The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Overview and Summary.

The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians.

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.

Challenges and Pitfalls in Pancreatobiliary Cytopathology.

INTRODUCTION: The advances of minimally invasive endoscopy-guided procedures that usually yield limited diagnostic material changed pancreaticobiliary cytopathology into one of the most challenging areas of cytopathology given the abundance of differential diagnoses to be considered when dealing with limited specimens. CASE PRESENTATION: We describe a few challenging examples of potential pitfalls in pancreatobiliary cytopathology evaluation collected from a busy academic hospital (tertiary) center. Case 1 illustrates the challenges in handling paucicellular specimens from pancreatic solid lesions in which differential diagnoses may include acinar cell carcinoma, neuroendocrine tumors, adenocarcinoma, or even benign pancreatic tissue, among others. Case 2 illustrates the pitfalls in evaluating limited specimens from patients with chronic pancreatitis, specially when distinguishing exuberant reactive atypia from dysplastic changes is mandatory. Case 3 illustrates pitfalls in distinguishing malignancy from reactive changes in biliary brushing specimens from patients with primary sclerosing cholangitis. Finally, cases 4 and 5 highlight the importance of including the possibility of pancreatic metastasis in the differential diagnoses of some pancreatic lesions. CONCLUSION: Over time, there has been an increasing demand for pathologists to render diagnoses on limited specimens obtained through minimally invasive procedures which can be frequently challenging even for the most experienced professionals. In many difficult cases, salvaging additional material for a cell block can turn out to be extremely helpful given the possibility of utilizing additional ancillary tests for diagnostic confirmation.

Diagnostic interobserver agreement for thyroid fine-needle aspirates: Effects of reviewer experience and molecular diagnostics.

OBJECTIVES: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience. METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

BACKGROUND: Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. DESIGN: Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). RESULTS: Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ = 0.73-0.91) and follow-up histopathology (κ = 0.66-0.85). The agreement was lowest in the inadequate (κ = 0.05) and atypical (κ = 0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). CONCLUSION: Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

Use of the Afirma Xpression Atlas for cytologically indeterminate, Afirma Genomic Sequencing Classifier suspicious thyroid nodules: Clinicopathologic analysis with postoperative molecular testing.

OBJECTIVES: Afirma has recently introduced its Xpression Atlas (XA) as an adjunct to its Genomic Sequencing Classifier (GSC) for risk stratification of cytologically indeterminate thyroid nodules. We evaluated the performance of Afirma XA and associated pathologic findings for Afirma GSC suspicious nodules. METHODS: Intradepartmental records of thyroid fine-needle aspirations (FNAs) from January 2021 to December 2022 were identified and reviewed for patient and nodule characteristics, FNA findings, molecular test results, and final surgical pathology, if available. RESULTS: Material for Afirma GSC testing was collected in 624 thyroid FNAs, and 148 (24%) were classified as cytologically indeterminate. Afirma GSC testing was successful in 132 (89%) of those cases, of which 35 (27%) were Afirma GSC suspicious. Afirma XA testing was positive in 11 cases (11/35 [31%]). Eight (73%) patients underwent surgery that revealed 7 patients with papillary thyroid carcinoma and 1 patient with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (risk of malignancy: 100% [8/8]). Among the 24 patients with negative Afirma XA results, 19 (79%) underwent surgery, revealing 5 patients with malignancy and 3 patients with NIFTP (risk of malignancy: 42% [8/19]). Overall, the risk of malignancy for Afirma GSC suspicious nodules was 59% (16/27). CONCLUSIONS: Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test.

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.

Optimal carcinoembryonic antigen (CEA) cutoff values in the diagnosis of neoplastic mucinous pancreatic cysts differ among assays.

AIM: Pancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL have been widely used to identify NMC. However, CEA values are unique to and significantly differ between individual assays with various optimal cutoffs reported in the literature for NMC. Here, we investigate the optimal CEA cut-off value of pancreatic cysts from two different assays to identify differences in thresholds. METHODS: Pancreatic cyst fluid CEA levels, CEA assay platform (Beckman Dxl (BD) or Siemens Centaur XP (SC)), and clinical/pathological information were retrospectively collected. Cases were categorised into either NMC or non-NMC. Optimal CEA cut-off values were calculated via a receiver operator characteristic curve. Cut-off values were then identified separately by assay platform. RESULTS: In total, 149 pancreatic cystic lesions with concurrent CEA values (SC: n=47; BD: n=102) were included. Histological correlation was available for 26 (17%) samples. The optimal CEA cut-off value for all samples at the study institution was 45.9 ng/mL (area under the curve (AUC)=86, Sn=85.7%, Sp=73.8%). When analysed separately by CEA assay, the cut-off values were 45.9 ng/mL (AUC=84.27, Sn=89.7%, Sp=71.4%) for BD and 24.4 ng/mL (AUC=77, Sn=81.8%, Sp=75%) for SC (p=0.48). CONCLUSIONS: This study showed an optimal pancreas cyst CEA cut-off threshold of 45.9 ng/mL, which is lower than commonly cited literature with different cutoffs on the two separate platforms (BD: 45.9 ng/mL, SC: 24.4 ng/mL).

Are we on track for diagnosing high-grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) has gained universal acceptance as the standard for reporting urine cytology requiring at least 5-10 malignant cells to diagnose high-grade urothelial carcinoma (HGUC) in lower and upper urinary tract specimens, respectively. These quantitation criteria are still subject to discussion, and this study specifically aims to validate the quantitation criterion of HGUC in lower urinary tract. DESIGN: The authors reviewed two cohorts of lower urinary tract cases. The first cohort consisted of 100 liquid-based ThinPrep slides with the diagnosis of HGUC having positive histology on concurrent or follow-up biopsies within 3 months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3 months. The number of high-grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid-like manner. RESULTS: The first 100 urine samples showed five cases (5.0%) with three HGCs, three cases (3.0%) had four HGCs, five cases (5.0%) showed five HGCs, and 25 cases (25.0%) had between 6-10 HGCs. The risk of high-grade malignancy (ROHM) in cases with five or more HGCs was 100%, whereas those with three HGCs was 60.0%. The second cohort of HGUC was considered "positive" despite a negative histology. CONCLUSION: This study confirms that quantitation is an essential key to diagnose HGUC. The current TPS criterion of a minimum of five malignant cells in lower tract is robust with a ROHM of 100%. Diagnosing HGUC with less than five HGCs runs the risk of lowering the ROHM.

Optimal fluid volume for detecting malignancy in serous effusions: a single institution experience.

INTRODUCTION: Detection of malignant cells in serous fluids is an indicator of advanced stage of malignancy and is critical in clinical management decisions and prompt treatment initiation. The minimum volume which is ideal for detecting malignancy in serous fluid is not well established. In this study, we aim to identify optimal volume that will be ideal for adequate cytopathological diagnosis. MATERIALS AND METHODS: A total of 1597 samples of serous fluids from 1134 patients were included in the study. Samples were diagnosed based on International System for Reporting Serous Fluid Cytopathology (ISRSFC). Clinicopathologic results from different diagnostic groups were compared and statistically analyzed. RESULTS: Pleural fluids comprised 890 (55.7%) specimens, followed by 456 (28.6%) peritoneal, 128 (8%) ascites, and 123 (7.7%) pericardial fluid specimens. The majority were negative for malignancy (1138, 71.3%), followed by malignant (376, 23.5%), atypical (59, 3.7%), and suspicious for malignancy (24, 1.5%). Malignancy was identified in sample with volumes from 5 mL to 5000 mL. Rate of detection of malignant cells increased significantly with higher sample volumes. For malignancy detection the optimal volume for overall serous fluid is 70 mL. Pericardial fluid is an exception, with lower mean volume and significantly lower proportion of cases with malignant diagnosis. CONCLUSIONS: Our study indicates that higher fluid volumes have a higher rate of malignancy detection and a low false-negative rate. We recommend a minimum of 70 mL of serous fluid for optimal cytopathologic examination and malignancy detection. Pericardial fluid is an exception, with lower mean volume and thus lower requirement.

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

The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer have developed an approach to standardized reporting of pancreaticobiliary cytopathology. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO System) revises the Papanicolaou Society of Cytopathology (PSC) System for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the 6 PSC categories with 7 categories: "Insufficient/Inadequate/Nondiagnostic"; "Benign/Negative for malignancy"; "Atypical"; "Pancreaticobiliary neoplasm, low risk/grade (PaN-low)"; "Pancreatic neoplasm, high risk/grade (PaN-High)"; "Suspicious for malignancy"; and "Malignant". In the PSC system, there is a single category for "Neoplastic" lesions that includes 2 groups, 1 for benign neoplasms and 1 named "Neoplastic-other", dominated by premalignant intraductal neoplasms primarily intraductal papillary mucinous neoplasms and low-grade malignant neoplasms (pancreatic neuroendocrine tumors (PanNET) and solid pseudopapillary neoplasms (SPN). In the WHO System, benign neoplasms with virtually no risk of malignancy are included in the "Benign" category and low-grade malignancies (PanNET and SPN) are included in the "Malignant" category, as per the 5th edition of the WHO Classification of Digestive System Tumors, while the non-invasive pre-malignant lesions of the ducts are divided by the cytomorphological grade of the epithelium into PaN-low and PaN-high with distinctly different risks of malignancy. Within each category, key diagnostic cytopathologic features and the ancillary studies for diagnostic and prognostic evaluation, as well as the implications of diagnosis for patient care and management, are outlined. Reporting and diagnostic management options recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries.

Primary Effusion Lymphoma in an HIV-Negative Patient with Chronic Myeloid Leukemia Treated with Dasatinib.

INTRODUCTION: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions. CASE PRESENTATION: We report a case of PEL in a young, relatively immunocompetent patient with no history of organ transplant receiving dasatinib for CML, BCR::ABL1-positive. DISCUSSION: We hypothesize that the loss of T-cell function secondary to TKI therapy (dasatinib) may have resulted in the unchecked cellular proliferation of Kaposi sarcoma herpesvirus (KSHV)-infected cells, leading to the emergence of a PEL. We recommend cytologic investigation and KSHV testing in patients being treated with dasatinib for CML who present with persistent or recurrent effusions.

SCS-Net: An efficient and practical approach towards Face Mask Detection.

Much work has been done in the computer vision domain for the problem of facial mask detection to curb the spread of the Coronavirus disease (COVID-19). Preventive measures developed using deep learning-based models have got enormous attention. With the state-of-the-art results touching perfect accuracies on various models and datasets, two very practical problems are still not addressed - the deployability of the model in the real world and the crucial cases of incorrectly worn masks. To this end, our method proposes a lightweight deep learning model with just 0.12M parameters having up to 496 times reduction as compared to some of the existing models. Our novel architecture of the deep learning model is designed for practical implications in the real world. We also augment an existing dataset with a large set of incorrectly masked face images leading to a more balanced three-class classification problem. A large collection of 25296 synthetically designed incorrect face mask images are provided. This is the first of its kind of data to be proposed with equal diversity and quantity. The proposed model achieves a competitive accuracy of 95.41% on two class classification and 95.54% on the extended three class classification with minimum number of parameters in comparison. The performance of the proposed system is assessed with various state-of-the-art literature and experimental results indicate that our solution is more realistic and rational than many existing works which use overly massive models unsuitable for practical deployability.

Chondroblastoma: Cytomorphologic Analysis of 10 Cases with Review of the Literature.

INTRODUCTION: Chondroblastoma (CB) is a rare, benign cartilage-producing tumor, typically affecting the epiphysis of long bones in skeletally immature individuals. There have been only limited case reports describing the cytomorphologic features of this tumor, and thus the cytopathologic diagnostic criteria are controversial. Herein, we report the cytologic findings of 10 CB cases, discuss the diagnostic criteria and critical differential diagnosis, along with a comprehensive review of the literature. METHODS: We performed a retrospective search of our cytopathology and surgical pathology databases for cases diagnosed as CB that had corresponding cytology specimens from four large medical institutions. All available cytopathology specimens were retrieved and reviewed. Clinicopathologic and radiologic data were recorded. RESULTS: Ten cases were retrieved from 8 patients aged 15-42 years (mean, 24 years), five of whom were males. Eight cases represented primary tumors while 2 cases were recurrences. Three cases occurred in the femur, two cases occurred in the humerus, while 1 case occurred in each of the glenoid, talus, and proximal phalanx of the 3rd toe. The cytologic diagnosis of CB was achieved in 7 cases. The neoplastic mononuclear cells were present in all cases and their cytologic features were similar. These cells displayed round to oval eccentric nuclei, evenly distributed chromatin, and inconspicuous nucleoli; few of which had nuclear indentations. Multinucleated giant cells were present in 9 cases (90%). Fragments of chondromyxoid matrix were present in 4 cases on cytologic preparations (40%). Cell blocks were available in 8 cases. Mononuclear and multinucleated giant cells were present in all adequate cell blocks and their cytologic features were identical to those seen in the smears. The chondroid matrix was present in only three of the adequate cell blocks (43%). CONCLUSION: We concluded that with the appropriate clinical and radiologic setting, the diagnosis of CB can be achieved on cytology if characteristic chondroblasts are present. The presence of chondromyxoid matrix is a helpful clue but is not necessary for the diagnosis. As in surgical pathology, cytologic evaluation of bone tumors should be interpreted in conjunction with clinical and radiologic findings.

The World Health Organization Reporting System for Pancreaticobiliary Cytopathology.

The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer, with expert contributors from around the world, present an international approach to standardized reporting of pancreaticobiliary cytopathology. This reporting system is one of the first in a series from various body sites that mirror the WHO Classification of Tumours series and provides an evidence-based terminology system with associated risk of malignancy and diagnostic management recommendation per diagnostic category. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO system) revises the Papanicolaou Society of Cytopathology (PSC) system for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the six-tiered system with a seven-tiered system: "insufficient/inadequate/nondiagnostic"; "benign (negative for malignancy)," "atypical," "pancreaticobiliary neoplasm of low risk/low grade," "pancreatic neoplasm of high risk/high grade," "suspicious for malignancy," and "malignant." The principal differences between the WHO and the PSC systems revolve around the classification of neoplasia. In the PSC system, there was a single category for "neoplastic" lesions that includes two groups, one for "benign neoplasms" [primarily serous cystadenoma] and one named "other," dominated by premalignant intraductal neoplasms (primarily intraductal papillary mucinous neoplasms) and low-grade malignant neoplasms [pancreatic neuroendocrine tumors (PanNETs) and solid pseudopapillary neoplasms (SPNs)]. In the WHO system, benign neoplasms with virtually no risk of malignancy are included in the "benign" category and low-grade malignancies (PanNET and SPN) are included in the "malignant" category, as per the WHO Classification of Digestive System Tumours, thus leaving in the "neoplasm" category primarily those noninvasive premalignant lesions of the ductal system. These neoplasms are divided by the cytomorphological grade of the epithelium into low risk/low-grade and high risk/high-grade, with distinctly different risks of malignancy. As with the PSC system, the WHO system advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (CEA and amylase) and molecular testing of cyst fluid and bile duct brushings. Key diagnostic cytopathological features of specific lesions or neoplasms, ancillary studies for diagnostic and prognostic evaluation, and implications of diagnosis for patient care and management are discussed. In addition, the WHO system includes reporting and diagnostic management options that recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries, where cytopathology is particularly useful and is increasingly available in the absence of histopathological services.

Cytopathology of rare gastric mesenchymal neoplasms: A series of 25 cases and review of literature.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.

Evaluating the role of Z-stack to improve the morphologic evaluation of urine cytology whole slide images for high-grade urothelial carcinoma: Results and review of a pilot study.

BACKGROUND: Whole slide imaging (WSI) adoption has been slower in cytopathology due, in part, to challenges in multifocal plane scanning on 3-dimensional cell clusters. ThinPrep and other liquid-based preparations may alleviate the issue by reducing clusters in a concentrated area. This study investigates the use of Z-stacked images for diagnostic assessment and the experience of evaluating urine ThinPrep WSI. METHODS: Thirty ThinPrep urine cases of high-grade urothelial carcinoma (n = 22) and cases of negative for high-grade urothelial carcinoma (n = 8) were included. Slides were scanned at 40× magnification without Z-stack and with Z-stack at 3 layers, 1 µm each. Six cytopathologists and 1 cytotechnologist evaluated the cases in 2 rounds with a 2-week wash-out period in a blinded manner. A Cohen's Kappa (CK) calculated concordance rates. A survey after each round evaluated participant experience. RESULTS: CK with the original report ranged from 0.606 to 1.0 (P < .05) without Z-stack and 0.533 to 1.0 (P < .05) with Z-stack both indicating substantial-to-perfect concordance. For both rounds, interobserver CK was moderate-to-perfect (0.417-1.0, P < .05). Intraobserver CK was 0.697-1.0 (P < 0.05), indicating substantial to perfect concordance. The average scan time and file size for slides without Z-stack and with Z-stack are 6.27 minute/0.827 GB and 14.06 minute/2.650 GB, respectively. Surveys demonstrated a range in comfort and use with slightly more favorable opinions for Z-stacked cases. CONCLUSIONS: Z-stack images provide minimal diagnostic benefit for urine ThinPrep WSI. In addition, Z-stacked urine WSI does not justify the prolonged scan times and larger storage needs compared to those without Z-stack.

Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine-needle aspirates: A quality-assurance metric for evaluating diagnostic performance in a cytopathology laboratory.

BACKGROUND: Molecular testing (MT) of thyroid fine-needle aspiration (FNA)-derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. METHODS: Neoplasia-associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS-like mutations (HRAS, NRAS, or KRAS mutations or non-V600E BRAF mutations), or other mutations. RESULTS: Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1-8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4-9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8-89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS-like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. CONCLUSIONS: Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.