Cancer Cytopathol [JOURNAL]
Sun
200 papers
New progress in addressing cancer pain: Recent studies have offered revealing insights into predisposing, precipitating, and perpetuating factors as well as underlying mechanisms and potential interventions.
Nelson B, Faquin W
Cancer Cytopathol · 2026 Jul · PMID 42383545 · Publisher ↗
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Molecular profiling of breast cancer pleural effusions using cytology specimens: Impact of sample source and cytological features on next-generation sequencing performance.
Virk H, Michael C, Pfeil KA … +3 more , Sadri N, Bomeisl P, Harbhajanka A
Cancer Cytopathol · 2026 Jul · PMID 42374817 · Full text
BACKGROUND: Malignant effusions in breast cancer are a minimally invasive source for molecular profiling. Effusion-derived cytology specimens, cell blocks (CB) and post-ThinPrep PreservCyt (PTPC) supernatant, are reliabl...
BACKGROUND: Malignant effusions in breast cancer are a minimally invasive source for molecular profiling. Effusion-derived cytology specimens, cell blocks (CB) and post-ThinPrep PreservCyt (PTPC) supernatant, are reliable sources for molecular testing but differ in DNA concentration and turnaround time (TAT). This study evaluates mutational profiles, cytology characteristics, and clinical correlates to assess the utility of effusion-based molecular testing in breast cancer. METHODS: The authors screened 2400 malignant effusion cases, identifying 22 cases of breast adenocarcinoma effusions that underwent next-generation sequencing (NGS). Both CB and PTPC supernatant were evaluated for tumor cellularity, fluid volume, DNA concentration, TAT, and mutation detection. Associations with clinicopathological features and outcomes were explored. RESULTS: NGS was successful in all 22 cases (mean volume, 426.5 mL; mean tumor cellularity, 50%). Successful sequencing was achieved in low volume samples with high tumor cellularity. Higher tumor cellularity (>50%) was associated with bloody effusions (p = .016). PTPC supernatant yielded 5-fold higher DNA (mean 177.4 ng/µL vs. 33.8 ng/µL) and shorter TAT by 9 days (15 vs. 24 days). TP53 mutations were more common in estrogen receptor (ER)-negative and triple-negative breast effusions (p = .025). Mutations in PIK3CA, TP53, CCND1, and AKT were reliably detected. Time from diagnosis to effusion development was significantly shorter in ER negative disease (p = .001) CONCLUSIONS: Effusion cytology using PTPC supernatant, support successful NGS even in low-volume samples. ER-negative and triple-negative effusions demonstrate more aggressive molecular features including enrichment of TP53 mutations and earlier effusion development. Effusion-based molecular testing yields clinically relevant genomic information in advanced breast cancer.
Accurate focal-plane selection is crucial for artificial intelligence assessment of three-dimensional urine cytology specimens for bladder cancer screening and surveillance.
Sayegh Y, McNutt B, Le MK … +12 more , Liao IC, Yao K, Ng C, Kohsar A, Shou D, Yu M, Jin Y, Vaickus LJ, Liu X, VandenBussche CJ, Harvey SE, Levy JJ
Cancer Cytopathol · 2026 Jul · PMID 42363782 · Publisher ↗
BACKGROUND: Bladder cancer is a common and highly recurrent malignancy requiring lifelong surveillance. Urine cytology serves as a noninvasive triage tool to guide cystoscopy but is limited by variable sensitivity and ma...
BACKGROUND: Bladder cancer is a common and highly recurrent malignancy requiring lifelong surveillance. Urine cytology serves as a noninvasive triage tool to guide cystoscopy but is limited by variable sensitivity and manual review. Although deep learning enables quantitative cell-level assessment, limited work has examined three-dimensional urine cytology preparations (e.g., SurePath) containing residual cellular fragments, where restricting analysis to a single nominal focal plane may obscure diagnostically relevant features. This study aimed to quantify focal-plane heterogeneity, measure degradation of nuclear-to-cytoplasmic (NC) ratio and nuclear area estimates off plane, and evaluate focal-plane selection algorithms for performance recovery. METHODS: A total of 325 SurePath whole-slide images scanned as 11-plane Z-stacks were analyzed that spanned negative through high-grade urothelial carcinoma cases. A detection model identified cells and clusters across planes, and 343 clusters (2435 urothelial cells) were reannotated at the optimal nuclear and cytoplasmic focal depths. Classical focus metrics and vision-transformer models were evaluated for focal-plane prediction. A U-Net segmentation model generated NC ratios and nuclear areas, and Spearman correlations compared annotated and predicted measurements across optimal, off-plane, and algorithm-selected conditions. RESULTS: Focal-plane prediction accuracy ranged from 42% to 88%, with classical focus metrics outperforming deep-learning approaches. NC ratio correlation was 0.774 at optimal focus and declined progressively off plane (∼0.50 at ±5 planes). Algorithm-selected planes partially recovered performance (up to 0.748). Similar trends were observed for nuclear area estimation. CONCLUSIONS: Accurate focal-plane selection is critical for artificial intelligence-based assessment of three-dimensional urine cytology. Future work will extend this analysis to cluster- and patient-level outcomes in multi-institutional validation studies.
Application of the International System for Serous Fluid Cytopathology in cerebrospinal fluid cytology: Overall survival analysis associated with diagnostic categories.
Yildiz Aktas IZ, Chakraborty B, Zhang JM … +10 more , Wang Y, Chandler J, Mejia Arbelaez CM, Wegener M, Fenlon TB, Ould Ismail AA, Marotti JD, Zhang Z, Liu X, Wang H
Cancer Cytopathol · 2026 Jul · PMID 42324785 · Publisher ↗
BACKGROUND: Cerebrospinal fluid (CSF) cytopathology lacks standardized reporting, leading to diagnostic variability and inconsistent clinical management. Although the International System for Reporting Serous Fluid Cytop...
BACKGROUND: Cerebrospinal fluid (CSF) cytopathology lacks standardized reporting, leading to diagnostic variability and inconsistent clinical management. Although the International System for Reporting Serous Fluid Cytopathology (TIS) has been established for effusions, its utility in CSF remains underexplored. For this study, the authors applied TIS categories to CSF specimens from three academic centers across two continents and evaluated their association with overall survival (OS). METHODS: A retrospective review of pathology databases (2019-2022) across three institutions was performed. Data included demographics, cytologic diagnosis, and OS. Diagnoses were reclassified using TIS criteria. OS was analyzed using Kaplan-Meier curves and Cox proportional hazards models, and multivariable analysis was used for predictors of mortality. RESULTS: In total, 1137 patients underwent CSF cytologic evaluation. Diagnostic distribution was as follows: 3.2% nondiagnostic, 67.1% negative for malignancy, 6.2% atypia of undetermined significance, 2.7% suspicious for malignancy, and 20.8% malignant. Among 579 patients with follow-up, OS differed across categories (p < .001). Mean survival was longest in patients who were diagnosed as negative for malignancy (53.9 months), followed by atypia of undetermined significance (48.4 months), and suspicious for malignancy (40.3 months), and it was shortest in patients who were diagnosed with malignancy (18.7 months). CONCLUSIONS: Leveraging a large, multi-institutional cohort with up to 5 years of follow-up, this study demonstrated that TIS categories effectively stratify CSF specimens into distinct prognostic groups. The authors identified a significant correlation between diagnostic classification and OS, with a clear decline in patient outcomes from those who had diagnoses of negative for malignancy/atypia of undetermined significance to those who had diagnoses of suspicious for malignancy and malignancy. These findings support the TIS system as a standardized, evidence-based framework that enhances risk stratification and clinical decision-making in CSF cytopathology.
The performance of intraoperative peritoneal washings in detecting pancreatic ductal adenocarcinoma.
Patel SD, Burns WR, VandenBussche CJ
Cancer Cytopathol · 2026 Jul · PMID 42322121 · Publisher ↗
BACKGROUND: Accurate peritoneal staging is critical in pancreatic ductal adenocarcinoma (PDAC), as the presence of peritoneal metastases significantly alters prognosis and treatment strategy. In this setting, some center...
BACKGROUND: Accurate peritoneal staging is critical in pancreatic ductal adenocarcinoma (PDAC), as the presence of peritoneal metastases significantly alters prognosis and treatment strategy. In this setting, some centers use peritoneal washings (PWs), which allow the sampling of a large area of the peritoneal surface in the absence of a visible lesion, to improve peritoneal staging and improve selection for curative-intent surgery. METHODS: The authors conducted a retrospective review of 28 patients who underwent cytopathologic evaluation of intraoperative PWs collected between July 2019 to July 2024. RESULTS: There was high concordance between PWs and concomitant biopsy. Six patients had positive PWs. Of these six patients, five of them had concordant findings noted on biopsy. There was one patient who had benign findings on biopsy despite having a malignant PW. In a similar fashion, 22 patients had PWs that were negative. Nineteen of these patients had concordant findings noted on biopsy. The remaining three patients had biopsy-confirmed metastasis despite benign findings noted on PW. CONCLUSION: Peritoneal washings can enhance the detection of peritoneal involvement by PDAC while minimizing false-positive diagnoses.
Supernatant: What's in a name?
Bellevicine C, Vigliar E, Troncone G … +1 more , Roy-Chowdhuri S
Cancer Cytopathol · 2026 Jul · PMID 42290536 · Publisher ↗
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Application of The International System for Serous Fluid Cytopathology to cerebrospinal fluid and adjunct flow cytometry analysis improves diagnostic accuracy.
Wang M, Cai G
Cancer Cytopathol · 2026 Jul · PMID 42283197 · Publisher ↗
BACKGROUND: Cerebrospinal fluid (CSF) is an important diagnostic tool for detecting leptomeningeal involvement by malignancy or other etiologies. Currently, there is no standardized reporting system for CSF cytology. Thi...
BACKGROUND: Cerebrospinal fluid (CSF) is an important diagnostic tool for detecting leptomeningeal involvement by malignancy or other etiologies. Currently, there is no standardized reporting system for CSF cytology. This study aims to assess the application of The International System for Serous Fluid Cytopathology (TIS) in categorizing CSF diagnoses and the role of flow cytometry in improving diagnostic performances. METHODS: CSF cases at our institution between January 1, 2023, and December 31, 2023, were reviewed and selected slides were examined. Based on the retrospective review of cytomorphologic findings and flow cytometry results, cases were reclassified into five diagnostic categories according to TIS: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). RESULTS: The study cohort included 854 CSF cases from 439 patients. Flow cytometry was performed in 185 (21.7%) cases with a positive result in 23 cases. After applying TIS, final cytological diagnoses included NFM (87.2%), AUS (7.1%), SFM (0.6%), and MAL (5.0%). The calculated risk of malignancy was 0.3% for NFM, 4.5% for AUS, 66.7% for SFM, and 100% for MAL. The diagnostic performance metrics were 95% sensitivity, 100% specificity, and 99% diagnostic accuracy. CONCLUSIONS: The application of TIS to CSF specimens helps standardize reporting terminology, improves diagnostic accuracy, and offers predictive risk stratification. The conjunction with flow cytometry to CSF cytology helps reduce indeterminate diagnosis, especially for those with an uncertain etiology or prior history of hematological malignancy.
TRBC1/CD3 dual color immunohistochemistry: An effective test to support a diagnosis of T-cell lymphoma in cytology specimens.
Wu SJ, Mito JK
Cancer Cytopathol · 2026 Jul · PMID 42283121 · Publisher ↗
The diagnosis of T-cell lymphoma is challenging, and establishing clonality is an important aspect of the workup. Molecular testing to establish T-cell clonality though T-cell receptor (TCR) gene rearrangement polymerase...
The diagnosis of T-cell lymphoma is challenging, and establishing clonality is an important aspect of the workup. Molecular testing to establish T-cell clonality though T-cell receptor (TCR) gene rearrangement polymerase chain reaction is the most common modality and can detect clonal rearrangements in ∼90% of T-cell lymphomas, but is limited by increased turnaround time and cost and the need for sufficient material for testing. In the maturation of T cells, the TCR locus rearrangement will result in the mutually exclusive expression of either the TCR beta-chain constant domain 1 or 2 (TRBC1, TRBC2). Antibodies to TRBC1 and TRBC2 have been used in the setting of flow cytometry, and more recently immunohistochemistry, to establish T cell clonality. This study evaluates the utility of a TRBC1/CD3 dual stain for the diagnosis of T-cell lymphoma. The laboratory information system was searched from 2019 through 2025 for cytology samples with a diagnosis of T-cell lymphoma. Twelve samples were identified along with controls. Dual color immunohistochemistry for TRBC1 and CD3 was performed using a brown chromogen for TRBC1 and a red chromogen for CD3. The proportion of cells staining for TRBC1 and CD3 was scored. A monoclonal T-cell population was detected in all samples of T-cell lymphoma. All B-cell lymphomas and benign samples showed a polyclonal staining pattern consisting of a mixture of brown and red cells. Using immunohistochemistry for TRBC1 paired with CD3 is a reliable surrogate for T-cell clonality testing in cytology specimens and can support a diagnosis of T-cell lymphoma on limited material.
Successful simplified genomic profiling of cytology specimens using Aspyre Clinical Test for Lung (Tissue).
Gentile C, Herlihy SE, Shapiro E … +15 more , Evans RT, Green AS, King C, Rossi MB, Gillon-Zhang E, Schaffernoth J, Knudsen KE, Kiser C, Yuen T, Silva AL, Gray ER, Balmforth BW, Levin WJ, Gregg J, Van Deerlin V
Cancer Cytopathol · 2026 Jul · PMID 42252866 · Full text
BACKGROUND: Testing patients with non-small cell lung cancer for actionable variants is essential for guiding treatment decisions in accordance with established cancer care guidelines, though limited quantity and quality...
BACKGROUND: Testing patients with non-small cell lung cancer for actionable variants is essential for guiding treatment decisions in accordance with established cancer care guidelines, though limited quantity and quality of tumor tissue often leaves insufficient material for comprehensive testing. Cytopathology specimens obtained through minimally invasive techniques are a potential source of diagnostic material for genomic profiling, though typically challenging to analyze. METHODS: A total of 85 DNA or total nucleic acid non-small cell lung cancer samples derived from 45 fine-needle aspirate rinse or pleural fluid samples from the Hospital of the University of Pennsylvania archive were tested using the Aspyre Clinical Test for Lung (Tissue) in Biofidelity's CAP/CLIA laboratory. All samples were previously characterized by the Oncomine Precision Assay Genexus assay (the orthogonal reference method). RESULTS: Eighty-four of 85 passed Aspyre Lung quality control, one failed. Twenty-six samples were positive for variants in the Aspyre Lung panel: 17 for single nucleotide variants (KRAS, EGFR), three for EGFR insertions/deletions, two for MET exon 14 skipping, and five for gene fusions. Eighty-two of 85 samples were run at standard input levels; three of 85 were run at low input but passed Aspyre Lung controls and include one EGFR exon 20 insertion variant-positive. All results were concordant between methods. Positive Percent Agreement and Negative Percent Agreement were 100%. CONCLUSIONS: Aspyre Clinical Test for Lung performs effectively on samples derived from fine needle aspirate rinses and pleural fluid. Using these cytology-based specimens for biomarker testing enables pathologists to perform simplified genomic profiling while preserving valuable tissue specimens, potentially reducing the need for additional invasive procedures.
Cysteine-mapping efforts offer new tools for drug development and discovery: Research groups are characterizing cysteine binding and reactivity traits to provide important new starting points for drug design.
Nelson B, Faquin W
Cancer Cytopathol · 2026 Jun · PMID 42226703 · Publisher ↗
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Artificial intelligence-assisted urine cytology based on the Paris System for Reporting Urothelial Carcinoma.
Chen L, Cao X, Lu Z … +4 more , Liu L, Sun M, Wu Y, Zhang W
Cancer Cytopathol · 2026 Jun · PMID 42223163 · Publisher ↗
BACKGROUND: Urine cytology is a noninvasive and valuable tool for detecting urothelial carcinoma but suffers from variable sensitivity and observer dependency. Artificial intelligence (AI) may enhance the diagnostic accu...
BACKGROUND: Urine cytology is a noninvasive and valuable tool for detecting urothelial carcinoma but suffers from variable sensitivity and observer dependency. Artificial intelligence (AI) may enhance the diagnostic accuracy and efficiency of urine cytology. The objective of this study was to develop and validate an AI-based cytology system for urothelial carcinoma detection in both clinical and screening contexts. METHODS: In total, 328 retrospective clinical cases and 1489 prospective health screening samples were analyzed. All specimens underwent liquid-based cytology and were digitized at ×20 magnification. For model development, ed 269 annotated training slides (56,710 cells) were used. The AI pipeline mimicked cytopathologist workflow, integrating deep learning-based cell detection and segmentation with feature extraction and support vector machine classification into AI-negative, AI-atypical, and AI-positive categories according to The Paris System for Reporting the Urinary Cytology. Agreement was assessed using weighted κ values and prevalence-adjusted, bias-adjusted κ values. RESULTS: In the clinical cohort, AI achieved 83.0% agreement with histopathology and 82.6% agreement with expert cytology. Weighted κ values (κ, 0.631-0.661) reflected substantial agreement, with discrepancies mainly between adjacent categories. In the health screening cohort, the prevalence-adjusted, bias-adjusted κ was 0.647 despite low prevalence. AI demonstrated a high negative predictive value of 99.7% and negative percent agreement of 82.3%, with a minimal false-omission rate (0.25%). CONCLUSIONS: AI-assisted urine cytology exhibited substantial concordance with expert interpretation and histopathologic standards. Its capability of screen-out and high negative predictive value support its potential as a reliable triage tool, improving workflow efficiency while maintaining diagnostic reliability in large-scale screening.
Correction to "Evaluating the role of metaplasia in the cytologic diagnosis of pleomorphic adenoma: A multi-institutional study of 253 cases".
Cancer Cytopathol · 2026 Jun · PMID 42186349 · Publisher ↗
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Atypical and suspicious diagnoses in solid pancreatic lesions: Cytomorphologic features and interobserver variability in FNA smears and biopsies.
Al-Attar MM, Sardana R, Zhao M … +4 more , Pitman MB, Torous VF, Chebib I, Zhang ML
Cancer Cytopathol · 2026 Jun · PMID 42145212 · Publisher ↗
BACKGROUND: Atypical (ATY) and suspicious (SUS) diagnoses in fine-needle aspiration/biopsy (FNA/B) of solid pancreatic lesions remain challenging to consistently apply. The most relevant cytomorphologic features and repr...
BACKGROUND: Atypical (ATY) and suspicious (SUS) diagnoses in fine-needle aspiration/biopsy (FNA/B) of solid pancreatic lesions remain challenging to consistently apply. The most relevant cytomorphologic features and reproducibility of these interpretations across direct smears and FNBs are not well characterized. METHODS: In total, 124 FNA/B specimens (87 smears, 37 FNBs) from solid pancreatic masses originally diagnosed as ATY or SUS were identified (from 2014 to 2024). Clinical/pathologic follow-up was reviewed, and morphologic features were systematically assessed. Interobserver variability was evaluated using blinded re-interpretation of 40 smears and 20 FNBs by four cytopathologists and three cytopathology fellows. RESULTS: Non-adenocarcinoma malignancies (16 smears and 3 FNBs) were excluded for outcomes and morphologic analysis. The risk of malignancy was high in both categories (smears: ATY, 72.3%; SUS, 90.0%; FNBs: ATY, 80.0%; SUS, 100%). ATY smears more often showed scant cellularity (87.8% vs. 59.1% of SUS smears; p = .011), whereas SUS cases more commonly demonstrated anisonucleosis ≥4:1 (54.5% vs. 20.4%; p = .010). On FNBs, background chronic pancreatitis was significantly more frequent in SUS cases (75.0% vs. 11.5%; p = .001). Interobserver agreement was fair for smears (κ = 0.355) and lower for FNBs (κ = 0.218), with fellows rendering ATY/SUS diagnoses more frequently than staff cytopathologists. CONCLUSIONS: Both ATY and SUS interpretations in solid pancreatic lesions carry high malignancy risk. Smears show clearer morphologic features for upgrading from ATY to SUS, whereas FNBs demonstrate fewer discriminating features and lower reproducibility. These findings support continued refinement of specimen-type-specific morphologic criteria and ongoing education to reduce variability in reporting.
Lung adenocarcinoma with malignant serous effusions: A comprehensive clinicopathologic, molecular, and outcome analysis.
Ma W, Li J, Ould Ismail AA … +4 more , Li T, Kerr DA, Tafe LJ, Liu X
Cancer Cytopathol · 2026 Jun · PMID 42145151 · Publisher ↗
BACKGROUND: Malignant serous effusions (MSEs), including pleural, pericardial, and peritoneal effusions, are common in advanced lung adenocarcinoma (LUAD). However, integrated clinicopathologic, molecular, treatment, and...
BACKGROUND: Malignant serous effusions (MSEs), including pleural, pericardial, and peritoneal effusions, are common in advanced lung adenocarcinoma (LUAD). However, integrated clinicopathologic, molecular, treatment, and outcome data across effusion sites remain incompletely defined. METHODS: This study retrospectively analyzed 120 cytology-confirmed LUAD-associated MSE cases from a single academic center by integrating gross fluid features, cytopathology, immunohistochemistry, targeted next-generation sequencing (NGS), systemic therapy, and clinical outcomes, including survival from first malignant effusion (SME) and overall survival (OS). RESULTS: Effusions were pleural (85 of 120; 70.8%), pericardial (28 of 120; 23.3%), and peritoneal (7 of 120; 5.8%). Median SME was 3.8 months, and was shortest in the small peritoneal effusion subgroup (1.0 months). OS differed by site, with pericardial involvement showing the shortest OS (6.1 months). Thyroid transcription factor 1 (TTF-1) was positive in 72.5% of cases. Programmed death ligand 1 (PD-L1) testing (n = 85) showed a tumor proportion score (TPS) of ≥1% in 80% of cases and TPS of ≥50% in 36.5% of cases. Molecular profiling was completed in 111 of 120 cases (92.5%) by identifying TP53 mutations in 47 of 111 (42.3%) and actionable driver alterations in 42.3% of cases, most commonly involving EGFR, KRAS, BRAF, ALK, and ROS1. TTF-1 positivity was associated with higher rates of actionable driver alterations and higher PD-L1 expression. PD-L1 negativity, TTF-1 negativity, and an absence of actionable driver alterations were associated with shorter SME and OS. Dual TTF-1/PD-L1 negativity defined the poorest risk subgroup (median SME, 1.2 months; median OS, 1.4 months). Multivariable analysis confirmed that TTF-1 negativity and a lack of actionable drivers remained independently adverse. Among treated patients, immunotherapy-based regimens were associated with the longest SME (6.7 months), whereas tyrosine kinase inhibitor-based therapy was associated with the longest OS (26.0 months). CONCLUSIONS: Integration of cytology, immunophenotype, genomics, and treatment delineates distinct prognostic subsets in LUAD with MSE. The absence of actionable driver alterations and TTF-1 negativity remains an independent adverse prognostic factor, with dual TTF-1/PD-L1-negative MSE showing particularly poor SME and OS.
Scrape versus imprint cytology in sentinel lymph nodes of breast cancer patients after neoadjuvant therapy: Does combination add value?
Akıncıoğlu E, Kadan E, Kıvrak H … +3 more , Sadioğlu A, Seçinti İE, Şimşek G
Cancer Cytopathol · 2026 Jun · PMID 42145150 · Full text
BACKGROUND: The primary objective of this study is to evaluate the feasibility of cytological methods in intraoperative consultation for patients receiving neoadjuvant therapy (NT), to compare the sensitivity, specificit...
BACKGROUND: The primary objective of this study is to evaluate the feasibility of cytological methods in intraoperative consultation for patients receiving neoadjuvant therapy (NT), to compare the sensitivity, specificity, and accuracy of imprint, scrape, and combined cytology, and to assess the reliability of these methods in lymph nodes (LNs) affected by treatment-related changes. Additionally, this study aims to investigate the impact of metastatic tumor size on the diagnostic accuracy of cytological methods. METHODS: Ninety-two patients who underwent sentinel LN sampling during breast surgery between June 2023 and December 2024 were included in this retrospective study. Diagnostic performance of imprint, scrape, and combined cytology was evaluated according to NT status, metastatic tumor size, and treatment-related changes. Overall accuracy was assessed using Receiver operating characteristic (ROC) analysis, with pairwise comparisons performed using DeLong's test. RESULTS: A total of 300 LNs were evaluated, of which 161 (53.6%) were from patients receiving NT. In this subgroup, imprint cytology showed high specificity but limited sensitivity, whereas scrape and combined cytology demonstrated higher sensitivity and overall diagnostic accuracy. ROC analysis showed significantly higher diagnostic performance for scrape and combined cytology compared with imprint cytology in patients receiving NT (p = .005). Across all subgroup analyses, including metastasis size and therapy-related changes, combined cytology consistently showed the highest sensitivity, whereas imprint cytology maintained the highest specificity. CONCLUSION: Scrape cytology showed significantly higher diagnostic performance than imprint cytology, particularly after NT. Combined cytology improved performance compared with imprint cytology but did not significantly outperform scrape cytology.
Practical exploration of real-time visual interactive artificial intelligence technology in cytopathology education.
Ren W, Rong L, Wang Q … +4 more , Wang J, Cheng C, Zhu Y, Lu J
Cancer Cytopathol · 2026 Jun · PMID 42145147 · Publisher ↗
BACKGROUND: Proficiency in cytopathologic diagnosis depends heavily on extensive hands-on practice and immediate error correction. Traditional teaching models, however, are constrained by limited practice opportunities a...
BACKGROUND: Proficiency in cytopathologic diagnosis depends heavily on extensive hands-on practice and immediate error correction. Traditional teaching models, however, are constrained by limited practice opportunities and delayed feedback, which fails to meet the core skill-development needs of residents. METHODS: In total, 45 pathology residents were enrolled and assigned to two groups. The experimental group (n = 20) adopted a tripartite teacher-artificial intelligence-resident collaborative teaching model, whereas the control group (n = 25) received conventional instruction. Both groups underwent an identical 8-week teaching cycle. RESULTS: The questionnaire results from the experimental group indicated that 19 of 20 residents (9%) deemed the new model highly necessary, and 15 of 20 (75%) believed it significantly improved their diagnostic competence. Semistructured interviews further revealed that the model enhanced diagnostic ability, facilitated personalized learning, and alleviated learning anxiety. For objective metrics, the experimental group demonstrated a significantly higher postintervention concordance rate for gray-zone cell identification (78.65%) compared with both their preintervention baseline (64.38%) and the contemporaneous control group (66.84%; t = 8.962; p < .001). In addition, the experimental group exhibited a markedly faster diagnostic speed (mean ± standard deviation, 3.05 ± 0.52 minutes per case) compared with their preintervention performance (5.92 ± 0.85 minutes per case) and the control group (5.63 ± 0.79 minutes per case; t = 14.821; p < .001). No statistically significant changes were observed in the control group (p > .05). CONCLUSIONS: This study demonstrates that artificial intelligence technology integrated with real-time visual interaction effectively improves the cytopathologic diagnostic skills of residents and merits wider promotion in pathology education.
Enhancing urothelial carcinoma diagnosis with artificial intelligence-integrated urine cytology: Biopsy-validated accuracy and efficiency gain.
Lajara S, Cuda J, Geisler DL … +9 more , Staniszewski C, Yang WL, Atkison K, Lin CY, Shao G, Liu TJ, Crothers B, Dhir R, Khader SN
Cancer Cytopathol · 2026 Jun · PMID 42144873 · Full text
BACKGROUND: Urine cytology is a noninvasive tool for detecting urothelial carcinoma, yet its performance depends heavily on expert cytologists and time-intensive glass slide review. Artificial intelligence (AI)-assisted...
BACKGROUND: Urine cytology is a noninvasive tool for detecting urothelial carcinoma, yet its performance depends heavily on expert cytologists and time-intensive glass slide review. Artificial intelligence (AI)-assisted digital cytology has emerged as a potential solution to improve diagnostic sensitivity and workflow efficiency. This retrospective study aimed to evaluate the diagnostic performance and workflow impact of AIxURO, an AI-assisted digital urine cytology system, in a high-volume US medical center. METHODS: Two hundred ThinPrep cytology slides were digitized with two distinct customized scanners integrated into the AIxURO imaging system (AIS-1 and AIS-2). Three reviewers independently assessed each case across three diagnostic modalities: microscopy, AIxURO-AIS-1, and AIxURO-AIS-2. Performance for binary bladder cancer detection was compared against expert consensus cytology diagnoses; review time, biopsy correlation, and performance in patients presenting with hematuria were also evaluated. RESULTS: AIxURO (AIS-1 and AIS-2) improved diagnostic sensitivity (85.0% and 88.3%) and negative predictive value (NPV) (85.1% and 87.6%) relative to microscopy (79.3% and 82.0%), whereas accuracy remained comparable across modalities. These sensitivity gains were accompanied by lower specificity (85.7% and 82.3% vs. 94.3%) and positive predictive value (PPV) (85.6% and 83.3% vs. 93.3%) compared with microscopy. Both AI modalities reduced classifying atypical urothelial cells and above cases as negative for high-grade urothelial carcinoma cases, and shortened median review time by 66%-78% (p < .0001). Among the 200 cases, 98 (49%) had biopsy confirmation, in which AIxURO showed higher sensitivity and NPV than microscopy. In 16 hematuria cases with biopsy correlation, AI-assisted screening achieved superior diagnostic performance. CONCLUSIONS: AIxURO enhances sensitivity for detecting urothelial carcinoma and markedly improves screening efficiency, with a tradeoff of reduced specificity/PPV compared with microscopy.
Risk of malignancy for biliary cytology based on World Health Organization (WHO) reporting system for pancreaticobiliary cytopathology.
Abraham AE, Wang X, Hargett I … +9 more , Pharaa Z, Sears C, Gonen M, Murali R, Lin O, Wei A, Gonzalez-Aguirre A, Shah P, Sigel C
Cancer Cytopathol · 2026 Jun · PMID 42142111 · Publisher ↗
BACKGROUND: The World Health Organization (WHO) classification for pancreaticobiliary cytopathology stratifies risk of malignancy (ROM) and outcome for pancreatic fine-needle aspirations (FNAs). ROM for biliary cytology,...
BACKGROUND: The World Health Organization (WHO) classification for pancreaticobiliary cytopathology stratifies risk of malignancy (ROM) and outcome for pancreatic fine-needle aspirations (FNAs). ROM for biliary cytology, particularly for WHO categories Pan-low (IV) and Pan-high (V), has not been well examined. METHODS: Retrospective data of biliary cytology diagnosed from 2016 to 2019 were collected. WHO classification was assigned. Malignant outcome was determined by histologic correlation or clinical progression/death. Excluding clinical follow-up <3 months (if no histology), the ROM, odds ratio, performance characteristics, and overall survival were calculated. RESULTS: A total of 1056 biliary cytology cases (from 789 patients) were included. Sample types were: 757 (72%) biliary brush/wash, 115 (11%) FNA, and 184 (17%) other. Same-site histologic correlation was 292 (28%) and histology of metastasis in 124 (12%). The median follow-up (for benign) was 1431 days. Malignant outcome occurred in 704 (n = 789, 89%) of patients. Absolute ROM (%) for WHO I to VII by biliary brush/wash and FNA were: 92, 72, 87, 0, 100, 94, 100, and 50, 46, 73, N/A, 100, 80, 100, respectively. A high-tier (V-VII) category had significantly higher odds of malignancy regardless of biopsy modality, presence of stent, or autoimmune cholangitis. CONCLUSION: Absolute ROM for biliary lesions is high for WHO I through III and is at least partly because of difficulty in sampling cancers, particularly those extrinsically obstructing the bile duct. The rarity of low-grade biliary lesions impedes AROM assessment for Pan-low (WHO IV). The clinical value of biliary Pan-high (WHO V) remains uncertain because of rarity of high-grade noninvasive lesions and difficulty in cytology diagnosis.
Prediction of lymphocyte-predominant breast cancer using microRNA expression in cytology specimens.
Kai A, Arihiro K, Shigematsu H … +5 more , Ohue-Uchihata Y, Nakamura M, Amioka A, Sasada S, Okada M
Cancer Cytopathol · 2026 Jun · PMID 42137987 · Full text
BACKGROUND: Tumor-infiltrating lymphocytes are prognostic and predictive biomarkers of breast cancer; however, conventional assessment is hindered by invasiveness and subjective evaluation, limiting clinical reproducibil...
BACKGROUND: Tumor-infiltrating lymphocytes are prognostic and predictive biomarkers of breast cancer; however, conventional assessment is hindered by invasiveness and subjective evaluation, limiting clinical reproducibility. This study investigated the utility of microRNA (miRNA) profiles in predicting lymphocyte-predominant breast cancer (LPBC). METHODS: This study included 56 patients with breast cancer who underwent fine-needle aspiration cytology at the time of diagnosis (28 LPBC and 28 non-LPBC cases). Total RNA was extracted from cytology smear specimens, and the expression levels of six candidate miRNAs (miR-30a-3p, miR-187, miR-196b, miR-1247, miR-4485, and miR-6510) were quantified using reverse-transcriptase polymerase chain reaction. The performance in identifying LPBC was evaluated using receiver operating characteristic curve analysis and logistic regression models. RESULTS: All six miRNAs showed significantly lower expression levels in the LPBC group than in the non-LPBC group (all p < .05). Receiver operating characteristic curve analysis demonstrated moderate to high diagnostic accuracy, with an area under the curve of 0.708 for miR-30a-3p, 0.739 for miR-187, 0.783 for miR-196b, 0.777 for miR-1247, 0.790 for miR-4485, and 0.673 for miR-6510. Multivariate analysis further identified each miRNA as an independent diagnostic predictor for LPBC. CONCLUSIONS: miRNA profiling of cytologic samples enabled the objective identification of LPBC. These findings suggest that specific miRNA expression patterns reflect the tumor immune microenvironment and can be used to evaluate the status of tumor-infiltrating lymphocytes in breast cancer.
Correction to "The fascinating history of papillary thyroid carcinoma nuclei: revelation of two nuclear morphologies-"Classical papillary" and "papillary-like", with different pathobiologic characteristics".
Cancer Cytopathol · 2026 Jun · PMID 42133834 · Publisher ↗
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