Precancerous cervical lesions and HPV genotypes identified in previously unsatisfactory cervical smear tests after inexpensive glacial acetic acid processing.

OBJECTIVE: To determine the effectiveness of using glacial acetic acid (GAA) to convert unsatisfactory bloody ThinPrep (TP) cervical smear test to satisfactory, and identify associated missed diagnoses and high-risk HPV (hrHPV) genotypes. METHODS: In a retrospective descriptive cross-sectional analysis, all TP tests performed in Mississippi, USA, 2012-2016, were evaluated for unsatisfactory results owing to blood. Tests that were converted to satisfactory by GAA treatment, and corresponding anomalies and HPV genotypes were identified. RESULTS: Among 106 384 TP tests, there were 1460 (1.37%) unsatisfactory results, of which 1442 (98.77%) were converted to satisfactory after GAA treatment. Laboratory preprocessing with GAA increased costs minimally. Precancerous lesions were detected in 166 (11.51%) of 1442 GAA-treated samples, of which 12 (7.2%) were high-grade lesions, 110 (66.3%) were atypical squamous cells of undetermined significance, and 63 (57.3%) tested positive for hrHPV. Of 60 genotyped samples, 39 (65%) had non-HPV16 and non-HPV18. Including mixed infections, 48 (80%) contained less-common hrHPV types, reflecting an unexpected distribution in bloody specimens. CONCLUSIONS: GAA pretreatment of bloody TP tests would reduce the incidence of unsatisfactory results and missed high-grade lesions, and prevent the cost of repeat tests and delayed treatment. Clinicians without access to GAA should consider HPV testing.

A prospective assessment defining the limitations of thyroid nodule pathologic evaluation.

BACKGROUND: Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined. OBJECTIVE: To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses. DESIGN: Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010. SETTING: 14 academic and 35 community clinical sites. PATIENTS: 653 patients with 776 surgically resected thyroid nodules of 1 cm or greater. MEASUREMENTS: Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists. RESULTS: Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%). LIMITATIONS: Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule. CONCLUSION: Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis. PRIMARY FUNDING SOURCE: Veracyte.

Quality and patient safety in the diagnosis of breast cancer.

The media, medical legal, and safety science perspectives of a laboratory medical error differ and assign variable levels of responsibility on individuals and systems. We examine how the media identifies, communicates, and interprets information related to anatomic pathology breast diagnostic errors compared to groups using a safety science Lean-based quality improvement perspective. The media approach focuses on the outcome of error from the patient perspective and some errors have catastrophic consequences. The medical safety science perspective does not ignore the importance of patient outcome, but focuses on causes including the active events and latent factors that contribute to the error. Lean improvement methods deconstruct work into individual steps consisting of tasks, communications, and flow in order to understand the affect of system design on current state levels of quality. In the Lean model, system redesign to reduce errors depends on front-line staff knowledge and engagement to change the components of active work to develop best practices. In addition, Lean improvement methods require organizational and environmental alignment with the front-line change in order to improve the latent conditions affecting components such as regulation, education, and safety culture. Although we examine instances of laboratory error for a specific test in surgical pathology, the same model of change applies to all areas of the laboratory.

Multimodal hyperspectroscopy as a triage test for cervical neoplasia: pivotal clinical trial results.

OBJECTIVE: To prospectively evaluate a new non invasive device that combines fluorescence and reflectance spectroscopy in a population in women at risk for cervical dysplasia. METHODS: A total of 1607 women were evaluated with multimodal hyperspectroscopy (MHS), a painless test with extremely high spectral resolution. Subjects who were referred to colposcopy based on abnormal screening tests or other referral criteria underwent the MHS test and also had a sample taken for additional cytology and presence of high risk human papilloma virus (HPV) prior to undergoing biopsy. RESULTS: Sensitivity of MHS for cervical intraepithelial neoplasia (CIN) 2+ was 91.3% (252/276). Specificity, or the potential reduction in referrals to colposcopy and biopsy, was 38.9% (222/570) for women with normal or benign histology and 30.3% (182/601) for women with CIN1 histology. Two year follow-up data, collected for a subgroup of 804 women, revealed 67 interval CIN2+ that originally were diagnosed at enrollment as normal or CIN1. MHS identified 60 of these (89.6%) as positive for CIN2+ prior to their discovery during the two year follow-up period. CONCLUSIONS: MHS provides an immediate result at the point of care. Recently, the limitations of cytology have become more obvious and as a consequence greater emphasis is being placed on HPV testing for cervical cancer screening, creating a need for an inexpensive, convenient and accurate test to reduce false positive referrals to colposcopy and increase the yield of CIN2+ at biopsy. MHS appears to have many of the attributes necessary for such an application.

Evaluating the connections between primary care practice and clinical laboratory testing: a review of the literature and call for laboratory involvement in the solutions.

CONTEXT: Growing evidence has demonstrated a high frequency of quality gaps in laboratory medicine, with recent studies estimating that 15% to 54% of primary care medical errors reported by primary care physicians and staff are related to the testing process. However, there is lack of evidence-based performance metrics in the preanalytic and postanalytic phases of the testing pathway for primary care practices. OBJECTIVE: To use results of the literature review to assist in the development of quality indicators that could improve preanalytic and postanalytic processes in primary care-based laboratory medicine. DATA SOURCES: Literature in Ovid/MEDLINE from 2001 through 2011 was searched as a primary source of information. Ninety-five peer-reviewed and non-peer-reviewed publications were retrieved following title and abstract review and 10 articles were reviewed in their entirety by the authors. A systematic review of the literature was conducted regarding the connections between clinical laboratories and primary care offices and the resulting errors. Root causes of errors were categorized into 7 major themes: process failures, delays, communication gaps, errors in judgment and cognition, influence of minorities/language, practice culture, and lack of patient centeredness. Selected articles were evaluated for evidence quality using the Systematic Evidence Review and Evaluation Methods for Quality Improvement grading scale developed by the Centers for Disease Control and Prevention. CONCLUSIONS: The focused literature review documented 7 key error themes in the laboratory medicine/primary care testing process. Performance metrics related to these themes are proposed that deserve future study for evidence-based improvement.

Discrepancies in dermatopathology diagnoses: the role of second review policies and dermatopathology fellowship training.

BACKGROUND: Expert consultation and institutional policies mandating second review of pathologic diagnoses in the course of referral have been advocated to optimize patient care. OBJECTIVE: We sought to investigate the rate of diagnostic discrepancies between pathologists with and without dermatopathology fellowship training. METHODS: All available outside pathology reports were reviewed for material sent to the University of Pittsburgh Medical Center Dermatopathology Unit during 1 year. The outside diagnosis was compared with the diagnosis rendered by the referral dermatopathology service. Cases were assigned into 1 of 4 categories: melanocytic neoplasm, nonmelanocytic neoplasm, inflammatory, and other. For each case, the outside pathologist's level of dermatopathology training was noted. Any change in diagnosis resulting in significant alteration in therapy or prognosis, as dictated by the accepted standard of care, was considered a major discrepancy. RESULTS: A total of 405 cases were reviewed. In 51 cases (13%), no preliminary diagnosis was rendered at the outside facility. The referral diagnosis differed from the outside diagnosis in 226 cases (56%), and major discrepancies were identified in 91 cases (22%). Of these 91 cases, 84 were received from outside pathologists who were not dermatopathology trained and 7 were received from pathologists with dermatopathology training. The 91 cases with major discrepancies were categorized as: 36 nonmelanocytic neoplasms (40%), 30 inflammatory (33%), 23 melanocytic neoplasms (25%), and 2 other (2%). LIMITATIONS: This was a retrospective study limited to 2 consultant dermatopathologists at an academic referral center, which typically receives and reviews select cases. CONCLUSION: Dermatopathology fellowship training is associated with a substantial decrease in major diagnostic discrepancies. Pathologists without dermatopathology fellowship training tend to successfully identify those cases for which expert consultation is most useful.

Preoperative diagnosis of benign thyroid nodules with indeterminate cytology.

BACKGROUND: Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. METHODS: We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed. RESULTS: Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. CONCLUSIONS: These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).

Liquid-based Papanicolaou tests in endometrial carcinoma diagnosis. Performance, error root cause analysis, and quality improvement.

Recent reports show that the sensitivity of endometrial carcinoma detection on liquid-based Papanicolaou (Pap) tests (88%) is considerably higher than that reported on conventional Pap smears (20%-30%), although few laboratories have corroborated these results. We performed a 5-year retrospective review of all liquid-based Pap tests (n = 69) in women who later were given a diagnosis of endometrial carcinoma, performed error root cause analysis, and developed quality improvement initiatives as a means of error reduction. The original and rescreened Pap test sensitivity rates for endometrial carcinoma were 31.9% and 59.3%, respectively. Root cause analysis showed that poor specimen quality and cognitive failures contributed to a false-negative error in 67% (18/27) and 59% (16/27), respectively, of all cases. System analysis showed that latent factors contributing to error included lack of redundant and educational systems. We conclude that system redesign of liquid-based Pap test screening processes has the potential to improve sensitivity in endometrial carcinoma diagnosis.

Lessons learned from successful Papanicolaou cytology cervical cancer prevention in the Socialist Republic of Vietnam.

UNLABELLED: In 1996, we documented that the burden of cervical cancer in Vietnam was associated with troop movements during the Vietnam War. Subsequently, establishment of Papanicolaou screening in southern Vietnam was associated with reductions in cervical cancer incidence from 29.2/100,000 in 1998 to 16/100,000 in 2003. This is one of the first English-language reports of a real-world cervical cancer prevention effort associated with a decisive impact on health outcomes in a contemporary developing country. LESSONS LEARNED: if our ideological commitment is to improve health outcomes as rapidly as possible among as many people as possible, then Papanicolaou screening (with or without HPV or visual screening) must be implemented without further delay in any setting where cervical screening is appropriate but unavailable; consideration must be given to HPV vaccination after, rather than before, full coverage of target demographic groups by screening services has been achieved and/or the possibility has been excluded that HPV vaccination may be ineffective for cancer prevention. Competing ideological commitments engender imprudent yet commercially useful alternative strategies prone to decelerate global reductions in mortality by suppressing the more-rapid uptake of less-expensive open-source technology in favor of the less-rapid uptake of more-expensive proprietary technologies with uncertain real-world advantages and unfavorable real-world operational limitations. Global cervical cancer prevention efforts will become more effective if global health leaders, including the Bill & Melinda Gates Foundation, embrace an ideological commitment to improving health outcomes as rapidly as possible among as many people as possible and assimilate the policy implications of that commitment.

Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing.

Although rapid prescreening (RPS) has been shown to be an effective quality control procedure for detecting false-negative conventional Papanicolaou (Pap) tests, RPS has not been widely implemented in the United States. In our laboratory, cytotechnologists performed RPS in 3,567 liquid-based Pap tests: 1,911 SurePath (BD Diagnostics-TriPath, Burlington, NC) preparations that were manually screened and 1,656 ThinPrep Pap tests (Hologic, Bedford, MA) that were imaged using the ThinPrep Imaging System (Hologic). We compared the sensitivity of RPS, 10% rescreening (R-10%), and routine screening (RS). In contrast with previously published findings, we found that RS + RPS did not improve screening sensitivity compared with RS + R-10%. These results support the following hypotheses: (1) Higher baseline RS sensitivity as a result of Pap test diagnoses standardization implemented for quality improvement purposes decreases the performance impact of RPS. (2) R-10% and RPS quality assurance methods detect diagnostic failures caused by different types of cognitive errors.

Assessment of latent factors contributing to error: addressing surgical pathology error wisely.

CONTEXT: Methods to improve surgical pathology patient safety include measuring the frequency of error in specific steps of the surgical pathology testing process, root cause analysis of active and latent components, and implementation of quality improvement initiatives. OBJECTIVE: To determine the frequency and cause of near-miss events in the specimen accessioning, setup, and biopsy-only gross examination testing steps of anatomic pathology. DESIGN: We used an observational checklist method to identify near-miss events. We performed root cause analysis to determine latent factors contributing to near-miss events. We conducted observations for 45 hours during 5 days, involving the accessioning and processing of 335 specimens. RESULTS: We detected a total of 2310 process-dependent and 266 operator-dependent near-miss events, resulting in a near-miss-event frequency of 5.5 per specimen. Root cause analysis showed that all process and operator near-miss events were associated with multiple system latent factors, including lack of standardized protocols, appropriate knowledge transfer, and focus on safety culture. CONCLUSION: We conclude that the increased focus on surgical pathology near-miss events will reveal latent factors that may be targeted for improvement.

Cytologic-histologic correlation.

The process of cytologic-histologic correlation is highly valuable to the fields of both cytopathology and surgical pathology, because correlation provides a wealth of data that may be used to improve diagnostic testing and screening processes. In this study, overall improvement appeared to be driven largely by improvement in preanalytic Papanicolaou (Pap) test sampling, because longer institutional participation also was associated with improved sampling sensitivity. The authors hypothesized that Pap test sampling may have improved secondary to the introduction of liquid-based technology, which was implemented in many laboratories during the study time frame. Through the performance of continuous data tracking and retrospective root cause analysis to identify factors that may have influenced any observed changes in performance indicators, institutions may learn which initiatives are successful or unsuccessful. The future of correlation lies in the standardization of methods, the development of more formal and rigorous root cause analysis processes to determine system components underlying correlation discrepancies, and the active use of correlation data to redesign testing and screening processes for quality and patient safety improvement.