Search

Background: Cytopathological examination serves as a tool for diagnosing solid tumors and hematologic malignancies. Artificial intelligence (AI)-assisted methods have been widely discussed in the literature for increasing sensitivity, specificity and accuracy in the diagnosis of cytopathological clinical samples. Many of these tools are also used in clinical practice. There is a growing body of literature describing the role of AI in clinical settings, particularly in improving diagnostic accuracy and providing predictive and prognostic insights., Methods: A comprehensive search for this systematic review was conducted using databases Google, PUBMED (n = 450) and Google Scholar (n = 1067) with the keywords "Artificial Intelligence" AND "cytopathological" and "fine needle aspiration" AND "Deep Learning" AND "Machine Learning" AND "Hematologic Disorders" AND "Lung Cancer" AND "Pap Smear" and "cervical cancer screening" AND "Thyroid Cancer" AND "Breast Cancer" and "Sensitivity" and "Specificity". The search focused on literature reviews and systematic reviews published in English language between 2020 and 2024. PRISMA guidelines were adhered to with studies included and excluded as depicted in a flowchart. 417 results were screened with 34 studies were chosen for this review., Results: In the screening of patients with cervical cancer, bone marrow and peripheral blood smears and benign and malignant lesions in the lung, AI-assisted methods, particularly machine learning and deep learning (a subset of machine learning) methods, were applied to cytopathological data. These methods yielded greater diagnostic accuracy, specificity and sensitivity and decreased interobserver variability. Data sets were collected for both training and validation. Human machine combined performance was also found to be comparable to standalone performance in comparison with medical performance as well., Conclusions: The use of AI in the analysis of cytopathological samples in research and clinical settings is increasing, and the involvement of pathologists in AI workflows is becoming increasingly important., Competing Interests: Declarations Ethical approval and consent to participate Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance., Methods: A total of 657 hrHPV-positive women aged 25-64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1 m ) , Glycophorin C methylation (GYPC m ), cytology, and combinations between them or with HPV16/18., Results: The area under the receiver operating characteristic curves (AUCs) for PAX1 m and GYPC m in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796-0.937) and 0.873 (95% CI: 0.808-0.938), respectively. The sensitivities of PAX1 m and GYPC m were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 m and GYPC m for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33-2.45) and 3.09 (95% CI: 2.40-3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 m and GYPC m for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96-3.86) and 3.67 (95% CI: 3.15-4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 m and GYPC m resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57-409.12, p < 0.001) and 23.87 (95% CI: 6.49-115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results., Conclusions: PAX1 m and GYPC m demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer., (© 2024. The Author(s).)

Objectives: We studied the diagnostic accuracy and discordance of upper tract urothelial carcinoma (UTUC) by comparing biopsy and urinary cytology with matched nephroureterectomy specimens., Methods: Sixty-nine patients with UTUC without neoadjuvant treatment were retrospectively identified who had matched biopsy and nephroureterectomy specimens. Twenty patients had concurrent upper tract cytology. H&E and cytology slides were re-reviewed. Statistical analysis was performed., Results: Patients included 48 men and 21 women with a mean age of 69 years. A concordant grade between biopsy and surgical specimen was present in 49 (71%) patients. The mean size of biopsy specimens in the discordant group was significantly smaller than that in the concordant group. Invasion was evaluated in 48 biopsy cases that had adequate subepithelial tissue, and 33 of them were diagnosed with concordant invasion status. Mean tumor size in both tumor grade and invasion discordant groups was significantly larger than that in the concordant group. High-grade urothelial carcinoma was detected in 84% of cases using urinary cytology., Conclusions: Our study demonstrates the diagnostic challenges of UTUC on small biopsy specimens. Biopsy specimen size and tumor size are significantly associated with the diagnostic discordance. Upper tract cytology showed high diagnostic accuracy and should be complementary to the biopsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

To investigate the diagnostic value of intraoperative cytology and rapid immunocytochemistry in primary central nervous system lymphoma. 254 cases of lymphoma and 82 cases of non-lymphoma were collected from 2010 to 2023. Frozen section(FS) was using alone in 44 cases during 2010-2014, FS and intraoperative cytology(IC) were using in 251 cases during 2015 to 2022. Rapid immunocytochemical(RICC, CD20, GFAP) were using with FS + IC in 41 cases during 2021 to 2023. Method One: According to the results of archives, statistic the diagnostic accuracy of lymphoma during three time periods. Method Two: All cases were randomly renumbered, 4 neuropathologists compared the accuracy of independent histology and that of combining cytology. The archives showed the diagnostic accuracy of FS in PCNSL was 77.27%, FS + IC was 86.06%, FS + IC + RICC was 92.68%. The retrospective study demonstrated the diagnostic accuracy of FS was 79.76%, FS + IC was 87.33% and FS + IC + RICC was 92.68%. The positive predictive value, negative predictive value, sensitivity, specificity and accuracy of CD20 were 100%, 76.92%, 90.32%, 100% and 92.68%, respectively. The results of the paired χ 2  test was no statistically significant difference (0.05 < P < 0.1) between FS + IC + RICC and immunohistochemical (IHC) diagnosis of paraffin sections. The integration of IC + RICC + FS diagnosis can significantly enhance the intraoperative diagnostic accuracy of PCNSL and rectify potential errors that may occurred when relying solely on FS diagnosis., (© 2024. The Author(s).)

Background/aim: The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features., Patients and Methods: We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed., Results: Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features., Conclusion: In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate efficacy of the AIxURO system, a deep learning-based artificial intelligence (AI) tool, in enhancing the accuracy and reliability of urine cytology for diagnosing upper urinary tract cancers., Materials and Methods: One hundred and eighty-five cytology samples of upper urine tract were collected and categorized according to The Paris System for Reporting Urinary Cytology (TPS), yielding 168 negative for High-Grade Urothelial Carcinoma (NHGUC), 14 atypical urothelial cells (AUC), 2 suspicious for high-grade urothelial carcinoma (SHGUC), and 1 high-grade urothelial carcinoma (HGUC). The AIxURO system, trained on annotated cytology images, was employed to analyze these samples. Independent assessments by a cytotechnologist and a cytopathologist were conducted to validate the initial AIxURO assessment., Results: AIxURO identified discrepancies in 37 of the 185 cases, resulting in a 20% discrepancy rate. The cytotechnologist achieved an accuracy of 85% for NHGUC and 21.4% for AUC, whereas the cytopathologist attained accuracies of 95% for NHGUC and 85.7% for AUC. The cytotechnologist exhibited overcall rates of roughly 15% and undercall rates of greater than 50%, while the cytopathologist showed profoundly lower miscall rates from both undercall and overcall. AIxURO significantly enhanced diagnostic accuracy and consistency, particularly in complex cases involving atypical cells., Conclusion: AIxURO can improve the accuracy and reliability of cytology diagnosis for upper urine tract urothelial carcinomas by providing precise detection on atypical urothelial cells and reducing subjectivity in assessments. The integration of AIxURO into clinical practice can significantly ameliorate diagnostic outcomes, highlighting the synergistic potential of AI technology and human expertise in cytology., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Concepts in thyroid diagnostics are evolving. As cytopathologists, we benefit from understanding the changes taking place in cytopathology practice as well as intersecting areas that may have implications for us. In this review, we discuss recent changes to 1. Classification systems, 2. Ancillary molecular testing modalities, and 3. Key metrics that affect thyroid cytopathology. The recent World Health Organization, Bethesda Thyroid Cytopathology, and American Joint Committee on Cancer classification systems have aspects that are designed to harmonize the clinical, cytopathologic, histomorphologic, and molecular findings for improved communication and patient management. New terminologies such as thyroid follicular nodular disease and low-risk follicular cell-derived thyroid neoplasms are introduced to reflect the subtle biologic nuances involving benign non-neoplastic and low-grade neoplastic conditions. The Bethesda Thyroid Cytopathology System has simplified its terminology, updated risk of malignancy estimates, and expanded the discussions on molecular testing, clinical and imaging assessments, and pediatric cytopathology. There is now a single term for each of the 6 diagnostic categories. The American Joint Committee on Cancer has refined the staging criteria to provide improved stratification of patient prognostication. Molecular testing using next-generation technology now offers large panels of markers that are sensitive for detecting the wide range of thyroid neoplasms. These panels were developed in North America and whether other regions of the world will choose similar tests remain to be seen. Finally, metrics such as molecular-derived risk of malignancy and molecular risk group may be viewed as surrogates of resection information and used to complement diagnostics, management, and quality assurance., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Oral exfoliative cytology has emerged as a valuable tool in the early detection of oral cancer and other systemic diseases. This review comprehensively examines the current applications and recent advancements in oral exfoliative cytology techniques. We analyzed published literature from the past decade, focusing on methodological improvements, diagnostic accuracy, and emerging applications. Key findings include: (1) Enhanced cell collection and preparation methods have significantly improved sample quality and diagnostic reliability. (2) Integration of molecular markers and DNA analysis with traditional cytomorphological assessment has increased diagnostic sensitivity and specificity for oral cancer detection. (3) Novel applications in systemic disease detection, including diabetes and iron overload disorders, demonstrate the expanding utility of this technique. (4) Computer-assisted analysis and deep learning algorithms show promise in improving diagnostic accuracy and efficiency. Despite these advancements, challenges remain in standardization and widespread clinical implementation. This review provides a critical evaluation of oral exfoliative cytology's current status and future potential in oral and systemic disease diagnosis., (© 2024 Wiley Periodicals LLC.)

Objective: Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC., Methods: We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC)., Results: A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases., Conclusions: Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC., (© 2024 John Wiley & Sons Ltd.)

Introduction: Cytological analysis of effusion specimens provides critical information regarding the diagnosis and staging of malignancies, thus guiding their treatment and subsequent monitoring. Keeping in view the challenges encountered in the morphological interpretation, we explored convolutional neural networks (CNNs) as an important tool for the cytological diagnosis of malignant effusions., Materials and Methods: A retrospective review of patients at our institute, over 3.5 years yielded a dataset of 342 effusion samples and 518 images with known diagnoses. Cytological examination and cell block preparation were performed to establish correlation with the gold standard, histopathology. We developed a deep learning model using PyTorch, fine-tuned it on a labelled dataset, and evaluated its diagnostic performance using test samples., Results: The model exhibited encouraging results in the distinction of benign and malignant effusions with area under curve (AUC) of 0.8674, F-measure or F1 score which denotes the harmonic mean of precision and recall, to be 0.8678 thus, demonstrating optimal accuracy of our CNN model., Conclusion: The study highlights the promising potential of transfer learning in enhancing the clinical pathology laboratory efficiency when dealing with malignant effusions., (© 2024 Wiley Periodicals LLC.)

Background: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time., Methods: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers., Results: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers., Conclusions: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Immunocytochemistry (ICC) is essential for enhancing diagnostic accuracy and identifying markers for diagnosis, prognosis and targeted therapies. While cell blocks (CBs) are preferred for standardization and optimized staining, cytological smears are an alternative when CBs are unavailable. However, the literature on ICC protocols for smears is sparse. This review addresses preparation, fixation and protocols for nuclear and cytoplasmic antibodies on smears, drawing from our laboratory's experience., Methods: We reviewed procedures for ICC on cytological smears using existing literature and practical insights from our laboratory., Results: Commercially available antibodies were found to be reliable for ICC on smears if specimens are properly prepared and fixed. Protocols developed in our laboratory maintained antigenicity and provided clear staining results., Conclusions: Although ICC on CBs is the gold standard for standardization, cytological smears are a viable alternative when CBs are unavailable. Success in ICC on smears depends on proper preparation and fixation. This review offers practical protocols and insights to help laboratories optimize ICC on cytological smears. Further research and standardization are necessary to enhance reproducibility and reliability of ICC on smears. The practical information provided is based on personal experience in our laboratory., (© 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.)

Background: The World Health Organization (WHO) reporting system for pancreaticobiliary cytopathology was released to internationalize the reporting, assisting in correct diagnosis and patient treatment with significant revisions from the previous Papanicolaou Society of Cytopathology (PSC) system. The "neoplastic: benign" and "neoplastic: other" categories have mostly been superseded by two new ones: "pancreatic neoplasia-low-grade" (PaN-low) and "pancreatic neoplasia-high-grade" (PaN-high), which classify intermediate neoplastic lesions based on cytological atypia. We aim to assess the reproducibility and risk of malignancy (ROM) for reporting pancreaticobiliary cytopathology by the WHO system in comparison with the PSC system., Materials and Methods: A retrospective study by reviewing archival slides sent for pancreaticobiliary cytological evaluation from June 2021 to June 2023, by two pathologists blinded to each other's findings. Absolute ROM was determined by histopathology/cell block study/clinical follow-up (minimum 6 months)/overtly malignant imaging/metastasis., Results: A total of 332 cases from 329 patients met the inclusion criteria, comprising pancreatic, gallbladder, and biliary lesions. The median patient age was 54 years (range, 14-86 years). The overall sensitivity of the test is 74.9% specificity is 93.2%, positive predictive value of 96.8%, negative predictive value of 57.6%, and a diagnostic accuracy of 81.8%. The absolute ROM for each site in all categories was comparable with that of the published data from the WHO system., Conclusion: Our study highlights the reliability of the WHO system for guiding clinical decision-making and patient management in the context of pancreaticobiliary. However, continual efforts among pathologists are essential to maintain consistent accuracy in cytological interpretations., (© 2024 Wiley Periodicals LLC.)

Liquid-based cytology (LBC) has changed the landscape of gynaecological cytology. A growing demand exists for LBC in diagnostic cytology, particularly for ancillary testing, such as immunocytochemistry and molecular testing. Ancillary testing solely based on conventional preparation (CP) methods remains challenging. Recently, the increased demand for specialist testing and minimally invasive techniques, such as endoscopic ultrasonography fine-needle aspiration, to obtain cellular samples has led to an increasing demand for ancillary testing on cytology LBC supernatant, slides and cell block (CB). This facilitates the diagnosis and prognosis in cytology samples enabling personalized treatment. An understanding of the history and future prospects of LBC is crucial for its application in routine diagnostics by cytopathologists and cytotechnologists. In this review, we initiated an internet search using the keyword 'liquid-based cytology', and we conducted a literature review to discuss the usefulness of combined diagnosis of LBC and CP, immunocytochemistry and molecular testing and assessed the quality of nucleic acids in diagnostic LBC. High-quality and cell-rich diagnostic LBC surpassed the CP method alone in terms of reliability and versatility of ancillary testing in cytological diagnosis. Conclusively, diagnostic LBC lends itself to various new technologies and is expected to continue evolving with innovations in the future., (© 2024 John Wiley & Sons Ltd.)

Cytopathology represents a well established diagnostic approach because of its limited cost, reliability, and minimal invasiveness with respect to other methodologies. The evolving complexity of the different classifications systems and the implementation of ancillary techniques to refine the diagnosis is progressively helping in the risk of malignancy stratification, and the adoption of next-generation sequencing techniques contributes to enrich this valuable tool with predictive information, which is always more essential in the tailored medicine era. The recent introduction of digital and computational pathology is further boosting the potentialities of cytopathology, aiding in the interpretation of samples to improve the cost effectiveness of large screening programs and the diagnostic efficiency within intermediate/atypical categories. Moreover, the adoption of artificial intelligence tools is promising to complement molecular investigations, representing a stimulating perspective in the cytopathology field. In this work, the authors tried to summarize the multifaceted nature of this complex and evolving field of pathology, synthesizing the most recent advances and providing the young pathologists' perspective on this fascinating world., (© 2024 American Cancer Society.)

Introduction: The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories., Materials and Methods: The  Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM., Results: A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies., Conclusion: This study demonstrates the high specificity and ROM for 'malignant' and 'suspicious for malignancy' categories in the TIS reporting system and highlights the modest negative predictive value for the 'negative for malignancy' category. Although Tissue biopsies are usually considered as 'gold standard', any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making., (© 2024 John Wiley & Sons Ltd.)

The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses., (© 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.)

Background: Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies., Methods: Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed., Results: A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies., Conclusion: Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types., (© 2024 Wiley Periodicals LLC.)

Cerebrospinal fluid (CSF) cytology of primary central nervous system lymphoma arising in the immune deficiency/dysregulation setting (IDD-PCNSL) has not been described. This study presented a case of IDD-PCNSL-DLBCL, a GCB phenotype who was successfully diagnosed by CSF cytology in conjunction with ICC, ISH, FCM and clinical information., (© 2024 John Wiley & Sons Ltd.)

Introduction: Salivary gland neoplasm of uncertain malignant potential (SUMP) is an important diagnostic category of the Milan System for reporting salivary gland cytology (MSRSGC). Further subcategorization by cytomorphologic subtypes has been recommended to risk-stratify cases. In this study, our institutional experience with the risk of neoplasm (RON) and risk of malignancy (ROM) based on cytomorphologic subcategorization of SUMP is reported. We also report the prevalence of malignancy (POM) at our institution., Methods: The pathology database was queried for cases of fine-needle aspiration (FNA) diagnosed as SUMP along with follow-up at our institution from 2018-February 2024. This study was approved by an institutional review board., Results: Of 1159 cases of salivary gland FNA specimens reported as per MSRSGC at our institution, 14.8% (171/1159 cases) were diagnosed as SUMP, with these reports verified by at least 16 cytopathologists. Surgical follow-up was available for 139/171 (81.3%) of these cases, for which the original cytomorphologic subgroups were as follows: 65 (46.8%) basaloid, 48 (34.5%) oncocytic/oncocytoid, 14 (10.1%) myoepithelial, 9 (6.5%) other, 2 (1.4%) clear cell, and 1 (0.7%) mucinous. The POM within SUMP at our institution is within a range of 29.8%-36.7%. When considering all cases, our institutional RON for SUMP was 97.8% (136/139), and the ROM was 36.7% (51/139). Notably, a significant portion of cases (36%, 50/139) underwent review at a daily intradepartmental consensus conference. Analysis revealed that SUMP cases that underwent consensus review had a ROM of 46% (23/50), versus 31.5% (28/89) in independently verified cases (p = .13). Of the cytomorphologic subgroups, basaloid SUMP in particular was more likely to be benign on resection when the case had been independently verified than after consensus review (p = .0082). When considering only the independently verified cases, the ROM for each subgroup was as follows: 38.7% (12/31) in oncocytic/oncocytoid, 20% (9/45) in basaloid, 33.3% (2/6) in myoepithelial, 60% (3/5) in "other", and 100% (1/1) in both mucinous and clear cell (p = .0407)., Conclusion: While the RON is high across all cytomorphologic subgroups of SUMP, the ROM does vary across the groups, with basaloid cytomorphology having the lowest ROM. This effect is seen in independently verified cases but not in cases having undergone consensus review., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Context: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system., Aims: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters., Materials and Methods: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated., Results: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system., Conclusion: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases., (© 2024 John Wiley & Sons Ltd.)

Objective: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice., Patients and Methods: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test., Results: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result., Conclusion: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: The specific aims of the study are to assess whether answer changing on a high-stakes cytomorphology examination will lower the cytology examinees' scores and to examine whether there is a difference in the frequency of responses changed between high-, average-, and low-performing cytology learners. The paper also seeks to explore if there is a correlation between outcomes of answer changes (success rates) and cytology learner's levels of performance., Materials and Methods: The eraser marks and pen cross-outs on the cytology final image examinations from 2019-2023 were reviewed and the number of changes made by the examinees and the frequency to which scores were raised or lowered as a result was recorded. Moreover, the response change patterns and outcomes across low-, medium-, and high-performing cytology learners were further analyzed for possible relationships., Results: Among the total number of questions where answer(s) were changed (n = 98), close to half (n = 47, 48.0%) of the changes resulted in raising the score, compared with about one-third (n = 34, 34.7%) that lowered it. When the students were classified into academic abilities, there was a significant correlation between the success rates of answers changed across low-, medium-, and higher-performing learners χ 2 (df = 24, n = 24) = 10.24, P < 0.05. Our data also showed the average student group to have the highest "scores raised" to "scores lowered" ratio., Conclusions: Based on these findings, those cytology examinees who are overly cautious about changing initial responses during a high-stake multiple-choice question BOC test may put themselves at a disadvantage., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A standardized reporting system for bone and soft tissue tumor cytopathology has not yet been established. The objective of this study was to explore the potential utility of a classification modified from the Milan System for Salivary Gland Cytopathology and compared it with the upcoming World Health Organization (WHO) system for fine-needle aspiration of soft tissue lesions., Methods: The authors reviewed 285 cytology cases of bone/joint (n = 173) and soft tissue (n = 112) lesions, scoring each within diagnostic categories. The results were compared with histologic diagnoses and the risk of malignancy (ROM) for each category, and diagnostic reliability was analyzed., Results: All 285 cases were successfully classified into one of the following categories: nondiagnostic (6.3%), non-neoplastic (11.9%), atypia of uncertain significance (11.9%), benign neoplasm (5.6%), bone and soft tissue neoplasm of uncertain malignant potential (25.3%), suspicious for malignancy (1.4%), and malignant (37.5%). The ROM was 44.4% (eight of /18 cases) in nondiagnostic, 0% (zero of 34 cases) in non-neoplastic, 32.4% (11 of 34 cases) in atypia of uncertain significance, 0% (zero of 16 cases) in benign neoplasm, 16.7% (12 of 72 cases) in bone and soft tissue neoplasm of uncertain malignant potential, 75.0% (three of four cases) in suspicious for malignancy, and 100% (107 of 107 cases) in malignant categories. Using the WHO system, the proportion and ROM of the benign category (non-neoplastic and benign neoplasm) was 17.5% and 0%, respectively. Among benign and malignant lesions, the diagnostic accuracy, sensitivity, and specificity for detecting malignancy were 99.4%, 100%, and 98.0%, respectively., Conclusions: The modified Milan system as well as the WHO system may be a useful cytopathologic classification tool for both bone and soft tissue lesions., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Endoscopic ultrasound guide fine needle biopsy (EUS-FNB) is the main diagnostic tool for pancreatic adenocarcinoma. In most instances, only histology is obtained via FNB, without sending cytological slides. The aim of our study was to assess the additive diagnostic yield of cytology performed through FNB., Methods: We conducted a retrospective study of all patients with histological diagnosis of pancreatic adenocarcinoma who were diagnosed by EUS-FNB., Results: Overall, 80 patients were included in the study period. The overall concordance between cytology and histology all FNB needles was 78.2%. Notably, cytological assessment improved the diagnostic yield for malignancy by 12.8%. The overall kappa coefficient correlation between histology and cytology was .501, 95% CI 0.361-0.641. However, the kappa correlation for suspicious of malignancy and malignant was excellent of .872, 95% CI 0.733-1, suggesting that cytology is crucial when histology is inconclusive. Further analysis showed that the Acquire and Sharkcore needles outperformed the Procore needle in term of concordance between cytology and histology (kappa correlation of .527, 95% CI 0.331-0.724, .515, 95% CI 0.265-0.764, and .297, 95% CI -0.051-0.646), respectively., Conclusion: Performing cytology specimen when using FNB improves the diagnostic yield in pancreatic adenocarcinoma., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Background: Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy., Methods: We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015-2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis., Results: The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%., Conclusion: Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid., (© 2024 John Wiley & Sons Ltd.)

Introduction: Compared to urothelial carcinomas (UCs), the cytomorphology of renal cell carcinomas (RCCs) is underdescribed. This study aims to investigate whether UCs and RCCS of the upper urinary tract can be differentiated cytologically, and to identify distinguishing cytomorphological features., Methodology: Consecutive urine cytology specimens with atypical/C3, suspicious/C4 or malignant/C5 diagnoses matched with a nephrectomy or ureterectomy specimen with UC or RCC over a 15-year period were reviewed for cellularity, architecture, background composition and cytomorphologic features., Results: Totally 132 specimens were retrieved, comprising 24 RCCs and 108 UCs. Clear cell RCC (CCRCC) (n = 18) was the most common RCC. Urine cytology specimens from UC showed a trend of higher cellularity (p = 0.071) against RCC and was significant in subgroup analysis with CCRCC (p < .001). Epithelial structures in sheets, tubules, and papillae were exclusive in specimens of UC (p < .05). For background features, squamous cells were more common for RCC (p = .006) including CCRCC (p = .003), whereas polymorphs (p = .011) and necrotic material (p = .010) were associated with UC. Average nuclear size was larger and nuclear size variation (p < .001) and nuclear-cytoplasmic ratio (p = .001) were greater in UC (p = .001) than RCC. Comparing RCC to high-grade UCs only, nuclear-cytoplasmic ratio maintained statistical significance (p = .006) while average nuclear size showed a trend (p = .063)., Conclusion: A clean background free of tumor necrosis and polymorphs, and the lack of complex tumor fragments favors RCC. UCs also display larger nuclear size, higher nuclear size variation and nuclear-cytoplasmic ratio. These cytomorphological features with corroboration of clinical/radiological findings, can aid in raising a diagnosis of RCC., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

To address the background-bias problem in computer-aided cytology caused by microscopic slide deterioration, this article proposes a deep learning approach for cell segmentation and background removal without requiring cell annotation. A U-Net-based model was trained to separate cells from the background in an unsupervised manner by leveraging the redundancy of the background and the sparsity of cells in liquid-based cytology (LBC) images. The experimental results demonstrate that the U-Net-based model trained on a small set of cytology images can exclude background features and accurately segment cells. This capability is beneficial for debiasing in the detection and classification of the cells of interest in oral LBC. Slide deterioration can significantly affect deep learning-based cell classification. Our proposed method effectively removes background features at no cost of cell annotation, thereby enabling accurate cytological diagnosis through the deep learning of microscopic slide images., (© 2024. The Author(s).)

Objective: Over the past decade, liquid-based cytology has replaced conventional cytology for cervical cancer screening in many countries, including Japan. We aimed to evaluate the efficacy of liquid-based cytology using a large database and compare two major liquid-based cytology platforms, SurePath and ThinPrep, to conventional cytology., Methods: Cervical cancer screening data were collected from the Japan Cancer Society between 2015 and 2019. The efficacy of liquid-based and conventional cytology in detecting cervical intraepithelial neoplasia (CIN) was evaluated. Detection rates and positive predictive values were compared using a Poisson regression model., Results: We collected data of 3,918,149 participants, including 2,248,202 conventional cytology, 874,807 SurePath and 795,140 ThinPrep smears. The detection rate of CIN2 or more was 1.14 times higher using SurePath than that using conventional cytology (95% confidence interval [CI], 1.09-1.20; p < 0.001). Contrastingly, the detection rate of CIN2 or more was 0.91 times lower using ThinPrep (95% CI, 0.86-0.96; p < 0.001). The detection rates of CIN3 or more did not differ significantly between SurePath and conventional cytology (detection rate ratio, 1.04; 95% CI, 0.97-1.12; p = 0.224). The positive predictive value ratios of CIN2 or more were 0.80 using SurePath (95% CI, 0.76-0.84; p < 0.001) and 0.83 using ThinPrep (95% CI, 0.79-0.87; p < 0.001) compared with conventional cytology., Conclusions: Liquid-based cytology, particularly SurePath, was useful for detecting CIN2 or higher in population-based cervical cancer screening. Further widespread use of liquid-based cytology methods would lead to efficient detection of cervical precancerous lesions., (© 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.)

In recent years, technological innovation have emerged to standardize pathology laboratory processes and reduce the handling of diagnostic samples. Among them is an automatic tissue embedding system that eliminates the need for manual activity in tissue paraffin embedding, thereby improving sample preservation. Unfortunately, this system cannot be used for cytological specimens due to the lack of an effective holder to support the procedure steps. In this study, we evaluated the performance of a commercial polymer matrix to enable and standardize the automatic paraffin embedding of cytological material from different organs and sources. Cytological samples from 40 patients were collected on the matrices and submitted for fully automatic workflow preparation, from formalin fixation until paraffin block, using the Sakura embedding system. Our results demonstrated the feasibility of the automated procedure, from loading cytological sample onto the matrix to obtaining the paraffin cellblock, thereby avoiding manual manipulation of cellular material. All samples resulted adequately processed and paraffin-embedded showing satisfactory tissue permeation by processing reagents, optimal preservation of cytoplasmic and nuclear details, and good quality of staining results on paraffin sections. Automated embedding of cytological samples eliminates the risk of lost specimens, reduces laboratory burden, standardizes procedures, increases diagnostic yield, and ultimately improves patients' management., (© 2024 Wiley Periodicals LLC.)

Computer-assisted diagnosis (CAD) plays a key role in cancer diagnosis or screening. Whereas, current CAD performs poorly on whole slide image (WSI) analysis, and thus fails to generalize well. This research aims to develop an automatic classification system to distinguish between different types of carcinomas. Obtaining rich deep features in multi-class classification while achieving high accuracy is still a challenging problem. The detection and classification of cancerous cells in WSI are quite challenging due to the misclassification of normal lumps and cancerous cells. This is due to cluttering, occlusion, and irregular cell distribution. Researchers in the past mostly obtained the hand-crafted features while neglecting the above-mentioned challenges which led to a reduction of the classification accuracy. To mitigate this problem we proposed an efficient dual attention-based network (CytoNet). The proposed network is composed of two main modules (i) Efficient-Net and (ii) Dual Attention Module (DAM). Efficient-Net is capable of obtaining higher accuracy and enhancing efficiency as compared to existing Convolutional Neural Networks (CNNs). It is also useful to obtain the most generic features as it has been trained on ImageNet. Whereas DAM is very robust in obtaining attention and targeted features while negating the background. In this way, the combination of an efficient and attention module is useful to obtain the robust, and intrinsic features to obtain comparable performance. Further, we evaluated the proposed network on two well-known datasets (i) Our generated thyroid dataset (ii) Mendeley Cervical dataset (Hussain in Data Brief, 2019) with enhanced performance compared to their counterparts. CytoNet demonstrated a 99% accuracy rate on the thyroid dataset in comparison to its counterpart. The precision, recall, and F1-score values achieved on the Mendeley Cervical dataset are 0.992, 0.985, and 0.977, respectively. The code implementation is available on GitHub. https://github.com/naveedilyas/CytoNet-An-Efficient-Dual-Attention-based-Automatic-Prediction-of-Cancer-Sub-types-in-Cytol., (© 2024. The Author(s).)

Aims: The international system for reporting serous fluid cytopathology (ISRSFC) set forth a five-tiered reporting system with comprehensive validation on pleural and peritoneal fluid cytology. An algorithmic approach for cytomorphological assessment and immunocytochemistry was also described in ISRSFC. Limited data on pericardial fluid are supportive but would benefit from further investigation., Methods: Consecutive pericardial fluid cytology over a 4-year period was reviewed by multiple board-certified pathologists according to the ISRSFC. Cytomorphology and immunocytochemistry were assessed sequentially, with respective diagnostic performances computed and compared. Literature review was performed., Results: In total 358 specimens, including 53 with immunocytochemistry available, were reviewed. There were 137 benign and 221 malignant (MAL) cases. The risks of malignancy were 23.5% non-diagnostic (ND), 29.2% negative for malignancy (NFM), 56.0% atypia of undetermined significance (AUS), 82.6% suspicious for malignancy (SFM) and 99.2% (MAL) for cytomorphological assessment, improving to 23.5% (ND), 29.1% (NFM), 56.8% (AUS), 78.9% (SFM) and 99.3% (MAL) incorporating immunocytochemistry. Ten cases (2.8%) received a change in diagnosis after review of immunocytochemistry. All revisions of diagnostic category were appropriate upgrades/downgrades referenced against clinical information. Cytomorphological typing was accurate for adenocarcinoma (n=81/83, 97.6%), while other carcinomas and lymphomas required immunocytochemistry. Certain subcategories within AUS and SFM pertaining to bland indeterminate epithelial cells or mucinous material were not seen for pericardial fluid., Conclusions: The ISRSFC shows robust diagnostic performance for pericardial fluid cytology. For pericardial effusion, disease composition and applicable cytological subcategories differ from its peritoneal and pleural counterparts. Incorporating immunocytochemistry by an algorithmic approach improves diagnostic accuracy. Cytomorphology is accurate for identifying adenocarcinomas, but further typing necessitates immunocytochemistry is necessary., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Angiosarcoma, a very rare malignant tumor constituting 2%-4% of soft tissue sarcomas, manifest in diverse organs including skin, soft tissues, and bones. Histologically, angiosarcoma presents a wide range of morphologies, with epithelioid angiosarcoma (EAS) resemblance to carcinoma. The difficulty arises from the shared epithelial-like morphology and expression of epithelial markers in immunohistochemistry., Case: This study reports a case where EAS diagnosis was achieved through a combination of gross findings in a lung resection sample, imprint cytology, and immunocytochemistry. Imprint cytology revealed clusters of epithelioid cells, while immunocytochemistry showed positive results for CD31, ERG, Fli-1, and AE1/AE3, proving instrumental in diagnosing EAS. The described immunocytochemical protocol facilitates prompt diagnosis exclusively through cytology samples., Conclusion: This report emphasizes the potential for diagnosing EAS using cytological specimens, which is especially useful in cases where obtaining tissue samples proves challenging., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

This study conducts the first meta-analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords "(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)". Articles underwent risk of bias assessment using the QUADAS-2 tool. After excluding inadequate samples, a meta-analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross-sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the "atypical and higher risk categories" considered positive were 77% (95% confidence interval [CI], 68%-84%) and 95% (95% CI, 93%-97%) respectively. For the "suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 57% (95% CI, 49%-65%) and 100% (95% CI, 99%-100%) respectively. Sensitivity and specificity for the "malignant" category considered positive for malignancy were 70% (95% CI, 60%-77%) and 99% (95% CI, 98%-99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta-analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy., (© 2024 American Cancer Society.)

Our study compared the diagnostic accuracy of the 10% alcohol-formalin cell-block (CB) technique against traditional smears (CS) in serous effusions over 1 year. CB outperformed CS by detecting 7 missed cases and diagnosing 177 benign, 5 suspicious and 26 malignant cases compared to CS's 180 benign, 9 suspicious and 19 malignant cases. Using histopathology as a gold standard, CB showed a sensitivity of 96.4%, specificity of 98.3% and diagnostic accuracy of 98.1%, significantly higher than CS's 79.3% sensitivity, specificity of 97.7% and 95.2% accuracy. Using a 10% alcohol-formalin method, CB also excelled in cytomorphological characterization, especially in background elements, cellularity and cellular architecture. CB offered improved diagnostic accuracy and allowed extra sections for additional tests. In resource-constrained settings, combining CS and CB enhances cytological assessment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Fine-needle aspiration cytology (FNAC) is widely utilized for thyroid lesion diagnosis but faces challenges such as sample inadequacy and overlapping cytological features. This study examines how accurately these patterns correlate with histopathological diagnoses, shedding light on FNAC's limitations and diagnostic potential., Aims: To study the application of the architectural pattern of follicular cells in the interpretation of thyroid lesions and to demonstrate the diagnostic accuracy (DA) of FNAC., Settings and Design: Cross-sectional study carried over 1 year., Subjects and Methods: A total of 110 cases were reviewed by the cytopathologists. The prominent follicular cell architecture, namely macrofollicular, microfollicular, papillary, trabecular, three-dimensional clusters, and dispersed cells, was described in each case. In addition to these patterns, cellular morphology and background features were also noted, and a final cytological diagnosis was established. The cytology diagnosis was correlated with the histopathological diagnosis., Statistical Analysis Used: Sensitivity, specificity, positive predictive value, negative predictive value, DA of FNAC in diagnosing nonneoplastic and neoplastic lesions., Results: Macrofollicular pattern was seen in 80.26% of colloid goiter cases. Microfollicular pattern was observed in 72.2% of follicular neoplasm. About 62.5% of papillary thyroid carcinomas showed a papillary pattern. The trabecular pattern was seen in 42.86% of chronic lymphocytic thyroiditis and 16.67% of follicular neoplasms. The sensitivity and specificity of FNAC in diagnosing neoplastic lesions was 92.59% and 97.59%, respectively., Conclusions: FNAC is a simple, rapid, definite, and cost-effective primary diagnostic tool for thyroid evaluation. Cell architecture pattern is a simple and appropriate approach that complements cell morphology and background details in arriving at the final cytological diagnosis of thyroid lesions., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: Molecular testing of thyroid nodules is an essential tool to help risk stratify nodules with indeterminate cytology. Although ThyroSeq testing has been around for over a decade, there is a paucity of long-term follow-up data on cytologically indeterminate nodules that are determined to be molecularly negative or low-risk. The objective of this study is to assess the outcomes of nodules with indeterminate cytology (Bethesda III or IV) and negative or low-risk ThyroSeq results., Methods: This is a single academic institution retrospective cohort study. Patients with at least one thyroid nodule sampled with fine-needle aspiration who underwent ThyroSeq testing from 2012 to 2018 and had negative or low-risk ThyroSeq results on a cytologically indeterminate sample (n = 159 patients, 167 nodules) were included in the study. Outcomes include the false-negative rate and negative predictive value of each test version, as well as follow-up length for each nodule., Results: There were 159 patients with a mean age of 58 years (7-84 years) included in this study; the majority were female (81.8%). The mean follow-up was 4.0 years. Of 167 nodules, three were found to be malignant on resection (1.8%). The negative predictive value for the entire cohort was 98.2% and it was 89.3% for the surgical series., Conclusion: ThyroSeq testing has good negative predictive value and can help risk stratify cytologically indeterminate nodules. Routine follow-up allows for safe monitoring of nodules for features suggestive of malignancy., (© 2024 American Cancer Society.)

Background: The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category., Methods: An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems., Results: In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival., Conclusions: The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management., (© 2024 American Cancer Society.)

Background: The objective of this study was to evaluate the diagnostic performance of the category atypia of undetermined significance (AUS) at the authors' institution based on the Milan System for Reporting Salivary Gland Cytopathology., Methods: All AUS cases diagnosed at Fimlab Laboratories between January 1, 2018, and December 31, 2022, were included. Histologic verifications were checked until May 31, 2023. The upper-bound and lower-bound risk of malignancy and risk of neoplasm were calculated. The timelines between the pathology laboratory workflow and patient management were also calculated., Results: From 1157 fine-needle aspirations (FNAs), 162 (14.0%) AUS cases were diagnosed in 146 patients, with an average ± standard deviation age of 66.1 ± 14.9 years. There was variation in the AUS percentages, with higher values during the coronavirus disease 2019 pandemic years (15% and 17.5% in 2020 and 2021, respectively). Seventy-five cases (46.3%) had histologic follow-up: 16 were malignant neoplasms, and 36 were benign neoplasms. The upper and the lower bounds of the-risk of malignancy and risk of neoplasm were 21.3% and 69.3% and 9.9% and 32.1%, respectively. The average time from the first FNA with an AUS diagnosis to surgical resection ranged from 6 to 682 days, and the time to the first repeat FNA ranged from 10 to 691 days., Conclusions: The results indicated higher percentages of AUS cases compared with the reference value, which may be attributed to the impact of the coronavirus disease 2019 pandemic. The risk of malignancy calculated in this study was closer to the reference value from the first edition of the Milan System for Reporting Salivary Gland Cytopathology compared with the second edition., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave-enhanced multi-view acoustofluidic rotation cytometry (MARC) technique is developed for pre-cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi-angle observations and amplifies subtle cell differences, particularly in the nuclear-to-cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC-screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance., Materials and Methods: Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record., Results: A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4-13 mL; range, 1-800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p = .175)., Conclusions: CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Previous studies have shown that rapid on-site evaluation (ROSE) improves the diagnostic yield of bronchoscopy using endobronchial ultrasound with a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPL). While ROSE of imprint cytology from forceps biopsy has been widely discussed, there are few reports on ROSE of brush cytology. This study investigated the utility of ROSE of brush cytology during bronchoscopy. We retrospectively analyzed data from 214 patients who underwent bronchoscopy with EBUS-GS for PPL. The patients in the ROSE group had significantly higher diagnostic sensitivity through the entire bronchoscopy process than in the non-ROSE group (96.8% vs. 83.3%, P = 0.002). The use of ROSE significantly increased the sensitivity of brush cytology with Papanicolaou staining (92.9% vs. 75.0%, P < 0.001). When ROSE was sequentially repeated on brushing specimens, initially negative ROSE results converted to positive in 79.5% of cases, and the proportion of specimens with high tumor cell counts increased from 42.1 to 69.0%. This study concludes that ROSE of brush cytology improves the diagnostic accuracy of bronchoscopy and enhances specimen quality through repeated brushing., (© 2024. The Author(s).)

Background: Prognostic implications of peritoneal washing cytology (CY) in patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing surgical resection following preoperative chemoradiotherapy (CRT) remain unclear. This study aimed to elucidate the prognostic significance and predictors of a positive CY status (CY+) after preoperative CRT., Methods: Clinical data from 141 patients with localized PDAC who underwent curative-intent resection after preoperative CRT were retrospectively analyzed to examine the association between CY+ and clinicopathological factors and survival., Results: CY+ was observed in six patients (4.3%). The CY+ group exhibited significantly higher preoperative serum levels of CA19-9 and a substantially greater incidence of tumor location in the pancreatic body or tail, along with pathological invasion to the anterior pancreatic capsule, than the CY- group. The CY+ group had a significantly higher incidence of peritoneal recurrence compared with the CY- group (83.3% vs. 18.5%, p = 0.002). Overall survival (OS) and recurrence-free survival (RFS) after surgery were significantly shorter in the CY+ group than in the CY- group (CY+ vs. CY-: 18.3 vs. 46.2 months, p = 0.001, and 8.9 vs. 17.7 months, p = 0.009, respectively). Multivariate analyses identified CY+ as an independent prognostic factor for worse OS (hazard ratio 5.00, 95% confidence interval 1.03-12.31) and RFS (hazard ratio 2.58, 95% confidence interval 1.04-6.43). Local invasion grade on imaging before CRT, limited histological response to CRT, and absence of adjuvant chemotherapy were independent predictors of worse OS and RFS., Conclusion: Despite the relatively low incidence of CY+ after preoperative CRT, it emerged as an independent prognostic factor in patients with localized PDAC undergoing curative-intent resection following preoperative CRT., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yuge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force., Materials and Methods: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed., Results: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice., Conclusions: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The practice of cytopathology has been significantly refined in recent years, largely through the creation of consensus rule sets for the diagnosis of particular specimens (Bethesda, Milan, Paris, and so forth). In general, these diagnostic systems have focused on reducing intraobserver variance, removing nebulous/redundant categories, reducing the use of "atypical" diagnoses, and promoting the use of quantitative scoring systems while providing a uniform language to communicate these results. Computational pathology is a natural offshoot of this process in that it promises 100% reproducible diagnoses rendered by quantitative processes that are free from many of the biases of human practitioners., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Over the last decade, cancer diagnostics has undergone a notable transformation with increasing complexity. Minimally invasive diagnostic tests, driven by advanced imaging and early detection protocols, are redefining patient care and reducing the need for more invasive procedures. Modern cytopathologists now safeguard patient samples for vital biomarker and molecular testing. In this article, we explore ancillary testing modalities and the role of biomarkers in organ-specific contexts, underscoring the transformative impact of precision medicine. Finally, the advent of more than 80 Food and Drug Administration-approved predictive biomarkers signals a new era, guiding cancer care toward personalized and targeted strategies., Competing Interests: Acknowledgments Author DBA and this manuscript were supported by the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558). Disclosure The other authors have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Thoracic cytology can be challenging due to limited procured material or overlapping morphology between benign and malignant entities. In such cases, expert consultation might be sought. This study aimed to characterize all pulmonary and pleural cytology consult cases submitted to our practice and provide recommendations on approaching difficult cases., Materials and Methods: All thoracic (pulmonary and pleural) cytology cases submitted for expert consultation to the University of Michigan (MLabs) from 2013 to mid-2022 were reviewed. Cases where cytology was only part of a hematopathology or surgical pathology consult were excluded. Patient demographics, specimen location, procedure performed, referring diagnosis, and our diagnoses were recorded for each case. Diagnoses were categorized according to the Papanicolaou Society of Cytopathology recommendations for pulmonary and effusion cytology. Discordant diagnoses were stratified as major or minor. Data was analyzed using chi-square analysis and logistic models., Results: We received 784 thoracic cytology consult cases, including 530 exfoliative samples and 307 fine-needle aspirations. The most common anatomic locations sampled were the bronchial wall (n = 194, 23%), lung nodule (n = 322, 38%), and pleura (n = 296, 35%). 413 cases had a diagnostic discrepancy (48.3%), with 274 (66%) minor and 139 (34%) major discrepancies. By location, pleural effusion specimens had the highest probability of a discrepant diagnosis (P = 0.003). By specimen type, fine-needle aspiration samples were more likely to have a discrepant diagnosis (P = 0.09), approaching significance., Conclusion: Nearly half of the thoracic cytology cases submitted for expert second opinion had diagnostic discrepancies. Consequently, consulting a tertiary medical care center with cytopathology expertise for challenging thoracic cytology diagnoses is beneficial., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)