Ethical problems in cytology

Great advances in medical science have raised a number of ethical issues, many of which affect cytopathology. Some of the main issues addressed in this paper relate to the organization of a cytology laboratory: internal and external quality control, adequate staffing levels and staff education, cytopathology reporting format and contents, confidentiality issues, relationship with the clinicians and involvement of cytopathologists in clinical management teams. Quality control has to be provided within cytology departments but external quality assurance is also essential, with national monitoring. New technologies should be used according to the best scientific methods, following cytological analysis. Scientific work in cytology has to respect the general principles of scientific ethics. The patient's interest has to be the main reason for such work.     

Vaginal vault cytology tests: analysis of a decade of data from a UK tertiary centre

H. Stokes‐Lampard, S. Wilson, C. Waddell and L. Bentley Vaginal vault cytology tests: analysis of a decade of data from a UK tertiary centre Objectives: To examine temporal trends in the use of vault cytology tests in primary and secondary care and the demographics of those women tested. Methods: Retrospective analysis of routinely collected data concerning women who had a vault cytology test processed during a 10‐year period (1 April 1995 to 31 March 2005) at Birmingham Women’s NHS Foundation Trust. Results: A total of 8457 vault cytology tests from 3164 women (range 1–17 tests, median = 2) were processed, representing approximately 2% of the cervical cytology workload of the Department of Cytopathology at Birmingham Women's Hospital. There was a significant reduction in annual numbers processed (Pearson correlation ?0.958, P < 0.001). Significant abnormalities (mild dyskaryosis or worse) were detected in 4.5%, with malignancy being detected in <0.1%. The unsatisfactory cytology test rate was 10.7% overall. There was a reduction in the numbers of vault cytology tests coming from the community, hospital outpatient clinics and operating theatres over time (χ² for linear trend = 139.53, 9 d.f., P < 0.0001). Tests originating from community settings had the lowest disease detection rates: no malignancies and only two severe abnormalities were detected from almost 4000 primary care samples; abnormal results represented 2.8% (n = 113), of which the majority (n = 73) were borderline results. All cancers (n = 8) were detected in samples taken in gynaecology and colposcopy clinics. Conclusions: Vault cytology test usage appears to be reducing, particularly from outpatient clinics and primary care. Community detection rates are very low. Further research is required to establish the true costs and benefits of vaginal vault cytology.     

Liquid-based cytology and conventional smears compared over two 12-month periods.

BACKGROUND AND OBJECTIVE: Liquid based cytology (LBC) was introduced across the Scottish Cervical Screening Programme in 2003-2004. The objective of this study was to compare in a large cytopathology laboratory the results of cervical samples over two twelve-month periods, 2001-2002, when the great majority of smears were conventional, with 2003-2004, when all were LBC. METHODS: The results of smears in both periods were analysed to give overall reporting profiles, and correlated with results of cervical biopsies. The numbers of patients referred for colposcopy were compared. RESULTS: The percentage of unsatisfactory smears fell from 13.6% to 1.9%. Colposcopic referrals for repeated unsatisfactory smears fell from almost 25% to 0.5%. There was a decrease in overall smear numbers, but despite this there was an increase in the number of smears reported as showing dyskaryosis of any grade. There was an increase in positive predictive value for moderate dyskaryosis and above, from 79.5% to 86.1%. The outcome of biopsies from patients referred with mild dyskaryosis showed no decrease in accuracy of predicting a low grade histological lesion. Workload in the laboratory decreased, due to fewer smears received overall, more rapid primary screening times and fewer multi-slide cases. Primary screening backlogs all but disappeared, and reporting times greatly improved. CONCLUSIONS: Introduction of liquid based cytology led to improvements in unsatisfactory smear rates, with significant benefits to colposcopic referrals and laboratory turnaround times. Pick-up rates of dyskaryosis were maintained, and the positive predictive value of a dyskaryotic smear report was improved.     

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit
A breast FNA cytology service for palpable breast lumps was commenced in 1989 using the cytospin method. Over the following 6 years 2314 aspirates were received. The results were audited in detail in 1990, 1991/1992 and 1994. Multidisciplinary clinical audit meetings followed each audit cycle. Practice change was agreed after each audit. Each audit cycle was followed by demonstrable improvement in the complete sensitivity of the technique, being respectively 79%, 88% and 96%. The cytospin method is a viable alternative to the conventional smear method.     

Urinary cytology and the Paris system for reporting urinary cytology: Implications for urological management

By reducing the rate of indeterminate (atypical) diagnoses and standardising reporting terminology, The Paris System for Reporting Urine Cytology helps focus the application of cytology towards the detection primarily of high‐grade urothelial carcinoma. We present a urology‐based perspective of how the new system has influenced clinical decision‐making.     

Fine needle aspiration (FNA) cytology of the breast: the influence of unsatisfactory samples on patient management

FNA continues to play an important role in the management of patients with breast lesions. However, the reliability and efficiency of the FNA service depends heavily on the quality of the specimens. We have audited the rate of 'inadequate FNAs' at intervals over the last 5 years and related our findings to the clinical expertise of the aspirator. We have also correlated the rate of inadequate FNAs with the percentage of patients who had an FNA preceding a definitive diagnosis of cancer. We report trends in the rate of inadequate samples, and subsequent diagnosis of cancer, over a 5‐year period. The percentage of breast FNA samples reported as inadequate was 46.8% in 1988–89, falling to 20% in 1991–92 with the introduction of an FNA clinic, and rising to 30.6% in 1993. The rates of cancer following inadequate FNA were 15.7%, 16.1% and 4.2%, respectively, and the percentage of patients with cancer having a preceding inadequate FNA were 37.5%, 13.2% and 7.1%. Possible explanations for the apparent paradox between increasing numbers of inadequate FNA specimens and a falling breast cancer rate are discussed.     

Transthoracic fine needle aspiration cytology of lung for suspected malignancy: an audit of cytological findings with histopathological correlation

Transthoracic fine needle aspiration cytology (TFNAC) is an invasive procedure and should therefore be subject to regular review. We report an audit of TFNAC from 146 patients. One hundred and thirty‐six samples (93%) were adequate and 86 were malignant, 16 suspicious and 34 contained no malignant cells. TFNAC was the sole means of diagnosis of malignancy in 55 patients. However, further pathological data were available in 58 of the adequate samples; TFNAC was malignant in 31, suspicious in eight and contained no malignant cells in 19. All malignant TFNAC were confirmed (absolute sensitivity=85%; positive predictive value=100%); as were five of eight with suspicious cytology. Of 19 patients with negative TFNAC, nine were subsequently found to have a malignancy (specificity=68%).     

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations

The objective of this study was to estimate: (i) the sensitivity of cytologists in recognizing abnormal smears; (ii) the sensitivity of cervical cytology as a method of detecting abnormal smears among those obtained in the presence of cervical intraepithelial neoplasia (CIN). Study subjects were 61 women with a histologically confirmed CIN identified through colpohistological and cytologic screening. For objective (i) new smears were taken from study subjects just before treatment, mixed with routine preparations, interpreted by unaware cytologists and then blindly reviewed by a group of three expert supervisors, who reached a consensus diagnosis. Cytologists classified as positive for squamous intraepithelial lesion (SIL) 30 of the 34 smears judged as positive by supervisors (100% of smears classified as high-grade and 67% of smears classified as low-grade SIL by the supervisors). Our approach, based on creating a set of smears with a high a priori probability of being positive, proved to be an efficient way of estimating errors of interpretation. For objective (ii), smears taken at the moment of diagnosis, just before biopsy, were also reviewed by the same supervisors. These CIN cases were identified among asymptomatic women independently of cytological findings and results are therefore not subject to verification bias. Among the 33 histological CINII/III, four (12%) smears had no atypical cells (three negatives and one unsatisfactory) at review. The same proportion was 26% (four negatives and one unsatisfactory) among the 19 histological CINI. No significant differences in smear content were found between the seven ‘false negatives’ and a sample of ‘true positives’ and ‘true negatives’ for a number of formal adequacy criteria (including presence of endocervical cells). Strong differences were found between positive smears taken just before biopsy and those taken just before treatment (in 11 women the first smear only was positive, while the opposite was never observed), suggesting an effect of punch biopsy in removing lesions.     

Expression of cytokeratin 20 in urine cytology smears: a potential marker for the detection of urothelial carcinoma

BACKGROUND: Urine cytomorphology is one of the oldest methods for screening and monitoring patients with transitional cell carcinoma (TCC). Sensitivity of urine cytology is relatively low. Ancillary techniques on urine sample may increase the sensitivity. AIM: To explore the utility of cytokeratin 20 (CK20) immunostaining in identifying malignant cells in urine cytology smears. MATERIALS AND METHODS: Fourteen cases each of confirmed TCC and benign urinary cytology along with five cases of atypical cells in urine were immunostained with a monoclonal CK20 antibody. Of 14 cases of TCC, 12 showed strong positive staining with the antibody. All benign cases were negative except for a few cases in which the umbrella cells were weakly to moderately positive. In all five cases of atypical urine cytology the atypical cells stained positive with the antibody. These cases were later confirmed as TCC on histopathology of bladder wall biopsy. CONCLUSION: CK20 is an important biomarker that can be used to identify TCC in urine cytology smears. It is particularly useful in those cases where malignancy cannot be confirmed by morphology alone.     

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue We have evaluated the possibility of using the same specimen for both cytological diagnosis and multitarget multicolour FISH (MtMcFISH) analysis in order to determine whether the routinely processed specimens used for diagnosis were also suitable for this ancillary procedure. For this purpose 18 positive samples (11 voided urine and seven bladder washings) were selected, together with a representative section of the corresponding immediately previous or subsequent histological specimens. Two negative cytology slides were added as negative controls. FISH analysis revealed a normal pattern for each probe in the two negative controls and an abnormal pattern in the 18 positive cases. In the latter the same FISH alterations were found in the cytology samples and in the corresponding histological sections, and superimposable cytological/histological features were observed in two cases where two different histology samples were analyzed. The results clearly show that MtMcFISH may be successfully applied to destained routinely processed cytology slides.     

Comparison of conventional Papanicolaou smear and SurePath® liquid-based cytology in the Copenhagen population screening programme for cervical cancer

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.     

External quality assessment in gynaecological cytology: The Trent Region experience

A Department of Health Executive Letter stated in 1998 that the principal function of external quality assessment (EQA) is educational. Subsequently, in England, it has no longer been acceptable to assess performance in gynaecological cytology by proficiency testing. This paper describes the EQA scheme in gynaecological cytology that has been run by the Trent Regional Gynaecological Pathology Quality Assurance Group for the NHS Cervical Screening Programme (NHSCSP) since 1998. It conforms as closely as possible to the recommendations published by the Department of Health Working Group on Histopathology EQA Accreditation, and replaced the national proficiency testing protocol. The educational value of the scheme is derived predominantly from a numerical score which provides confidential and quantitative feedback to all participants. Personal performance monitoring occurs as a secondary function. For primary screeners and checkers, this is based purely on the distinction between negative, inadequate and abnormal smears. For pathologists, personal performance monitoring also includes grading of abnormalities. The EQA has been designed so that all professional groups participate in a manner that closely mimics normal practice. Only slides that have achieved an 80% consensus amongst participants are used in the EQA. Substandard performance has been defined as those participants with scores falling below the 2.5%ile. The paper describes the EQA in detail and illustrates its use by means of the second round results. The EQA protocol developed within Trent and described in this paper has contributed to proposals contained in the current national EQA in gynaecological cytology for the NHSCSP. In particular this paper highlights the effectiveness of the scoring system contained within the Trent and National EQA protocols.     

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990–1995 a total of 13 537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra-aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.     

Urine analysis using FTIR spectroscopy: A study on healthy adults and children

Urine spectra from 108 healthy volunteers are studied by attenuated total refraction-Fourier transform infrared (ATR-FTIR) spectroscopy. The spectral features are correlated with observable urine components. The variation of spectra within a healthy population is quantified and a library of reference spectra is constructed. Using the band assignments, these spectra are compared with both age-wise and gender-wise. Children show the least intensity variations compared to both adult groups. Young adults show the highest variation, particularly in the 1650 to 1400 cm⁻¹ and 1200 to 900 cm⁻¹ regions. These results indicate the importance of the size of the control group in comparative studies utilizing FTIR. Age-wise comparisons reveal that phosphate and sulfate excretion decreases with age, and that the variance of phosphate among individuals is higher with adults. As for gender-wise comparisons, females show a slightly higher citrate content at 1390 cm⁻¹ regardless of the age and they show a higher variance in the 1200 to 1000 cm⁻¹ region when compared to men.     

Digital cytology: A short review of technical and methodological approaches and applications

The recent years have been characterised by a rapid development of whole slide imaging (WSI) especially in its applications to histology. The application of WSI technology to cytology is less common because of technological problems related to the three‐dimensional nature of cytology preparations (which requires capturing of z‐stack information, with an increase in file size and usability issues in viewing cytological preparations). The aim of this study is to provide a review of the literature on the use of digital cytology and provide an overview of cytological applications of WSI in current practice as well as identifying areas for future development.     

Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage

Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance.