Advances in diagnostic liquid-based cytology.

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.

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study.

BACKGROUND: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019. METHODS: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. RESULTS: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. CONCLUSION: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Papillary glioneuronal tumors: Distinctive cytological characteristics and cyto-histologic correlation.

Intraoperative cytological examination and cyto-histologic correlation of papillary glioneuronal tumors have rarely been described in detail in the literature. A 23-year-old female presented at our institution with seizure-like activity, and a 3.0 cm left temporal lobe hypoattenuating lesion. She was accurately diagnosed with papillary glioneuronal tumor on Intraoperative cytology. The patient subsequently proceeded to stealth-guided awake left temporal craniotomy, confirming the diagnosis. In this article, we present a detailed report of papillary glioneuronal tumor (extremely rare central nervous system neoplasm) describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature.

The cytopathologist's role in developing and evaluating artificial intelligence in cytopathology practice.

Artificial intelligence (AI) technologies have the potential to transform cytopathology practice, and it is important for cytopathologists to embrace this and place themselves at the forefront of implementing these technologies in cytopathology. This review illustrates an archetypal AI workflow from project conception to implementation in a diagnostic setting and illustrates the cytopathologist's role and level of involvement at each stage of the process. Cytopathologists need to develop and maintain a basic understanding of AI, drive decisions regarding the development and implementation of AI in cytopathology, participate in the generation of datasets used to train and evaluate AI algorithms, understand how the performance of these algorithms is assessed, participate in the validation of these algorithms (either at a regulatory level or in the laboratory setting), and ensure continuous quality assurance of algorithms deployed in a diagnostic setting. In addition, cytopathologists should ensure that these algorithms are developed, trained, tested and deployed in an ethical manner. Cytopathologists need to become informed consumers of these AI algorithms by understanding their workings and limitations, how their performance is assessed and how to validate and verify their output in clinical practice.

Current state of whole slide imaging use in cytopathology: Pros and pitfalls.

Whole slide imaging (WSI) allows generation of large whole slide images and their navigation with zoom in and out like a true virtual microscope. It has become widely used in surgical pathology for many purposes, such as education and training, research activity, teleconsultation, and primary diagnosis. However, in cytopathology, the use of WSI has been lagging behind histology, mainly due to the cytological specimen's characteristics, as groups of cells of different thickness are distributed throughout the slide. To allow the same focusing capability of light microscope, slides have to be scanned at multiple focal planes, at the cost of longer scan times and larger file size. These are the main technical pitfalls of WSI for cytopathology, partly overcome by solutions like liquid-based preparations. Validation studies for the use in primary diagnosis are less numerous and more heterogeneous than in surgical pathology. WSI has been proved effective for training students and successfully used in proficiency testing, allowing the creation of digital cytology atlases. Longer scan times are also a barrier for use in rapid on-site evaluation, but WSI retains its advantages of easy sharing of images for consultation, multiple simultaneous viewing in different locations, the possibility of unlimited annotations and easy integration with medical records. Moreover, digital slides set the laboratory free from reliance on a physical glass slide, with no more concern of fading of stain or slide breakage. Costs are still a problem for small institutions, but WSI can also represent the beginning of a more efficient way of working.

Review of different platforms to perform rapid onsite evaluation via telecytology.

There is increased utilisation of cytopathology to provide a rapid onsite evaluation (ROSE) of fine needle aspiration and touch preparations of small biopsies. A well-executed ROSE procedure can significantly impact the diagnostic quality and appropriate specimen triage of procured biopsy materials. To accommodate the demand for ROSE, telecytology has been increasingly implemented to facilitate ROSE occurring remotely. Telecytology can be categorised based on camera systems including eyepiece system, camera port system and robotic microscope/whole slide image scanner system. Image sharing methods include static images, broadcast only live video streaming, teleconferencing and whole slide image management system. In this review, we will discuss the advantages and disadvantages of each of these systems and deployment considerations.

The utility of cell blocks for international cytopathology teleconsultation by whole slide imaging.

INTRODUCTION: Telecytology for second opinion consultation has largely been limited by technical issues, such as the inability to focus well on cellular material. Nevertheless, international telecytology consultation was undertaken at our institution with partners in China and Italy. To overcome issues with scanning cytology slides, we adopted a cell-block (CB) preference for teleconsultation. METHODS: Telecytology consultation cases received over a 7.5-year period were retrospectively reviewed. Cytology glass slides were scanned without Z-stacking using different whole slide scanners. For one referring site, only haematoxylin-eosin-stained CBs were scanned, as well as immunostains requested by consultants. For another host centre, aspirate smears were also scanned in some cases. RESULTS: A total of 51 non-gynaecological cases (44 CB only) were evaluated from 48 patients. The specimens included pleural fluids (19), pancreas (14), lymph nodes (6), peritoneal fluids (2) and miscellaneous samples (10). The cytological diagnoses spectrum included 16 (31.37%) cases positive for malignancy, 7 (13.72%) positive for neoplasm, 6 (11.76%) suspicious for malignancy, 10 (19.60%) atypical, 10 (19.60%) negative for malignancy and 2 (3.92%) non-diagnostic. In 42 (82.35%) cases, immunocytochemistry was requested. Turn-around-time ranged from 1.5 to 306 hours. CONCLUSIONS: Our experience shows that international telecytology for consultation purposes involving non-gynaecological cases is feasible. A second opinion interpretation was rendered in the majority (64.7%) of cases. Utilising CB only for cytology consultations by whole slide imaging solved focus issues that typically plague evaluation of cytology aspirate smears.

Impact of image analysis and artificial intelligence in thyroid pathology, with particular reference to cytological aspects.

OBJECTIVE: Thyroid pathology has great potential for automated/artificial intelligence algorithm application as the incidence of thyroid nodules is increasing and the indeterminate interpretation rate of fine-needle aspiration remains relatively high. The aim of the study is to review the published literature on automated image analysis and artificial intelligence applications to thyroid pathology with whole-slide imaging. METHODS: Systematic search was carried out in electronic databases. Studies dealing with thyroid pathology and use of automated algorithms applied to whole-slide imaging were included. Quality of studies was assessed with a modified QUADAS-2 tool. RESULTS: Of 919 retrieved articles, 19 were included. The main themes addressed were the comparison of automated assessment of immunohistochemical staining with manual pathologist's assessment, quantification of differences in cellular and nuclear parameters among tumour entities, and discrimination between benign and malignant nodules. Correlation coefficients with manual assessment were higher than 0.76 and diagnostic performance of automated models was comparable with an expert pathologist diagnosis. Computational difficulties were related to the large size of whole-slide images. CONCLUSIONS: Overall, the results are promising and it is likely that, with the resolution of technical issues, the application of automated algorithms in thyroid pathology will increase and be adopted following suitable validation studies.

Bladder Cancer Diagnosis and Follow-Up: The Current Status and Possible Role of Extracellular Vesicles.

Diagnostic methods currently used for bladder cancer are cystoscopy and urine cytology. Cystoscopy is an invasive tool and has low sensitivity for carcinoma in situ. Urine cytology is non-invasive, is a low-cost method, and has a high specificity but low sensitivity for low-grade urothelial tumors. Despite the search for urinary biomarkers for the early and non-invasive detection of bladder cancer, no biomarkers are used at the present in daily clinical practice. Extracellular vesicles (EVs) have been recently studied as a promising source of biomarkers because of their role in intercellular communication and tumor progression. In this review, we give an overview of Food and Drug Administration (FDA)-approved urine tests to detect bladder cancer and why their use is not widespread in clinical practice. We also include non-FDA approved urinary biomarkers in this review. We describe the role of EVs in bladder cancer and their possible role as biomarkers for the diagnosis and follow-up of bladder cancer patients. We review recently discovered EV-derived biomarkers for the diagnosis of bladder cancer.

Thyroid cytopathology: updates and molecular testing.

The utility of fine needle aspiration (FNA) is well described in the context of evaluating thyroid lesions. Among the various international systems of classification of thyroid cytology, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has also provided a sound framework to standardize the reporting of FNA cytology results. New molecular evidence and clinical studies demonstrated the need for revision of the nomenclature resulting in introduction of new categories, such as the noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Indeterminate thyroid cytology results pose a challenge for further management and the continued development of molecular markers may aid in the management of indeterminate thyroid lesions.

Cytodiagnostics in Pneumology - State of the Art 2019.

Pulmonary cytology represents one of the basic diagnostic methods in pneumopathology. It is primarily focused on: 1) assessment of biologic nature of the pathologic process (recommended terminology and classification according to the The Papanicolaou Society of Cytopathology guidelines, 2016), 2) typing of malignant tumors (according to the WHO Classification of Tumours of the Lung, 2015), 3) assessment of mediastinal and hilar lymph nodes (including preoperative staging), 4) attaining adequate material for ancillary testing, 5) bronchoalveolar lavage (BAL) differential cell count and cytopathology studies. The need for sufficient amount of material especially in tumour diagnostics in the era of targeted therapy/personalized medicine is increasing. In pneumocytology, the diagnostic yield is greatly improved by endobronchial ultrasound-guided (EBUS) fine-needle aspiration accompanied by rapid on-site evaluation (ROSE) provided by a cytopathologist. This process gives the possibility to carefully handle and triage the specimen for diagnostic procedures as well as specific ancillary studies. When carcinoma is suspected, both cytology and biopsy specimens should be obtained whenever possible and reviewed together to achieve the highest specificity and diagnostic concordance. If no histology sample is available, attaining adequate material in the cell block becomes crucial, as it enables to carry out immmunohistochemical methods and molecular genetic testing from cytology material. For optimal acquisition, processing and testing of limited specimens in pneumocytology, as well as in pulmonary histopathology, the key issue is to establish and operate a multidisciplinary team including a cytopathologist/surgical pathologist, radiologist and pulmonologist.

NASAL cytology: practical aspects and clinical relevance.

Nasal cytology is a simple and safe diagnostic procedure that allows to assess the normal and pathological aspects of the nasal mucosa, by identifying and counting the cell types and their morphology. It can be easily performed by a nasal scraping followed by May-Grunwald-Giemsa staining and optical microscopy reading. This procedure allows to identify the normal cells (ciliated and mucinous), the inflammatory cells (lymphocytes, neutrophils, eosinophils, mast cells), bacteria, or fungal hyphae/spores. Apart from the normal cell population, some specific cytological patterns can be of help in discriminating among various diseases. Viral infections, allergic rhinitis, vasomotor rhinitis and overlapping forms can be easily identified. According to the predominant cell type, various entities can be defined (named as NARES, NARESMA, NARMA). This implies a more detailed knowledge and assessment of the disease that can integrate the standard diagnostic procedures. Nasal cytology also represents a useful research tool for diagnosis and therapy.

The 'Morph'ology of cytotechnology education.

'Morph' means to change gradually and completely from one thing into another usually in a way that is surprising or seems magical. How can cytotechnology education be morphed into an expanded curriculum to teach new skills for advanced practice? The challenges cytotechnology programmes are facing today are many. The biggest of these challenges is the decreasing volume of Pap tests. Pap tests have been our 'bread and butter' throughout history; however, advances in health care and technology are inevitable, thus requiring changes in our educational practices. While these challenges seem insurmountable, we have the ability to expand the field of cytotechnology by taking advantage of existing opportunities. One example of these opportunities is performing rapid on site evaluation (ROSE) for specimen adequacy and perhaps taking it one step further by giving a preliminary diagnosis as a billable procedure. Now is the time to take gradual steps towards change in the current practice of cytotechnology. Let's join together and make the journey surprising and magical.

Education and training in cytology in Europe.

Education and training in cytology in Europe is hampered by the fact that there is no homogenous programme across Europe. This can be observed for (Cyto)Pathologists and Cytotechnologists. However, lack of workforce and lack of a pan-European Cytology diploma are decreasing motivation among junior staff to dedicate their professional interests to cytology. Cytology and histology are complementary approaches for the diagnosis or exclusion of disease in patients and there are many individual efforts of National Societies to maintain competencies in cytology by workshops, seminars, tutorials and congresses. Furthermore, professional organizations such as the European Federation of Cytology Societies (EFCS), the European Society of Pathology (ESP) and Union of European Medical Specialists (UEMS) - Section Pathology are working together in order to develop a pan-European Cytology diploma. The EFCS is part supported by EU funding in this endeavour. Activities are ongoing in the fields of training (Eurocytology) and examination (QUATE Aptitude Test - Quality Assurance, Training and Examination) or both (Cy-Test). Modern techniques such as Webatlas with teaching modules in cytology and Tele(cyto)pathology are more and more integrated in daily teaching activities resulting in standardization of cytology in Europe.

Training for cytotechnologists and cytopathologists in the developing world.

Currently there is a major challenge to train sufficient cytopathologists and cytotechnicians in developing countries that have poor medical and pathology infrastructure. Cytology requires well trained pathologists and laboratory staff but it needs only minimal laboratory resources. Cytology can provide the material for rapid, accurate and inexpensive diagnoses of infections such as tuberculosis and of benign and malignant palpable and impalpable lesions. Cytology can achieve this in the developing world by utilizing fine needle aspiration biopsy cytology, general fluids cytology and cervical cytology, in the same manner as is currently done in the developed world where cytology specimens are used to make cytomorphological diagnoses and increasingly to provide material for the full range of ancillary testing including molecular pathology. There are a number of ways to develop sustainable training in cytology in developing countries, especially in fine needle aspiration biopsy cytology, and these are presented and discussed.

Precision Medicine in Cytopathology.

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.

Urinary Tract Cytopathology: Current and Future Impact on Patient Care.

Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation.