Impact factor in cytopathology journals: what does it reflect and how much does it matter?

B. AbdullGaffar
Impact factor in cytopathology journals: what does it reflect and how much does it matter? Objective: To study the trends of impact factor (IF) in four cytopathology journals. To investigate the factors that might influence IF in cytopathology literature and whether IF has any impact on cytopathology practice. Methods: The IFs of four cytopathology journals were searched from 2005 to 2009. The IFs and their relationships with the types and number of publications, publishers, the official societies, readership, the quality of their contents, the topics covered and the levels of evidence were compared. Results: Cancer Cytopathology (CC) had the highest IF. Acta Cytologica (AC) had the lowest IF, which appeared to be in decline. Cytopathology (C) and Diagnostic Cytopathology (DC) had a slow but steady increase in their IF. Components that might influence these differences could include the category and the society of the journal, targeted readers and certain types of publications. Publishers, the number of publications, the types of topics covered and the levels of evidence probably have no major effect on IF. Conclusions: IF has its own benefits and original applications. IF is a quantitative measure that does not reflect the levels of evidence in cytopathology journals. IF should not be abandoned because it might encourage competition between cytopathology journals, but it should not dictate their contents.     

Training in molecular cytopathology testing

Training in molecular cytopathology testing is essential in developing and maintaining skills in modern molecular technologies as they are introduced to a universal health care system such as extant in the UK and elsewhere. We review the system in place in Northern Ireland (NI) for molecular testing of solid tumours, as an example to train staff of all grades, including pathologists, clinical scientists, biomedical scientists and equivalent technical grades. We describe training of pathologists as part of the NI Deanery medical curriculum, the NI training programme for scientists and laboratory rotation for Biomedical Scientists. Collectively, the aims of our training are two‐fold: to provide a means by which individuals may extend their experience and skills; and to provide and maintain a skilled workforce for service delivery. Through training and competency, we introduce new technologies and tests in response to personalised medicine therapies with a competent workforce. We advocate modifying programmes to suit individual needs for skill development, with formalised courses in pre‐analytical, analytical and postanalytical demands of modern molecular pathology. This is of particular relevance for cytopathology in small samples such those from formalin‐fixed paraffin‐embedded cell blocks. We finally introduce how university courses can augment training and develop a skilled workforce to benefit the delivery of services to our patients.     

Fine needle aspiration cytology: a survey of current European practice

Fine needle aspiration cytology (FNAC) is practised widely throughout Europe. The majority of countries have dedicated cytopathologists as well as histopathologists practicing cytology. Despite this, FNAC is performed mostly by clinicians and radiologists except in the larger centres with dedicated staff with a special interest in cytopathology. The advent of One-Stop diagnostic services and image-guided procedures are prompting further development of FNAC clinics where cytopathologists take their own samples, issue reports in the same clinical session and take extra material for ancillary tests to complete the diagnosis. The volume of FNAC work varies accordingly; in dedicated centres FNAC represents up to 80% of the workload whilst, in the majority of countries, it represents one quarter or less. Hence, the rate of inadequate FNAC varies widely, depending on the local sampling policies and the organ, but does not exceed 25% in any of the countries. The most sampled organs are breast and thyroid, followed by lymph nodes. Most countries have dedicated training in cytopathology for pathology trainees, the duration varying between 6 months and 2 years of the total training time. This discussion, focusing on European practices, highlights the heterogeneity of FNAC activity but also its success in many centres where it is practiced to a high standard, particularly in breast, thyroid and lymph node pathology. The relatively high rate of inadequate material in some centres reflects local policies and calls for greater uniformity of FNAC practice, particularly specimen sampling. To achieve this, the future direction should concentrate on specialist training, to include performing as well as interpreting FNAC, as part of the curriculum. Current emphasis on web-based training may not provide first hand experience of the FNAC procedure and should be supplemented by attending FNAC clinics and developing the technique to its full potential.     

Relevance of the College of American Pathologists guideline for validating whole slide imaging for diagnostic purposes to cytopathology

Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guideline includes three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been beyond the scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology. A systematic search was carried out in PubMed-MEDLINE and Embase databases up to November 2021 to identify all publications regarding validation of WSI in cytology. Each article was reviewed to determine if SRs and/or GPSs recommended by the CAP guideline were adequately satisfied. Of 3963 retrieved articles, 25 were included. Only 4/25 studies (16%) satisfied all three SRs, with only one publication (1/25, 4%) fulfilling all three SRs and nine GPSs. Lack of a suitable validation dataset was the main missing SR (16/25, 64%) and less than a third of the studies reported intra-observer variability data (7/25, 28%). Whilst the CAP guideline for WSI validation in clinical practice helped the widespread adoption of digital pathology, more evidence is required to routinely employ WSI for diagnostic purposes in cytopathology practice. More dedicated validation studies satisfying all SRs and/or GPSs recommended by the CAP are needed to help expedite the use of WSI for primary diagnosis in cytopathology.     

The BSCC Code of Practice – exfoliative cytopathology (excluding gynaecological cytopathology)

Exfoliative cytopathology (often referred to as non‐gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non‐neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on‐site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non‐gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes.     

The UEMS Section/Board of Pathology,Chapter 6: Requirement for Recognition of Postgraduate Training in Pathology: a presentation of the Paris Document

M. Tötsch, C. Cuvelier, L. Vass and A. Fassina and on behalf of the participants of the UEMS Section/Board of Pathology meeting in Paris 2012
The UEMS Section/Board of Pathology, Chapter 6: Requirement for Recognition of Postgraduate Training in Pathology: a presentation of the Paris Document After more than five years discussion the UEMS Section/Board of Pathology agreed a specification of requirements for recognition of post‐graduate training in pathology, which is the key to the future of our discipline. The document published here, subject to ratification by UEMS Council, was voted on and accepted by the Pathology Board at the UEMS Paris meeting of 9 June 2012. Cytopathology is regarded as integral part of pathology: in general, training in pathology takes five years and maintains a common trunk of four (minimum three) years where surgical pathology, autopsy pathology and basic knowledge of neuropathology, dermatopathology and cytopathology are adequately trained and assessed. Training in so‐called ‘areas of interests’ covers the remaining 12–24 months. Certificates of ‘advanced level of competence’ remain within the authority of national boards. As senior members of its Executive Board, we believe that the European Federation of Cytology Societies (EFCS) should take responsibility for establishing 1) standards in the quality of cytopathology training, 2) training guidelines and qualification for advanced levels of competence in cytopathology, 3) manpower planning, 4) tutorials for pathologists and cytotechnologists and 4) standards of cytotechnologist training.     

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England

R.G. Blanks
ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low‐grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.     

ABC3 Part I: a review of the guidelines for terminology,classification and management of cervical cytology in England

J. H. F. Smith ABC3 Part I: a review of the guidelines for terminology, classification and management of cervical cytology in England The provision of guidance on cytology reporting and evaluation, first outlined in 1995 with the publication of Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology (ABC), and subsequently revised and expanded in a second edition in 2000, has been pivotal to the success of the National Health Service Cervical Screening Programme (NHSCSP), ensuring that standards are upheld, and that rigorous evaluation and quality assurance take place. In the last decade, major changes to the NHSCSP, notably the adoption of revised age ranges and screening intervals for all women in England, implementation of liquid‐based cytology and, most recently, the decision to introduce high‐risk human papillomavirus (HR‐HPV) testing for triage of low‐grade and borderline (equivalent to 'atypical') cytological abnormalities and test of cure after treatment of cervical intraepithelial neoplasia (CIN) determined that an updated version of ABC was required. The third edition of ABC recommends adoption, with minor modification, of the revised British Society for Clinical Cytology terminology and provides guidance on the management of abnormal cytology results linked to this terminology taking account of HR‐HPV testing. To accommodate these changes, expanded result codes, which are electronic codes used to transfer management information to central computers for follow‐up, call and recall of individual women, have been developed. Further guidance on specimen adequacy is also provided. Revised performance indicators are described and explained in a separate article by R. Blanks in this issue of Cytopathology. All the changes in ABC3 are designed to support the mission statement of the NHSCSP that ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’.     

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18 :213–9). A woman with a high‐grade cytological lesion, a repeated low‐grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow‐up for each woman seen. Reflex testing for high‐risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow‐up of low‐grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high‐grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC‐H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow‐up of special cases such as women who are pregnant, postmenopausal or immunocompromised.     

Primary HPV testing: a proposal for co‐testing in initial rounds of screening to optimise sensitivity of cervical cancer screening

As explained by Kitchener in a previous issue of Cytopathology (2015; 26 :4‐6), primary human papillomavirus (HPV) testing is likely to be introduced in the UK for all women aged 25–64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false‐negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV‐negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co‐testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas’ Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce.     

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

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

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

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

Cytopathology training in the United States – a personal view

In this review we present an outline of cytopathology training in the United States, for a non-US readership.     

Measuring screening skills in gynecologic cytology. Results of voluntary self-assessment

When the Clinical Laboratory Improvement Act (CLIA) was passed in 1967, the Centers for Disease Control (CDC) became interested in evaluating screening performance in cytodiagnosis. Finding no validated performance measurement methods that could be used on a national scale, the CDC initiated a program of sequential investigations to develop information that would describe the state of the art in microscopic performance in gynecologic cytopathology. The first of these experiments developed a method, the Self-Assessment Workshop, to measure performance at the microscope by using sets of glass slides. This paper describes the method, its validation process and participant performance over a 15-year period. Study results indicated that cytotechnologists and pathologists tended to correctly identify specimens (slides) in the negative and benign reaction categories in up to 95% of responses, but on slides of dysplasia they made 12% of their calls too low. Carcinomas in situ and invasive squamous cancers were undercalled in only about 5% of responses, but endometrial adenocarcinomas and other rare malignancies were undercalled in as much as 20%. The self-assessment technique is a practical, useful tool for identifying cytology personnel with serious deficiencies in cell location/identification skills and is well accepted by cytotechnologists and pathologists. However its limitations should be kept in mind: screening results from this simulated test should not be extrapolated to routine work performance; the screening time limit of five minutes per slide may adversely affect performance; and, finally, these results may reflect state-of-the-art performance only in voluntary, not mandatory, settings.     

p16INK4a/Ki‐67 dual labelling as a marker for the presence of high‐grade cancer cells or disease progression in urinary cytopathology

E. Piaton, A. S. Advenier, C. Carré, M. Decaussin‐Petrucci, F. Mege‐Lechevallier and A. Ruffion
p16 ^INK4a /Ki‐67 dual labelling as a marker for the presence of high‐grade cancer cells or disease progression in urinary cytopathology Objective: Overexpression of p16^INK4a independent of the presence of E6–E7 oncoproteins of high‐risk papillomaviruses has been identified in bladder carcinoma in situ lesions with or without concurrent papillary or invasive high‐grade (HG) urothelial carcinoma. As p16^INK4a and Ki‐67 co‐expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16^INK4a/Ki‐67 dual labelling in urinary cytology samples. Methods: Immunolabelling was performed in demounted, destained Papanicolaou slides after ThinPrep^® processing. A total of 84 urinary cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37 high grade) were analysed for p16^INK4a/Ki‐67 co‐expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow‐up data in every case. Results: Compared with raw histopathological results, p16 ^INK4a/Ki‐67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant potential or low‐grade carcinomas (P = 0.05). All cases with high‐grade/malignant cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG lesions were dual labelled. Extended follow‐up allowed three cases of progression to be diagnosed in dual‐labelled cases with negative/low‐grade cytology results after a 9‐ to 11‐months delay. Conclusions: The data show that p16^INK4a/Ki‐67 co‐expression allows most HG cancer cells to be detected initially and in the follow‐up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine.     

Molecular diagnostic cytopathology: definitions, scope and clinical utility

Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Although it is not widely used in routine molecular cytological practice, some examples are presented here of the application of molecular techniques to the routine cytopathological diagnosis of solid tumours and lymphoreticular malignancies. The term 'molecular diagnostic cytopathology' is proposed to define the application of molecular diagnosis to cytopathology, and the challenges of the introduction of molecular diagnosis into routine diagnostic histopathology and cytopathology are discussed. Finally, the importance of a combined morphological, immunophenotypic and molecular approach to maintain the diagnostic pathologist at the heart of the clinical decision-making process is emphasized.     

Comparative cytopathology of Crinivirus infections in different plant hosts

We used transmission electron microscopy to compare the cytopathology induced in plants by five criniviruses (genus Crinivirus; Lettuce infectious yellows virus (LIYV), Cucurbit yellow stunting disorder virus (CYSDV), Tomato infectious chlorosis virus (TICV), Tomato chlorosis virus (ToCV) and Beet pseudo‐yellows virus (BPYV) (Hartono et al., 2003)). We also compared the patterns of infection for plants and mesophyll protoplasts infected by LIYV and Beet yellows virus (BYV), type members of genera Crinivirus and Closterovirus, respectively. The main cytopathological effects induced in plants by criniviruses were common in young leaves and included alterations of the chloroplasts and the presence of BYV‐type inclusion bodies in companion cells. Virus‐like particles were present in sieve tubes and vascular parenchyma cells as scattered particles, or in companion cells as large masses forming cross‐banded inclusions. Depending on the virus and the plant, it was possible to find virions or virus‐like particles out of the phloem cells, but only in cells of the bundle sheath. Virion‐like particles were never found outside of the vascular tissue. Accumulation of electron‐dense material at the plasmalemma was common for criniviruses, but only LIYV infections produced characteristic conical electron‐dense plasmalemma deposits (PDs). The LIYV‐induced PDs have a crystalline‐like structure and were found at the internal side of plasmalemma.     

Finnish cytotechnologists' views on the competencies of newly graduated biomedical scientists in clinical cytology

Objective

This study asked 40 cytotechnologists for their views on the competencies of newly graduated biomedical scientists in clinical cytology during the national conference of the Finnish Association of Cytotechnologists in November 2015.

Methods

The questionnaire mainly consisted of statements that were scored on a five‐point Likert‐scale, where 1 was not important and 5 was very important. It covered five sections of clinical cytology: sampling and techniques, gynaecological screening, non‐gynaecological screening, safety and quality management, and miscellaneous.

Results

Of the 40 delegates approached to complete the questionnaire, 37 (92.5%) agreed. Respondents felt that important sampling and technique competencies were specimen fixation, with a mean score of 4.9 out of 5.0, types of specimens (4.7), Papanicolaou smear collection (4.7), Papanicolaou smear request information (4.7) and evaluation of specimen sufficiency (4.6). Less important competencies were examining FNAs (2.0) and nasopharyngeal specimens (2.2). The respondents had many expectations about how education in cytology could be developed, for example more theoretical lessons, more practice in microscope use, and consistent criteria for training and cooperation between cytology laboratories and universities of applied sciences.

Conclusions

The cytotechnologists who took part in our survey expected newly graduated biomedical scientists to have basic competencies in cytology. These were sampling and techniques, laboratory safety and quality management, specimen adequacy and identifying normal cells taken during gynaecological screening. They were also keen to develop education in cytology.