Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

INTRODUCTION: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. MATERIALS AND METHODS: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. RESULTS: LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). CONCLUSIONS: Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Impact of laboratory work-up of lymphoma guidelines on cytopathology practices.

A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: "primary diagnosis and classification of lymphoma can be achieved with a variety of specimens." The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary testing, and that either flow cytometry or immunohistochemical immunophenotyping be performed for any type of specimen. Either excisional or core biopsy should be obtained when there is a high suspicion of lymphoma, and excision is recommended when feasible for Hodgkin lymphoma primary diagnosis. The use of cerebrospinal fluid to diagnose central nervous system lymphoma is discussed. For any patient with initial negative biopsy or fluid specimens and a high suspicion of lymphoma, additional tissue samples should be obtained. Additional molecular testing and good practice statements are summarized in the guideline. Cytopathologists should continue to advocate for judicious use of lymph node FNAB as an excellent triage tool that may require additional tissue biopsy for definitive diagnosis.

The Differential Diagnosis of Reparative Changes and Malignancy: Performance in the College of American Pathologists Pap Education and Proficiency Testing Programs.

CONTEXT.­: Repair is a challenging diagnosis and a significant source of false-positive (FP) interpretations in cervical cytology. No large-scale study of performance of repair in the liquid-based era has been performed. OBJECTIVE.­: To evaluate the performance of repair in the College of American Pathologists Pap Education and Proficiency Testing (PT) programs. DESIGN.­: The FP rate for slides classified as repair was evaluated by preparation type, participant type (cytotechnologist, pathologist, or laboratory), and program. The specific misdiagnosis category and individual slide performance were also evaluated. The rate of misclassification of slides as repair by participants for other diagnostic categories in the Pap Education program was assessed. RESULTS.­: The overall FP rate was 1700 of 12 715 (13.4%). There was no significant difference by program or preparation type. Within the Education program there was no difference by participant type, but pathologists' FP rate in the PT program (47 of 514, 9.1%) was significantly better than cytotechnologists in the PT program (51 of 380, 13.4%) and pathologists in the Education program (690 of 4900, 14.1%). High-grade squamous intraepithelial lesions/cancers (HSIL+) accounted for 1380 of 1602 FP interpretations (86%) in Education, but 43 of 98 (43.9%) in PT. Most slides had a low rate of misclassification, but a small number were poor performers. False-negative diagnosis of HSIL+ as repair was less common, ranging from 0.7% to 1.8%. CONCLUSIONS.­: Despite initial indications that liquid-based cytology might reduce the rate of misclassification of repair, FP interpretations remain common and are no different by preparation type. Misclassification is most commonly as HSIL or carcinoma, potentially resulting in significant patient harm.

Trends in Thyroid Fine-Needle Aspiration Cytology Practices: Results From a College of American Pathologists 2016 Practice Survey.

CONTEXT.­: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2016 survey concerning thyroid fine-needle aspiration (FNA). OBJECTIVE.­: To provide a cross-sectional survey of thyroid cytology practices in 2016. DESIGN.­: In 2016, a survey was sent to 2013 laboratories participating in the College of American Pathologists Non-Gynecologic Cytology Education Program (NGC-A) requesting data from 2015-2016 on several topics relating to thyroid FNA. RESULTS.­: A total of 878 laboratories (43.6% of 2013) replied to the survey. Radiologists performed the most thyroid FNA procedures in most laboratories (70%; 529 of 756), followed by endocrinologists (18.7%; 141 of 756), and most of these were performed under ultrasound guidance (92.1%; 699 of 759). A total of 32.6% of respondents (251 of 769) provided feedback on unsatisfactory rates for nonpathology providers who performed FNA. Intraprocedural adequacy assessment was primarily performed by attending pathologists (77.4%; 490 of 633) or cytotechnologists (28.4%; 180 of 633). Most laboratories used the Bethesda System for Reporting Thyroid Cytopathology (89.8%; 701 of 781) and performed molecular testing based on clinician request (68.1%; 184 of 270) rather than FNA diagnosis. Correlation of thyroid excisions with prior cytology results most often occurred retrospectively (38.4%; 283 of 737) and was used for pathologist interpretive quality assurance purposes. CONCLUSIONS.­: These survey results offer a snapshot of national thyroid FNA cytology practices in 2016 and indicate that standardized cytology terminology is commonly used; pathologists perform most immediate adequacy assessments for thyroid FNA; laboratories use correlation statistics to evaluate pathologists' performance; and molecular tests are increasingly requested for indeterminate interpretations, but reflex molecular testing is rare.

Bethesda 2014 Implementation and Human Papillomavirus Primary Screening: Practices of Laboratories Participating in the College of American Pathologists PAP Education Program.

CONTEXT.­: Cervical cancer screening laboratory practices may evolve with new terminology and technologies. OBJECTIVE.­: To investigate changes in cervical cytopathology practice resulting from the 2014 Bethesda System updates and screening technologies. DESIGN.­: Questionnaires accompanied 2016 and 2017 mailings of the College of American Pathologists PAP Education program. RESULTS.­: In 2016, most laboratories surveyed had adopted or were planning to adopt 2014 Bethesda System updates, and the majority (53%; 365 of 689) used an age cutoff of 45 for reporting benign-appearing endometrial cells. However, 51.3% (354 of 690) of laboratories used the term low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion, for cases with indeterminate features, and 44.9% (298 of 664) of laboratories used a 5000-cell cutoff for minimum squamous cellularity for posthysterectomy and posttherapy specimens. Reporting rates for cervical cytology metrics changed very little from 2013 to 2016, and the median ratio of atypical squamous cells to squamous intraepithelial lesion cases was 1.9 for ThinPrep and 1.8 for SurePath preparations. Most laboratories (59.4%; 389 of 655) did not offer stand-alone primary human papillomavirus (HPV) testing in 2017, and primary HPV testing accounted for a low proportion of HPV testing volumes. The Roche Cobas method was the most common platform for HPV primary screening. CONCLUSIONS.­: These questionnaire surveys provide data about the current status of cervical cytology screening, including changes related to the 2014 Bethesda System updates and the adoption of HPV primary screening techniques.

Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program.

CONTEXT.­: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. OBJECTIVE.­: To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. DESIGN.­: We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. RESULTS.­: There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). CONCLUSIONS.­: More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.

Performance Characteristics of Body Fluid Cytology Analysis of 344 380 Responses From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: - Body fluid cytology is an important diagnostic tool used to identify various conditions. However, an accurate diagnosis in this setting can sometimes be challenging. OBJECTIVE: - To identify the performance characteristics of body fluid cytology by analyzing participant responses from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. DESIGN: - Participant responses from 5102 slides were analyzed for concordance to the general category (GC) and to the reference diagnosis (RD). Nonlinear mixed models were used to analyze concordance. RESULTS: - The overall GC concordance was 95.2%. The GC type, participant type, and preparation type were significantly associated with GC concordance ( P < .001). Concordance for malignant cases was higher than it was for benign cases. Cytotechnologists had better GC concordance compared to pathologists. ThinPrep (Hologic, Marlborough, Massachusetts) slides had the highest GC concordance. Participant type, fluid type, preparation type, and participant interpretation were significantly associated with RD concordance ( P < .001). Pathologists performed better than cytotechnologists did for RD concordance. Pericardial fluid had the lowest RD concordance, especially for cases with normal or reactive findings. Modified Giemsa-stained slides performed best for lymphoma and hematopoietic malignancy. Small cell carcinoma had the highest GC concordance, and its RD concordance was higher in pleural than in peritoneal fluids. Adenocarcinoma showed the highest concordance rates for both GC and RD. CONCLUSIONS: - This study illustrates the challenges associated with interpreting body fluid cytology, particularly in pericardial fluid, and the factors that may affect accurate diagnoses. The results also highlight the value of using multiple preparation types in challenging cases.

Team-Based Learning Is Effective in Teaching Appropriate Utilization of Hemostasis Laboratory Tests Using Storyline Case-Authoring Software.

Introduction: Team-based learning (TBL) is an effective way to teach medical students a challenging topic: coagulation. This TBL requires students to discuss a differential diagnosis, order and analyze laboratory tests, and decide upon appropriate treatment. Methods: The coagulation TBL was utilized in a hematology/oncology system-based medical course. The TBL began with Individual and Group Readiness Assurance Tests (IRAT and GRAT, respectively) consisting of the same 10 multiple-choice questions. Next came a team application activity with the goal of evaluating a bleeding patient. Each team was given the clinical case and a whiteboard. Each team recorded a differential diagnosis and chose relevant laboratory tests from 20 hematology/coagulation assays placed in case-authoring software. Next, teams recorded the laboratory results, final diagnosis, and treatment on the whiteboards. Teams then voted for the best whiteboard. After discussing the highly voted whiteboard, instructors provided case discussion and elaboration about all 20 laboratory tests and their interpretation. Results: The IRAT average score was 77.0% compared to the GRAT group average of 99.5% for the year 2016-2017. Instructors noted great enthusiasm and teamwork. Institutional module evaluation feedback results showed that students were pleased and felt competent analyzing laboratory tests in a bleeding patient. Discussion: TBL provides a powerful way of teaching students the clinical reasoning approach to a bleeding patient and the appropriate use of laboratory test ordering and analysis. It is enjoyable and interactive and teaches students how to narrow their differential diagnosis by effective laboratory utilization.

An advocacy victory: final USPSTF cervical cancer screening recommendations revised to include cotesting option.

The recent reversal of the US Preventive Services Task Force decision to drop cotesting (Papicolaou test + high-risk human papillomavirus test) as an option for cervical cancer screening in women aged 30 to 65 years from their recommendations for cervical cancer screening was directly attributed to advocacy efforts by professional organizations and individuals. This communication summarizes the pathology and laboratory medicine community's role in this advocacy effort by collaboration of all major US Pathology organizations, via the Cytopathology Education and Technology consortium.

Strong performance on the Progressive Evaluation of Competency fellowship final examination predicts American Board of Pathology Certification.

INTRODUCTION: The Progressive Evaluation of Competency (PEC) program was developed to help cytopathology fellowship directors evaluate the progress of fellows before program completion. There are no data on how PEC examination results compare with American Board of Pathology (ABP) certification status. MATERIALS AND METHODS: PEC final examination results from the 2011/2012 academic year were compared with performance on the ABP cytopathology examination. The total and section PEC scores were compared with ABP scaled written and practical scores, and individuals who failed the certification examination were analyzed in detail. RESULTS: Of the 103 fellows who took the final PEC examination in spring of 2012, 88 took the ABP examination, and 79 became certified. The total and the fine-needle aspiration scores on the PEC exam were positively and significantly correlated with performance on both ABP exam sections. Every fellow who scored in the upper one-third on the PEC exam became certified. The failing candidates scored significantly lower in both total scores and the fine-needle aspiration section of the PEC exam. CONCLUSIONS: The PEC final examination performance is positively correlated with ABP certification status, and fellows who score in the top one-third of the PEC examination become certified. These findings can help provide guidance to both fellowship directors and fellows on competency and readiness for board certification.

The impact of the Clinical Laboratory Improvement Amendments of 1988 on cytopathology practice: a 25th anniversary review.

The Clinical Laboratory Improvement Amendments of 1988 were passed into law on October 31, 1988; regulations implementing this law have had a dramatic impact on the practice of cytology as well as the operations of the entire laboratory. Articles in the popular press followed by congressional hearings exposed faulty laboratory practices, with false-negative Pap tests being a major focus. The impact of this law on the cytology profession is reviewed in this paper. We discuss the response by professional organizations and laboratories to proposed regulations, including formation of consortium groups, development of interlaboratory comparison programs, and more stringent laboratory accreditation and inspection procedures. Public perceptions related to false-negative Pap tests and the litigation crisis are reviewed, as well as the development of new technologies that would improve test accuracy. Finally, the role of the Clinical Laboratory Improvement Advisory Committee in advising the government on laboratory regulations and cytology proficiency testing is discussed. Many of the regulations have promoted quality practices and cytology accuracy, but others have proven relatively inflexible and may have blocked innovation.