Cytology Laboratory Research Articles

The Efficacy of Using the Tissue Fragments Present in Cervical Scrapes for the Histologic Diagnosis of Cervical Neoplasia

Cervical scrapes to diagnose cervical neoplasia, collected by the clinician with brushes, are sent to the Leiden Cytology and Pathology Laboratory (LCPL) in vials containing BoonFix, a noncross-linking coagulant fixative. Because the residual material left in the vials contains tissue fragments with important diagnostic information, we stored the residual material in our archives. The tissue fragments can be mummified and archived in commercially available histology cassettes. We can produce paraffin sections thereof. Immunostaining is beautiful on serial paraffin sections cut from these blocks. We experienced that it is important to leave the brush in the vial such that all tissue fragments can be used for histologic diagnosis. In order to optimize the system, tissue fragments left in the endocervical part of the brush are removed in a paint shaker. We illustrate this principle of recovering mummified tissue fragments in a false negative case with cytology containing many undiagnosable collapsed tissue fragments. This case shows clearly the efficacy of using the tissue fragments present in cervical scrapes for the histologic diagnosis of cervical neoplasia.

Cervical cancer screening in Serbia

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Cervical smear cytology on routine screening in a semi urban population in New Delhi: A review of 610 cases

Background: Cervical cancer is an important public health problem among adult women in many developing countries. Cervical cytology became the standard screening test for cervical cancer and premalignant cervical lesions with the introduction of the Papanicolau (Pap) smear. The most widely used system for describing PAP smear result is the Bethesda System 2001. Material and Methods: This study was aimed at evaluating the entire spectrum of types and frequencies of cervical cytological abnormalities i.e. infective, pre-cancerous and cancerous, in women who underwent routine cytological cervical screening at our hospital which caters largely to women of low socio-economic status. Results: A total of 610 cases of cervical pap smears were received in our cytology laboratory during this two year period, 348(57%) abnormal Pap smears, and 238(39%) cases which were normal. Out of the 348 cases, 306(50.2%) cases were reported to have inflammatory/reactive/reparative changes whereas epithelial cell abnormality was reported in 42 cases. Discussion: Cervical smear cytology also plays an important role in the diagnosis of cervical infections which are common in women of the reproductive age group. Conclusion: Hence, the need of the hour is an effective screening programme that is based on available resources and is readily available to the low socio-economic and disadvantaged sections of our society.

Anticipating the impact of the new screening guidelines on cytology and molecular laboratories

Anticipating the impact of the new screening guidelines on cytology and molecular laboratories

AB 38. The smoking habits in rural population and its effects on the lung

Background From the mid-20th century, widespread smoking habit and environmental pollution associated with the epidemic increase in the incidence and death from lung cancer. Smoking is the main cause of over 90% of lung cancers which have made the disease a public health problem in endemic proportions. The risk of disease depends on the number of cigarettes smoked. The risk for a smoker of 25 or more cigarettes a day is 25 to 30 times higher than a non-smoker. The purpose of this study was to examine and evaluate in the cytology laboratory retrospectively material samples from 3,064 patients with a history of smoking. We studied the epidemiological characteristics of patients, histological type and smoking habit.

Comparison of Pap Smear Screening Results between Akha Hill Tribe and Urban Women in Chiang Rai Province, Thailand

Cervical cancer is an important woman's health problems worldwide, especially in low socio-economic countries. The aim of this study was to compare the Pap smear screening results between Akha hill tribe and urban women who live in Chiang Rai province, Thailand. Screening was conducted for 1,100 Akha women and 1,100 urban women who came to have the Pap smear at Chiangrai Prachanukroh Hospital and 1 private cytology laboratory from January to June 2008. The demographic characteristics and factors related to abnormal Pap smears of these women were gathered using closed model questionnaires. Abnormal Rap smears were defined according to the Bethesda 2001 system. The results showed that the prevalence of abnormal Pap smears was 12.2% in Akha women and 4.5% in urban women. The highest prevalence of Pap abnormalities was found in the 41-50 years age group in both populations (4.5% in Akha and 1.7% in urban women). In both populations, abnormal Pap smears were found in <21 years age groups. From the questionnaires, the possible risk factors related to the higher prevalence of abnormal Pap smears in Akha women were early age at marriage (≤17 years), high frequency pregnacies and high parity and no/low education level. In conclusion, cervical cancer control by education and early detection by Pap smear screening is necessary for hill tribe women. More Pap smear screening service units should be set to improve the coverage for the risk group women who got married in young age, especial in ethnic groups.

Patterns of CNS Involvement in Relapsed and/or Refractory Multiple Myeloma.

AbstractAbstract 2925 Background:Multiple myeloma (MM) patients can present with neurologic manifestation either as part of the disease process or as a therapeutic complication, such as due to metabolic disorders such as hypercalcemia, uremia and hyperviscosity; due to peripheral neuropathy, spinal cord compression and cranial nerve infiltration. Invasion of the central nervous system (CNS) in MM disease is an extremely rare occurrence and is associated with advanced disease with poor prognosis. Herein, we are presenting the UARK experience of CNS involvement in MM. Patients and Methods:The UARK MM database was used to conduct a retrospective analysis identifying CNS MM cases presenting between January 1996 and March 2012. Cases were identified from a review of the cytology laboratory archive material; data were also retrieved from the cytogenetic laboratory database, and magnetic resonance imaging (MRI). Descriptive analyses were performed on available data on patient characteristics, disease course and outcomes. Results:35 patients were identified with mean age at diagnosis being 55.4 years (range: 32–80 years) presenting with neurologic symptoms enlisted in Table 1. All patients had received prior systemic chemotherapy (SC) alone (n=11), or combination of SC and autologous stem cell transplant (ASCT, n=21), or combination of ASCT and allogeneic stem cell transplant (n=3). Eight (23.5%) patients had elevated B2M >5.5 mg/L, twenty four (71%) patients had elevated LDH (> 2 times upper limit of normal) and 5 (14%) had secondary plasma cell leukemia. The mean interval from diagnosis of MM to diagnosis of CNS MM was 23.5 months (range: 3–121 months). At the time of diagnosis of CNS MM, 3 (8.6%) patients were in complete remission (CR) by standard criteria and 15 (42.9%) patients were in progressive disease (PD). Magnetic resonance imaging (MRI) was performed in 34 patients, showing diffuse or localized leptomeningeal disease in 20 (58.8%) patients, 3 (8.8%) patients had a combination of both leptomeningeal disease with adjacent breakout MM focal lesion, and 2 (6%) patients had MM focal lesions adjacent to the meninges and sinuses without leptomeningeal disease. All 35 patients had malignant plasma cells in CSF analysis. 31 patients received chemotherapy to include intrathecal chemotherapy (IT) as a part of their treatment. IT consisted of cytarabine, methotrexate and hydrocortisone +/− thiotepa. 28 patients were treated with both IT and SC together: alone (n=8), or in combination of ASCT (n=13), or combination of ASCT and cranial irradiation (CI) (n=4), or combination with CI (n=1), or combination with both CI and Allogeneic SCT (n=1), or with Allogeneic SCT (n=1). Conclusion:In our experience, CNS MM is an aggressive terminal disease feature associated with other poor prognostic disease features such as high B2M, LDH and secondary plasma cell leukemia. The present review suggests that the patterns for CNS involvement are variable, such as hematogenous spread of plasma cells seen in PCL, or direct continuous spread from the eroded lytic lesions of the skull. The available novel agents do not provide therapeutic concentrations of drug in the CSF as they do not cross the blood-brain barrier. The study highlights an unmet need in this subset of high risk, relapsed/refractory MM patients. Adequate CNS penetration needs to be considered in MM novel drug development.Table 1Neurological symptoms and signs with CNS-MMLimb Weakness37%Confusion29%Headache26%Seizure17%Visual disturbances17%Cranial nerve palsies17%Paraesthesia14%Nausea/Vomiting11%Speech disturbances6%Paraparesis6%Urinary incontinence2%Gait disturbances2% Disclosures:No relevant conflicts of interest to declare.

Detection of Malignancy in Body Fluid Cytology: A Comparison of the Hematology and the Cytology Laboratory

Detection of Malignancy in Body Fluid Cytology: A Comparison of the Hematology and the Cytology Laboratory

Establishing a cytology laboratory in a low-resource setting for cervical cancer screening

Background Against the background of the substantial burden of cervical cancer in low- and middleincome countries and the well-established and efficient Papanicolaou (Pap) smear screening as a preventive measure against this cancer, we set up a cytology laboratory in a jungle hospital in South India for indigenous people living under poor economic and hygienic conditions who may be prone to the development of these cancerous lesions.

Cost and logistics of alternative roll-out options for implementing human papillomavirus testing as a triage in cervical screening: results of the sentinel sites study

Background:Previous studies have indicated that human papillomavirus (HPV) testing as a triage for managing equivocal cytology is cost-effective. The aim of this study was to assess the costs of alternative roll-out options.Methods:Detailed cost estimates were collected from six laboratories where HPV triage had been implemented. Costs were assessed for the two different service delivery models that were implemented; a ‘hub and spoke model’ of central HPV testing in a microbiology laboratory with separate cytology laboratories, and an ‘integrated model’ where HPV testing was conducted within the cytology laboratory.Results:Comparison of alternative delivery models indicated that setting up HPV processing within existing cytology laboratory, i.e., an ‘integrated cytology/HPV laboratory’ generated savings in staff time amounting to between £2.54 and 4.86 per sample processed. Running full HPV testing batches was also an important consideration. For full batches to be run on a twice weekly basis requires having no more than two laboratories per Strategic Health Authority.Conclusions:To be cost-efficient, and to meet turn-around times, HPV testing needs to be conducted at integrated cytology/HPV testing centres with sufficient throughput to run full batches of HPV tests.

Commercial Molecular Panels Are of Limited Utility in the Classification of Pancreatic Cystic Lesions

The PathfinderTG biomarker panel is useful in the evaluation of pancreatic cysts that have clinical features suspicious for malignancy, but its utility in classifying fine-needle aspiration biopsies from small pancreatic cystic lesions is yet to be proven. We used morphology to classify 20 pancreatic cyst cytology aspirates, all of which met radiographic criteria for close observation. Cases were cytologically classified as consistent with pseudocyst, serous cystadenoma, or mucinous neoplasm with low-grade, intermediate-grade, or high-grade dysplasia and analyzed for carcinoembryonic antigen. Redpath Integrated Pathology Inc. rendered diagnoses of nonmucinous (reactive/indolent or serous) or mucinous (low-risk or at risk) cyst on the basis of results of the PathfinderTG panel (KRAS mutations, DNA content, and loss of heterozygosity at microsatellites linked to tumor suppressor genes). Cytologic and commercial laboratory diagnoses were concordant in only 7 (35%) cases. Seven cysts classified as mucinous with low-grade dysplasia by cytology were interpreted as nonmucinous on the basis of the PathfinderTG panel, 2 of which were resected mucinous cysts. Two pancreatitis-related pseudocysts were misdiagnosed as low-risk mucinous cysts; 1 mucinous cyst with low-grade dysplasia was considered at risk for neoplastic progression using the PathfinderTG panel. Only 1 cyst misclassified as pseudocyst by cytology, but low-risk mucinous cyst by molecular analysis, proved to be a mucinous cystic neoplasm with low-grade dysplasia after surgical resection. We conclude that the PathfinderTG panel may aid the classification of pancreatic lesions, but is often inaccurate and should not replace cytologic evaluation of these lesions.

Papanicolaou Test Results in a Cytology Laboratory: What Does It Take to Cause a Shift?

Papanicolaou Test Results in a Cytology Laboratory: What Does It Take to Cause a Shift?

Organization and evolution of organized cervical cytology screening in Thailand

ObjectiveTo describe phase 1 of an organized cytology screening project initiated in Thailand by the Ministry of Public Health and the National Health Security Office. MethodsWomen aged 35–60years were encouraged to undergo cervical screening in primary care units and hospitals through awareness programs. Papanicolaou smears were processed and reported at district or provincial cytology laboratories. Women with normal test results were advised to undergo repeat screening after 5years, while those with precancerous and cancerous lesions were referred for colposcopy, biopsy, and treatment. Information on screening, referral, investigations, and therapy were logged in a computer database. ResultsBetween 2005 and 2009, 69.2% of the 4030833 targeted women were screened. In all, 20991 women had inadequate smears; 27253 had low-grade squamous intraepithelial lesions; 15706 had high-grade squamous intraepithelial lesions; and 2920 had invasive cancers. Information on the management of precancerous lesions was available for only 17.4% of women referred for colposcopy. ConclusionAlthough follow-up data on women with positive test results were inadequately documented, the present findings indicate that provision of cytology services through the existing healthcare system is feasible.

Cervical Smear Photodiagnosis by Fluorescence

Fluorescence is widely investigated and can characterize general changes occurring in the state of the cell and the tissue during physiological and/or pathological processes, but the method has not been adopted for clinical use. We present a photodiagnostic device and a relevant evaluation method fitted to classical screening procedures. This method is based on the discovery of smear content intrinsic fluorescent markers. Meaningful spectral components of cervical smear samples differ from those measured in the entire live cervix. This article deals with the identification of changes in smear spectra in cervicitis and CIN2+ (cervical intraepithelial neoplasia of the second degree or higher) at 355 nm excitation. Methods used in the study: microlaser-induced fluorescence spectroscopy of liquid cytology samples and histological evaluation of the biopsies of the same cervix (and/or only cytological evaluation) was performed for 78 cases. The fluorescence spectra of cervical cytology supernatant sediment were approximated with several Gaussian components. The ratios of the area under each Gaussian component to the whole area under the experimental curve were calculated and compared among histological groups by using the Mann-Whitney test and receiver operating characteristic (ROC) analysis. The results of this study are a concise summary of the essential features verified by the data: the spectral regions 402-416 nm and 424-438 nm are important for the discrimination of both normal and CIN2+ groups (in terms of sensitivity, specificity, and positive predictive value). The spectral regions 480-515 nm and 595-625 nm are important for the identification of cervicitis. Cervical smear autofluorescence diagnostics could be useful for cancer screening at the point of care, in a simple cytology laboratory, and for the monitoring of treatment. We suggest possible fluorophores in the smear content.

American society of cytopathology workload recommendations for automated pap test screening: Developed by the productivity and quality assurance in the era of automated screening task force

Based on current literature and the best available research to date, the current FDA workload limits for automated image-assisted screening, including the ThinPrep Imaging System and the FocalPoint GS, of 100 slides/day (imaged only slides counted as 0.5) are extremely high and may be associated with significant reduction in sensitivity. This task force has proposed six recommendations relating to cytotechnologist (CT) workload in automated image-guided Pap test screening, which have already been endorsed by major pathology professional societies. These evidence-based recommendations, however, pertain only to gynecologic specimens with image-assisted screening, as there is no current available data to justify modifying screening practices regarding non-gynecologic specimens. The proposed recommendations are as follow: 1) CT workday should not include more than 7 hours of Pap test screening in a 24-hr period, and an 8-hr shift day must include at least 2 paid mini-breaks of 15 minutes each and a 30-minute lunch break. 2) Future Studies examining CT workload should use actual hours of screening rather than lesser number of hours extrapolated to 8-hour days. 3) Average laboratory CT workload should NOT exceed 70 slides/day (slides counted per 2010 FDA bulletin). 4) Proportion of imaged slides that undergo full manual review should be at least either 15%, or twice (2×) the epithelial cell abnormality (ECA) rate, whichever is greater. 5) ECA-adjusted workload measure is a promising method for calculating and monitoring CT workload, but further studies of this method are necessary before full endorsement. 6) CT productivity and workload limits are just one aspect of a good quality assurance program in a cytology laboratory, so other quality indicators to assess CT performance are essential.

The Positive Impact of Simultaneous Implementation of the BD FocalPoint GS Imaging System and Lean Principles on the Operation of Gynecologic Cytology

Our cytology laboratory, like many others, is under pressure to improve quality and provide test results faster while decreasing costs. We sought to address these issues by introducing new technology and lean principles. To determine the combined impact of the FocalPoint Guided Screener (GS) Imaging System (BD Diagnostics-TriPath, Burlington, North Carolina) and lean manufacturing principles on the turnaround time (TAT) and productivity of the gynecologic cytology operation. We established a baseline measure of the TAT for Papanicolaou tests. We then compared that to the performance after implementing the FocalPoint GS Imaging System and lean principles. The latter included value-stream mapping, workflow modification, and a first in-first out policy. The mean (SD) TAT for Papanicolaou tests before and after the implementation of FocalPoint GS Imaging System and lean principles was 4.38 (1.28) days and 3.20 (1.32) days, respectively. This represented a 27% improvement in the average TAT, which was statistically significant (P < .001). In addition, the productivity of staff improved 17%, as evidenced by the increase in slides screened from 8.85/h to 10.38/h. The false-negative fraction decreased from 1.4% to 0.9%, representing a 36% improvement. In our laboratory, the implementation of FocalPoint GS Imaging System in conjunction with lean principles resulted in a significant decrease in the average TAT for Papanicolaou tests and a substantial increase in the productivity of cytotechnologists while maintaining the diagnostic quality of gynecologic cytology.

36. What is the optimal pleural fluid volume?

<h3>Background</h3> Cytological examination of pleural fluid is a fast, efficient, and minimally invasive technique for establishing a diagnosis of cancer. Although many studies have looked at diagnostic yield comparing cytology with other modalities, few have evaluated the optimal pleural fluid volume needed to make a diagnosis of malignancy. <h3>Aims</h3> To determine if a diagnosis of malignancy becomes more likely as the volume of pleural fluid sampled increases. <h3>Method</h3> The volumes of cytologically diagnosed malignant pleural fluid samples submitted to The Prince Charles Hospital Cytology Laboratory between 2000 and 2009 were retrospectively compared to a control group comprising the negative samples submitted during the months of January of the same period. A total of 326 malignant samples from 271 patients were submitted during this interval. The control group consisted of 61 samples from 57 patients. Six groups of pleural fluid volume were establish-ed:<5mL, 5–10mL, >10–20mL, >20–50mL, >50–200mL, and >200mL. <h3>Results</h3> 27.6% of the malignant samples were in the >20–50mL group compared to 8.2% of the controls; 32.8% of the control samples were in the <5mL group compared to 12.6% of the malignant samples. The likelihood of a malignant diagnosis being reached increases as the volume of fluid increases. Conversely, as the volume approaches zero, the likelihood of returning a malignant diagnosis approaches zero. The peak in likelihood is at 20–200mL but odds remain high at >200mL. <h3>Conclusion</h3> Submitting 20–200 mL is optimal and <10mL is not advisable as it is likely to return a false negative result. Possible reasons for the decline at >200mL are discussed.

Improvement in the routine screening of cervical smears

High rates of false-negative results constitute a routine problem in cytology laboratories. Of currently available internal quality control methods, 10% random review is the least effective in detecting false-negatives in routine screening. There is evidence that 100% rapid review and rapid prescreening perform well for this purpose. This study compared the performance of rapid prescreening and 100% rapid review as internal quality control methods for cervical cytology exams. Over 27 months, 12,208 cervical cytology smears were submitted to rapid prescreening and routine screening. The 100% rapid review method was performed on all smears classified as negative or unsatisfactory at routine screening. Conflicting results obtained with either method were reviewed in detail to define final diagnosis, which was considered the gold standard for evaluating the performance of rapid prescreening and 100% rapid review. Compared with final diagnosis, the sensitivity of routine screening and rapid prescreening was 72.9% and 75.6%, respectively. Considering only smears classified as negative or unsatisfactory at routine screening, the sensitivity of rapid prescreening and 100% rapid review was 90.2% and 57,0%, respectively. Of 244 cases (2.0%) of false-negative results at routine screening, rapid prescreening identified 220 cases (1.80%), whereas 100% rapid review identified 140 (1.15%). Rapid prescreening detected all cases of HSIL identified as false-negatives. Rapid prescreening is more effective than 100% rapid review for the detection of false-negatives at routine screening, thus providing subsidies for the performance of cervical cytology, the principal function of which is to detect precursor lesions of cervical cancer.

Quality control in cervicovaginal cytology by cytohistological correlation

Frequent studies attest to the correlation of cytological interpretations with defined histopathological entities. Nevertheless, as part of quality control, cytology laboratories are required to compare Papanicolaou smear reports with those of cervical biopsies to search for discrepancies. We have attempted to determine and categorize the causes of existing discrepancies in our laboratory in order to clarify the source of errors. We reviewed 670 cervical smears that were paired with subsequent punch biopsy or endocervical curettage samples, obtained within 2 months of the cytology, and found out that 60 smear-biopsy pairs were discrepant regarding the diagnosis. These cases were categorized into four error groups after careful re-evaluation of the original smear and biopsy slides. In 51 (85%) of 60 cervical smear-biopsy pairs with reports that disagreed, the initial diagnoses of both cervical smear and biopsy were confirmed by the review opinion; in these cases, cytology and biopsy 'sampling errors' were responsible for 40 and 11 instances of discrepancy, respectively. Seven cases (11.1%) were discrepant due to 'smear interpretation errors' and consisted of five cases with initial under-diagnosis and two cases with initial over-diagnosis. One case (1.7%) was due to 'screener error'. In another case, discordance was due to cervical 'biopsy interpretation error', with initial over-diagnosis as squamous intraepithelial lesion. In this retrospective study, we determined the causes of cytohistological discrepancies in cervical samples. The main explanation for discrepancy was 'sampling error'.

Korrelation zytologischer und histologischer Befunde an der Cervix uteri

A lack of correlation of cytological diagnoses with subsequent histological tissue diagnoses in cervical pathology is caused by either sampling or by interpretation errors. The term sampling error refers to both obtaining cytological material by a cervical smear as well as obtaining tissue samples by surgical procedures such as biopsy or conization. The term interpretation error refers to a lack of correlation as a consequence of the subjective variability in the diagnostic evaluation of cytological, histological or colposcopic findings. This so-called interobserver variability is well known and of considerable significance. Cytological-histological correlation is an important and mandatory method of quality assurance in the cytology laboratory. Lack of correlation can be crucial for the patient because of possible over treatment or under treatment. It can also undermine the relationship between cytopathologists and clinicians. It is therefore crucial to recognize the sources of error presented in this review and to make an effort to resolve discordances by communication and second review.