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Serous effusions are common specimens in cytopathology, yet their reporting has historically lacked uniformity. The International System for Reporting Serous Fluid Cytopathology (TIS) provides a standardized five-tiered classification system to improve diagnostic clarity and clinical communication. This study was conducted to assess the diagnostic utility and applicability of TIS by determining the Risk of Malignancy (ROM) and diagnostic accuracy metrics for each category. A retrospective analysis was conducted on all serous effusions (pleural, pericardial, ascitic fluids, and peritoneal washes) reported from January 2021 to December 2023. Cases were re-categorized according to the TIS framework. The ROM for each category was calculated with Diagnostic accuracy metrics, including sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). A total of 1,447 cases were included in the analysis. Distribution across TIS categories was as follows: Nondiagnostic (ND) (8 cases; 0.6%), Negative for malignancy (NFM) (1,170 cases; 80.9%), Atypia of undetermined significance (AUS) (40 cases; 2.8%), Suspicious for malignancy (SFM) (35 cases; 2.4%), and Malignant (MAL) (194 cases; 13.4%). The calculated ROM for each category was 62.5% for ND, 28.8% for NFM, 66.7% for AUS, 93.8% for SFM, and 98.7% for MAL. The sensitivity, specificity, PPV, and NPV is 33.8%, 99.5%, 97.9%, and 69.7%, when AUS and NFM are considered negative. Sensitivity, specificity, PPV and NPV is 38.1%, 98.1%, 92.9%, and 70.8%, when AUS, SFM and MAL cases are considered positive. The implementation of TIS provides a standardized framework for reporting serous effusions with definite categorization. The ROM for each category helps in risk stratification of cases reported under TIS. The system demonstrates high specificity and PPV, making it a robust tool for detection of malignancy.

Serous effusion is a common complication in patients with advanced lung cancer, which often indicates that the tumor has metastasized to the pleura or other serosal membranes. It is essential to achieve an accurate diagnosis and pathological classification of tumor cells in effusion to guide clinical treatment. However, there are limitations to relying solely on morphological diagnosis, especially in atypical cases where diagnostic uncertainty is common. The International System for Serous Fluid Cytopathology (TIS) proposes a standardized hierarchical diagnostic framework that integrates morphology and auxiliary techniques. Nevertheless, its clinical application value in the Chinese lung cancer population remains insufficiently validated. This study aimed to systematically evaluate the diagnostic performance of the TIS system in the assessment and classification of serous effusions based on a large sample of lung cancer cases. A retrospective analysis was conducted on 1274 serous effusion specimens from the Cancer Hospital Chinese Academy of Medical Sciences between January 2018 and December 2023, all of which were derived from patients with lung cancer confirmed by histopathology and/or clinical history. The diagnostic procedure strictly followed the TIS protocol, which commenced with the morphological evaluation and assignment to categories I-V. For some cases with ambiguous morphology (categories III and IV) and category V, immunocytochemistry (ICC) was performed using cell blocks to comprehensively determine the final diagnostic category, tumor subtyping, and tumor origin. Statistical analyses were applied to assess the diagnostic concordance between initial morphology and combined ICC. Additionally, the trend in category changes and the clinical value of ICC in pathological subtyping and origin determination were analyzed. Based on morphology alone, 83.1% (1059/1274) of cases were classified as malignant (category V), while 12.3% (157/1274) were categorized as indeterminate (categories III or IV). Further analysis of the 69 cases that underwent ICC detection revealed that the rate of upgraded diagnosis was 85.5% (59/69), and the upgrading proportion in category IV cases (89.6%, 43/48) was significantly higher than that in category III cases (76.2%, 16/21). Furthermore, 7.2% (5/69) of category III cases were downgraded to benign (category II), while another 7.2% (5/69) remained unchanged due to insufficient cellularity or poor differentiation. These findings indicate that ICC can markedly improve the diagnostic accuracy for indeterminate serous effusions in lung cancer. Among definitively malignant cases, ICC was employed to enable subtyping and origin assessment in 542 cases, achieving precise pathological classification in 533 cases (98.3%): including adenocarcinoma (86.7%), small cell carcinoma (4.4%), and squamous cell carcinoma (3.9%), and confirming pulmonary origin in 510 cases (94.0%). Analysis of key ICC marker expression profiles revealed that lung adenocarcinoma in serous effusions showed high expressions of thyroid transcription factor-1 (TTF-1) and Napsin A (positivity rates: 93.0% and 76.2%, respectively); lung squamous cell carcinoma characteristically expressed P40 and P63 (positivity rates: 60.0% and 73.7%, respectively); and small cell carcinoma strongly expressed Syn and CD56 (positivity rates: 87.0% and 81.8%, respectively). Integrated interpretation using a complementary antibody panel effectively validated and supplemented morphological findings, providing a reliable basis for subtype differentiation. The TIS-based stratified diagnostic pathway of "initial morphological diagnosis followed by ancillary techniques confirmation" significantly improves diagnostic accuracy for lung cancer-associated serous effusions, optimizes the management of indeterminate cases, and achieves high-precision pathological subtyping and determination of tumor origin. It is recommended to widely implement the TIS system in clinical practice to enhance standardization and diagnostic precision in serous fluid cytopathology. 【中文题目：浆膜腔积液细胞病理学国际报告系统在肺癌相关浆膜腔积液分层诊断中的临床应用研究】 【中文摘要：背景与目的 浆膜腔积液是中晚期肺癌患者常见并发症，其出现往往提示肿瘤已发生胸膜或其他浆膜转移。准确诊断积液中的肿瘤细胞并进行病理分型，对指导临床治疗至关重要。然而，单纯依赖细胞形态学诊断存在局限性，尤其在不典型病例中易出现不确定性诊断。《浆膜腔积液细胞病理学国际报告系统》（The International System for Serous Fluid Cytopathology, TIS）提出了形态学与辅助技术相结合的标准化分层诊断框架，但其在国内肺癌人群中的临床应用价值尚缺乏大规模验证。本研究旨在基于大样本肺癌病例，系统性评估TIS系统在肺癌浆膜腔积液诊断与分型中的效能。方法 回顾性纳入2018年1月至2023年12月中国医学科学院肿瘤医院的1274例浆膜腔积液样本，其均来源于组织病理学和/或临床病史确诊的肺癌患者。严格遵循TIS系统诊断流程，先进行形态学评估并分级（I-V级），对部分形态学不确定（III、IV级）及V级病例，利用细胞蜡块进行免疫细胞化学（immunocytochemistry, ICC）检测，综合确定最终诊断级别并进行肿瘤分型与起源判断。统计分析形态学初诊与联合ICC诊断一致性、分级变化趋势及ICC检测在病理分型与溯源中的临床价值。结果 形态学初诊中，83.1%（1059/1274）的病例直接诊断为恶性（V级），12.3%（157/1274）的病例为不确定性诊断（III或IV级）。对69例接受ICC检测的病例进一步分析显示，升级诊断率为85.5%（59/69），其中IV级病例的升级比例（89.6%, 43/48）高于III级（76.2%, 16/21）；7.2%（5/69）的III级病例降级为良性（II级），另7.2%（5/69）因细胞量不足或分化差而维持原级，表明ICC可显著提升肺癌浆膜腔积液不确定性诊断的明确性。在最终诊断恶性的病例中，ICC对542例进行分型与溯源，533例（98.3%）实现精准病理分型（腺癌86.7%、小细胞癌4.4%、鳞癌3.9%），510例（94.0%）明确为肺来源。关键ICC标志物表达谱分析显示，浆膜腔积液中肺腺癌甲状腺转录因子-1（thyroid transcription factor-1, TTF-1）与Napsin A呈高表达，阳性率分别为93.0%和76.2%；肺鳞癌特征性表达P40和P63，阳性率分别为60.0%和73.7%；小细胞癌强表达Syn与CD56，阳性率分别达87.0%和81.8%。通过采用一组互补抗体进行综合判读，可以对形态学初诊报告进行验证与补充，为亚型鉴别提供可靠依据。结论 TIS系统构建的“形态学初诊、辅助技术确证”分层诊断路径，能显著提高肺癌浆膜腔积液诊断的准确性，有效优化不确定性病例分流，实现高精度的病理分型与组织起源判断。建议在临床实践中推广应用TIS系统，以促进浆膜腔积液细胞病理学诊断的规范化与精准化。
】 【中文关键词：肺肿瘤；浆膜腔积液；浆膜腔积液细胞病理学国际报告系统；免疫细胞化学；分层诊断】.

The World Health Organization (WHO), together with the International Academy of Cytology and the International Agency for Research on Cancer, has introduced a standardized framework for reporting lung cytopathology. This approach clarifies diagnostic tiers, provides malignancy risk estimates, and integrates with the latest WHO Tumour Classification. Derived partly from the Papanicolaou Society of Cytopathology model, it strengthens diagnostic reproducibility and clinical risk categorization. The aim of this study is to evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) in lung lesions reported under the WHO system. A comprehensive search of Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov and conference abstracts was carried out using predefined terms ("lung," "diagnostic accuracy," "FNAB"). Studies applying the WHO reporting scheme to lung FNAB were eligible, with histopathology or clinical follow-up as reference standards. Meta-analysis examined sensitivity and specificity at 3 thresholds: (1) malignant only, (2) suspicious or higher, and (3) atypical or higher. Pooled diagnostic odds ratios and summary receiver operating characteristic analyses were undertaken. Four studies met inclusion criteria. Risk of malignancy increased across WHO categories, from 27% in benign to 92% in malignant. Sensitivity and specificity differed by cut-off: malignant only (33%, 100%), suspicious or higher (73%, 96%), atypical or higher (83%, 84%). Aggregate diagnostic odds ratios and summary receiver operating characteristic curves supported the diagnostic robustness of the system. The WHO reporting system provides effective stratification of lung FNABs. Defining positivity at "suspicious" or higher offers the best diagnostic balance, while including "atypical" increases sensitivity with minimal loss of specificity, supporting its clinical utility.

The World Health Organization (WHO) Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (WHO System) offers a standardized five-category framework to enhance diagnostic consistency. Although globally applicable, its risk of malignancy (ROM) and management protocols are largely generalized. This study explores the system's specific applicability and clinical utility within the pediatric population. The study presents a pediatric diagnostic pathway centered on fine-needle aspiration biopsy, implemented according to the protocols established by the WHO System. The methodology emphasizes the integration of a multidisciplinary approach. The five WHO categories are evaluated through the lens of pediatric-specific differential diagnoses. In pediatric practice, the Benign category often includes exuberant immunoblastic proliferation (e.g., Epstein-Barr virus) that mimics malignancy. Atypical and Suspicious categories represent a critical "gray zone" where the ROM is significantly influenced by the rarity of malignancy. Findings suggest that for Suspicious and Malignant categories, the use of rapid on-site evaluation (ROSE) under optimal conditions allows for an immediate transition to ancillary testing and clinical staging. Pediatric application requires shifted interpretive thresholds. Monotonous small cell populations, which might suggest low-grade B-cell lymphoma in adults, typically represent reactive processes or aggressive small round blue cell tumors in children. The interventional pathologist is vital in reducing "non-diagnostic" rates. Furthermore, a "malignant" or "suspicious" diagnosis should trigger immediate multidisciplinary intervention to prevent complications. The WHO System is a robust tool for pediatric evaluation when contextualized within pediatric-specific biological parameters. Integrating ROSE and interventional pathology minimizes invasive procedures and accelerates time-to-treatment for life-threatening malignancies.

Accurate diagnosis of pancreatic lesions remains challenging. This study evaluated the diagnostic value of targeted DNA-based next-generation sequencing (NGS) of tissue obtained by endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) and its contribution to pancreaticobiliary multidisciplinary tumor board (MDTB) discussions. A retrospective analysis was conducted using a prospectively maintained database at Ghent University Hospital (March 2021-September 2024). Only patients undergoing targeted DNA NGS on EUS-FNA/FNB samples were included and reviewed during MDTB meetings. Diagnostic performance and influence on management were compared with final diagnoses established by clinical follow-up and/or surgical pathology. The final cohort comprised 120 focal pancreatic lesions. Ninety-one percent of solid masses (50/55) were malignancies. Cytopathology alone identified pancreatic cancer (PC) or high-grade dysplasia (HGD) in 27 cases (sensitivity 54%), whereas NGS alone identified 42 (sensitivity 84%). Combined cytopathology and NGS detected 45/50 malignancies (90%). Only two samples were non-diagnostic, yielding an overall diagnostic success of 96% (53/55). NGS was technically successful in 33/65 (51%) cystic lesions. Surgery was undertaken in 20 patients, with HGD or carcinoma confirmed in 11 (55%). Molecular profiling combined with cytopathology guided surgical decision-making in 6/11 patients (54%) compared with 3/11 (27%) with cytopathology alone. Targeted NGS improves diagnostic accuracy in solid pancreatic lesions and supports surgical decision-making for cystic lesions. Integration of molecular findings into MDTB discussions enhances precision and timeliness of pancreatic cancer treatment.

Cytopathology is the first field of pathology in which artificial intelligence (AI) models were successfully developed and commercialized for routine clinical screening of cervical cytology, a practice that has been in place for the past 2 to 3 decades. However, the development and deployment of AI applications for nongynecologic cytology has just begun. The variety of cytology specimen types and preparations with associated unique characteristics presents technical challenges for the complete digitization of the cytology workflow. Despite of these challenges, a few institutions have adopted a complete digital cytology workflow. Technical advancement in digital cytopathology have replaced conventional rapid onsite evaluation by a variety of virtual telecytology systems. Novel digital diagnostic solutions for cytology are evolving. Among these, Hologic Genius is the only one approved by the Food and Drug Administration (FDA) for routine clinical screening of cervical cytology in the United States. The recommendations for AI validation and best-practice guidelines for digital cytopathology are currently being developed. Prospect of technical and AI advances in digital cytopathology include automation of sample preparation, ROSE using telecytology, automation of screening of gynecologic and nongynecologic cytology specimens, automated quantitation of biomarkers, quality control, and beyond. This review article uncovers recent advances in digital cytopathology and discusses potential use cases of AI applications for routine cytopathology practice in this modern era of digital cytopathology.

Fine needle aspiration (FNA) is the primary diagnostic tool for evaluating thyroid nodules. However, 10%-21% of FNAs yield non-diagnostic (ND) results (Bethesda category I). Repeated ND findings occur in 25%-67.5% of cases, creating diagnostic uncertainty and increased healthcare costs. Our aim was to evaluate whether cumulative analysis of repeated ND cytology samples enables reclassification into a diagnostic Bethesda category. This retrospective observational study (2013-2024) included patients with ≥ 2 ND FNA results from the same thyroid nodule. Two blinded cytopathologists performed cumulative assessment of cellular material from consecutive ND samples to determine if reclassification into diagnostic Bethesda categories was feasible. Among 1861 FNA procedures, 29 patients (1.56%) had ≥ 2 ND results. Cumulative assessment enabled reclassification in 3/29 patients (10.3%), into Bethesda category II (benign). In selected cases, cumulative cytological assessment of multiple ND FNAs may provide sufficient diagnostic material to allow reclassification. This novel cost-effective approach may help reduce diagnostic uncertainty and unnecessary procedures, and improve patient care.

Endometrioid intraepithelial neoplasia (EIN) is a preinvasive precursor of endometrial carcinoma, yet its recognition in secretory-phase endometrium remains diagnostically challenging. Current criteria for EIN diagnosis do not account for female reproductive physiology, including the effects of endogenous progestins on the endometrium or EIN. Because women spend a substantial proportion of reproductive life in the secretory phase, failure to recognize EIN in this context represents an important gap in early detection. We systematically analyzed 40 cases of EIN arising in unequivocal physiological secretory endometrium, excluding patients with exogenous hormone exposure or other confounding factors. All cases exhibited architectural and cytologic distinctiveness relative to the background endometrium. Paradoxically, most lesions demonstrated diminished or absent secretory differentiation, challenging prevailing assumptions. Morules were identified in 38% of cases and represented a useful diagnostic clue. Additional features, including eosinophilic cytoplasm, epithelial stratification, mitotic activity, and apoptotic bodies, were variably present and functioned as supportive but nonessential findings. Immunohistochemistry demonstrated aberrancy for at least 1 of 3 established biomarkers (PAX2, PTEN, or β-catenin) in 95% of cases, underscoring the diagnostic value of this panel in the secretory phase, whereas Ki-67 proved unreliable. Collectively, these findings delineate morphologic and immunophenotypic features of EIN in secretory phase endometrium. Because most lesions have diminished secretory differentiation, the term "secretory EIN" is diagnostically problematic. We recommend adoption of the term "EIN in the secretory phase" and emphasize that improved recognition of this entity has direct implications for diagnostic accuracy and cancer prevention.

Artificial intelligence (AI) and machine learning (ML) are transforming diagnostic medicine, particularly in pathology, where image-based interpretation is central to clinical decision-making. This systematic review aimed to examine recent advances, performance outcomes, and practical challenges associated with incorporating AI and ML into diagnostic pathology. A comprehensive literature search was conducted across major scientific databases for studies published between 2010 and 2025. Titles and abstracts were screened independently, full texts were assessed against predefined eligibility criteria, and data were extracted using standardised procedures. Methodological quality was evaluated using established critical appraisal tools appropriate to study design, with structured risk-of-bias assessment reported for diagnostic accuracy studies. A total of 13 studies fulfilled the inclusion criteria, covering multiple pathological domains including breast pathology, cytopathology, neuropathology, head and neck oncology, and multi-organ computational pathology. Across the included studies, deep learning approaches demonstrated high diagnostic performance for tumour detection, classification, and staging tasks. While several investigations incorporated external validation, most were retrospective in design and relied on secondary datasets. Risk-of-bias assessment indicated predominantly moderate overall risk, primarily related to study design and applicability concerns. The evidence suggests that AI and ML systems demonstrate strong technical performance in controlled validation settings and may function as assistive tools within digital pathology workflows.

In June 2019, the World Health Organization Reporting System for Soft Tissue Cytopathology (WHORSSTC) was proposed at the European Congress of Cytology in Malmö, Sweden, for reporting soft tissue cytology. In this retrospective review, we evaluate the diagnostic categories of the proposed WHORSSTC. Five hundred ninety-two fine needle aspiration cytology and touch preparation specimens from core needle biopsies from musculoskeletal lesions were identified (2015-2021), of which 62 cases (10%) had an associated surgical resection. Of these cases, 15 cases with resection were diagnosed with fine needle aspiration, and 47 cases with resection were diagnosed with touch preparation samples. Cytology specimens were reclassified into the proposed WHORSSTC Categories: I) nondiagnostic/unsatisfactory, II) benign, III) atypical, IV) soft tissue neoplasm of uncertain malignant potential, V) suspicious for malignancy, and VI) malignant. The rate of malignancy was calculated based on corresponding surgical resections where a malignant resection diagnosis was considered a positive result. The observed rate of malignancy within the tested categories were as follows: Category I: nondiagnostic (5/17, 29%), Category II: benign (1/14, 7%), Category III: atypical (0/2, 0%), Category IV: soft tissue neoplasm of uncertain malignant potential (7/10, 70%), Category V: suspicious for malignancy (1/1, 100%), and Category VI: malignant (18/18, 100%). Our study showed a sensitivity of 96%, a specificity of 83%, a positive predictive value of 90%, and a negative predictive value of 94%. Our results support the potential utility of a standardized soft tissue reporting system for cytology to improve the clinical management of patients.

Pancreaticobiliary cytology is a highly specific but variably and often insufficiently sensitive diagnostic method. This study evaluated the utility of next-generation sequencing (NGS) in difficult-to-classify pancreaticobiliary specimens. A total of 136 patients were prospectively included, with cytology or small biopsy specimens from the pancreas (n = 74), extrahepatic biliary tree (n = 56), pancreatic duct (n = 4), gallbladder (n = 1), and peripancreatic lymph node (n = 1). All cases were diagnosed by cytopathologists with expertise in pancreaticobiliary (cyto)pathology using 2022 WHO Reporting System for Pancreaticobiliary Cytopathology. Large scale pan-cancer panel was used for NGS testing. Forty-five cases (33,1%) were non-analyzable by NGS, and no genetic changes were found in 21 cases (23,1% of analyzable cases). Separate acquisition and storage of cytology/biopsy materials in RNAlater solution significantly decreased the rate of non-analyzable samples (23.3% versus 44.4%; Fisher's exact test: p = 0.0108, OR = 0.379, 95% CI 0.182-0.792). Diagnostic genetic alterations were identified in 70/91 of analyzable cases (76.9%). Suspicion was raised for the presence of germline mutation in 10 patients. Potentially druggable alterations (n = 42) were found in 36/91 patients (39,5%), including mutations in homologous recombination genes, PI3K/AKT/mTOR pathway, Cyclin D1-CDK4/6-Rb pathway, and potentially targetable KRAS mutations (KRAS G12D mutation occurred in 19/41 [46,3%] of KRAS-mutated tumors). Supplementing pancreaticobiliary (cyto)pathology with information from NGS increased the sensitivity for tumor diagnosis from 35.9% to 86.6% (with specificity 100%), improved negative predictive value from 14.2% to 41.2%, and enhanced overall diagnostic accuracy from 42.1% to 87.8%, respectively. In challenging cases, NGS significantly improves preoperative pancreaticobiliary diagnosis and informs clinical decision-making.

Multicategory diagnostic tests are frequently utilized in clinical practice. Estimation of the predictive value of each category is an essential part of these tests, yet they are often wrongly reported due to inappropriate analysis as a proportion ignoring pretest probability or prevalence. Also, some systems do not have fully ordered categories, making meta-analysis difficult. Analyses are often performed under the assumption that data are continuous, a premise that may not be appropriate and can result in unreliable confidence or credible intervals. These shortcomings can be rectified by multinomial mixed models, which can model both categorical as well as ordinal data, and estimation of predictive values through likelihood ratios (LRs). However, such multinomial models not requiring ordering have rarely, if at all, been used as a meta-analytical tool. This study aimed to employ a multinomial hierarchical linear mixed model appropriate for both ordered as well as partially ordered categories for such an analysis. The proposed Bayesian multinomial mixed model estimates the proportions of each diagnostic category among cases with and without disease. This model was run on data extracted from a previous meta-analysis of the Milan System for Reporting Salivary Gland Cytopathology, which only partially follows ordered categories. The model was checked for proper mixing. From the posterior draws, the proportions of each category and the LRs were estimated. Fit of the data was checked by posterior predictive checks for location and width of distribution. The Monte Carlo Markov chains mixed well. The predictions of the model fitted the data well. From this, we could estimate the LR and predictive values, which were more informative than the previously reported Risk of Malignancy. Sensitivities and specificities could be calculated for different thresholds after ordering by the risk information derived from the LRs. Interpretation was aided by graphical examination of the predictive value to the prevalence of each category. The proposed model is a relatively assumption free method that should be useful in meta-analysis of multicategory diagnostic tests if combined with subsequent LR estimation.

Ocular surface squamous neoplasia (OSSN) presents diagnostic challenges in resource-limited rural settings where access to histopathology is constrained. This exploratory study evaluates the feasibility and clinical utility of impression cytology (IC) as a non-invasive diagnostic approach for OSSN in a rural Indian tertiary care center. We conducted a retrospective analysis of seven patients with clinically suspected OSSN. IC was performed using cellulose acetate filter paper (0.22 μm pore size) applied to the lesion surface for 5-10 s. For each lesion, separate samples were collected: one fixed immediately in 95% ethanol for Hematoxylin and Eosin (H&E) staining, and one air-dried followed by methanol fixation for May-Grünwald-Giemsa (MGG) staining. Cytological assessment focused on cellular atypia, nuclear-cytoplasmic ratio, pleomorphism, and chromatin pattern. Clinical management and outcomes were correlated with IC findings. IC provided adequate cellular samples in all cases, enabling cytological grading across the OSSN spectrum: mild dysplasia (3 cases), high-grade dysplasia (3 cases), and cytological features suspicious for possible invasive squamous cell carcinoma (1 case). In cases treated with topical mitomycin C (MMC) based on IC guidance, complete lesion resolution was achieved at last follow-up (ranging from 3 to 6 months) without recurrence. Histopathological confirmation was available in 3 cases (including the case suspicious for invasion) and showed complete concordance with IC findings. The procedure was well-tolerated with 100% patient compliance. Impression cytology is a feasible, minimally invasive diagnostic tool for OSSN that can identify dysplastic changes and guide clinical management in resource-limited settings. While it cannot definitively diagnose stromal invasion and histopathological confirmation remains necessary when invasion is suspected, IC serves as a useful screening and monitoring modality in rural healthcare environments. Larger prospective studies are needed to validate these preliminary findings.

Cytology is central to the initial work-up of lymphadenopathy in the era of minimally invasive procedures, but some inherent limitations such as loss of tissue architecture require ancillary testing in some cases. The WHO Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (2024) standardizes category-based reporting and management, while the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) defines diagnostic entities and criteria. We review the real-world application of the WHO Reporting System across the five diagnostic categories, highlight cytomorphologic patterns that map to WHO-HAEM5 entities, and provide an overview for triaging material to flow cytometry, immunohistochemistry, as well as molecular and genetic testing. We posit that properly selected and validated ancillary studies enable WHO-concordant diagnoses from cytology and reduce repeat procedures.

This article analyzes the role of Scientific Medical Societies (SMS) in continuing education in Cytopathology, emphasizing their impact on professional development, diagnostic quality, and patient safety. In recent years, Cytopathology has undergone significant growth driven by technological and molecular advances, which have expanded its scope and complexity. In this context, SMS play a crucial role by offering training activities such as congresses, courses, workshops, and publications, acting as a bridge between scientific evidence and clinical practice. The article also addresses current challenges related to equitable access, pedagogical innovation, and the integration of new technologies, as well as potential strategies for strengthening continuing education and international cooperation.

Effusion specimens are frequently encountered in cytopathology practice. As in surgical pathology, candidate markers for effusion diagnosis require thorough assessment prior to inclusion in diagnostic panels. This review discusses some of the currently used markers, with focus on immunohistochemistry. A literature search of relevant publications, with focus on markers with established diagnostic role. BAP1 and MTAP protein expression by immunohistochemistry has been shown to be useful in the differentiation of reactive mesothelial proliferations from mesothelioma, as well as in differentiating the latter from metastatic carcinoma, in multiple studies. Molecular analysis analyzing CDK2NA, MTAP, BAP1 and NF2 status has been additionally applied to the differential diagnosis of mesothelioma from reactive mesothelium. Robust markers for the differentiation between mesothelioma and carcinoma, such as TAG-72/B72.3, claudin-4, calretinin and HEG1, are available, as are markers that support a specific origin for metastatic adenocarcinoma, such as PAX8, TTF1 and TRPS1. Effusion diagnosis remains central to staging, and consequently prognosis of cancer patients. Effusions additionally constitute optimal material for predictive studies and thereby guide the choice of targeted therapy.  .

There is a lack of consensus and data validating lower cell counts for sample adequacy of thyroid fine-needle aspiration (FNA). We investigated less stringent adequacy thresholds under the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and evaluated malignancy risks for "nondiagnostic" nodules by ultrasound features. A total of 2459 nodules with initial FNA were included. We built 11 new adequacy criteria based on the number of cell groups and total follicular epithelial cells. Diagnostic performance of each criterion was compared with the original criterion using the general estimating equation. Nondiagnostic nodules under each criterion were categorized by the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS), and malignancy rates of each ACR TIRADS category were compared. Malignancy rates of nondiagnostic nodules were under 3.5% across all criteria, and showed no significant differences compared with the original. More than 40 cells, regardless of cell group, or more than three cell groups showed no significant difference in diagnostic accuracy and false negative rates compared with the original criterion. Malignancy rates of nondiagnostic nodules were above 28.6% for ACR TIRADS 5, and below 5% for ACR TIRADS 1 to 4, in all criteria. Less stringent thresholds for sample adequacy can show comparable diagnostic performances to the original criterion of the TBSRTC. Given their markedly higher malignancy rates, nondiagnostic ACR TIRADS 5 nodules may warrant more active management than lower category nodules.

Nondiagnostic cytology for thyroid nodules, consistent with The Bethesda System for Reporting Thyroid Cytopathology category I (B1) poses a management dilemma for clinicians. The objective of this study was to define the malignancy risk of nodules with B1 cytology using American College of Radiology Thyroid Imaging Reporting & Data System (TI-RADS) and to assess whether TI-RADS can help guide the decision to perform a repeat biopsy of these nodules. This retrospective cohort study evaluated 139 B1 nodules that had a definitive diagnosis on repeat biopsy or surgical excision. Sonographic features were evaluated and classified according to TI-RADS. TI-RADS category and total points were compared to the final diagnosis to determine the malignancy risk of B1 thyroid nodules. Of the 139 nodules, 11 (7.9%) were malignant. The malignancy risk of nodules assigned TI-RADS category 1 and 2 were both 0%, TI-RADS 3 was 2.9%, whereas TI-RADS 4 and 5 were 5.9% and 46.2%, respectively. The optimal cutoff for TI-RADS points predicting malignancy was 5 points. B1 thyroid nodules in TI-RADS categories 1-3 may not require repeat biopsy given low malignancy risk. However, B1 nodules in TI-RADS categories 4 and 5 have a higher malignancy risk and thus should undergo repeat biopsy.

Deep learning (DL) systems could improve diagnostic accuracy and efficiency in detecting cervical atypia, but their effectiveness remains insufficiently explored. This multicentre, randomised crossover trial evaluated the clinical utility of a DL system in cervical cytopathology. A total of 1,920 women aged 18 years or older undergoing liquid-based cytology for cervical cancer screening were included, and their slides were digitized and randomly assigned (1:1) to two reading sequences. Four non-expert cytopathologists with 1-3 years of experience assessed slides using DL assistance for one group and manual microscopy for the other, and then switched roles after a four-week washout period. Each slide was evaluated twice in a randomly shuffled order. DL significantly improved sensitivity (85.7% vs 71.3%, p&#x2009;<&#x2009;0.001), with a difference of 14.3% (95% CI: 7.6% to 21.1%), exceeding the 5% superiority margin. Specificity was comparable (86.5% vs 85.1%, p&#x2009;=&#x2009;0.238), and non-inferiority was supported, as the lower limit of the 95% CI for the difference (1.4%; 95% CI: -1.0% to 3.8%) was above the pre-specified margin of -5%. Reading time was markedly reduced with DL (175&#x2009;seconds vs 31&#x2009;seconds, p&#x2009;<&#x2009;0.001). DL assistance could enhance both sensitivity and efficiency while rigorously preserving specificity in cervical cytology interpretation. Trial registration: ChiCTR2300078722.