Updates in head and neck cytopathology: Insights from European Congress of Pathology Short Course.

Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in Head and Neck Cytopathology Short Course ran during the 35th European Congress of Pathology held in Dublin, Ireland, in 2023 and brought together experts in cytopathology, pathology, and related fields to share their expertise and experience in the field of head and neck cytopathology and its future directions. Topics such as a one-stop clinic, the Milan System for Reporting Salivary Gland Cytopathology, next generation sequencing, and human papilloma virus detection in the head and neck area were covered during the short course. These topics are briefly summarized in the present review.

Pitfalls in Urinary Tract Cytopathology.

Urine cytopathology is a cost-effective method to diagnose and follow patients with high grade urothelial carcinoma (HGUC). However, some benign, reactive and metaplastic changes may mimic HGUC and pose a diagnostic challenge for cytopathologists. Summary: Our comprehensive review focuses on summarizing common pitfalls encountered in urine cytopathology, based largely on the experience of the senior author (AC) utilising the diagnostic criteria described in the 2nd edition of The Paris system (TPS) for reporting urinary tract cytopathology and in recent published literature. These include urothelial tissue fragments, instrumented samples, degenerative changes, treatment effects, viral cytopathic changes, iatrogenic and metaplastic changes. Our aim is to provide a clear understanding of these challenges to assist cytopathologists in making accurate diagnoses. Key Message: It's crucial for cytopathologists to recognize benign, reactive and metaplastic lesions that could resemble HGUC. Awareness of these cytological features is essential to minimise diagnostic errors.

Resident training in interventional pathology: Ultrasound-guided fine-needle aspiration and rapid on site evaluation-5 years of teaching experience in a single university hospital.

INTRODUCTION: Despite the established role of the interventional pathologist, their diagnostic performance is difficult to establish. At least in Spain training of pathology residents in ultrasound-guided interventional procedures for specimen collection is limited or absent in most institutions. We present our teaching experience in the instruction of ultrasound-guided fine-needle aspiration (FNA) to pathology residents in a tertiary-level hospital. MATERIALS AND METHODS: The training of pathology residents who rotated through the interventional unit of the pathology department and the application of ultrasound-guided FNA and rapid on-site evaluation (U-ROSE) was documented over 5 years. The training period was broken down into learning phases and included the number of ultrasound-guided FNA performed, anatomical location, and their diagnostic performance, among other aspects. RESULTS: Nineteen (19) pathology residents were trained in U-ROSE, and performed a total of 4003 procedures, with a mean of 211 per resident. In 53% of cases only one pass was required for an adequated sample. The specimen was diagnostic in more than 97% of cases. The most frequently sampled anatomical sites were the thyroid gland (n = 2347), followed by lymph node (n = 667), soft tissues (n = 663) and salivary glands (n = 322). CONCLUSION: The results support the training programme followed by pathology residents in learning U-ROSE, which is essential to lay the foundations for the future interventional pathologist.

Review of the impact of the International System for Serous Fluid Cytopathology.

The International System for Reporting Serous Fluid Cytology (TIS) has been proposed by an expert working team composed of the International Academy of Cytology and the American Society of Cytopathology, following an international survey. Since its introduction, the TIS has gained worldwide acceptance, and this review aims to assess its global impact. A literature search revealed 25 studies which have presented data on the impact of the TIS. Most of them provide data, including risk of malignancy (ROM) for each diagnostic category, separately for pleural, peritoneal and pericardial effusions, while a few do not separate them. A few studies focus on specific diagnoses like mesothelioma on specific types of fluids or more specific issues like the optimal fluid volume for cytology or interobserver variability. A synopsis of the data from the literature search is presented in four tables. The ROM assessment is discussed, as well as interobserver variability and the use of ancillary diagnostic immunochemistry. In conclusion, our review of the published data suggests that the TIS is a valid classification scheme that has been widely accepted by pathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management.

A brief review of the WHO reporting system for lung cytopathology.

The International Academy of Cytology has joined with the International Agency for Research on Cancer to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians, and improve patient care. The WHO System describes 5 categories for reporting lung cytopathology: 'Insufficient/Inadequate/Nondiagnostic', 'Benign', 'Atypical', 'Suspicious for malignancy', and 'Malignant', each one with a clear descriptive term, a definition, a risk of malignancy, and a suggested management algorithm. The key diagnostic cytopathologic features of each of the lesions within each category have been established by consensus through an Expert Editorial Board, who are also the authors of this review and selected for each reporting system and chosen based on their expertise in the field and/or diversity of geographical representation. Many other co-authors from around the world also contributed. The assignment of writing and editing responsibilities used the same model as that used for the WHO Classification of Tumours (https://whobluebooks.iarc.fr/about/faq/). The WHO System provides the best practice application of ancillary testing, including immunocytochemistry and molecular pathology, and guides in sampling and processing techniques to optimize the handling and preparation of specimens. The WHO System was created by the authors to be applicable globally and is based on cytomorphology with possibilities for additional diagnostic management of the patient. The authors are aware that local medical and pathology resources would differ, especially in low- and middle-income countries. The WHO Tumour Classification for Thoracic Tumors, Fifth Edition, is directly accessible through the online WHO System.

The international system for reporting serous fluid cytopathology: The initial project survey.

OBJECTIVE: An international panel in the field of body fluid cytology, supported by the International Academy of Cytology and the American Society of Cytopathology, conducted a survey to identify opinions and explore existing practice patterns regarding body fluid cytopathology. METHODS: The study group, formed during the 2018 European Congress of Cytology in Madrid, generated a survey of 54 questions related to the practice and taxonomy of body fluid cytology. The survey was available online from 28 August 2018 until 10 December 2018. Participants were invited through the websites and listserves of the professional societies. RESULTS: The survey collected 593 international participant responses. Questions pertained to practice patterns and diagnostic language. Information was collected regarding credentials, work setting, work volume (4-10,000 samples) and years in practice (0-60 years). The responses revealed variations in diagnostic practice and sample management. Direct smears and ThinPrep® preparations are the most popular methods, followed by Cytospin® and SurePath®. Most (70%) respondents perform ancillary studies on their material, with over 50% preferring a cell block preparation. Approximately 32% indicated that they are capable of performing genetic studies on the samples. Nearly 78% of participants would accept a two-stage cytology report, with a preliminary assessment followed by a final diagnosis that accounts for ancillary studies to generate a more precise cytological interpretation. Approximately one-third (36%) never report adequacy on body fluid samples. Most (78%) report a general category result (negative, atypical, suspicious, or positive) and 22% provide a detailed surgical pathology type report. Most (73.6%) participants believe that both Papanicolaou stains and a modified Giemsa stain (eg Diff Quik) should be standard preparations for all serous fluid cytology. CONCLUSIONS: The results of the survey demonstrated strong support for the development of a unified system for reporting body fluid cytopathology among respondents.

The World Health Organization Reporting System for Lung Cytopathology.

The International Academy of Cytology has joined with the International Agency for Research on Cancer (IARC) to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This WHO System defines five categories for reporting lung cytopathology, that is, "Insufficient"/"Inadequate"/"Non-diagnostic," "Benign," "Atypical," "Suspicious for malignancy," and "Malignant," each with a clear descriptive term for the category, a definition, a risk of malignancy and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category have been established by consensus and will be presented more fully in a subsequent IARC e-book and published hard cover book.The WHO System provides the best practice application of ancillary testing, including immunocytochemistry and molecular pathology, and provides a review to guide sampling and processing techniques to optimize the handling and preparation of the cytopathology sample emphasizing the cytomorphological differential diagnosis to aid low-resourced settings. The authors recognize that local medical and pathology resources will vary, particularly in low- and middle-income countries, and have developed the WHO System to make it applicable worldwide based on cytomorphology with options for further diagnostic management of the patient.The online WHO System provides a direct link to the WHO Tumour Classification for Thoracic Tumours 5th Edition. It will raise the profile and use of cytopathology by increasing awareness of its current role and its potential role in the era of personalized medicine based on molecular pathology utilizing "small biopsies." Ultimately, the System will improve patient care and outcomes.This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians and improve patient care. The System is based on the current role of lung cytopathology and synthesizes the existing evidence while highlighting areas requiring further research and the future potential role of lung cytopathology.

A Bibliometric Analysis of Digital Health & Mobile Health Related Global Research Publications.

The dataset was generated from Scopus database for the study due to its compatibility with bibliometrix R package. The dataset shows that there is a gradual increase in publication of research articles on digital health and mobile health till 2016 before a sudden rise in number of publications from 2017 onwards. This paper contributes by providing a consolidation of fragmented literature in the research domain giving us information on significant sources, authors and documents. The analysis of conceptual structure reveals that the topics of study have evolved from mobile health to digital health, e-health, technology acceptance model, privacy, implementation and self-management.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

Cytologic diagnosis of "atypical" in serous fluid cytopathology. Approach of the international system for reporting serous fluid cytopathology.

Diagnostic uncertainty may occur with almost any entity on cytological evaluation, depending on the quality and quantity of the provided sample. In serous fluid cytopathology, until recently, there had been no defined or agreed criteria for atypia and suspicious categories. Historically, the two descriptive terms appear to have been used almost interchangeably. The international system for serous fluid cytopathology is the first attempt by an expert international authorship to suggest the scenarios in which these terms are used and propose some diagnostic criteria and clinical management strategies.

A Review of Effusion Cytomorphology of Small Round Cell Tumors.

BACKGROUND: Small round cell tumors (SRCTs) are a broad category of diverse malignant tumors composed of monotonous undifferentiated cells. Involvement of serous fluids by SRCT is rare; however, the identification of exfoliated malignant cells is a crucial component of management and has significant implications for treatment and prognosis. The most common effusion tumors with SRCT morphology include Ewing sarcoma, synovial sarcoma, rhabdomyosarcoma (RMS), small-cell neuroendocrine carcinoma (SCNC), and desmoplastic SRCT, and the cytomorphologic distinction between these tumors is challenging. The purpose of this article is to describe the morphologic features of the most common SRCT in fluids and propose helpful ancillary testing. SUMMARY: Effusion SRCTs display similar primitive and undifferentiated morphologic features although each has subtle variations. Ewing sarcoma is a mesenchymal neoplasm and harbors characteristic translocations t(11;22) (EWSR1-FLI1) or t(21;22) (EWSR1-ERG). In fluids, Ewing sarcoma shows poorly differentiated cells of variable size with round to oval nuclei, prominent nucleoli, and scant cytoplasm. In contrast, synovial sarcoma typically involves extremities and expresses a fusion transcript in t(X;18) (SS18-SSX). This soft tissue neoplasm demonstrates uniform cells with irregular nuclear contours, characteristic nuclear folding, and scant cytoplasm. RMS is a neoplasm arising from skeletal muscle, and the alveolar subtype demonstrates a translocation in t(2;13) (PAX3-FOXO1). The malignant cells show a spectrum of small round cells and pleomorphic large cells with rhabdoid morphology. RMS cells characteristically express myogenin and MyoD1, markers of skeletal muscle differentiation. Although SCNC is not a classic SRCT, the morphology is similar. SCNC demonstrates tight clusters of malignant cells with nuclear molding and salt-and-pepper chromatin. This tumor classically has neuroendocrine differentiation and is positive for synaptophysin and chromogranin on immunohistochemistry. And last, desmoplastic SRCT typically presents as an intra-abdominal mass in young men and characteristically harbors the translocation t(11;22) (p13;q12) (EWSR1-WT1). Cytomorphologically, the tumor shows small monomorphic cells occasionally arranged as rosette-like structures. KEY MESSAGE: The diagnosis of SRCT can be made in effusion samples and is best achieved with a combination of morphologic features, clinical history, and ancillary testing.

Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.

Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.

Selection of metastasis competent subclones in the tumour interior.

The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates. We then integrated coordinates with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. We observed a phenotype of advanced and more aggressive subclonal growth in the tumour centre, characterized by an elevated burden of somatic copy number alterations and higher necrosis, proliferation rate and Fuhrman grade. Moreover, we found that metastasizing subclones preferentially originate from the tumour centre. Collectively, these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to a greater opportunity for driver somatic copy number alterations to arise and expand due to selective advantage. Tumour subclone growth is predominantly spatially contiguous in nature. We found only two cases of subclone dispersal, one of which was associated with metastasis. The largest subclones spatially were dominated by driver somatic copy number alterations, suggesting that a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution.

The practice of cytopathology during the era of COVID-19: challenges and changes.

This paper reviews the challenges faced by cytology laboratories during the COVID-19 pandemic. Various safety guidelines regarding collection, handling, transport and sampling in cytology laboratory are presented. A brief literature overview of adapted changes regarding new safety techniques, processing, sampling techniques implemented by the cytology laboratories in this part of the world is presented. The use of cytology in COVID-19 patients is discussed. The authors have also tried to present the challenges and changes faced for training and education during this time. Migration from multi-headed scope in-person sign-out to digital based platforms were adapted to continue medical education. The potential long-term implications of these adaptations on cytology services are also touched upon.

The international system for reporting serous fluid cytopathology-diagnostic categories and clinical management.

INTRODUCTION: Effusions can develop inside serous cavities in several pathologic states, both neoplastic and non-neoplastic. They are easy to drain and can provide useful diagnostic information. However, the reported diagnostic efficacy of these specimens has not been uniform across different laboratories. To standardize practices, the international system for reporting serous fluid cytology (TIS) was developed in accordance with the best international practices, the most up-to-date reported data, and expert consensus. RESULTS: TIS has set the basic principles for laboratory handling of serous effusion specimens, defined the adequacy criteria, and set a standardized reporting terminology with well-defined criteria for each diagnostic category. These include nondiagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. Each can provide useful inherent information for appropriate clinical management and follow-up, with a defined expected diagnostic category incidence and risk of malignancy. CONCLUSIONS: TIS applies to serous fluids collected from the pleura, peritoneal, and pericardial cavities. Using TIS, indeterminate categories are presented as either preliminary or as options of last resource. TIS has emphasized the role of ancillary tests in arriving at the correct interpretation within each category. It also has emphasized the importance of a malignant diagnosis as a definitive diagnosis, comparable to histologic examinations. Because of the well-documented outcomes in the adoption of uniform cytology terminology for other organ systems, we recommend the use of the upcoming TIS and believe its use will be paramount to improving the diagnostic yield in this area of cytology.

Targeted and systematic cognitive freehand-guided transperineal biopsy: is there still a role for systematic biopsy?

OBJECTIVES: To assess whether targeted cognitive freehand-assisted transperineal biopsies using a PrecisionpointTM device still require additional systematic biopsies to avoid missing clinically significant prostate cancer, and to investigate the benefit of a quadrant-only biopsy approach to analyse whether a quadrant or extended target of the quadrant containing the target only would have been equivalent to systematic biopsy. PATIENTS AND METHODS: Patients underwent combined systematic mapping and targeted transperineal prostate biopsies at a single institution. Biopsies were performed using the Precisionpoint device (Perineologic, Cumberland, MD, USA) under either local anaesthetic (58%, 163/282), i.v. sedation (12%, 34/282) or general anaesthetic (30%, 85/282). A mean (range) of 24 (5-42) systematic and 4.2 (1-11) target cores were obtained. Magnetic resonance imaging (MRI) scans were reported using the Likert scale. Clinically significant cancer was defined as Gleason 7 or above. Histopathological results were correlated with the presence of an MRI abnormality within a spatial quadrant and the other adjoining or non-adjoining (opposite) quadrants. Histological concordance with radical prostatectomy specimens was analysed. RESULTS: A total of 282 patients were included in this study. Their mean (range) age was 66.8 (36-80) years, median (range) prostate-specific antigen level 7.4 (0.91-116) ng/mL and mean prostate volume 45.8 (13-150) mL. In this cohort, 82% of cases (230/282) were primary biopsies and 18% (52/282) were patients on surveillance. In all, 69% of biopsies (195/282) were identified to have clinically significant disease (Gleason ≥3 + 4). Any cancer (Gleason ≥3 + 3) was found in 84% (237/282) of patients. Of patients with clinically significant disease, the target biopsies alone picked up 88% (171/195), with systematic biopsy picking up the additional 12% (24/195) that the target biopsies missed. This altered with Likert score; 73% of Likert score 3 disease was detected by target biopsy, 92% of Likert score 4 and 100% of Likert score 5. Target biopsies with additional same-quadrant-only systematic cores picked up 75% (18/24) of significant cancer that was missed on target only, found in the same quadrant as the target. CONCLUSION: Systematic biopsy is still an important tool when evaluating all patients referred for prostate biopsy, but the need is decreased with increasing suspicion on MRI. Patients with very high suspicion of prostate cancer (Likert score 5) may not require systematic cores, unless representative surrounding biopsies are required for other specific treatments (e.g. focal therapy, or operative planning). More prospective studies are needed to evaluate this in full.