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.     

External quality assurance for cervical cytology in developing countries. Experience in Peru and Nicaragua

Given interest from the professionals concerned, an external quality assurance scheme for cervical cytology can successfully be introduced in developing countries. This is a very important precondition if screening programs are to be expanded and decreases in mortality from cervical cancer are to occur in developing countries. Nicaragua and Peru have been experimenting with an external quality assurance system adapted from the Scottish and Northern Ireland scheme. It has been received with enthusiasm and acceptance and has helped cytology laboratories in these countries focusing on quality issues. Nevertheless, a successful quality control scheme that is to result in improvements in the quality of professionals' diagnostic skills needs to be accompanied by a remedial program for subperformers.     

Quality assurance activities of the College of American Pathologists

Since its inception, the College of American Pathologists (CAP) has played a fundamental and pivotal role in the development and execution of quality assurance programs for laboratories. Within the realm of anatomic pathology, operational programs include those in surgical pathology, immunohistochemistry and cytopathology. The emphasis of prior cytopathology programs on cervical cytology has now been expanded to include body fluids and fine needle aspiration material. CAP's role in the expansion of quality assurance programs in cytology may be enhanced in the future by intersociety cooperation with established cytology organizations and will also be influenced by and closely linked to the expansion of its quality assurance programs in surgical pathology. As for the Papanicolaou smear, it can no longer be regarded as the "Cinderella of cytology"; it is in fact the present-day cynosure in the laboratory. In recognition of this, CAP has undertaken efforts to help heighten public awareness about the value of Papanicolaou smear testing and is encouraging women to become more informed about the process involved in the examination of their smears.     

Head and neck cancer in the UK: what is expected of cytopathology?

Objective:  This review highlights the role of cytopathology in cancer management within UK Head and Neck Cancer Networks and informs on the issues raised by recent UK Department of Health documents and other UK professional guidance. UK guidance requires the formal involvement of cytopathologists within multidisciplinary cancer teams, with medical and non-medical cytopathology staff setting up and running rapid access lump clinics, and support for image-guided fine needle aspiration cytology (FNAC) services. UK guidance also makes recommendations for training, resources and quality control. This review also highlights the resource gap between best practice evidence-based guidance for head and neck (HN) cancer services and existing UK provision for cytopathology, as evidenced by lack of availability of experienced staff and adequacy of training and quality control (QC). Finally, it stresses the importance in the UK of the Royal College of Pathologists' guidance, which defines the need for training, the experience needed for new consultants, the requirements for audit and QC. The implications for the additional resources required for HN cancer cytopathology services are discussed. Recent professional guidance specifying the provision of HN cancer services in the UK includes a cytopathology service for cancer networks, such as rapid access FNAC clinics. Although these clinics already operate in some institutions, there are many institutions where they do not and where the provision of cytopathology services would have to be restructured. This would need the support of local cancer networks and their acceptance of the detailed requirements for cytopathology, including resources, training and QC. The standards are not defined locally, as Strategic Health Authorities and Primary Care Trusts have been instructed by the Department of Health to support, invest and implement them.     

BSCC Code of Practice – fine needle aspiration cytology

The British Society for Clinical Cytology Code of Practice on fine needle aspiration cytology complements that on exfoliative cytopathology, which was published in the last issue ( Cytopathology 2009; 20 :211–23). Both have been prepared with wide consultation within and outside the BSCC and have been endorsed by the Royal College of Pathologists. A separate code of practice for gynaecological cytopathology is in preparation. Fine needle aspiration (FNA) cytology is an accepted first line investigation for mass lesions, which may be targeted by palpation or a variety of imaging methods. Although FNA cytology has been shown to be a cost-effective, reliable technique its accurate interpretation depends on obtaining adequately cellular samples prepared to a high standard. Its accuracy and cost-effectiveness can be seriously compromised by inadequate samples. Although cytopathologists, radiologists, nurses or clinicians may take FNAs, they must be adequately trained, experienced and subject to regular audit. The best results are obtained when a pathologist or an experienced and trained biomedical scientist (cytotechnologist) provides immediate on-site assessment of sample adequacy whether or not the FNA requires image-guidance. This COP provides evidence-based recommendations for setting up FNA services, managing the patients, taking the samples, preparing the slides, collecting material for ancillary tests, providing rapid on-site assessment, classifying the diagnosis and providing a final report. Costs, cost-effectiveness and rare complications are taken into account as well as the time and resources required for quality control, audit and correlation of cytology with histology and outcome. Laboratories are expected to have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd.     

Cell blocks in cytopathology: a review of preparative methods,utility in diagnosis and role in ancillary studies

The cell block (CB) is a routine procedure in cytopathology that has gained importance because of its pivotal role in diagnosis and ancillary studies. There is no precise review in the published literature that deals with the various methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC) or molecular testing, and its drawbacks. An extensive literature search on CB in cytology using internet search engines was performed for this review employing the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever since its introduction more than a century ago, the CB technique has undergone numerous modifications to improve the quality of the procedure; however, the overall principle remains the same in each method. CBs can be prepared from virtually all varieties of cytological samples. In today's era of personalized medicine, cytological specimens, including CBs, augment the utility of cytological samples in analysing the molecular alterations as effectively as surgical biopsies or resection specimens. With the availability of molecular targeted therapy for many cancers, a large number of recent studies have used cytological material or CBs for molecular characterization. The various techniques of CB preparation with different fixatives, their advantages and limitations, and issues of diagnostic yield are discussed in this review.     

Survey of medical training in cytopathology carried out by the journal Cytopathology

Anshu, A. Herbert, B. Cochand‐Priollet, P. Cross, M. Desai, R. Dina, J. Duskova, A. Evered, A. Farnsworth, W. Gray, S. S. Gupta, K. Kapila, I. Kardum‐Skelin, V. Kloboves‐Prevodnik, T. K. Kobayashi, H. Koutselini, W. Olszewski, B. Onal, M. B. Pitman, ?. Marin?ek, T. Sauer, U. Schenck, F. Schmitt, I. Shabalova, J. H. F. Smith, E. Tani, L. Vass, P. Vielh and H. Wiener
Survey of medical training in cytopathology carried out by the journal Cytopathology This report of the Editorial Advisory Board of Cytopathology gives the results of a survey of medical practitioners in cytopathology, which aimed to find out their views on the current situation in undergraduate and postgraduate training in their institutions and countries. The results show that training in cytopathology and histopathology are largely carried out at postgraduate level and tend to be organized nationally rather than locally. Histopathology was regarded as essential for training in cytopathology by 89.5% of respondents and was mandatory according to 83.1%. Mandatory cytopathology sections of histopathology were reported by 67.3% and specific examinations in cytopathology by 55.4%. The main deficiencies in training were due to its variability; there were insufficient numbers of pathologists interested in cytology and a consequent lack of training to a high level of competence. Pathologists without specific training in cytopathology signed out cytology reports according to 54.7% of responses, more often in centres where training was 3–6 months or less duration. Although 92.2% of respondents thought that specialist cytology should not be reported by pathologists without experience in general cytopathology, that practice was reported by 30.9%, more often in centres with small workloads. The survey report recommends that 6–12 months should be dedicated to cytopathology during histopathology training, with optional additional training for those wanting to carry out independent practice in cytopathology. Formal accreditation should be mandatory for independent practice in cytopathology. When necessary, temporary placements to centres of good practice should be available for trainees intending to practise independently in cytopathology. There should be adequate numbers of pathologists trained in cytopathology to a high level of competence; some of their time could be released by training cytotechnologists and trainee pathologists to prescreen cytology slides and assess adequacy of fine‐needle aspiration samples when immediate diagnosis was not required. The survey demonstrated a clear need for European and international guidelines for training in cytopathology.     

Quality control in cytopathology. A system for simultaneous monitoring of accuracy and education and for proficiency testing

Because of its very nature, cytopathology has not lent itself well to quality control. At the University of North Carolina, we practice an internal quality control system based on peer review, interprofessional dialogue and utilization of follow-up information. Recently reported cytology specimens are rescreened and correlated with related surgical specimens. This review is summarized in a weekly conference, at which retrospective accuracy judgments are made for each case under the supervision of the medical director and head cytotechnologist. Diagnostic accuracy is thus monitored. Accuracy is also improved since education is simultaneously monitored. A practical proficiency-testing program built into this system is described.     

The evaluation of human papillomavirus genotyping in cervical liquid-based cytology specimens; using the Roche Linear Array HPV genotyping assay

Objective:  To ascertain the usefulness of the Roche Linear Array human papillomavirus (HPV) genotyping assay for assessing HPV genotypes in liquid-based cytology (LBC) samples and to evaluate this methodology within a cytopathology laboratory. These tests are of importance as persistent infection with high-risk HPV genotypes is considered a causal factor in the development of cervical cancer.
Methods:  A total of 175 cervical LBC samples were tested using the Roche Linear Array HPV genotyping test. The suitability of the assay use in routine cytopathology laboratory was considered. HPV genotypes were matched to the cervical cytology results, which included negative, borderline nuclear abnormalities, mild, moderate and severe dyskaryosis.
Results:  The assay could be applied to screening samples with the combined result available at the reporting stage. There were no test failures. All samples used after cytological analysis had sufficient DNA for testing. The results were reproducible and easily read and there was concordance of results between biomedical scientists. The results of the assay showed co-infection with multiple HPV genotypes was common in both high-grade and low-grade cytology samples. The percentage of HPV+ samples in the normal cytology samples (although in this grouping the number of samples was low) was 37%. In the cytology samples reported as severe dyskaryosis the HPV genotypes most commonly found were HPV16 and HPV51.
Conclusion:  The assay was able to detect multiple HPV infection with a wide range of genotypes in LBC samples sent for routine cytological analysis. It would be suitable for use in a cytopathology laboratory. The results of the assay show that the genotype profile has some variation from other geographical regions, and more work is needed to determine population prevalence, to ascertain the impact of the HPV vaccine, to evaluate test for cure and HPV triage management.     

Toward implementation of a regional quality assurance program in cytopathology: the Hong Kong experience

OBJECTIVE: To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources. STUDY DESIGN: A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes. RESULTS: The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost. CONCLUSION: In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.     

Telepathology: a tool to aid in diagnosis and quality assurance in cervicovaginal cytology

Telepathology: a tool to aid in diagnosis and quality assurance in cenicovaginal cytology
The purpose of this study is to evaluate the use of a Teletransmission System with regard to quality of diagnosis and screening so as to establish its potential role in gynaecological cytology. Three aspects of its use in cytopathology have been considered: diagnosis, training, and quality control. The circumstances in which the system may be used for diagnosis, together with its advantages and disadvantages, are examined and discussed. In general, the costbenefit in diagnostic use related to the experience of both the expert and the peripheral pathologist. The system may also contribute to training and quality assessment, particularly if combined with other automated services, such as an image data bank.     

External quality control for immunocytochemistry on cytology samples: a review of UK NEQAS ICC (cytology module) results

I. S. Kirbis, P. Maxwell, M. S. Fle?ar, K. Miller and M. Ibrahim External quality control for immunocytochemistry on cytology samples: a review of UK NEQAS ICC (cytology module) results Objective: To date, external quality control for immunocytochemistry on cytology samples is provided only by the United Kingdom national external quality assessment service for immunocytochemistry and in situ hybridisation (UK NEQAS ICC & ISH). For the purpose of this study a retrospective analysis of a comprehensive collection of quality‐related data regarding immunocytochemistry on cytology samples collected through this service was analysed. Methods: The quality of immunocytochemical reactions, using on‐line collected data, was analysed for the last 23 UK NEQAS ICC cytology module external quality assessments carried out on cytology samples completed in the period from 2004 to 2010. Results: Our study showed that the majority of participants in the cytology module (66%) sent formalin‐fixed paraffin‐embedded (FFPE) tissue sections for assessment as in‐house control slides and only 34% sent cytology slides of various types. The highest UK NEQAS ICC score for the quality of immunocytochemical staining among in‐house control slides was achieved on cell block sections, followed by cytospins, FFPE tissue sections, liquid‐based cytology slides and smears. With regard to fixation, acetone‐fixed slides achieved significantly lower scores than other reported fixatives. The strength of agreement in perception of immunocytochemical staining quality was good between in‐house assessors (Kappa = 0.64) but only fair between in‐house and UK NEQAS ICC assessors (Kappa = 0.22). Conclusions: Good quality of immunocytochemical staining can be achieved on cytology slides prepared and fixed in different ways as well as on cell blocks. Unified criteria for high‐quality immunocytochemical staining and proper internal and external quality assurance could facilitate further improvement and standardization of immunocytochemistry on cytology samples.     

Cytopathology laboratory accreditation, with special reference to the American Society of Cytology programs

The features of the Laboratory Accreditation Program of the American Society of Cytology that pertain to quality assurance in cytopathology are reviewed. The areas considered include: (1) specimen procurement and cytopreparation, (2) the role of the cytotechnologist in cytoscreening, evaluation and reporting, (3) the role of the cytopathologist and (4) quality control measures. Attention to the issues raised in these areas is essential to achieving the best possible cytopathology practice in the most efficient and economical manner.     

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 randomized controlled trial in studies using biomarkers

The randomized controlled trial (RCT) is a scientific experiment during which observations on the effects of therapy or a preventive action are conducted by the researcher under rigorous control. The purpose of the experiment is to clear the uncertainties surrounding a clinical/research issue and involves isolating the 'treatment' and 'end result' variables from external influences. RCTs therefore make use of scientific method standards: measuring, which includes the possibility of reproducing observations; controlling factors unconnected to the cause-effect relationship of interest; and the external verification or 'falsification' of the cause-effect relationship. Many RCTs are now including biomarkers to answer scientific questions in a more accurate way. In the present methodological paper, the main aspects involved in the design and conduction of a trial are discussed, with special emphasis on the use of biomarkers. Aspects that are often overlooked by scientists involved in the design of trials include multiple comparisons, subgroup analysis, the duration of the observations, the use of surrogate endpoints, and ethical issues. This review summarizes the main issues that should be addressed in a protocol, and illustrates these with an example.     

Quality control measures for cervical cytology laboratories

The results of three quality control measures for evaluating a cytopathology laboratory's performance in the diagnosis of cervical abnormalities are presented. The sensitivities of cervical cytology were estimated to be 95.5% or 93.1% (using two different methods of analysis) for the detection of histologically diagnosed invasive squamous cell carcinoma of the cervix and 60% for the detection of adenocarcinoma and adenosquamous carcinoma of the cervix in 1983. The positive predictive values for a histologic diagnosis of neoplasia after cytologic reports of CIN III and invasive carcinoma were 92.5% and 99%, respectively. Repeatability of a negative cytologic result exceeded 98%. These results indicate that accurate cervical cytologic reporting can be achieved. Regular monitoring of the type described, which is both practical and reasonably comprehensive, is recommended for all laboratories.     

CytoJournal joins 'open access' philosophy

Welcome to CytoJournal! We would like to introduce you to your journal, one that is run by and for the scientific cytopathology community with incontestable benefits of Open Access, and support from Cytopathology Fondation, Inc http://www.cytopathology-foundation.org/index.html. CytoJournal is a peer-reviewed, PubMed indexed, online journal, publishing research in the field of cytopathology and related areas, with world wide free access. Authors submitting to CutoJournal retain the copyright to their hard earned work.     

The randomized controlled trial in studies using biomarkers

The randomized controlled trial (RCT) is a scientific experiment during which observations on the effects of therapy or a preventive action are conducted by the researcher under rigorous control. The purpose of the experiment is to clear the uncertainties surrounding a clinical/research issue and involves isolating the 'treatment' and 'end result' variables from external influences. RCTs therefore make use of scientific method standards: measuring, which includes the possibility of reproducing observations; controlling factors unconnected to the cause-effect relationship of interest; and the external verification or 'falsification' of the cause-effect relationship. Many RCTs are now including biomarkers to answer scientific questions in a more accurate way. In the present methodological paper, the main aspects involved in the design and conduction of a trial are discussed, with special emphasis on the use of biomarkers. Aspects that are often overlooked by scientists involved in the design of trials include multiple comparisons, subgroup analysis, the duration of the observations, the use of surrogate endpoints, and ethical issues. This review summarizes the main issues that should be addressed in a protocol, and illustrates these with an example.     

The century for cytopathology

By the end of the 19th century, exfoliated cancer cells had been described in all of the types of specimen in which we find them today. However, it was not until Drs. Papanicolaou and Traut published their account of the diagnosis of uterine cancer from exfoliated cells (1941 and 1943) that cytopathology acquired the momentum to develop into the powerful presence that it has in human medicine today. These and the subsequent publications by Papanicolaou stimulated the development and application of cytopathology worldwide, resulting in abundant literature on the subject and a galaxy of outstanding practitioners. The 1980s saw the development and widespread use of aspiration cytology. This was followed in the 1990s by the development of automated screening systems, marking the latest stage in the evolution of cytopathology. These and other events and achievements in cytopathology, from its meager beginnings in the early 20th century to its worldwide use and acceptance today, mark this century as the "century for cytopathology."     

Cervical cancer screening from the public health perspective

Many state health departments have a significant role in cervical cancer screening. Given that role, a group of public health personnel from eight southeastern states drafted a set of questions and quality assurance issues to be discussed with a laboratory under consideration as a contract provider of cytology services. The major points of concern included: (1) quality of laboratory services (accreditation, personnel, facilities and operational and quality control procedures); (2) quality of sampling (including techniques used and the training and monitoring of sample takers); (3) terminology for cytology reporting; and (4) protocols used for diagnostic evaluation of abnormal Papanicolaou smears.