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 rationale for the development and publication of the World Health Organization reporting systems for cytopathology and a brief overview of the first editions of the lung and pancreaticobiliary systems.

The International Academy of Cytology has joined with the International Agency for Research on Cancer and the World Health Organization (WHO) to develop international systems for reporting the cytopathology of lung, pancreas and biliary tract, lymph nodes, soft tissue, liver, breast, and kidney and adrenal gland. The WHO recently published the reporting systems for lung and pancreaticobiliary cytopathology. The objectives of this collaboration are to standardize the reporting of cytopathology; improve the quality of reporting by establishing the key diagnostic cytopathological features of entities and neoplasms; provide detailed best-practice guidelines in sampling techniques, specimen handling and processing, and the use of ancillary techniques; and facilitate communication between cytopathologists and clinicians to improve patient care. Each WHO system has defined specific categories and terminology for reporting cytopathology, and each category has an estimated risk of malignancy as far as the current literature allows and a suggested diagnostic management algorithm to assist clinicians. The WHO systems recognize that local medical and pathology infrastructure will vary, particularly in low-income and middle-income countries, and the WHO systems and their diagnostic management recommendations have been developed to allow them to be applied worldwide in all resource settings. The process of the selection of editors and authors and the writing and editing responsibilities has used the same model as that used for the fifth edition WHO Classification of Tumours, to which the WHO cytopathology systems are directly linked. This review provides the rationale and history of this joint International Academy of Cytology, International Agency for Research on Cancer, and WHO cytopathology project and a brief overview of the WHO reporting systems for lung and pancreaticobiliary cytopathology.

Factors determining whether diffuse large B-cell lymphoma samples are detected by flow cytometry.

INTRODUCTION: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. METHODS: Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. RESULTS: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. CONCLUSION: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.

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.

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.

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.

The International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology: Analysis and discussion of the response to a web-based survey.

BACKGROUND: A group of international experts in breast fine needle aspiration biopsy (FNAB) cytopathology, supported by the International Academy of Cytology (IAC), drafted a comprehensive system for reporting breast FNAB cytopathology in 2017-2018. The editorial team produced a survey to assess the international response to the proposed category structure, definitions, and management recommendations in this draft. METHODS: A web-based survey of 186 questions was generated using the Qualtrics software package (Provo, Utah) supported by the Division of Information Technology at the University of Wisconsin-Madison. The survey was advertised widely-including through the IAC, American Society of Cytopathology, Japanese Society of Clinical Cytology, Papanicolaou Society of Cytopathology, and Australian Society of Cytology and to audiences at national and international meetings-and was available from April to June 2018. The data obtained from the 265 respondents was assessed by the editorial team. RESULTS: The survey provided a snapshot of the current role and use of breast FNAB and the international variations. Demographic questions were followed by specific questions based on the draft category definitions and statements and focused on issues that had generated discussion among the authors, including the FNAB diagnosis of ductal carcinoma in situ. CONCLUSION: The survey results strongly supported the development of the IAC Yokohama System and informed subsequent discussions among the authors regarding the final text.

A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology: The Sydney System.

BACKGROUND: The evaluation of lymph nodes (LN) by fine-needle aspiration cytology (FNAC) is routinely used in many institutions but it is not uniformly accepted mainly because of the lack of guidelines and a cytopathological diagnostic classification. A committee of cytopathologists has developed a system of performance, classification, and reporting for LN-FNAC. METHODS: The committee members prepared a document that has circulated among them five times; the final text has been approved by all the participants. It is based on a review of the international literature and on the expertise of the members. The system integrates clinical and imaging data with cytopathological features and ancillary techniques. The project has received the endorsement and patronage of the International Academy of Cytology and the European Federation of the Cytology Societies. RESULTS: Clinical, imaging, and serological data of lymphadenopathies, indications for LN-FNAC, technical procedures, and ancillary techniques are evaluated with specific recommendations. The reporting system includes two diagnostic levels. The first should provide basic diagnostic information and includes five categories: inadequate/insufficient, benign, atypical lymphoid cells of undetermined/uncertain significance, suspicious, and malignant. For each category, specific recommendations are provided. The second diagnostic level, when achievable, should produce the identification of specific benign or malignant entities and additional information by utilizing ancillary testing. CONCLUSION: The authors believe that the introduction of this system for performing and reporting LN-FNAC may improve the quality of the procedure, the report, and the communication between cytopathologists and the clinicians. This system may lead to a greater acceptance and utilization of LN-FNAC and to a better interdisciplinary understanding of the results of this procedure.

Breast fine needle aspiration biopsy cytology: the potential impact of the International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology and the use of rapid on-site evaluation.

The present report reviews the current problems associated with the routine use of breast fine needle aspiration biopsy (FNAB) and discusses the potential impact that the new International Academy of Cytology (IAC) Yokohama Reporting System and the use of rapid on-site evaluation (ROSE) should have on reducing these problems to optimize breast care for patients. The recently reported IAC System aims to establish the best practice guidelines for breast FNAB, emphasizing the importance of the FNAB technique and the skillful preparation of direct smears. The IAC System proposes a standardized report and established clear terminology for defined reporting categories, each of which has a risk of malignancy and is linked to management options. The FNAB techniques that will optimize the biopsy specimen and reduce poor quality smears are reviewed and the benefits of ROSE are discussed. FNAB can diagnose accurately the vast majority of breast lesions, and ROSE has been recommended whenever possible to reduce the rate of insufficient/inadequate cases and increase the number of specific benign and malignant diagnoses. ROSE performed by a cytopathologist provides a provisional diagnosis, reducing patient anxiety and facilitating management through cost-effective immediate triage and patient selection for ancillary testing. Thus, patients can be selected for immediate core needle biopsy, as required.

Histopathology and Cytopathology of Neuroendocrine Tumors and Carcinomas of the Breast: A Review.

Neuroendocrine tumors (NET) and carcinomas (NEC) of the breast are rare diseases, but NEC has attracted attention in both cytopathology and surgical pathology because of its specific management and prognosis. Fine-needle aspiration biopsy (FNAB) cytology can make the diagnosis in many cases particularly with high-grade NEC, with definitive diagnosis based on histopathology and immunohistochemistry. This review describes the characteristics of the disease based on the WHO classification 2012 and recent literature and -includes discussion related to the International Academy of Cytology Yokohama System of Reporting Breast FNAB -cytology.

Spindle Cell Lesions of the Breast on Fine-Needle Aspiration Biopsy: A Miscellany of Masses.

A variety of primary breast and metastatic lesions to the breast can present with spindle cell cytomorphology. These lesions may range from benign reactive or inflammatory lesions to high-grade malignancies. Spindle cell lesions of the breast are not often seen on fine-needle aspiration biopsy (FNAB) but need to be correctly managed when they are encountered. While mesenchymal lesions of the breast have a spindle morphology, lesions derived from the epithelium and myoepithelium can be spindled as well. By assessing if the lesion comprises spindle cells only or if other components such as epithelial cells are apparent and then determining whether the spindle cells appear bland or pleomorphic, together with close clinicoradiologic correlation and prudent use of ancillary tests, a variety of lesions can be diagnosed on FNAB. However, core needle biopsy or excision biopsy may be required in some patients. The cytomorphology, ancillary studies, and clinicoradiologic findings of a range of spindle cell lesions of the breast are further discussed.

The International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology: A Single Institutional Retrospective Study of the Application of the System Categories and the Impact of Rapid Onsite Evaluation.

OBJECTIVES: To review the performance and utility of the International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy (FNAB) Cytology five category stratification and evaluate the impact of rapid onsite evaluation (ROSE). METHOD: A retrospective analysis of breast FNAB cytology cases with matched histopathological results at a single institution over a 32 months period using a structured reporting system with 5 diagnostic categories ("inadequate/insufficient," "benign," "atypical," "suspicious of malignancy" and "malignant") closely paralleling the proposed IAC System. RESULTS: Of 2,696 breast FNAB cases, there were 579 with matched histopathology and 456 of these had ROSE. ROSE decreased the number in the "insufficient" category (17.1% without ROSE to 4.0% with ROSE) and increased the number in the "malignant" (17.9 to 39.0%) with a lesser impact on the "atypical," "benign" and "suspicious of malignancy" categories. The performance data showed a positive predictive value of 96.4%, negative predictive value of 97.6%, and a risk of malignancy of a FNAB categorized as "insufficient" to be 2.6%, "benign" 1.7%, "atypical" 15.7%, "suspicious of malignancy" 84.6%, and "malignant" 99.5%. CONCLUSION: Breast FNAB is an accurate test enabling effective diagnosis of breast lesions. ROSE improved the performance by decreasing the proportion of "insufficient" and "atypical" and increasing the "suspicious of malignancy" and "malignant" diagnoses and enabling immediate triage for further biopsy where necessary.

The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology.

The International Academy of Cytology (IAC) gathered together a group of cytopathologists expert in breast cytology who, working with clinicians expert in breast diagnostics and management, have developed the IAC Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy (FNAB) Cytology. The project was initiated with the first cytopathology group meeting in Yokohama at the 2016 International Congress of Cytology. This IAC Yokohama System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy (ROM) and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category will be presented more fully in a subsequent atlas. The System emphasizes that the crucial requirements for diagnostic breast FNAB cytology are a high standard for the performance of the FNAB and for the making of direct smears, and well-trained experienced cytopathologists to interpret the material. The performance indicators of breast FNAB, including specificity and sensitivity, negative predictive value, positive predictive value and ROM stated in this article have been derived from the recent literature. The current practice of breast FNAB has evolved with the increasing use of ultrasound guidance and rapid on-site evaluation. Two recent publications have shown a range of ROM for the insufficient/inadequate category of 2.6-4.8%, benign 1.4-2.3%, atypical 13-15.7%, suspicious of malignancy 84.6-97.1%, and malignant 99.0-100%. The management algorithm in the System provides options because there are variations in the management of breast lesions using FNAB and core-needle biopsy in those countries utilizing the "triple test" of clinical, imaging, and FNAB assessment, and also variations in the availability of CNB and imaging in low- and middle-income countries. The System will stimulate further discussion and research, particularly in the cytological diagnostic features of specific lesions within each category and in management recommendations. This will lead to continuing improvements in the care of patients with breast lesions and possible modifications to the IAC Yokohama System.

Cytopathology in Low Medical Infrastructure Countries: Why and How to Integrate to Capacitate Health Care.

Fine-needle aspiration cytology is a rapid, accurate, minimally invasive, inexpensive biopsy technique requiring minimal laboratory infrastructure and proceduralist costs. It provides infectious and noncommunicable disease diagnoses and will play an essential role in the establishment of cancer services in low-income and middle-income countries (LMICs). The use of molecular and other ancillary tests on cytology material is rapidly expanding in high-income countries and will spread to LMICs. Establishing cytology services requires increased training of cytopathologists and cytotechnologists, increased education of clinicians in the use of diagnostic cytopathology, and commitment and funding from governments and specialist training groups.

IAC Standardized Reporting of Breast Fine-Needle Aspiration Biopsy Cytology.

There have been many changes in the roles of fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in the diagnostic workup of breast lesions in routine breast clinics and in mammographic breast screening programs, as well as changes in the management algorithms utilized and the treatments available, since the NCI consensus on breast FNAB cytology in 1996. A standardized approach will improve training and performance of FNAB and smear-making techniques, and structured reporting will improve the quality and reproducibility of reports across departments, cities and countries providing a basis for quality assurance measures and improving patient care and facilitating research. Linking cytology reports to management algorithms will increase the clinicians' use of FNAB cytology and where appropriate CNB, and enhance the use of ancillary tests for prognostic testing. The IAC recognizes that the local medical infrastructure and resources for breast imaging, biopsy and treatment will influence the diagnostic workup and management of breast disease, but best practice guidelines should be established and modified as required.

Role of fine needle aspiration biopsy cytology in the diagnosis of infections.

The role of fine needle aspiration biopsy (FNAB) cytology in diagnosing infections has expanded due to the increase in the number of immune compromised patients and the increasing role of FNAB in the developing world where infection is a major cause of illness. FNAB has become the first procedural test in cases where the clinical and imaging findings suggest an infectious lesion or where there is a differential diagnosis of infection or metastatic or primary tumor. This applies to FNAB of palpable or image directed or deep seated lesions accessed by EUS and EBUS. This article details a recommended approach and technique for FNAB of infectious lesions, and discusses the role of rapid on site evaluation and the application of ancillary testing including the rapidly expanding array of molecular tests based on FNAB material. The utility of recognizing suppurative and granulomatous infectious patterns in FNAB direct smears, and the specific cytomorphological features on routine Papanicolaou and Giemsa stains and on special stains of FNAB smears is described for a large number of bacterial, fungal, viral, parasitic, and protozoan infections. The role of cytopathologists is to now train cytopathologists in sufficient numbers to provide FNAB services, teach trainee cytopathologists and cytotechnologists, and to encourage our clinical colleagues to use FNAB in the diagnosis of infections and other lesions to the benefit of patients and the medical system. Diagn. Cytopathol. 2016;44:1024-1038. © 2016 Wiley Periodicals, Inc.

Intestinal microsporidiosis.

Infection by the ingested pathogens of microsporidia occur primarily in immunosuppressed patients (including untreated HIV/AIDS) and are diagnosed by stool examination, small bowel biopsy with special stains, or electron microscopy (for definitive speciation), or by various molecular techniques. Although electron microscopy has been the definitive diagnostic tool for speciation, genetic sequencing increasingly provides the definitive diagnosis for new species, such as Anncaliia algerae. Further genetic sequencing of the common pathogens may allow for the development of advanced molecular diagnostics providing high diagnostic sensitivity and throughput.