, two pleura, two bone, and one adrenal gland. Ten patients (22%) had change or potential change in therapy based on NGS results. For one patient with poorly differentiated carcinoma previously thought to be urothelial, a <i>TMPRSS2:ERG</i> fusion confirmed prostatic origin. NGS confirmed lung origin for one patient diagnosed initially as metastatic prostatic adenocarcinoma. For one patient, NGS demonstrated <i>TP53</i> and <i>RB1</i> mutations, supporting transformation to high-grade neuroendocrine carcinoma. Change or potential change in therapy was planned for two patients with <i>CDK12</i> mutations, one with <i>IDH1</i> mutation, three with <i>BRCA2</i> mutations, and one with <i>PTEN</i> and <i>TP53</i> mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NGS on cytology material showed diagnostic and therapeutic utility in a subset of patients, with 10 of 46 patients (22%) having a change or potential in therapy based on NGS results.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891684","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}
Adam Kowalewski MD, PhD, MIAC, Jędrzej Borowczak MD, PhD, Hervé J. Brisse MD, PhD, Olivier Choussy MD, Jerzy Klijanienko MD, PhD, MIAC
{"title":"Application of the Milan and IAC–IARC–WHO Systems in diagnosing soft tissue and bone tumors of the salivary glands: The Institut Curie experience","authors":"Adam Kowalewski MD, PhD, MIAC, Jędrzej Borowczak MD, PhD, Hervé J. Brisse MD, PhD, Olivier Choussy MD, Jerzy Klijanienko MD, PhD, MIAC","doi":"10.1002/cncy.70040","DOIUrl":"10.1002/cncy.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Soft tissue and bone tumors of the salivary gland were compared using classic 4-tier, Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), and the International Academy of Cytology-International Agency for Research on Cancer-World Health Organization (IAC–IARC–WHO) Reporting System for Soft Tissue Cytopathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors retrospectively analyzed 2219 salivary gland fine-needle aspiration (FNA) samples collected at the Institut Curie in Paris between 1954 and 2022. A total of 86 cases (3.9%) were identified as soft tissue and bone tumors, with histological follow-up in 63 cases (73%). Cytology was classified according to the classic European 4-tier system, the MSRSGC, and the IAC–IARC–WHO System.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>According to the MSRSGC, eight cases were classified as nonneoplastic, 30 as benign, one as salivary gland neoplasm of uncertain malignant potential, five as suspicious for malignancy, and 42 as malignant. Benign or malignant nature was accurately assessed in 78 cases (90.7%), with exact histologic-cytologic concordance in 51 cases (59.3%). FNA correctly identified 42 of 44 malignant tumors (95.5%), with exact diagnostic matches in 30 cases (68.2%). The MSRSGC achieved 88.3% overall accuracy, 93.6% sensitivity, and 82.7% specificity. Risk of malignancy (ROM) was comparable for malignant tumors across the classic European system, the MSRSGC, and the IAC–IARC–WHO System, with minor discrepancies observed in benign and indeterminate categories. No cases were assigned as nondiagnostic, atypia of undetermined significance, atypical.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite their rarity, soft tissue and bone tumors of the salivary gland can be effectively diagnosed using the MSRSGC, with a high accuracy achieved for malignant cases. Minor discrepancies in ROMs were observed between specific categories of the classic European system, the MSRSGC, and the IAC–IARC–WHO System.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881504","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":"Decoding the mysterious surge in early-onset colorectal cancers","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70032","DOIUrl":"10.1002/cncy.70032","url":null,"abstract":"<p>The change began slowly. In the 1990s, colorectal cancer rates started creeping up by a few percentage points every year in adults who often were told they were too young to have cancer. At the same time, the incidence decreased markedly in those over the age of 55 years. Researchers noticed the diverging trends but were unable to determine why they continued year after year.</p><p>By 2019, epidemiological data revealed that the incidence of early-onset colorectal cancer had risen by an alarming 63% in less than 3 decades.<span><sup>1</sup></span> Although the mystery behind its increase remains, several large research projects are digging into a wide range of modifiable and nonmodifiable risk factors to determine what may have changed in the 1950s or 1960s to cause the persistent and worrisome uptick.</p><p>“The short answer is we don’t know what’s causing it,” says Robin Mendelsohn, MD, clinical director of the Gastroenterology, Hepatology, and Nutrition Service at Memorial Sloan Kettering Cancer Center in New York. “Obviously we want to figure this out, but we also want people to be taken care of promptly because the earlier cancer’s detected, the better the prognosis and treatment.”</p><p>In March 2018, Memorial Sloan Kettering opened its Center for Young Onset Colorectal Cancer to focus on patients who are diagnosed before they turn 50 years old. In January 2021, because of growing demand, the center was expanded to include all gastrointestinal cancers. “We’ve unfortunately been busy,” says Dr Mendelsohn, codirector of what is now called the Center for Young Onset Colorectal and Gastrointestinal Cancer. Although the number of early-onset cancers is highest in the 40- to 49-year-old age group, she notes, the biggest increase in incidence has been in the 20- to 29-year-old group.</p><p>To date, the center has seen more than 5500 patients, including nearly 3800 with colorectal cancer. Beyond providing coordinated care to patients who often have far different needs than older patients, Dr Mendelsohn says that the center has become a significant source of studies into why their risk has increased. All patients receive a lengthy questionnaire that asks about their history of medications, exposures, and habits to help to answer what might have shifted over the past 70 years.</p><p>Similar detective work has been launched by the new Colorectal Cancer Pooling Project (C2P2), which is also aiming to understand the potential role of a long list of modifiable and non-modifiable risk factors. Peter Campbell, PhD, a project leader and a professor of epidemiology and population health at Albert Einstein College of Medicine in New York, says that the logical starting point was a list of 12 known risk factors linked to regular-onset colorectal cancer, including physical inactivity; cigarette smoking; alcohol use; antibiotic use; eating red or processed meat; and eating low levels of fiber, fruits and vegetables, or calcium.</p><p>In puzzling over what exp","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773898","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}
Derek B. Allison MD, Christopher J. VandenBussche MD, PhD
{"title":"Diagnostic challenges in urinary cytology: Practical insights from The Paris System for Reporting Urinary Cytology","authors":"Derek B. Allison MD, Christopher J. VandenBussche MD, PhD","doi":"10.1002/cncy.70033","DOIUrl":"10.1002/cncy.70033","url":null,"abstract":"<p>Urinary cytology is an important tool for diagnosing high-grade urothelial carcinoma (HGUC) and plays a vital role in monitoring for disease recurrence. However, its diagnostic utility is often complicated by interpretive challenges, particularly when degenerative artifacts, sparse cellularity, or reactive atypia obscure key cytologic features. The Paris System for Reporting Urinary Cytology has significantly enhanced diagnostic reproducibility by establishing standardized criteria for the diagnosis of HGUC, but misclassification remains a risk, especially when evaluating subtle atypia, tissue fragments, or confounding factors like degenerative changes. One of the most frequent pitfalls in urinary cytology is differentiating HGUC from benign mimics, particularly in specimens affected by prolonged urine exposure, inflammation, or instrumentation artifacts. Similarly, the classification of atypical urothelial cells presents a diagnostic gray zone because its predictive value varies widely, depending on clinical context. Low-grade urothelial neoplasms further complicate risk stratification because these tumors infrequently exfoliate in voided specimens and can appear indistinguishable from reactive urothelial cells in these samples. Consequently, the goal of The Paris System for Reporting Urinary Cytology is to focus on the detection of HGUC to preserve the specificity and the positive predictive value of urinary cytology. Advancements in molecular profiling and artificial intelligence-driven cytopathology promise enhanced reproducibility and risk stratification, refining the role of urinary cytology in precision medicine. However, the success of urinary cytology remains rooted in a balanced approach, integrating morphologic expertise, molecular insights, and clinical data. By applying these essential practices, cytopathologists can improve diagnostic accuracy, reduce misclassification, and optimize patient management.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773899","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}
Rachel Jug MB, BCh, BAO, Wen-Chi Foo MD, Benjamin Wildman-Tobriner MD, Xiaoyin “Sara” Jiang MD
{"title":"Cytology-Radiology Correlation Series: Thyroid cytopathology","authors":"Rachel Jug MB, BCh, BAO, Wen-Chi Foo MD, Benjamin Wildman-Tobriner MD, Xiaoyin “Sara” Jiang MD","doi":"10.1002/cncy.70028","DOIUrl":"10.1002/cncy.70028","url":null,"abstract":"<p>Thyroid ultrasound is typically the first step in the workup of thyroid nodules. Ultrasonographic features of thyroid nodules can be used to evaluate their risk of malignancy using risk stratification systems to determine whether a nodule is suspicious enough to warrant a more invasive fine-needle aspiration (FNA) for further evaluation. For this review, the authors described and compared two major risk stratification systems, the American Thyroid Association classification system and the American College of Radiology Thyroid Imaging Reporting and Data System, and explored corresponding ultrasound and cytology findings in the thyroid for commonly encountered entities in cytopathology practice.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681092","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}
Yuri Noda DDS, PhD, Kaori Sando CT, Masato Kita MD, PhD, Koji Tsuta MD, PhD
{"title":"Hepatocyte nuclear factor 4 alpha immunocytochemistry: A useful marker for detecting endocervical glandular lesions in alcohol-fixed smears","authors":"Yuri Noda DDS, PhD, Kaori Sando CT, Masato Kita MD, PhD, Koji Tsuta MD, PhD","doi":"10.1002/cncy.70034","DOIUrl":"10.1002/cncy.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocyte nuclear factor 4 alpha (HNF4α) contributes to tumorigenesis and cancer progression. This study evaluated the diagnostic potential of HNF4α for detecting endocervical glandular lesions (EGLs), including endocervical adenocarcinomas (ECAs), adenocarcinomas in situ (AIS), and lobular endocervical glandular hyperplasias (LEGH) using alcohol-fixed cytological smears.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HNF4α expression was immunocytochemically assessed in alcohol-fixed smears and paired formalin-fixed paraffin-embedded tissue specimens obtained from 14 patients with histologically confirmed EGLs: eight papillomavirus-associated (HPVA) ECAs, one non-NHPVA ECA, two HPVA AIS, and three patients with LEGHs. Three cases of squamous cell carcinomas (SCCs) and two cases of non-neoplastic lesions were also analyzed as non-EGL controls. HNF4α positivity was defined as nuclear staining in one or more cell(s)/slide, regardless of intensity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Histologically confirmed EGL cases were cytologically diagnosed as four adenocarcinomas, eight atypical glandular cells, one misclassified atypical squamous cells of undetermined significance, and one misclassified SCC, with a sensitivity of 85.7% and specificity of 100%. Strong and diffuse nuclear HNF4α expression was observed in atypical glands in both smears and tissue specimens, whereas non-neoplastic glands and non-neoplastic/neoplastic squamous epithelium were HNF4α-negative. HNF4α expression showed 73.7% concordance between tissue and smear samples. Notably, HNF4α immunocytochemistry demonstrated 100% sensitivity and specificity for detecting EGLs, outperforming cytomorphological or immunohistochemical diagnosis (sensitivity, 71.4%; specificity, 100%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HNF4α is a reliable diagnostic marker when using alcohol-fixed smears, showing enhanced accuracy for EGLs detection regardless of human papillomavirus status. Immunocytochemical analysis of HNF4α in cervical smears can be used for EGL detection and early diagnosis of cervical cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666511","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}