Integrated morphologic and molecular analysis of Trichomonas vaginalis, Mycoplasma hominis, and human papillomavirus using cytologic smear preparations.

Pathogenic microbes may colonize the female genital tract via sexual transmission and cause health issues like inflammation or malignancy, summarized as sexually transmitted disease (STD). A major representative of such pathogens is Trichomonas vaginalis (T.v.), whose role in the etiology of cervical cancer remains elusive. Traditional morphologic screening of cervical smears is able to detect T.v., although its identification may be complicated by look-alikes such as degenerated granulocytes and basal cells. In addition, the parasite's endosymbiont Mycoplasma hominis (M.h.) cannot be detected in the Pap test. This investigation was aimed at designing a PCR-based method to detect specific pathogenic germs by using cervical cytology slides to overcome morphologic uncertainty and increase diagnostic accuracy. To test our molecular screening method on T.v., M.h., and HPV in archival smears, we elaborated a multiplex PCR approach based on microdissection. This assay was applied to a minute quantity of starting material which harbored or was suspected to harbor T.v.; the resulting isolated DNA was used for subsequent molecular analyses of T.v., M.h., and HPV. We clarified the diagnosis of genital T.v. infection in 88 and 1.8% of morphologically suspicious and T.v.-negative cases, respectively. We also revealed a tendency of M.h. co-infection in high-risk HPV cases. In conclusion, a microdissection-based approach to detect pathogenic microbes such as T.v., HPV, and M.h. is a molecular tool easy to implement and may help to better understand the interactivity of these germs with respect to pathogenesis.

European Guidelines for Quality Assurance in Cervical Cancer Screening. Second edition--summary document.

European Guidelines for Quality Assurance in Cervical Cancer Screening have been initiated in the Europe Against Cancer Programme. The first edition established the principles of organised population-based screening and stimulated numerous pilot projects. The second multidisciplinary edition was published in 2008 and comprises approximately 250 pages divided into seven chapters prepared by 48 authors and contributors. Considerable attention has been devoted to organised, population-based programme policies which minimise adverse effects and maximise benefits of screening. It is hoped that this expanded guidelines edition will have a greater impact on countries in which screening programmes are still lacking and in which opportunistic screening has been preferred in the past. Other methodological aspects such as future prospects of human papillomavirus testing and vaccination in cervical cancer control have also been examined in the second edition; recommendations for integration of the latter technologies into European guidelines are currently under development in a related project supported by the European Union Health Programme. An overview of the fundamental points and principles that should support any quality-assured screening programme and key performance indicators are presented here in a summary document of the second guidelines edition in order to make these principles and standards known to a wider scientific community.

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.

Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009.

A European Federation of Cytology Societies (EFCS) working party of 28 members from 14 European countries met at the European Congress of Cytology in Lisbon in September 2009, with two observers from the USA, to discuss the need for standardising thyroid FNA nomenclature in the light of the National Institute of Cancer (NCI) recommendations resulting from the State of the Science conference in Bethesda in 2007. The data were obtained through two questionnaires sent by email and a transcript of the live discussion at the congress, which is presented in full. The surveys and discussion showed that there were currently no national terminologies for reporting thyroid FNA in the different European countries except in Italy and the UK. Personal, 'local', surgical pathology and descriptive terminologies were in use. All but one of the working party members agreed that thyroid FNA reporting should be standardised. Whilst almost a third would adopt the NCI Bethesda terminology, which offers the advantages of a 'risk of cancer' correlation and is linked to clinical recommendations, more than half favoured a translation of local terminology as the first step towards a unified nomenclature, as has been done recently in the UK. There was some disagreement about the use of: a) the six-tiered as opposed to four or five-tiered systems, b) the use of an indeterminate category and c) the 'follicular neoplasm' category, which was felt by some participants not to be different from the 'suspicious of malignancy' category. The conclusions will be passed to the different national societies of cytology for discussion, who will be asked to map their local terminologies to the Bethesda classification, observe its acceptance by clinicians and audit its correlation with outcome.

European guidelines for clinical management of abnormal cervical cytology, part 2.

The current paper presents the second part of chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. The first part of the same chapter was published in a previous issue (Cytopathology 2008;19:342-54). This part provides guidance on how to manage and treat women with histologically confirmed cervical intraepithelial neoplasia. The paper describes the characteristics, indications and possible complications of excisional and ablative treatment methods. The three options to monitor the outcome after treatment (repeat cytology, HPV testing and colposcopy) are discussed. Specific recommendations for particular clinical situations are provided: pregnancy, immuno-suppression, HIV infection, post-menopause, adolescence and cyto-colpo-histological disparity. The paper ends with recommendations for quality assurance in patient management and some general advice on how to communicate screening, diagnosis and treatment results to the woman concerned. Finally, a data collection form is attached.

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.

The role of breast FNAC in diagnosis and clinical management: a survey of current practice.

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image-guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1-C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER-2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence-based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

Dietary long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: a randomized controlled trial.

BACKGROUND: Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids (LCPUFA) has been related to visual and cognitive development in healthy children in several studies. Children with phenylketonuria (PKU) consume diets with very low contents of preformed LCPUFA. We studied prospectively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life. SUBJECTS AND METHODS: Infants with PKU were enrolled at diagnosis (<4 weeks of age) and randomized double blind to phenylalanine-free amino acid supplements without LCPUFA (n = 11) or with both arachidonic (AA, 0.46 wt%) and docosahexaenoic acids (DHA, 0.27 wt%) (n = 10). At enrolment and again at 1, 2, 3, 4, 6, 9 and 12 months, plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocols. RESULTS: Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants. In contrast, supplemented infants had stable and higher LCPUFA levels than unsupplemented infants, reaching significant differences for AA values at 3, 4 and 6 months, and for DHA values at 1, 3, 4, 6, 9 and 12 months. Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA. CONCLUSION: Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life. Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes. LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants.

Cervical cancer screening in Germany.

Cervical cancer is one of the target cancers covered by the statutory German cancer screening programme which was introduced in West Germany in 1971 and expanded to the eastern part of the country in 1991. Women covered by statutory health insurance (over 90% of the female population) are eligible to receive an annual cervical examination including a Papanicolaou (PAP) smear beginning at age 20 years. Annual uptake currently slightly exceeds 50% of the eligible population. Shortly after implementation of the national screening programme in the early 1970s the incidence of invasive cervical cancer decreased moderately and the incidence of cervical carcinoma in situ increased substantially in the state of Saarland. These observations would be expected as a result of a cervical cancer screening programme with substantial uptake. Although quality assurance guidelines for cervical cancer screening have been adopted and updated since the inception of the screening programme, only minor changes have been made in the cross-sectional programme documentation. Implementation of population-based documentation and evaluation of screening activities is currently being developed for the German cancer screening programme in pilot studies implementing the European guidelines on the quality assurance of mammography screening. After demonstration of feasibility and effectiveness, improvements in the quality management of breast cancer screening will subsequently be applied to the cervical cancer screening programme.

Allogeneic BMT vs. chemotherapy in late bone marrow relapsed childhood non-T/non-B ALL: results of BFM ALL relapse studies. BFM Relapse Study Group.

In first BM relapsed non-T/non-B ALL, the outcome is not significantly different after radio-chemotherapy compared with allogeneic BMT. Therefore, radio-chemotherapy is convenient af first late BM relapse and BMT may be performed not before a second BM relapse had occurred. Only a small subgroup of children with isolated BM relapse and peripheral blast cells > or = 10,000/microliter at diagnosis of first relapse has a dismal prognosis after radio-chemotherapy and might benefit from BMT.

Fine needle aspiration and mammary secretion, cytology and core biopsy.

Cytology of breast secretions, fine needle aspiration cytology (FNA) of the breast and core biopsy of the breast have been used for a long time. However, the application of the different approaches and their benefit for patients is still discussed. While FNA has challenged surgical biopsy since many years, additionally, core biopsy gets more important due to simplification of handling and decreasing tissue trauma. In conjunction with imaging techniques the number of necessary surgical biopsies has dramatically decreased in many places. Characteristics of the two approaches are tabulated in this contribution, which focuses on symptomatic patients presenting with either lumps of the breast or mammary secretions. Cytologic examination of breast secretions allows early diagnosis of intraductal carcinoma in situ and invasive ductal carcinoma in about 1% of all breast secretions. Careful localisation of the lesions is necessary. Most cases of breast cancer do not cause secretions, so, breast secretion cytology will contribute only in a minority of cases. In cases showing both, breast secretion and lumps, these should be considered as possibly caused by different lesions.

Difficulties in evaluating urinary specimens after local mitomycin therapy of bladder cancer.

In order to describe the cytological changes induced by mitomycin in urinary specimens, we re-examined cytological specimens from patients with recurring bladder cancer treated by long-term intravesical mitomycin therapy after transurethral resection. Local mitomycin therapy causes an increase of leukocytes and urothelial cells, especially of the umbrella-cell type, in urinary specimens. During and after the application of mitomycin, the nucleus and the cytoplasm of urothelial cells are enlarged, usually proportionally. Urothelial cells frequently show a giant nucleus, multiple prominent nucleoli, and an enlarged foamy cytoplasm of the umbrella-cell type. Anisokaryosis is also seen. Such cytological changes are more remarkable later in the course of therapy and after the end of therapy, and they often confuse cytological interpretation. However, the nuclei of urothelial cells are usually translucent and not hyperchromatic, and there is rarely a coarse chromatin pattern. On the other hand, in positive specimens during or after local mitomycin therapy, usually a number of tumor cells showing nuclear enlargement, hyperchromatic nuclei, coarse chromatin pattern, and/or increased nuclear-cytoplasmic ratio are found beside the atypical cells changed by mitomycin.

Detection of false negative Pap smears by rapid reviewing. A metaanalysis.

OBJECTIVE: To explore the diagnostic validity of rapid reviewing (RR) as a quality control method in cytologic laboratories. STUDY DESIGN: Fourteen studies dealing with the detection of false negative Pap smears by RR were included in a metaanalysis. RESULTS: The overall additional yield of positive slides, expressed as the percentage of all reviewed slides, is: 0.18% (95% confidence interval [CI]: .14-.21) for all cytologic abnormalities; 0.07% (CI: .05-.09) for squamous intraepithelial lesions (SIL) and 0.02% (CI: .01-.03) for high grade SIL. The false negative rate of primary screening, evaluated by RR, was 2.0% (CI: 1.5-2.6) for all cytologic abnormalities and 1.4% (CI: .8-2.1) for high grade SIL. The specificity of rapid rescreening was estimated as 97.2% (CI: 96.4-98.1). The positive predictive value of suspicion at RR is about 8.8%. Seven references contained historical data on full rescreening of a random sample of slides reported originally as negative. The results were also pooled and compared with RR. Complete rescreening is more sensitive, but if applied on only 10% of the negative workload, it would yield, on average, 4.7 times fewer extra positives, 5.6 times fewer SIL and 7.9 times fewer high grade SIL in comparison with RR of all sides. CONCLUSION: RR of all smears initially reported as nonpositive is a more effective and a fortiori a more cost effective quality control method in comparison with full rescreening of a 10% random sample.

Quality assurance by continuous recording of the microscope status.

OBJECTIVE: To assess continuous recording of the microscope status for quality assurance. STUDY DESIGN: Using a special microscope with coordinate registration and objective decoding, 8,653 cervical smears were read by five experienced cytotechnologists. Cytotechnologists could check their screening pattern on a TV monitor. Stage position and magnification were registered every 20 msec. RESULTS: The average screening time per case was 3.5 minutes followed by an approximately two-minute intercase interval. Daily workload profiles were generated to check compliance with workload regulations. Average screening time over a day and over a week was rather constant. CONCLUSION: Our experience demonstrates that continuous coordinate registration can be easily implemented as a method of quality assurance in routine cytology.

Cytology of the human seminiferous epithelium.

The appearances in cytologic specimens of the principal cell types in the normal human seminiferous epithelium are described and illustrated. Sertoli cells, which are larger than spermatogenic cells, are characterized by a slightly basophilic, ill-defined cytoplasm of triangular, elongated or columnar shape; the cytoplasm may be vacuolated and may contain spermatozoa. The nuclei of Sertoli cells are round, with a uniformly finely granulated chromatin and a single nucleolus. Spermatogenic cells are round or oval and show scanty cytoplasm with deeper basophilia and well-defined cytoplasmic borders. Multinucleation is common in spermatogenic cells. The Sertoli cells constitute a very homogeneous cell population as compared to the spermatogenic cells, which show several distinct cell types (spermatogonia, primary and secondary spermatocytes, spermatids and spermatozoa) whose nuclear structures depend on the stage of meiosis. Both cell types may occur as naked nuclei. Some problems of cell classification are discussed.

Terminology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Differences in type, structure, quality of health care systems and availability of resources influence reporting systems. In most countries, individual systems have a long history of usage that might preclude adoption of a uniform terminology worldwide. CONSENSUS POSITION: It is desirable but unrealistic at this time to aim for a unified terminology worldwide. It should be the stated objective of the International Academy of Cytology to serve as an umbrella organization for various terminologies and enhance mutual understanding and cooperation. Translation tables of equivalent terms have been created to allow increased communication. Consensus has been achieved in defining essential elements required of any terminology system: (1) the report must be text based: numerical Papanicolaou class designations alone are inadequate; (2) an assessment of the adequacy of the sample should be included; and (3) the diagnosis must address the primary purpose of cervical cytology: to indicate the presence or absence of epithelial abnormalities. Incorporating additional elements within a terminology system may be more or less appropriate, depending on the setting in which the system is used. ONGOING ISSUES: Despite the cited problems in adopting a uniform terminology worldwide, a single system would have many advantages in terms of communication and research and may be a long-term goal worth pursuing. Countries are invited to present their individual national terminology systems and participate in an ongoing dialogue, critically evaluating the advantages and disadvantages of all systems.

Evaluation of costs and benefits of advances in cytologic technology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Uterine cervical cytology smears are among the most cost-effective cancer prevention interventions available, but they are not infallible, and new or modified technologies have been and will be proposed to improve diagnostic accuracy. Before these new technologies are accepted, their performance attributes will be carefully studied and defined. Equally important in this era of fiscal constraints are cost/benefit analyses, for which we review certain guidelines. CONSENSUS POSITION: In an effort to control rising costs in the health care sector, there has been a strong incentive to move toward a market system, and a variety of forces are acting to drive down expenditures. These same pressures will continue to be brought to bear on the providers of cervical cytology services. It must be emphasized that the technical knowledge required to define cost-effective medical practice lies within the medical profession itself, which must recognize the following: (a) Resources are finite; (b) Elimination of fraud, abuse and waste is not enough to bring health care expenditures down to levels considered acceptable to government and business; (c) The medical profession must take the responsibility to identify the health and economic consequences of the services it provides and make wise recommendations for allocation of resources to optimize health consequences. The analysis of costs and benefits must be viewed from a societal perspective and presented in terms of the marginal impact on current practice. This does not mean that new technologies must reduce cost; on the contrary, improvements in health can be expected to come at a price, but at a price commensurate with value gained in lives saved or in added quality adjusted life years. To be of value, a new technology for cervical cytology must be more effective in preventing cervical carcinoma. Dysplasia is considered a precursor of carcinoma, and detection of dysplasia has been a surrogate for prevention of cervical carcinoma, but dysplasia does not always lead to carcinoma, least of all mild dysplasia, and policy makers ultimately will insist that a favorable change in health outcome be effected by new technology before it is allocated resources. Alternatively, new technologies may lower cost, perhaps by modifying screening or rescreening procedures according to known risk; by improved cytopreparatory techniques that simplify, improve or speed screening; or by monitoring devices that minimize screening error. In each case the performance attributes of the instrument or human instrument process should be evaluated in the intended use environment. ONGOING ISSUES: While current cervical cytology methodology is one of the most effective means of cancer prevention, there continues to be development of new techniques to increase the sensitivity and specificity of this test. With present fiscal constraints, these will be subject to stringent cost/benefit analyses in which the medical profession must play a key role. Such analyses can be quite complicated, considering the additional costs or cost savings of clinical follow-up procedures and the reliability of dysplasias detected by cytology as a surrogate for cervical carcinoma in calculating quality of life years saved.

Quality assurance and risk reduction guidelines.

Cervical cancer continues to be a major cause of death in women worldwide. The major problem facing most women is the unavailability of screening Pap tests in poor and underdeveloped countries. While rates of cancer deaths have decreased 60-80% in developed countries since the Pap test became available, the accuracy of Paps was challenged recently. In order to instill public confidence and promote optimal patient care, measures to improve the quality of the entire screening process should be undertaken. Continuous quality improvement processes are more appropriate than traditional quality assurance monitors. Although no standards can be defined that are applicable to all laboratory settings and nations, this document provides current views on universal quality procedures and risk reduction. Procedure/policy manuals, workload assessment, hierarchic/peer review, discrepancy analysis, rescreening studies and cytohistologic correlation are examples of universally applicable quality tools. The variability in practices in different parts of the world is also discussed.

Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials. CONSENSUS POSITION: The following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997. 1. The professional in charge of a clinical cytopathology laboratory continues to bear the ultimate medical responsibility for diagnostic decisions made at the facility, whether automated devices are involved or not. 2. The introduction of automated procedures into clinical cytology should under no circumstances lead to a lowering of standards of performance. A prime objective of any guidelines should be to ensure that an automated procedure, in principle, does not expose any patient to new risks, nor should it increase already-existing, inherent risks. 3. Automated devices should provide capabilities for the medical professional to conduct periodic tests of the appropriate performance of the device. 4. Supervisory personnel should continue visual quality control screening of a certain percentage of slides dismissed at primary screening as within normal limits (WNL), even when automated procedures are employed in the laboratory. 5. Specifications for the design of primary screening devices for the detection of cervical cancer issued by the IAC in 1984 were reaffirmed. 6. The setting of numeric performance criteria is the proper charge of regulatory agencies, which also have the power of enforcement. 7. Human expert verification of results represents the "gold standard" at this time. Performance characteristics of computerized cytology devices should be determined by adherence to defined and well-considered protocols. Manufacturers should not claim a new standard of care; this is the responsibility of the medical community and professional groups. 8. Cytology professionals should support the development of procedures that bring about an improvement in diagnostic decision making. Advances in technology should be adopted if they can help solve problems in clinical cytology. The introduction of automated procedures into diagnostic decision making should take place strictly under the supervision and with the active participation and critical evaluation by the professional cytology community. ONGOING ISSUES: Guidelines should be developed for the communication of technical information about the performance of automated screening devices by the IAC to governmental agencies and national societies. Also, guidelines are necessary for the official communication of IAC concerns to industry, medicolegal entities and the media. Procedures and guidelines for the evaluation of studies pertaining to the performance of automated devices, performance metrics and definitions for evaluation criteria should be established.

Use of diagnostic categories in urinary cytology in comparison with the bladder tumour antigen (BTA) test in bladder cancer patients.

In recent years the use of diagnostic categories for extragenital cytology has increasingly been discussed as an approach to improve the quality of reports. Diagnostic categories reflect the adequacy of the materials for interpretation and the presence or absence of cancer cells. There is a tendency to add intermediate groups as qualifying probably malignant cases or findings associated with a serious cancer risk. Since 1971 we have added one of the following to the final diagnosis in all cases: unsatisfactory for cytological diagnosis, negative for cancer, repeat test suggested, suspicious of cancer, and positive for cancer. To evaluate whether diagnostic categories are useful for comparison of cytological results with those of an alternative test, cytological data were compared with the results of the Bard bladder tumour antigen (BTA) test in voided urine from 119 patients (76 with and 43 without bladder cancer). The diagnostic categories enabled us to calculate sensitivities and specificities of cytology based on different thresholds or decision levels. The BTA test had significantly higher sensitivity (79%) and lower specificity (60%) than urinary cytology with three different thresholds in cytology results (sensitivities: 16-43%, specificities: 81-100%). The present findings suggest that diagnostic categories improve comparison of cytologic results with those of alternative screening and diagnostic aids such as the BTA test.