Journal of the American Society of Cytopathology最新文献

{"title":"The clinical significance of atypical glandular cells in Papanicolaou tests: changes in diagnostic patterns over 15 years at a single institution.","authors":"Terri E Jones, Xianxu Zeng, Jonee Matsko, Lakshmi Harinath, Esther Elishaev, Rohit Bhargava, Chengquan Zhao","doi":"10.1016/j.jasc.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.jasc.2025.05.003","url":null,"abstract":"<p><strong>Introduction: </strong>Detection of atypical glandular cells (AGCs) by Papanicolaou (Pap) test remains a significant challenge in gynecological cytology. We compared follow-up diagnoses, age groups, and human papillomavirus (HPV) results for AGC at our institution to that of our previous study (study period 2008-2013).</p><p><strong>Methods: </strong>AGC Paps diagnosed and HPV results between January 2020 and June 2024 were obtained from the database at UPMC Magee-Womens Hospital.</p><p><strong>Results: </strong>Of the total 188,320 Paps performed during the study period, 1025 had AGC diagnoses comprising 0.54% of the total. A total of 92.2% of cases had a companion HPV test, with positive HPV results seen in 32.9% of cases. Overall, 33.3% (286/859) of AGC cases had subsequent significant histologic findings (cervical intraepithelial neoplasia 2 and 3, adenocarcinoma in-situ, endocervical adenocarcinoma, endometrial lesions, metastatic carcinoma). Detection of cervical lesions was highest in women <30 years (50%) and significantly decreased with increasing age (P < 0.0001). Identification of endometrial lesions was highest in the ≥50-year group (P < 0.0001). Nearly half of AGC/HPV-positive cases had significant cervical findings, while these were detected in only 2.1% of AGC/HPV-negative cases (P < 0.0001). Endometrial lesions were identified in 25.7% of AGC/HPV-negative cases, but only in <1% of AGC/HPV-positive cases (P < 0.0001). Significant differences were identified comparing the 2 study periods: increased HPV testing (P < 0.0001), increased HPV-positivity (P = 0.0029), decreased AGC rate (P < 0.0001), and increased endometrial lesions on follow-up (P < 0.0001).</p><p><strong>Conclusions: </strong>Our findings continue to support HPV results and patient age as valuable data in triaging AGC. AGC/HPV-positive results frequently suggest a cervical/HPV-related lesion, often in younger patients. Conversely, AGC/HPV-negative results, especially in patients ≥50 years, support noncervical lesional origins.</p>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous clots in body fluids: can they cellblock?","authors":"Jessica Rech, Josh Howell, Alyssa Alford, Jennifer Kernodle-Zimmer, Leslie Huntsman, Kristen Ruddell","doi":"10.1016/j.jasc.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.jasc.2025.04.005","url":null,"abstract":"<p><strong>Introduction: </strong>Cell blocks have become a critical component in the diagnostic and prognostic analysis of cytologic specimens. Yet, it is common for cell blocks to lack sufficient cellularity for assessment and ancillary testing. Assessing cellularity in spontaneous clots that form in body fluids can aid in improving cell block utilization.</p><p><strong>Materials and methods: </strong>Eighteen body fluid specimens originally submitted for cytologic evaluation were selected for processing. For each fluid, 2 cell blocks were made, 1 using the spontaneous clot (SC) and 1 using the cell pellet (CP) from only the concentrated fluid. A hematoxylin and eosin-stained slide for each block was assessed for cellularity and ranked on a scale from 0 to 3. A score of 0 represented no cells present, while a score of 3 represented abundant cells of interest present.</p><p><strong>Results: </strong>For the CP blocks, 28% had a cellularity score of 0, 44% had a score of 1, 11% had a score of 2, and 17% had a score of 3. For the SC blocks, only 6% had a cellularity score of 0, 39% had a score of 1, 28% had a score of 2, and 28% had a score of 3.</p><p><strong>Conclusions: </strong>Cell blocks prepared using the SC method resulted in an overall higher cellularity compared to the CP blocks. The SC blocks prepared from malignant fluids also showed denser areas of pure tumor nuclei. This resulted in adequate spontaneous clot blocks for genomic testing, while the corresponding CP block was only adequate for diagnostic purposes.</p>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-informed experiences in an interventional cytopathology clinic: how can we maximize patient satisfaction.","authors":"Nikka Khorsandi, Aaron Blevins, Elham Khanafshar","doi":"10.1016/j.jasc.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.jasc.2025.04.004","url":null,"abstract":"<p><strong>Introduction: </strong>The pathologist-performed fine needle aspiration biopsy has been shown to be a diagnostically excellent study when performed by trained individuals. However, the patient perspective of pathology-performed fine needle aspiration biopsy, also known as interventional cytopathology, is less described.</p><p><strong>Materials and methods: </strong>This study investigates patient satisfaction at a single interventional cytopathology clinic between 2020 and 2023. The 34-question survey evaluated various aspects of patient satisfaction and included qualitative feedback to better understand factors contributing to patient satisfaction. Among the 682 survey respondents, the majority were Caucasian and English-speaking females ages 65-79 years, with either private insurance or Medicare.</p><p><strong>Results: </strong>Results demonstrated high satisfaction levels across all domains. Qualitative analysis identified key themes that improve patient satisfaction, including reduced anxiety, confidence in providers, perceived efficacy of the procedure, and overall procedural satisfaction.</p><p><strong>Conclusions: </strong>Based on these themes, we propose a conceptual model in which effective communication, a relaxed atmosphere, and thorough explanations play a crucial role in enhancing patient satisfaction. Our findings underscore the importance of patient-centered approaches in designing interventional cytopathology clinics. Clear communication between patients, providers, and care teams, along with adequate appointment time, is essential for improving patient experiences.</p>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance characteristics of ThyroSeq, ThyGeNEXT/ThyraMIR, and Afirma molecular platforms in evaluation of 1252 cytologically-indeterminate thyroid nodules","authors":"Courtney F. Connelly MD ,&nbsp;Marie C. Smithgall MD ,&nbsp;Niyati Desai MD ,&nbsp;Adela Cimic MD ,&nbsp;Swikrity U. Baskota MBBS, MD","doi":"10.1016/j.jasc.2025.04.003","DOIUrl":"10.1016/j.jasc.2025.04.003","url":null,"abstract":"<div><h3>Introduction</h3><div>The preoperative risk stratification of thyroid nodules with indeterminate cytology on fine needle aspiration has been streamlined with the application of molecular diagnostics. Most molecular platforms use genotyping and mRNA or microRNA expression profiling to assign a preoperative cancer risk to thyroid nodules.</div></div><div><h3>Materials and methods</h3><div>In this study, we discuss the general methodology and compare the diagnostic accuracy of 3 commercially available molecular platforms, ThyroSeq, ThyGeNEXT/ThyraMIR, and Afirma, in the evaluation of 1252 cytologically indeterminate thyroid nodules.</div></div><div><h3>Results</h3><div>Molecular evaluation showed an increased malignancy risk in 28.7% of cases. Of all cases, 209 underwent partial or complete thyroid resection. 34.9% of these resected thyroid nodules were benign and non-neoplastic, 16.3% were benign neoplasms and 48.8% were malignant neoplasms. 5.5% (n = 49) of cases with negative molecular testing were found to have a neoplasm on subsequent thyroid resection. 40.8% of these cases showed benign neoplasms and 59.2% showed a malignant neoplasm.</div></div><div><h3>Conclusions</h3><div>The ThyroSeq, ThyGeNEXT/ThyraMIR, and Afirma molecular platforms demonstrate similar efficacy in ruling out malignancy in our cohort's cytologically indeterminate thyroid nodules, with sensitivities of 87.5%, 66.7%, and 73.1%, respectively, and negative predictive values of 80.0%, 70.0%, and 66.0%, respectively. Overall performance characteristics of these molecular platforms in our study are inferior to some previously published studies.</div></div>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 243-254"},"PeriodicalIF":0.0,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celebrating the life and legacy of Dr. Yener S. Erozan (June 1, 1930 – July 22, 2023)","authors":"Güliz A. Barkan MD, FIAC ,&nbsp;Ibrahim Ramzy MD","doi":"10.1016/j.jasc.2025.03.003","DOIUrl":"10.1016/j.jasc.2025.03.003","url":null,"abstract":"","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 279-283"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The International System for Reporting Serous Fluid Cytopathology survey data reveal substantial variability in the reporting and utilization of pelvic washing and peritoneal fluid specimens among pathologists and gynecologic oncologists.","authors":"Christopher J VandenBussche, Amanda Jackson, Zaibo Li, Chengquan Zhao, Ashish Chandra, Fernando Schmitt, Daniel F I Kurtycz, Barbara Crothers","doi":"10.1016/j.jasc.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.jasc.2025.04.002","url":null,"abstract":"<p><strong>Introduction: </strong>Pelvic and peritoneal washings (PW) are often taken during gynecologic resections when the presence of a neoplastic process is known or suspected. A positive PW may upstage a patient and/or impact a patient's prognosis and treatment. Two surveys were created to inform The International System for Serous Fluid Cytology, a standardized reporting system, regarding the practice and utilization of PW cytology.</p><p><strong>Materials and methods: </strong>Pathologists and cytotechnologists (n = 475) responded to a survey which examined their reporting preferences. Gynecologic oncologists (GONC) (n = 168) answered a separate survey which examined how they utilized PW specimens.</p><p><strong>Results: </strong>Most pathologists/cytotechnologists felt that bland-appearing epithelial cells of unknown origin should be classified as benign. Most favored reporting psammomatous calcification without associated epithelial cells as benign (64.1%), whereas 8.6% did not report this finding at all, 20.5% would report as atypical, and 6.8% would report as suspicious of a neoplasm. Most GONCs (63.9%) routinely obtained PW specimens during endometrial cancer staging; of those, 53% reported that a positive cytology result could change their management. Sixty-six percent of GONCs indicated that they treat indeterminate PW results as negative. Others indicated that an indeterminate PW may result in review of slides with the pathologist, counseling the patient, and/or closer observation. Most GONCs did not find utility in the reporting of psammomatous calcifications, presence of mucin, atypical cells favored to be benign, endometrial cells, or iatrogenic material.</p><p><strong>Conclusions: </strong>Substantial variability exists among pathologists in how PW specimens are reported, as well as how gynecologic oncologists utilize these specimens.</p>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of fluorescence in situ hybridization and cytology for the accurate detection of malignant biliary strictures, with emphasis on unusual results","authors":"Beena U. Ahsan MD ,&nbsp;Michelle Jin MD ,&nbsp;Brian K. Theisen MD ,&nbsp;Sumit Singla MD ,&nbsp;Dhananjay Chitale MD ,&nbsp;Brandon Shaw PhD ,&nbsp;Nazila Azordegan MD ,&nbsp;Zhengfan Xu MD ,&nbsp;Daniel Schultz MD ,&nbsp;Ziying Zhang MD","doi":"10.1016/j.jasc.2025.04.001","DOIUrl":"10.1016/j.jasc.2025.04.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Biliary brushing cytology is the standard diagnostic approach for evaluating biliary strictures, but it has low sensitivity and a high rate of atypical diagnoses. Fluorescence in situ hybridization (FISH) has become an increasingly valuable adjunct to cytology. Therefore, the aim of this retrospective quality improvement study was to evaluate the relative diagnostic performance of traditional cytology and FISH for correctly determining malignant versus benign biliary strictures from biliary brushing samples and to evaluate whether adding FISH to the diagnostic pipeline improves diagnostic accuracy over relying on cytology alone.</div></div><div><h3>Materials and methods</h3><div>We conducted a retrospective study of biliary brushing and FISH results in patients evaluated for biliary strictures between April 2019 and March 2023.</div></div><div><h3>Results</h3><div>A total of 228 specimens were retrieved. For cytology results: 151 negative, 55 atypical, 6 suspicious, and 16 positive. For FISH results: 105 negative, 71 equivocal, and 52 positive. When calculating performance measures, cytology atypical and FISH equivocal were excluded; cytology suspicious was considered positive. The sensitivity and specificity of cytology were 45.8% and 100%, respectively. The sensitivity and specificity of FISH were 84.2% and 96.0%, respectively.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that FISH exhibits considerably higher diagnostic sensitivity than routine cytology in identifying malignant biliary strictures. Furthermore, combining cytology with FISH may provide a more comprehensive diagnostic approach, reducing the likelihood of false-negative results. However, positive and equivocal FISH results should be interpreted carefully and considered alongside more specific cytology findings to minimize the risk of false-positive diagnoses.</div></div>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 228-235"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human papillomavirus genotype distribution and its correlation with intraepithelial neoplasia, vaccination, and ethnicity","authors":"Rita Abi-Raad MD,&nbsp;Tong Sun MD, PhD,&nbsp;Uma Krishnamurti MD, PhD","doi":"10.1016/j.jasc.2025.03.006","DOIUrl":"10.1016/j.jasc.2025.03.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Cervical cancer is primarily attributed to high-risk human papillomavirus (HPV), specifically genotypes 16 and 18. The introduction of HPV vaccines aimed to reduce the incidence of cervical cancer.</div></div><div><h3>Materials and methods</h3><div>This study reviewed cases of High-Grade Squamous Intraepithelial Lesion (HSIL) and Atypical Squamous Cells Cannot Exclude HSIL (ASC-H) with positive high-risk HPV and HPV genotyping data. The prevalence of HPV genotypes 16/18 and non-16/18 was compared in cases with high-grade intraepithelial neoplasia (IN2+), across different ethnicities and with HPV vaccination status.</div></div><div><h3>Results</h3><div>A total of 274 patients (94 HSIL and 180 ASC-H) were evaluated. HPV non-16/18 was significantly more prevalent in ASC-H (68%) than in HSIL patients (50%); (<em>P</em> = 0.003). HPV non-16/18 was more common in cases without -IN2+ (69%), but a significant proportion of IN2+ cases were also positive for non-16/18 HPV genotypes (56%); (<em>P</em> = 0.04). Overall, HPV non-16/18 was more prevalent in all ethnic groups. There was a trend to a higher prevalence in non-white and vaccinated compared with white and nonvaccinated women respectively, but the difference was not significant.</div></div><div><h3>Conclusions</h3><div>HPV non-16/18 genotypes are more prevalent than HPV 16/18, even in women with high-grade lesions with a greater shift towards non-16/18 genotypes in non-white and in vaccinated women. The study suggests the need for extended HPV genotyping and vaccines targeting a broader range of HPV types to include HPV non-16/18 to improve prevention, particularly in certain ethnic groups.</div></div>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 273-278"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing tissue adequacy for next-generation sequencing in small biopsies and fine-needle aspirations for nonsmall cell lung cancer: a root cause analysis and proposed solutions","authors":"Liang Ding MD, PhD ,&nbsp;Brittney Thiele MD ,&nbsp;Angela Sorenson MA, SCT (ASCP) ,&nbsp;Ying-Chun Lo MD, PhD ,&nbsp;Joshua Deignan PhD ,&nbsp;Yajue Huang MD, PhD","doi":"10.1016/j.jasc.2025.03.005","DOIUrl":"10.1016/j.jasc.2025.03.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Molecular testing is essential for managing advanced nonsmall cell lung cancer, yet up to 40% of biopsies can be inadequate due to insufficient tissue. This study aimed to identify causes of inadequate sampling through fine needle aspiration (FNA) and core needle biopsy (CNB) and propose solutions.</div></div><div><h3>Materials and methods</h3><div>We analyzed 96 patients undergoing endobronchial ultrasound (EBUS)-guided FNA or CNB for nonsmall cell lung cancer, alongside 44 patients with CT-guided CNB. All patients were tested using the MayoComplete Solid Tumor Panel, a comprehensive next-generation sequencing assay. A root cause analysis identified factors affecting tissue adequacy, such as needle size, pass numbers, and specimen types.</div></div><div><h3>Results</h3><div>Among EBUS biopsies, 35.3% of cases with FNA smears were inadequate, compared to 20% for CNB alone. The combination of both smears and tissue cores had the highest adequacy rate, with only 11.4% inadequacy for next-generation sequencing. We investigated the discrepancy between lymph nodes and lung tissue by examining nonpulmonary lymph nodes, liver, and soft tissue biopsies. Lymph node CNB had a 30% inadequacy rate, while liver and soft tissue showed 14.3% and 15.4%, indicating that lymph node heterogeneity may affect tissue adequacy. For CT-guided CNB, cases with 5 or more passes showed 85% adequacy, increasing to 100% with over 7 passes.</div></div><div><h3>Conclusions</h3><div>Combining CNB with EBUS FNA improves sample adequacy, especially for lymph nodes. We recommend these approaches to optimize tissue yield for molecular testing, aiding timely therapy initiation and reducing repeat biopsies. Smaller gene panels may also be useful when tissue is limited.</div></div>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 255-264"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncocytic subtype of well differentiated neuroendocrine tumor: clinicopathologic and molecular associations of a cohort diagnosed on fine needle aspiration (FNA)","authors":"Wen-Yu Hsiao MD, PhD ,&nbsp;Shannon M. O’Brien MD ,&nbsp;Fareed Rajack MD ,&nbsp;Talaat Tadros MD ,&nbsp;Michelle D. Reid MD, MS","doi":"10.1016/j.jasc.2025.03.004","DOIUrl":"10.1016/j.jasc.2025.03.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Classical well differentiated neuroendocrine tumors (C-NETs) have plasmacytoid morphology and neuroendocrine differentiation. Oncocytic NETs (O-NETs) have been shown to be more clinically aggressive. Whether O-NETs are more akin to C-NETs or poorly differentiated neuroendocrine carcinomas (PDNECs) is not established.</div></div><div><h3>Materials and methods</h3><div>Clinicopathologic characteristics and immunohistochemical expression of death domain-associated protein (DAXX), α-thalassemia/mental retardation syndrome X-linked genes (ATRX), retinoblastoma 1, p53, and SMAD4 in 30 O-NETs (25 pancreatic and 4 from luminal gastrointestinal tract) was compared to 32 C-NETs (23 pancreatic and 8 from luminal gastrointestinal tract). Whole exome sequencing was performed in a subset of each cohort.</div></div><div><h3>Results</h3><div>O-NETs were male-predominant (65.6%) and had higher mean Ki-67 index (7.4% versus 2.9% in C-NETs) (<em>P</em> = 0.03), corresponding to more grade 2 or above (53.3%) tumors. O-NET patients had more advanced disease (pT3/pT4, 75% versus 36.8%) (<em>P</em> = 0.024), distant metastasis (50% versus 25%) (<em>P</em> = 0.042), progression (increased size/recurrence/new metastases) (n = 8 versus 3; <em>P</em> = 0.1), and death (n = 3 versus 1; <em>P</em> = 0.32). Forty percent of O-NETs (versus 12.5% of C-NETs; <em>P</em> = 0.041) showed DAXX/ATRX loss, with one showing coexisting retinoblastoma 1 and SMAD4 loss. P53 staining pattern was wild type in all cases. Whole exome sequencing of 10 cases showed <em>DAXX</em>, <em>ATRX,</em> and multiple endocrine neoplasia type 1 alterations in O-NETs and C-NETs, and coexisting <em>DNMT3A</em> and <em>MTOR</em> alterations in one O-NET.</div></div><div><h3>Conclusions</h3><div>O-NET subtype is associated with advanced disease and unfavorable outcomes compared to C-NETs. O-NETs are cytologically distinct, male-predominant tumors that often present with higher grade and advanced disease. Their aggressive behavior is possibly related to frequent DAXX/ATRX loss and less likely PDNEC-related molecular alterations. Pathologists should be mindful of this aggressive morphologic subtype and clearly convey its presence in pathology reports.</div></div>","PeriodicalId":38262,"journal":{"name":"Journal of the American Society of Cytopathology","volume":"14 4","pages":"Pages 209-221"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}