The current state of digital cytology and artificial intelligence (AI): global survey results from the American Society of Cytopathology Digital Cytology Task Force.

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.

Editorial: Optimizing Schools of Cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

[Bethesda 2023: A new terminology for thyroid cytopathology]. / Bethesda 2023: nouvelle terminologie en cytopathologie thyroïdienne.

A third update of The Bethesda System for Reporting Thyroid Cytopathology has been published in 2023 following the first (2010) and second (2017) versions. The main modifications are the following 1) a new co-Editor, 2) 4 associate editors, 3 of them from Europe, 3) the inclusion of 65 co-authors, 19 of them from Europe, 4) 2 new chapters: one dealing with pediatrics thyroid cytopathology and the other one describing molecular cytopathology profiling, 5) updated risks of malignancy (ROM), 6) a terminology in line with the 2022 WHO classification of thyroid tumors, 7) diagnostic categories now defined by a unique name, 8) 2 subtypes in the "Atypia of Undetermined Significance" category with corresponding ROM.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardized reporting systems for nongynecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung, and more. In February 2018, the first edition Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of Non-Neoplastic, benign, and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, and updates in nomenclature. CONCISE SENTENCE: The second edition of the Milan System for Reporting Salivary Gland Cytopathology, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, updates in nomenclature, and a guide to the practical application of the latest ancillary markers for the diagnosis of selected salivary gland fine-needle aspiration cases.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardized reporting systems for non-gynecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung, and more. In February 2018, the first edition Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of non-neoplastic, benign, and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, and updates in nomenclature.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardised reporting systems for non-gynaecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung and more. In February 2018, the first edition of the Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of non-neoplastic, benign and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published, confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarising the use of salivary gland imaging, new advances in ancillary testing and updates in nomenclature.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Digital cytology part 1: digital cytology implementation for practice: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytopathology laboratory. However, peer-reviewed real-world data and literature are lacking regarding the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper presented herein is a review and offers best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the results of a global survey regarding digital cytology are highlighted.

Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytology laboratory. However, peer-reviewed real-world data and literature are lacking in regard to the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper is presented as a separate paper which details a review and best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper presented here provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the cytology global survey results highlighting current AI practices by various laboratories, as well as current attitudes, are reported.

Real-World Diagnostic Accuracy of the On-Site Cytopathology Advance Report (OSCAR) Procedure Performed in a Multidisciplinary One-Stop Breast Clinic.

Fine-needle aspiration (FNA) cytology has been widely used for the diagnosis of breast cancer lesions with the objective of differentiating benign from malignant masses. However, the occurrence of unsatisfactory samples and false-negative rates remains a matter of concern. Major improvements have been made thanks to the implementation of rapid on-site evaluation (ROSE) in multidisciplinary and integrated medical settings such as one-stop clinics (OSCs). In these settings, clinical and radiological examinations are combined with a morphological study performed by interventional pathologists. The aim of our study was to assess the diagnostic accuracy of the on-site cytopathology advance report (OSCAR) procedure on breast FNA cytologic samples in our breast OSC during the first three years (April 2004 till March 2007) of its implementation. To this goal, we retrospectively analyzed a series of 1820 breast masses (1740 patients) radiologically classified according to the American College of Radiology (ACR) BI-RADS lexicon (67.6% being either BI-RADS 4 or 5), sampled by FNA and immediately diagnosed by cytomorphology. The clinicoradiological, cytomorphological, and histological characteristics of all consecutive patients were retrieved from the hospital computerized medical records prospectively registered in the central information system. Histopathological analysis and ultrasound (US) follow-up (FU) were the reference diagnostic tests of the study design. In brief, we carried out either a histopathological verification or an 18-month US evaluation when a benign cytology was concordant with the components of the triple test. Overall, histology was available for 1138 masses, whereas 491 masses were analyzed at the 18-month US-FU. FNA specimens were morphologically nondiagnostic in 3.1%, false negatives were observed in 1.5%, and there was only one false positive (0.06%). The breast cancer prevalence was 62%. Diagnostic accuracy measures of the OSCAR procedure with their 95% confidence intervals (95% CI) were the following: sensitivity (Se) = 97.4% (96.19-98.31); specificity (Sp) = 94.98% (92.94-96.56); positive predictive value (PPV) = 96.80% (95.48-97.81); negative predictive value (NPV) = 95.91% (94.02-97.33); positive likelihood ratio (LR+) = 19.39 (13.75-27.32); negative predictive ratio (LR-) = 0.03 (0.02-0.04), and; accuracy = 96.45% (95.42-97.31). The respective positive likelihood ratio (LR+) for each of the four categories of cytopathological diagnoses (with their 95% CI) which are malignant, suspicious, benign, and nondiagnostic were 540 (76-3827); 2.69 (1.8-3.96); 0.03 (0.02-0.04); and 0.37 (0.2-0.66), respectively. In conclusion, our study demonstrates that the OSCAR procedure is a highly reliable diagnostic approach and a perfect test to select patients requiring core-needle biopsy (CNB) when performed by interventional cytopathologists in a multidisciplinary and integrated OSC setting. Besides drastically limiting the rate of nondiagnostic specimens and diagnostic turn-around time, OSCAR is an efficient and powerful first-line diagnostic approach for patient-centered care.

[Serous fluid cytopathology : International system: Ancillary studies for serous fluids and special considerations for peritoneal washings]. / Cytopathologie des séreuses : la classification internationale : À propos des techniques ancillaires prédictives et du cas particulier des lavages péritonéaux.

The International System for serous fluids cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. The exponential discovery of prognostic and theranostic molecular alterations in many cancers, particularly in advanced stages, led the authors to describe the indications and the feasibility of these new markers on cytological samples from serous effusions. The various immunocytochemistry techniques, FISH and those testing DNA and RNA are reported in regard to their ability to identify the main targets currently explored in routine practice. The vast majority of these crucial markers can be reliably tested on effusion fluids. The International System for serous effusion fluids also includes a chapter dedicated to peritoneal washings and the application of the classification to this particular type of sample. The objective is to "wash" the peritoneal cavity with a saline solution to unfix cells from the cavity's wall and collect those that have previously naturally detached. This procedure, performed before surgery of tumors and before any manipulation, allows a cytological analysis that specifies the staging of gynecological and non-gynecological tumors and excludes occult malignant cells in the presence of tumors appearing benign.

Digital Examination of LYmph node CYtopathology Using the Sydney system (DELYCYUS): An international, multi-institutional study.

BACKGROUND: After a series of standardized reporting systems in cytopathology, the Sydney system was recently introduced to address the need for reproducibility and standardization in lymph node cytopathology. Since then, the risk of malignancy for the categories of the Sydney system has been explored by several studies, but no studies have yet examined the interobserver reproducibility of the Sydney system. METHODS: The authors assessed interobserver reproducibility of the Sydney system on 85 lymph node fine-needle aspiration cytology cases reviewed by 15 cytopathologists from 12 institutions in eight different countries, resulting in 1275 diagnoses. In total, 186 slides stained with Diff-Quik, Papanicolaou, and immunocytochemistry were scanned. A subset of the cases included clinical data and results from ultrasound examinations, flow cytometry immunophenotyping, and fluorescence in situ hybridization analysis. The study participants assessed the cases digitally using whole-slide images. RESULTS: Overall, the authors observed an almost perfect agreement of cytopathologists with the ground truth (median weighted Cohen κ = 0.887; interquartile range, κ = 0.210) and moderate overall interobserver concordance (Fleiss κ = 0.476). There was substantial agreement for the inadequate and malignant categories (κ = 0.794 and κ = 0.729, respectively), moderate agreement for the benign category (κ = 0.490), and very slight agreement for the suspicious (κ = 0.104) and atypical (κ = 0.075) categories. CONCLUSIONS: The Sydney system for reporting lymph node cytopathology shows adequate interobserver concordance. Digital microscopy is an adequate means to assess lymph node cytopathology specimens.

The 2023 Bethesda System for reporting thyroid cytopathology.

Since the publication of the first edition in 2010, The Bethesda System for Reporting Thyroid Cytopathology has allowed cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations. The third edition builds on the success of the 2 earlier editions and offers several key updates. The most important is the assignment of a single name for each of the 6 diagnostic categories: (i) nondiagnostic; (ii) benign; (iii) atypia of undetermined significance; (iv) follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. Each of the categories has an implied risk of malignancy (ROM), which has been updated and refined based on data reported after the second edition. The third edition offers an average ROM for each category, in addition to the expected range of cancer risk. The atypia of undetermined significance subcategorization is simplified into 2 subgroups based on the implied ROM and molecular profiling. A discussion of pediatric thyroid disease has been added, and pediatric ROMs and management algorithms are discussed in the relevant sections. Nomenclature has been updated to align with the 2022 World Health Organization Classification of Thyroid Neoplasms. Two new chapters have been added: one that addresses the significant and expanded use of molecular and ancillary testing in thyroid cytopathology, and another that summarizes clinical perspectives and imaging findings in thyroid disease.

The 2023 Bethesda System for Reporting Thyroid Cytopathology.

Since the publication of the first edition in 2010, The Bethesda System for Reporting Thyroid Cytopathology has allowed cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations. The third edition builds on the success of the 2 earlier editions and offers several key updates. The most important is the assignment of a single name for each of the 6 diagnostic categories: (i) nondiagnostic; (ii) benign; (iii) atypia of undetermined significance; (iv) follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. Each of the categories has an implied risk of malignancy (ROM), which has been updated and refined based on data reported after the second edition. The third edition offers an average ROM for each category, in addition to the expected range of cancer risk. The atypia of undetermined significance subcategorization is simplified into 2 subgroups based on the implied ROM and molecular profiling. A discussion of pediatric thyroid disease has been added, and pediatric ROMs and management algorithms are discussed in the relevant sections. Nomenclature has been updated to align with the 2022 World Health Organization Classification of Thyroid Neoplasms. Two new chapters have been added: one that addresses the significant and expanded use of molecular and ancillary testing in thyroid cytopathology, and another that summarizes clinical perspectives and imaging findings in thyroid disease.

[Serous fluid cytopathology: International system]. / Cytopathologie des séreuses : la classification internationale.

The International System for Serous Fluid Cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. Five diagnostic categories are proposed associated to an increased rate of malignancy and specific cytological criteria. The categories are reported as: (I) Non-diagnostic (ND), the cells are insufficient for interpretation; (II) Negative for malignancy (NFM), only benign cells are present; (III) Atypia of undetermined significance (AUS), the cells present mild atypia more likely to be benign, but a malignant process cannot be definitively excluded; (IV) Suspicious for malignancy (SFM), the cells are present with atypia or in a number suspect of malignancy but with insufficient ancillary studies to give a positive malignant diagnosis; (V) Malignant (MAL), the cytological criteria are absolutely and definitively malignant. Malignant neoplasia can be primitive, it involves mesothelioma and serous lymphoma but most are secondary and correspond mainly to adenocarcinomas in adults and leukemia/lymphoma in children. The diagnostic should always be provided in the appropriate clinical context and be as definitive as possible. The ND, AUS and SFM are temporary or last intention categories. Immunocytochemistry in association with FISH or flow cytometry allow in most cases a conclusive diagnosis. These ancillary studies as well as ADN and ARN tests on effusion's fluids are particularly suited to give reliable theranostic results for personalized therapies.

Reference standards for gene fusion molecular assays on cytological samples: an international validation study.

AIMS: Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. METHODS: Cell lines harbouring EML4(13)-ALK(20) and SLC34A2(4)-ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. RESULTS: Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. CONCLUSIONS: Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.

Deep learning for fully-automated nuclear pleomorphism scoring in breast cancer.

To guide the choice of treatment, every new breast cancer is assessed for aggressiveness (i.e., graded) by an experienced histopathologist. Typically, this tumor grade consists of three components, one of which is the nuclear pleomorphism score (the extent of abnormalities in the overall appearance of tumor nuclei). The degree of nuclear pleomorphism is subjectively classified from 1 to 3, where a score of 1 most closely resembles epithelial cells of normal breast epithelium and 3 shows the greatest abnormalities. Establishing numerical criteria for grading nuclear pleomorphism is challenging, and inter-observer agreement is poor. Therefore, we studied the use of deep learning to develop fully automated nuclear pleomorphism scoring in breast cancer. The reference standard used for training the algorithm consisted of the collective knowledge of an international panel of 10 pathologists on a curated set of regions of interest covering the entire spectrum of tumor morphology in breast cancer. To fully exploit the information provided by the pathologists, a first-of-its-kind deep regression model was trained to yield a continuous scoring rather than limiting the pleomorphism scoring to the standard three-tiered system. Our approach preserves the continuum of nuclear pleomorphism without necessitating a large data set with explicit annotations of tumor nuclei. Once translated to the traditional system, our approach achieves top pathologist-level performance in multiple experiments on regions of interest and whole-slide images, compared to a panel of 10 and 4 pathologists, respectively.