BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases.

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

The World Health Organization Reporting System for Lung Cytopathology-A Review of the First Edition.

The World Health Organization Reporting System for Lung Cytopathology is the first international system that was developed to standardize the reporting of lung cytopathology specimens across all settings of cytopathology practice. The system is composed of five diagnostic categories, which apply to all lung cytopathology specimen types. Each category contains cytomorphologic criteria, an estimated risk of malignancy, and clinical management recommendations. International uniformity in the reporting of lung cytopathology will refine the communication between cytopathologists and clinicians and ultimately improve patient care. Furthermore, standardizing the cytomorphologic criteria for each lesion will improve reproducibility among cytopathologists and highlight areas in lung cytopathology that require further research. The system also provides best practice recommendations for the selection of ancillary tests to aid in the diagnosis of each lesion, or group of lesions, keeping in mind that resources will vary across different practice settings. The goal of this review is to summarize the cytomorphologic criteria, potential diagnostic pitfalls, ancillary testing, estimated risk of malignancy, and clinical management recommendations for each diagnostic category.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Segmental arterial mediolysis leading to spontaneous rupture of splenic artery and fatal hemorrhage in pregnancy.

We report an unexpected death of a 22-year-old primigravida who was admitted to the hospital with sudden abdominal pain two days before a scheduled delivery. During an emergency caesarean section due to intrauterine asphyxia, intraabdominal bleeding was observed with no apparent source of bleeding. Newly formed blood clots in the subdiaphragmatic space and arterial bleeding near the splenic hilum required a surgery on the next day. Hemorrhagic shock led to multiple organ failure on the fourth day of admission. The autopsy revealed ruptured splenic artery at the pancreatic tail and near the splenic hilum. Microscopically, different stages of segmental arterial mediolysis were observed in partially thinned and aneurysmatic artery.

How the Milan System for Reporting Salivary Gland Cytopathology works in cytopathology practice: Meta-analysis of prospective studies and comparison with retrospective studies.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice. METHODS: A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program. RESULTS: Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1). CONCLUSIONS: This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.

The autonomic nerves around the vein of Marshall: a postmortem study with clinical implications.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

Cell block practices in European cytopathology laboratories.

BACKGROUND: There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories. METHODS: A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies. RESULTS: A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected. CONCLUSIONS: There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs.

Insufficient endobronchial ultrasound-guided transbronchial needle aspiration specimens. When and why? The analysis of criteria and reasons behind the insufficient specimens.

BACKGROUND: The classification terminology systems for pulmonary cytology specimens have recently emerged. Inadequate samples, classified as "nondiagnostic," raise challenges in determining the threshold of cell numbers and the risk of malignancy (ROM). METHODS: The study retrospectively reviewed 248 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples: 46 insufficient samples, 60 low cellularity samples, and 142 adequate samples. Characteristics as cellularity, number of benign and malignant cells, and background features were assessed. Receiver operating characteristic curve analysis was performed to establish cell sufficiency thresholds for the diagnosis. RESULTS: Out of the 248 samples analyzed, 108 were classified as benign, 94 as malignant, and 46 as insufficient. The study found that the cellularity thresholds for diagnosis in cell blocks and cytological samples were ≥50 cells and ≥100 cells, respectively. The thresholds for tumor cell counts were ≥1 - 10 cells for both types of cells, respectively. Considerably, some low cellularity samples were initially classified as insufficient despite meeting the diagnostic thresholds upon revision. The ROM varied across sample categories, with insufficient samples having a ROM of 10.9%, benign samples 15.7%, suspicious samples 92.0%, and malignant samples 100%. CONCLUSION: Insufficient EBUS-TBNA samples raise challenges in diagnosis and management. This study identified the root cause of insufficient samples, including factors related to humans, diagnostic methods, sampling, and laboratory processing. By understanding the root causes, diagnostic recommendations can be developed to improve the diagnostic process. The findings emphasize the importance of standardized classification and terminology systems for clear communication among healthcare professionals and institutions, ultimately improving patient care and enabling quality assurance measures.

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.

Aortic elastic fiber degeneration during acute type a aortic dissection and reverse aortic remodeling.

BACKGROUND: Progression of proximal or distal aortic dilatation is defined as reverse aortic remodeling after surgery for acute type A aortic dissection (ATAAD) that may be dependent on aortic wall degeneration. METHODS: We investigated whether aortic wall degeneration is associated with reverse aortic remodeling leading to aortic reoperation after surgery for ATAAD. Altogether, 141 consecutive patients undergoing surgery for ATAAD at Tampere were evaluated. The resected ascending aortic wall at surgery was processed for 42 degenerative, atherosclerotic and inflammatory histological variables. Patients undergoing aortic reoperations (Redos) were compared with those without aortic reoperations (Controls) during a mean 4.9-year follow-up. RESULTS: Redos were younger than Controls (56 and 66 years, respectively, P < 0.001), and had less frequently previous cardiac surgery prior to ATAAD. Initial surgery encompassed replacement of the ascending aorta in the majority. There were 21 Redos in which one patient died during follow-up as compared with 51 deaths in Controls (log Rank P = 0.002). Histology of the aortic wall revealed increased elastic fiber fragmentation, loss, and disorganization in Redos as compared with Controls (2.1 ± 0.5 vs. 1.9 ± 0.5, Point score unit (PSU), P = 0.043 and 1.7 ± 0.8 vs. 1.2 ± 0.8, PSU, P = 0.016, respectively). Moderate atherosclerosis occurred less often in Redos vs. Controls (9.5% vs. 33%, PSU, P = 0.037, respectively). CONCLUSIONS: According to this exploratory study, histopathology reveals distinctive aortic wall degeneration during ATAAD. Reverse aortic remodeling after ATAAD is associated with the presence of ascending aortic wall elastic fiber fragmentation, loss and disorganization during ATAAD.

Histopathology reveals concealed aortic valve inflammation.

BACKGROUND: The extent of aortic valve inflammation in patients undergoing aortic valve replacement (AVR) is unsettled. The significance of aortic valve histopathology in patients undergoing AVR is undetermined. METHODS: A total of 145 resected aortic valves of consecutive patients undergoing surgery for a local aortic valve disease with or without ascending aorta were investigated for histopathology. The extent of inflammation and degeneration were investigated. Unadjusted survival was evaluated by Kaplan-Meier analysis. Median follow-up was 2.7 years (interquartile range 1.5-3.9). RESULTS: Mean patient age was 69 (SD 11) years. Though endocarditis was apparent in only six patients preoperatively, severe aortic valve inflammation was diagnosed histologically in 32 patients of whom 12 patients had acute, subacute or chronic endocarditis. Despite complete aortic valve resection, survival was decreased in patients with severe aortic valve inflammation as opposed to those without (log rank, P = 0.044), even after exclusion of patients with endocarditis, emergency and aortic surgery. CONCLUSIONS: Aortic valve tissue analysis reveals severe inflammation that may require postoperative treatment. The association of severe but local aortic valve inflammation with patient outcome after aortic valve surgery merits further investigation.

Detailed study of collagen, vasculature, and innervation in the human cardiac conduction system.

BACKGROUND: The cardiac conduction system (CCS) creates and propagates electrical signals generating the heartbeat. This study aimed to assess the collagen content, vasculature, and innervation in the human sinoatrial and atrioventricular CCS, and surrounding tissue. MATERIALS AND METHODS: Ten sinoatrial and 17 atrioventricular CCS samples were collected from 17 adult human autopsied hearts. Masson trichrome stain was used to examine collagen, cardiomyocytes, and fat proportions. Immunohistochemically, vessels and lymphatics were studied by CD31 (pan-endothelial marker) and D2-40 (lymphatic endothelium marker) antibodies. General nerve densities were assessed by S100, while sympathetic nerves were studied using tyrosine hydroxylase, parasympathetic nerves with choline acetyltransferase, and GAP43 (neural growth marker) antibodies looked at these components. All components were quantified with QuPath software (Queens University, Belfast, Northern Ireland). RESULTS: Interstitial collagen was more than two times higher in the sinoatrial vs. atrioventricular CCS (55% vs. 22%). The fat content was 6.3% in the sinoatrial CCS and 6.5% in the atrioventricular CCS. The lymphatic vessel density was increased in the sinoatrial and atrioventricular CCS compared to the surrounding tissue and was lower in the sinoatrial vs. atrioventricular CCS (P=.043). The overall vasculature density did not differ between the SA and AV CCS. The overall innervation and neural growth densities were significantly increased in the CCS compared to the surrounding tissue. The overall innervation was higher in the atrial vs. ventricular CCS (P=.018). The neural growth was higher in the atrial vs. ventricular CCS (P=.018). The sympathetic neural supply was dominant in all the studied regions with the highest density in the sinoatrial CCS. CONCLUSIONS: Our results provide new insights into the unique morphology of the human CCS collagen, fat, vasculature, and innervation. A deeper understanding of the CCS anatomical components and morphologic substrates' role will help in elucidating the causes of cardiac arrhythmias and provide a basis for further therapeutic interventions.

Myth-busting the zone of injury concept: a prospective study on the vascular response to high-energy lower extremity trauma.

BACKGROUND: Although the zone of injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomena are reported. This prospective study investigated the vascular response to high-energy lower extremity trauma to evaluate the validity of the zone of injury concept. METHODS: The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age 46 [interquartile range 29.5-62.5] years) who underwent osteosynthesis and free-flap reconstruction due to high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity and control samples were harvested from the free-flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software. RESULTS: Vascular samples were harvested on post-injury days 1-11. Intimal thickness was >3 times greater in arteries harvested from the zone of injury than in control samples (P<0.01) and the intima/media ratio was 2-fold that in control samples (P=0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P<0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P<0.01) and the intima/media ratio (P=0.02) were superior in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P=0.45). CONCLUSIONS: These findings support the validity of the zone of injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.

False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis.

INTRODUCTION: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. METHODS: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. RESULTS: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). CONCLUSION: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.

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.

Atypical urothelial cells classified according to the Paris System for Reporting Urinary Cytology: A 2-year experience with histological correlation from a Finnish tertiary care center-low rate and high risk of malignancy.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) was issued to shift the focus of urine cytology to high-grade lesions to increase the diagnostic accuracy of urine cytology. The aim of this study was to evaluate the power of TPS in the atypical urothelial cells (AUC) category with histological correlation and follow-up. METHODS: The data cohort consisted of 3741 voided urine samples collected during a 2-year period between January 2017 and December 2018. All samples were prospectively classified using TPS. This study focuses on the subset of 205 samples (5.5%) classified as AUC. All cytological and histological follow-up data were analyzed until 2019, and the time between each sampling was documented. RESULTS: Of the 205 AUC cases, cytohistological correlation was possible in 97 (47.3%) cases. Of these, 36 (12.7%) were benign in histology, 27 (13.2%) were low-grade urothelial carcinomas, and 34 (16.6%) were high-grade urothelial carcinomas. Overall, the risk of malignancy was 29.8% for all cases in the AUC category, and 62.9% in the histologically confirmed cases. The risk of high-grade malignancy was 16.6% in all the AUC category samples and 35.1% in the histological follow-up group. CONCLUSIONS: The performance of 5.5% AUC cases is considered good and within the limits proposed by TPS. TPS is widely accepted by cytotechnologists, cytopathologists, and clinicians; it improves communication and patient management.

The diagnostic accuracy of pleomorphic adenoma in fine needle aspiration: Features leading to false positive and false negative diagnoses and the utility of cell blocks.

OBJECTIVE: Fine needle aspiration (FNA) is a well-established tool in preoperative diagnosis of salivary gland lesions with diagnostic accuracy of 90%. Pleomorphic adenoma (PA) is the most common salivary gland tumor comprising 45%-74% of all salivary gland tumors with FNA diagnostic accuracy of 89.5%-96.2%. The aim of the present study was to determine and analyze potential cytomorphological pitfalls and evaluate the diagnostic accuracy in FNA diagnosis of PA. METHODS: Salivary gland specimens with both cytological and histological diagnoses were searched over a 10-year-period (2009-2018) from a laboratory information system of Pathology Department, Fimlab Laboratories, Tampere and matched to determine concordant and discordant PA cases. Sufficient material in histological and cytological sample was found in 401 cases. In 218 cases (54.4%) diagnosis was true-negative PA, in 169 cases (42.1%) diagnosis was true-positive PA and there were 14 discordant cases: 4 false-positive cases and 10 false-negative cases. False-negative cases were reclassified and subgrouped according to The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). RESULTS: Cytomorphologically, cell type predominance was more often myoepithelial in true-positive cases (65%) and epithelial both in false-negative (70%, p = .007) and false-positive cases (75%, p = .027). Well-formed ducts were present in cytology in all true-positive cases (p < .001). Only 10% of true-positive cases did not show any matrix in cytology (p < .001). Nuclear changes were common in false-negative cases (80%, p = .002) and false-positive cases (75%, p = .003). Beneficial cell block (CB) was more common in true-positive cases (85%) than in false-negative cases (50%, p = .041) or in false-positive cases (50%, p = .116) and a lack of beneficial CB led more often to a false diagnosis (70% false diagnosis without beneficial CB versus 29% false diagnosis with beneficial CB). CONCLUSION: The present study showed diagnostic accuracy of 96.5% for FNA in PA diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value were 94.4%, 98.2%, 97.7%, and 95.6%, respectively. The benefit of CBs was more evident in true-positive cases (85%).

Ectopic thyroid in EBUS: experience from a quality assurance programme.

A diagnostic challenge is presented: Distinguishing ectopic thyroid tissue from metastatic well-differentiated follicular carcinoma in cytological material. Two cases of thyroid tissue in mediastinal lymph nodes were sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Later, the cases were presented in Labquality's nongynecological external quality scheme rounds in the years 2017, 2019, and 2020. The same case was presented two times, both in the 2017 and in the 2020 rounds. The results of the three rounds and the discussion of diagnostic pitfalls of ectopic thyroid tissue are presented. A total of 112 individual laboratories worldwide participated in the external quality assurance rounds with whole-slide scanned images and digital still images of alcohol-fixed Papanicolaou-stained cytospin specimens in the years 2017, 2019, and 2020. Fifty-three laboratories participated in both the 2017 (53 of 70, 75.71%) and the 2020 (53 of 85, 62.35%) rounds. The given Pap classes between rounds were compared. Twelve (12 of 53, 22.6%) of the laboratories gave the same Pap class value, whereas 32 (32 of 53, 60.4%) were in the range of ±1 class difference (Cohen's kappa -0.035, p < 0.637). When comparing the diagnoses, 21 (21 of 53, 39.6%) laboratories gave the same diagnosis in 2017 and in 2020 (Cohen's kappa 0.039, p < 0.625). Thirty-two of the laboratories gave the same diagnosis both in 2017 and in 2020 (Cohen's kappa 0.004, p < 0.979). Ten (10 of 53, 18.9%) laboratories changed their diagnose from malignant to benign, and 11 (11 of 53, 20.8%) changed their diagnose from benign to malignant between the 2017 and the 2020 rounds. In conclusions, the expert reference diagnosis was thyroid tissue in mediastinal lymph node. Thyroid tissue in mediastinal lymph node may be either of ectopic or of neoplastic origin. The diagnostic work-up should include cytomorphological, immunohistochemical, laboratory, and imaging results. If a neoplastic change is excluded, the benign category is the most feasible one. The quality assurance rounds showed a large variability in the given Pap classes. Mirroring the problematic issue both inter- and intralaboratory of such cases both in routine diagnostics and in the classification terminologies is requiring multidisciplinary evaluation approach in the diagnostics.

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.