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Sonya Naryshkin,1 R Marshall Austin21Department of Pathology, Mercy Health System, Janesville, WI; 2Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USAObjective: To increase awareness of the limitations of high-risk human papillomavirus (hrHPV) laboratory-developed testing (LDT) widely used in US cervical cancer screening.Methods and results: A young woman in her 30s was diagnosed and treated for stage 1B1 cervical squamous cell carcinoma in which HPV 16 DNA was detected using polymerase chain reaction testing. Both 1 month before and 42 months before cervical cancer diagnosis, the patient had highly abnormal cytology findings; however, residual SurePath™ (Becton, Dickson and Company, Franklin Lakes, NJ) vial fluid yielded negative Hybrid Capture 2 (HC2; Qiagen NV, Hilden, Germany) hrHPV LDT results from each of the two specimens. This prompted questions to be asked concerning the performance characteristics of hrHPV LDT. A review of the available data indicates that (1) purification of DNA from SurePath specimens requires complex sample preparation due to formaldehyde crosslinking of proteins and nucleic acids, (2) HC2–SurePath hrHPV testing had not been Food and Drug Administration-approved after multiple premarket approval submissions, (3) detectible hrHPV DNA in the SurePath vial decreases over time, and (4) US laboratories performing HC2–SurePath hrHPV LDT testing are not using a standardized manufacturer-endorsed procedure.Conclusion: Recently updated cervical screening guidelines in the US recommend against the use of hrHPV LDT in cervical screening, including widely used HC2 testing from the SurePath vial. The manufacturer recently issued a technical bulletin specifically warning that use of SurePath samples with the HC2 hrHPV test may provide false negative results and potentially compromise patient safety. Co-collection using a Food and Drug Administration-approved hrHPV test medium is recommended for HPV testing of patients undergoing cervical screening using SurePath samples.Keywords: HPV, SurePath, Hybrid Capture 2, LDT, cervical screening

This review includes the facts of bladder treatment by means of laser technologies application in historical perspective. Advantages and disadvantages of different laser technologies were considered in comparison with the traditional TUR of the bladder wall.

The article describes the clinical observation of the patient 84 years old with prostate cancer T2bNxM0, left kidney cancer T1N0M0 and severe comorbidity. Stepwise interstitial laser coagulation was performed using the Russian microsecond Nd: YAG laser surgical complex.

The article presents the results of endoscopic and nephrolithotripsy and ureterolithotripsy in 73 overweight patients (body mass index of over 30 kg/m2) with kidney stones and urinary tract infections of different locations compared with 30 patients without obesity. The features of choice of tactics of surgical treatment and access, possible complications and their prevention are described.

A comparative analysis of the effectiveness of open and percutaneous operations in the treatment of bilateral staghorn nephrolithiasis (SN) was performed. Of the 38 patients with bilateral SN, stage operation (without discharge) was performed in 26 (68.5%) patients, and single-step operation--in 12 (31.5%) patients. For the 47 patients with bilateral SN, who underwent open surgery, the interventions were following: pelviolithotomy (64 operations), nephrolithotomy (21 operations), nephrectomy (9 operations). Surgery was performed in stages on each side, but unlike percutaneous operations, with discharge from the hospital. When using open surgery, only in 27 of the 47 patients complete discharge of kidney stones was achieved. A comparative analysis of single-step and stage surgery for bilateral SN revealed no significant difference in the duration of surgery and intraoperative blood loss (p > 0.1); endoscopic surgery compared with open surgery is characterized by significantly lower intraoperative blood loss and postoperative in-hospital stay (p < 0.001).

Interstitial laser coagulation (ILC) is one of the effective methods of minimally invasive destruction of small renal tumors. For the safe use of ILC in clinical practice, it is necessary to select the optimal mode of action of laser radiation on the tissue of target organ and techniques for the procedure. The effects of ILC on kidney tissue in 6 rabbits weighing less than 3 kg and 5 mongrel dogs weighing up to 20 kg were investigated in vivo. The impact of ILC was made intraoperatively. Organ retrieval in experimental animals for the macro- and microscopic examination was performed immediately after the impact of ILC and at various times thereafter during the month in rabbits and 35 days in dogs. Morphological study in different periods after exposure allowed to establish phasing and volumes of changes in the tissues of the kidney, confirming the safety and efficacy of ND:YAG laser irradiation on kidney tissues. The results indicate the possibility of effective application of ILC of kidney tissues for destruction of small size tumors, without impairment of functions of the organ.

Context: The College of American Pathologists (CAP) conducted a national survey of gynecologic cytology quality assurance (QA) practices. Experts in gynecologic cytology were asked to join 5 working groups that studied the survey data on different aspects of QA. Evaluating the survey data and follow-up questions online, together with a review of pertinent literature, the working groups developed a series of preliminary statements on good laboratory practices in cytology QA. These were presented at a consensus conference and electronic voting occurred., Objective: To evaluate a set of QA monitors in gynecologic cytology. Working group 1 evaluated (1) monitoring interpretive rate categories for Papanicolaou tests (Pap tests), (2) concordance of cytotechnologist and pathologist interpretations before sign-out, and (3) turnaround time for Pap tests., Data Sources: The statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees., Conclusions: The outcomes of this process demonstrate the current state of practice patterns in gynecologic cytology QA. Monitoring interpretive rates for all Bethesda System categories is potentially useful, and it is most useful to monitor interpretive rates for cytotechnologists individually and in comparison to the entire laboratory. Laboratories need to determine what level of discrepancy between cytotechnologist and pathologist interpretations of Pap tests is important to track. Laboratories should consider formalizing procedures and policies to adjudicate such discrepant interpretations. Turnaround time should be monitored in gynecologic cytology, but individual laboratories should determine how to measure and use turnaround time internally.

Background: The reliability of patient history and clinical information on Pap test requisitions has been questioned but not previously objectively determined. The effect of incomplete/inaccurate information on quality of patient care has not been previously quantified. Our objectives were (1) to find out how clinicians and their assistants viewed the requisition slip, and whether they understood the reasons for supplying the information requested, (2) to measure the completeness and accuracy of information on the requisition slips, and (3) to determine whether the clinical information and patient history provided on Pap test requisitions could be relied upon to accurately assign a Pap test to the laboratory's "high-risk rescreen" pool., Methods: Clinicians and their assistants were surveyed. A total of 899 consecutive Pap test requisition slips were reviewed. Patient history and clinical information from the slips were compared to data from our laboratory information system and/or electronic patient medical records., Results: Most survey respondents felt that proper completion of requisitions was important, but only 17% of clinicians and less staff realized that negative high-risk Pap tests underwent a quality assurance rescreen. Clinicians and/or staff recorded the last menstrual period, specimen source, and clinical information on the requisition slips 96%, 97%, and 88% of the time, respectively. Of 695 Pap tests with applicable computerized records, 171 (25%) qualified for high-risk rescreen based upon information provided on the requisition slip alone. An additional 52 Pap tests (7%), or 23% of the total high-risk Pap tests were discovered to be of high risk only after review of the electronic records., Conclusions: Clinicians and staff were receptive to discussions concerning the completion of requisition slips, but laboratory expectations could be better communicated. Requisition slips were properly completed with a high frequency, but the check boxes did not elicit all the information expected, so revision was necessary. The high accuracy of the completion of requisition slips permitted 77% of high-risk Pap tests to be identified via the requisition slip alone. Our findings challenge the conventional anecdotal impressions of "notoriously unreliable" information on Pap test requisition slips, but our experience may not be applicable to other settings.

Proficiency testing in cytopathology and in other disciplines should be based on firm statistical and scientific foundations, because test theory in general is a heavily statistical subject. Statistical considerations have demonstrated that the design of "short" proficiency tests in cytopathology, including the current federally mandated test, fundamentally is unsound because of the lack of sufficient validity and reliability. Examinees too frequently are misclassified by such short-format tests: Competent examinees fail the test in surprisingly high numbers, whereas most of the examinees who have insufficient cytologic skills eventually pass the test after the allowed retakes. Only dichotomous tests are suitable for accurate computation of the effects of test design on reliability, but the statistical conclusions also are generalizable to nondichotomous tests. In conclusion, the current federally mandated proficiency test cannot reliably measure the level of expertise of cytologists and, thus, cannot assure that only adequately skilled individuals evaluate Papanicolaou test samples. To render the test suitable for its intended purpose, the authors believe that complete redesign of the test, with the participation of experts in modern test theory, would be advisable., (2007 American Cancer Society)

A clinically approved method for assessing the radiation load on surgical team members during an endourologic intervention under X-ray monitoring is described.

The Pap test is a successful method of preventing cervical cancer, but it does have significant false negative and false positive rates. The main aim of screening is the detection of precursor lesions, both regression and progression of which may occur, making it difficult to decide upon follow-up and further therapy. Around the world there are many differences, as a far as the frequency of the disease, the organization and economic background of the health care system, the use of different additional diagnostic tools and even the terminology considered. All these factors underline the importance of a consensus on a "minimum level" of obligations to provide appropriate patient management. The screening interval should be two to five years, in some cases even annually. The cytopathologist has an obligation to recommend repeat smears in cases of cytologic abnormalities likely to regress. We recommend the use of standard terminology and stress the importance of a "common language" in cervical cytology. Colposcopy and biopsy are obligatory in cases of HSIL and cancer. We suggest that in severe cases women should be provided with detailed written and verbal information.

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.

Screening error rates have been measured in various ways. The false-negative fraction is advantageous because it is valid for comparisons between laboratories, which is crucial if standards for error rates are to be developed. False-negative fractions reported or calculated from data in the literature range from approximately 2% to 28%. Some of the highest published rates have come from prestigious academic laboratories. The lowest rates are from studies that covered terms of a year or less and in which only small parts of each slide were rescreened or the rescreeners were relatively inexperienced. Before standards for false-negative fractions can be set, we must collect more data and encourage more laboratories to measure the false-negative fraction.

Objective: To evaluate current laboratory practices and rates for atypical squamous cells of undetermined significance (ASCUS), a category of epithelial cell abnormality in the Bethesda System., Design: Questionnaire surveys were mailed in December 1993 and March 1994., Setting: Cytopathology laboratory participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP)., Results: Most responding laboratories (82.5%) limited the use of "atypia" terminology to abnormalities of undetermined significance. Nearly half of the laboratories employed only the term ASCUS for squamous epithelial changes in this category. The median rate of ASCUS in 1993 was 2.8%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion rate was 2.0%, with a median ASCUS-squamous intraepithelial lesion ratio of 1.3. The majority of laboratories qualified a portion of ASCUS cases and issued recommendations for follow-up when appropriate. Fifty-six percent of laboratories surveyed included patients diagnosed with ASCUS in follow-up programs. Laboratories estimated that about 20% (median response) of patients with ASCUS smears had a squamous intraepithelial lesion or equivalent diagnosis made within a year's follow-up., Conclusions: The ASCUS category is used by the majority of laboratories as recommended by the Bethesda System, but reporting rates vary. The results of this survey and associated surveys provide laboratories with useful benchmark figures for interlaboratory comparison of ASCUS practices.

The Bethesda System recognizes "Atypical Squamous Cells of Undetermined Significance" (ASCUS) as a category of epithelial cell abnormality. Neither the acceptable rate of ASCUS nor the clinical follow-up are well defined. This study focused on interlaboratory comparison and quality assurance methods for evaluating the rate and outcome of ASCUS. Data was collected from questionnaire surveys from the College of American Pathologists Interlaboratory PAP Program and the four authors' laboratories. Most PAP laboratories (82.5%) limit the use of "atypia" terminology to abnormalities of undetermined significance. According to PAP data, the median rate of ASCUS in 1992 was 2.9%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion (SIL) rate was 2.2%, with a median ASCUS/SIL ration of 1.3. The authors' laboratories (university, independent, and hospital) revealed ASCUS rates of 1.6-9.0%, while SIL rates were 2.1-9.0%. The ASCUS/SIL ratio was less variable, 0.8-2.7. Follow-up of ASCUS patients in the authors' laboratories showed 10.3-43% with SIL, but less than 6% with high grade SIL. The ratio ASCUS/SIL may serve as a useful laboratory monitor. Peer review and follow-up studies of ASCUS serve to validate laboratory criteria and consequent clinical follow-up. Communication with clinicians is vital in ensuring optimal patient care.

The reproducibility of reporting squamous lesions by the Bethesda System (TBS) was evaluated by distributing 20 slides to be classified among 5 panelists considered experts in the field of cytopathology. Four cases were chosen for their classic morphology and the remainder were foreseen to produce possible discrepancies within one diagnostic category. For 7/20 (35%) cases there was unanimous agreement. Participants disagreed within one category of magnitude for seven (35%) cases. In six (30%) cases there was a range of more than one category disagreement. However, additional written comments modifying TBS diagnoses often diminished the clinical significance of these discrepancies. We conclude that despite the important role of TBS in standardization of Pap smear reports, a great degree of subjectivity exists in classifying squamous abnormalities without "classic" morphology. The lack of reproducibility should be taken into account in cytology proficiency testing.

At our institution, gynecologists perform Pap smears not only as an initial screening procedure but also at the time of colposcopy and biopsy. We compared the results of initial Papanicolaou (Pap) smears with those taken at colposcopic biopsy to determine if repeating the Pap smear at the time of colposcopy contributed to patient management. We found that repeat colposcopic smears often agreed with the referral smears and biopsies. When there was disagreement, the colposcopic smear was more often a lower grade than the referral smear and correlated best with the biopsy. Both referral and colposcopic smears underestimated the severity of cervical lesions with the same frequency. We could document only 5/414 (1.2%) colposcopic smears that contributed to patient care.

The few guidelines that exist for performing autopsy quality assurance are vague. Much has been written about the use of the autopsy to monitor clinical services, but not how to monitor the quality of the autopsy and autopsy reports. We present the comprehensive quality assurance program that has been developed and implemented at Hahnemann University Hospital, Philadelphia, Pa, for the past 2 years; this program has encompassed quality control of our diagnostic work. Key features have included in-depth peer review of completed reports, documentation of review at conferences, and careful monitoring of turnaround time. We have found that integrating quality assurance into departmental conferences is a useful supplement to in-depth peer review of randomly chosen autopsies. Our approach to quality assurance may serve as a model for other pathology departments, particularly those with pathology residency training programs.

Transmission electron microscopy (TEM) is an important adjuvant to light microscopy, but is underutilized in cytopathology because of technical obstacles. One should attempt to obtain properly fixed material for TEM whenever possible. If that is not available, TEM on the cell block requires no preplanning or additional needle passes, and avoids problems of inadequate tissue for diagnosis. However, cell blocks are often not examined because of the perception that their poor ultrastructural preservation precludes their utility. We describe our experience in performing TEM on cell blocks from 15 cytologic specimens. In 13 of 15 cases, the cell block material was adequate for ultrastructural evaluation, and it clarified or extended the diagnosis in seven of these cases. TEM is a useful adjuvant technique to cytodiagnosis and can be successfully performed on cell blocks when gluteraldehyde-fixed material is not available.

Respiratory cytology has its share of pitfalls. Some, such as vegetable cell contaminants, pose problems for only inexperienced observers, while others, such as reactive bronchoalveolar cells from pneumonia, can lead even experienced cytopathologists to make a misdiagnosis of malignancy. This review illustrates and analyzes those benign conditions or entities known to mimic malignancy in exfoliative respiratory cytology and fine-needle aspiration biopsy of the lung. Entities are grouped by the type of malignancy they mimic, and guidelines are presented for avoiding specific pitfalls.

The objective of this investigation was to test the hypothesis that blood glutathione levels are lower in aging human subjects as previously found in blood and tissues of standard rodent models of aging. Thus a study was conducted with 39 men and 130 women, 20 to 94 years old, who were selected by the criteria of being ambulatory, healthy, and free from diabetes mellitus, thyroid disease, anemias, and cancer. The reference group was comprised of the 20- to 39-year-old subjects, whose blood glutathione levels were 547 +/- 53.5 micrograms/10(10) erythrocytes (mean +/- SD) for 40 individuals and defined the reference range (95% confidence limits) of 440 to 654. Based on the 440 micrograms/10(10) erythrocyte cutoff, the incidence of low blood glutathione content in the older subjects increased significantly, particularly in the 60- to 79-year-old group. Their glutathione levels were 452 +/- 86.8 micrograms/10(10) erythrocytes, 17% lower than the reference group (p < 0.001). These findings demonstrate an increased incidence of low glutathione levels in apparently healthy elderly subjects, who thus may be at risk because of a decreased capacity to maintain many metabolic and detoxification reactions mediated by glutathione.

The reliability of bronchoscopic cytology relative to biopsy is controversial. Some still consider biopsy the definitive procedure. Comparative studies are few and limited in scope. Therefore, we compared simultaneously obtained biopsies and cytologies for 224 cases. One hundred and sixty-six cases (74.6%) correlated completely. Forty-four cases (19.6%) did not correlate and cytology was diagnostic in 24 of these. Biopsy was diagnostic in sarcoidosis and vasculitis, whereas cytology only excluded the presence of neoplasm or infection. In 14 cases (5.8%), biopsy and cytology showed pathologic changes, but one or the other was more definitive. Rarely, the 2 techniques provided complementary information. A specific diagnosis was obtained more often from the combination of cytology and biopsy than from either alone. However, when biopsy is contraindicated it is reassuring that cytology usually yields the same information as biopsy, and can detect neoplastic and infectious diseases when the biopsy is non-diagnostic.

We report a rare case of acute renal failure secondary to bilateral renal parenchymal metastases from carcinoma. Despite clinical investigation the cause of the renal failure remained undiagnosed and was discovered only upon microscopy at autopsy, which revealed metastatic gastric adenocarcinoma. The pattern of tumor infiltration was predominantly lymphatic involvement limited to the vascular bundles at the corticomedullary junction, and the lymphatics adjacent to the calices and pelves. The significance of lymphatic obstruction in the pathogenesis of renal failure is discussed. Renal parenchymal metastases should be considered in the differential diagnosis of acute renal failure in patients with carcinoma.

Fine-needle aspiration biopsy of pancreatic lesions is becoming widespread. Pathologists need to be familiar with the cytologic features of pancreatic tumors, of which cystic neoplasms are a distinct subset. Of our 31 pancreatic aspirates diagnostic of neoplasia, six were diagnosed as cystic by radiographic imaging. These cases were compared. Similar symptoms were experienced by all of these patients, although those with malignant tumors lost the most weight. Loss of border definition, ascites, and liver metastases were the only radiologic clues to malignancy. Each entity had distinguishing cytologic features. These cases illustrate the importance of knowing the clinical, radiologic, and cytologic features of pancreatic cystic neoplasms to arrive at a preoperative diagnosis and determine proper treatment.

Intraoperative fine needle aspiration biopsy (NAB) of undiagnosed pancreatic masses was studied in 166 patients over a 17-year period. The cytologic diagnoses were correlated with histologic specimens, autopsy results, or clinical follow-up (benign disease was documented if the patient was alive without malignancy at least 2 years after laparotomy). Aspirates were interpreted as benign, suspicious, malignant, or unsatisfactory. Malignant disease was the final diagnosis in 109 patients; the cytology was concordant in 101 and was interpreted as suspicious in four. Four patients with benign cytology later proved to have malignant disease--a false-negative rate of 2.5 per cent. A total of 57 patients had benign disease; 51 of these had benign cytology. The remaining patients had "unsatisfactory" cytology reports. A 93 per cent sensitivity, 100 per cent specificity, and 0 per cent complication rate are reported. There were no false-positive cytology reports. Complications are rare and represent case reports, thus, additional sampling is at minimal risk. Intraoperative pancreatic NAB is a safe, easy, more accurate biopsy technique than historical wedge or core needle biopsies. It is the biopsy method of choice for pancreatic masses found at laparotomy.