Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens.

CONTEXT: -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. OBJECTIVE: -To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non-small cell lung carcinoma using cytologic preparations. DESIGN: -Nine cytopathologists from different institutions submitted cases of non-small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. RESULTS: -Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). CONCLUSION: -Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience.

Respiratory Cytology--Current Trends Including Endobronchial Ultrasound-Guided Biopsy and Electromagnetic Navigational Bronchoscopy: Analysis of Data From a 2013 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: Nongynecologic cytology (NGC) practices are expanding in relationship to historical gynecologic cytology screening programs. Bronchopulmonary cytology is experiencing an evolution regarding new procedural types. The College of American Pathologists (CAP) tracks practice patterns in NGC by developing questionnaires, surveying participants, and analyzing respondent data. OBJECTIVE: To analyze responses to a 2013 CAP supplemental survey from the Interlaboratoy Comparison Program on bronchopulmonary NGC. DESIGN: The "NGC 2013 Supplemental Questionnaire: Demographics in Performance and Reporting of Respiratory Cytology" was mailed to 2074 laboratories. RESULTS: The survey response rate was 42% (880 of 2074) with 90% of respondents (788 of 880) indicating that their laboratories evaluated cytology bronchopulmonary specimens. More than 95% of respondents indicated interpreting bronchial washings (765 of 787) and bronchial brushings (757 of 787). A minority of laboratories (43%, 340 of 787) dealt with endobronchial ultrasound-guided samples, and an even smaller fraction of laboratories (14%, 110 of 787) saw cases from electromagnetic navigational bronchoscopy. Intraprocedural adequacy assessments by pathologists (and less often by cytotechnologists or pathologists-in-training) were routinely performed in percutaneous transthoracic aspiration cases (74%, 413 of 560) with less involvement for other case types. Most laboratories reported that newly diagnosed primary pulmonary adenocarcinomas were triaged for molecular testing of epidermal growth factor receptor and anaplastic lymphoma kinase. CONCLUSIONS: The parameters examined in this 2013 survey provide a snapshot of current pulmonary cytopathology practice and may be used as benchmarks in the future.

Trends in Cervical Cytology Screening and Reporting Practices: Results From the College of American Pathologists 2011 PAP Education Supplemental Questionnaire.

CONTEXT: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2011 gynecologic cytology survey. OBJECTIVE: To provide a cross-sectional survey of gynecologic cytology practices in 2010. DESIGN: In 2011, a survey was sent to 1604 laboratories participating in the College of American Pathologists gynecologic cytology interlaboratory comparison education program and proficiency testing programs requesting data from 2010 on the following topics: terminology/reporting, cytotechnologist workload, quality assurance, reagents, and ancillary testing. RESULTS: Six hundred and twenty-five laboratories (39%) replied to the survey. The nonstandard use of "low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion" is used by most laboratories to report the presence of low-grade squamous intraepithelial lesion with possibility of high-grade squamous intraepithelial lesion. Most laboratories also report the presence or absence of cells from the transformation zone. Most respondents do not limit cytotechnologist screening workload during the work shift. Only about one-third of laboratories (188 of 582; 32%) use image-assisted screening devices. Rapid prescreening as a quality assurance measure is used by only 3.5% (21 of 594) of the laboratories. When used for screening, most laboratories use the imager for retrospective review of slides to detect human locator and interpretive errors. Most laboratories receive both liquid-based cytology samples (mainly ThinPrep, Hologic, Marlborough, Massachusetts) and conventional Papanicolaou tests. Expiration dates of liquid-based cytology test vials are not usually recorded. CONCLUSIONS: The field of gynecologic cytology is evolving rapidly. These survey results offer a snapshot of national gynecologic cytology practices in 2010.

Performance Characteristics of Urinary Tract Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: Urine cytology is used in the evaluation of hematuria or to follow patients with known urothelial neoplasia. OBJECTIVE: To investigate the performance characteristics of urinary cytology challenges in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. DESIGN: Participant responses from 2000 to 2010 were evaluated for the reference diagnoses of high-grade urothelial carcinoma (HGUC), squamous cell carcinoma, adenocarcinoma, and benign diagnoses (including polyomavirus infection and ileal loop urine). Responses were compared for differences in sample preparation (conventional, liquid based, and cytospin) and participant type (laboratory, pathologist, cytotechnologist). RESULTS: There were 96 093 responses (46 637 pathologists [48.5%], 29 976 cytotechnologists [31.2%], and 19 480 laboratories [20.3%]); 69 814 of 74 821 responses (93.3%) for the general category positive for malignancy and 18 698 of 21 272 responses (87.9%) for positive for malignancy were concordant. Of the malignant reference diagnoses, 83.3% (59 985 of 71 581), 43.9% (732 of 1667), and 49.1% (370 of 756) were correctly identified as HGUC, adenocarcinoma, and squamous cell carcinoma, respectively. However, 802 of 1669 adenocarcinoma challenges (48.1%) and 275 of 755 squamous cell carcinoma challenges (36.4%) were misdiagnosed as HGUC. For the benign cases, the most common diagnostic pitfall was overinterpretation of ileal loop urines (330 of 5291; 6.2%) and Polyomavirus challenges (220 of 3535; 6.2%) as HGUC. For the general diagnosis of positive for malignancy, cytotechnologists performed slightly better that pathologists (94.5% [23 553 of 24 924] versus 92.3% [36 210 of 39 230]), whereas the reverse occurred for the negative category (85.6% [6423 of 7503] versus 88.8% [10 427 of 11 742]). CONCLUSIONS: Although the participants performed well in accurately classifying cases as benign and malignant, there were difficulties with the correct identification of adenocarcinoma and squamous cell carcinoma cases and with overinterpretation of ileal loop and Polyomavirus challenges as HGUC.

Do liquid-based preparations of pulmonary bronchial brushing specimens perform differently from classically prepared cases for the diagnosis of malignancies? Observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology.

CONTEXT: Pulmonary bronchial brushing specimens can be processed by liquid-based or conventional methods. The ability to accurately diagnose a pulmonary malignancy with a liquid-based preparation (LBP) versus a conventional preparation may differ. OBJECTIVE: To compare the performance of LBPs of malignant pulmonary bronchial brushing specimens with the performance of conventional preparations. DESIGN: Participant responses from 553 malignant pulmonary bronchial brushing samples were evaluated for concordance with the general diagnosis. The performance of LBPs was compared with that of classic preparations. A nonlinear mixed model was used to analyze the performance by reference diagnosis, preparation type, program years, participant type, and the interaction terms between these 4 factors. RESULTS: Concordance with the general category of malignant disease was observed in 95.2% of conventional Papanicolaou-stained, 90.9% of modified Giemsa-stained, and 96.9% of LBP (P < .001) samples. The results were significantly different between individual reference diagnoses (P < .001). The performance of LBPs was consistently higher for most diagnoses and was significantly better for squamous cell carcinoma (P = .005), small cell carcinoma (P < .001), and metastatic carcinoma not otherwise specified (P < .001). All participant types performed significantly better with LBPs of small cell carcinoma. Pathologists and cytotechnologists performed significantly better with LBPs of squamous cell carcinoma. A significantly higher concordance was observed between the general diagnosis and program years 2007-2011 versus 2001-2006 (P = .006). CONCLUSIONS: Liquid-based preparations performed better than conventional methods, with significantly higher performance in squamous cell, small cell, and metastatic carcinomas. Improved performance over time may reflect more frequent use of LBP methods and increased familiarity with interpreting the morphologic findings.

Human papillomavirus testing and reporting rates in 2012: results of a College of American Pathologists national survey.

CONTEXT: College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. OBJECTIVE: To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. DESIGN: Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. RESULTS: A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. CONCLUSIONS: There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.

Prior high-risk human papillomavirus testing and Papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.

CONTEXT: Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. OBJECTIVE: To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. DESIGN: Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. RESULTS: Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. CONCLUSIONS: These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.

The Tahoe Study: bias in the interpretation of Papanicolaou test results when human papillomavirus status is known.

CONTEXT: Knowledge of human papillomavirus (HPV) status is expected to bias the morphologic evaluation of Papanicolaou (Pap) test results. OBJECTIVE: To characterize Pap test result interpretive bias when the HPV status is known at the microscopic evaluation. DESIGN: Forty HPV-positive liquid-based Pap test results initially interpreted as negative for squamous intraepithelial lesion or malignancy were selected from a quality assurance program, separated into 2 groups of 20 slides each, and circulated in 2 groups to 22 members of the College of American Pathologists Cytopathology Committee. Each member reviewed each case and indicated whether the result was negative for squamous intraepithelial lesion or malignancy or was an epithelial cell abnormality (ECA). The participants assessed the severity of ECAs using the Bethesda System. The participants were not informed of the HPV status in the initial review round. Each group of 20 slides was then distributed to the opposite group (to avoid slide recall), and the participants were informed that all slides were from patients who were high-risk HPV positive. Differences in the responses between groups were analyzed by χ(2) test and Cochran-Mantel-Haenszel test at the .05 significance level. RESULTS: Without knowledge of the HPV status, slides were more often categorized as negative for squamous intraepithelial lesion or malignancy and less likely identified as an ECA (P < .001). There was an increase across all categories of ECAs in the biased responses compared with the unbiased responses (P = .002). CONCLUSIONS: Knowledge of positive HPV status biases morphologic Pap test result interpretation. If the HPV status is positive, observers are more likely to report a Pap test result as abnormal across all categories of ECAs.

Nongynecologic cytology practice patterns: a survey of participants in the College of American Pathologists interlaboratory comparison program in nongynecologic cytopathology.

CONTEXT: Nongynecologic cytology (NGC) practices are expected to expand relative to gynecologic cytology. The College of American Pathologists attempts to track practice patterns in NGC using a self-reported questionnaire. OBJECTIVE: To analyze self-reported laboratory staffing and practices from a 2010 survey relating to NGC specimens, stains, preparation, procedures, and ancillary testing. DESIGN: The "NGC 2010 Demographics and Supplemental Questionnaire: Current Nongynecologic Practices in Cytopathology Laboratories" was mailed to 2059 laboratories. RESULTS: Survey response rate was 51% (1048 of 2059), predominantly from voluntary, nonprofit hospitals, where NGC samples were reviewed in nontraining settings by pathologists without American Board of Pathology Added Qualification in Cytopathology. Cytotechnologists reviewed NGC cases in 67.4% (675 of 1002) of laboratories. The annual mean and median volumes of NGC cases were 1927 and 858, respectively. Laboratories used more than one method to process NGCs; cell-blocks were most frequently used (930 of 1029; 90.4%) and were created with centrifugation to pellet (538 of 961; 56%). Direct smears were second in preparation frequency; discrete staining was preferred to batch staining. Nongynecologic cytology was used for molecular studies in 34.9% (350 of 1002) of laboratories, most commonly for fluorescent in situ hybridization of urine specimens. Flow cytometric immunophenotyping was performed by 55.9% (554 of 991) and immunohistochemistry by 91.9% (911 of 991) of the responding laboratories. Most laboratories (911 of 993; 91.7%) report specimen completion in 2 or fewer days. Cytohistologic correlation was performed by 71.6% (722 of 1008) of the laboratories both concurrently and retrospectively. CONCLUSION: The various parameters examined in the 2010 survey provide a benchmark for future efforts in quality assurance and process improvement in NGC.

Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program.

CONTEXT: Immunohistochemistry (IHC) is important for cytology but poses special challenges because preanalytic conditions may differ from the conditions of IHC-positive controls. OBJECTIVE: To broadly survey cytology laboratories to quantify preanalytic platforms for cytology IHC and identify problems with particular platforms or antigens. To discover how validation guidelines for HER2 testing have affected cytology. DESIGN: A voluntary survey of cytology IHC practices was sent to 1899 cytology laboratories participating in the College of American Pathologists Nongynecologic Cytopathology Education Program in the fall of 2009. RESULTS: A total of 818 laboratories (43%) responded to the survey by April 2010. Three hundred fourty-five of 791 respondents (44%) performed IHC on cytology specimens. Seventeen different fixation and processing platforms prior to antibody reaction were reported. A total of 59.2% of laboratories reported differences between the platforms for cytology specimens and positive controls, but most (155 of 184; 84%) did not alter antibody dilutions or antigen retrieval for cytology IHC. When asked to name 2 antibodies for which staining conditions differed between cytology and surgical samples, there were 18 responses listing 14 antibodies. A total of 30.6% of laboratories performing IHC offered HER2 testing before publication of the 2007 College of American Pathologists/American Society of Clinical Oncologists guidelines, compared with 33.6% afterward, with increased performance of testing by reference laboratories. Three laboratories validated a nonformalin HER2 platform. CONCLUSIONS: The platforms for cytology IHC and positive controls differ for most laboratories, yet conditions are uncommonly adjusted for cytology specimens. Except for the unsuitability of air-dried smears for HER2 testing, the survey did not reveal evidence of systematic problems with any antibody or platform.

False-positive Papanicolaou (PAP) test rates in the College of American Pathologists PAP education and PAP proficiency test programs: evaluation of false-positive responses of high-grade squamous intraepithelial lesion or cancer to a negative reference diagnosis.

CONTEXT: In cytology proficiency testing (PT), participants fail for incorrectly interpreting a high-grade squamous intraepithelial lesion or cancer (HSIL+) Papanicolaou test result as negative. This penalty may lead to a false-positive interpretation of negative slides as HSIL+ to avoid failure. OBJECTIVE: To investigate factors related to false-positive responses in a PT versus an educational environment. DESIGN: We analyzed 420,079 responses from 9414 validated negative reference slides in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytopathology (PAP Education) and compared them with responses from the Gynecologic Cytology Proficiency Testing Program for the percentage of false-positive (HSIL+) interpretations in each of 7 negative subcategories. We evaluated the influence of preparation type (ThinPrep, SurePath, and conventional Papanicolaou test), participant type (pathologist or cytotechnologist), and program time interval (preproficiency test or PT) on a false-positive response. RESULTS: Reference diagnosis and participant type, but not preparation type, were statistically correlated to false-positive responses. The interaction between program time interval and participant type was also significant. Pathologists had higher rates of false-positive results on preproficiency test (1.2% [800 of 68,690]) than they did on PT (0.8% [993 of 129,857]). Cytotechnologists had no differences between program time intervals (preproficiency, 0.9% [515 of 63,281] versus PT, 1.0 [1231 of 121,621]; P = .91). Negative subcategories frequently mistaken for HSIL+ were reparative changes (4.7% [427 of 9069]), atrophic vaginitis (1.8% [18 of 987]), and negative for intraepithelial lesion or malignancy (1.2% [2143 of 178,651]), but during PT, false-positive rates were significantly increased only for the negative for intraepithelial lesion or malignancy and herpes simplex virus (P < .001). CONCLUSIONS: Pathologists had lower false-positive rates in the Gynecologic Cytology Proficiency Testing Program than they did in PAP Education, but participants were more likely to report a false-positive response (HSIL+) for negative for intraepithelial lesion or malignancy and herpes simplex virus in the Gynecologic Cytology Proficiency Test Program.

Primary pulmonary non-small cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone.

Context.-Subtyping of non-small cell lung carcinomas (NSCLCs) is necessary for optimal patient management with specific diagnoses triggering specific molecular tests and affecting therapy. Objective.-To assess the accuracy of the participants of the College of American Pathologists Interlaboratory Comparison Program in diagnosing and subtyping NSCLC fine-needle aspiration (FNA) slides, based on morphology alone, considering preparation and participant type and trends over time. Design.-The performance of program participants was reviewed for the 5-year period spanning 2007-2011. Lung FNA challenges with reference diagnoses of adenocarcinoma and squamous cell carcinoma (SCC) were evaluated for diagnostic concordance by using a nonlinear mixed model analysis. Results.-There were 10 493 pathologist and 6378 cytotechnologist responses with concordance rates of 97.4% and 97.9% for malignancy, respectively. Overall concordance rates for subcategorization were 54.6% for adenocarcinoma and 74.9% for SCC. For the exact reference diagnoses, pathologists performed better for adenocarcinoma and cytotechnologists performed better for SCC. Accurate subcategorization of adenocarcinomas significantly increased over time with 31.5% of adenocarcinomas classified as NSCLC in 2007 and 25.5% of adenocarcinomas classified as NSCLC in 2011 (P < .001). In comparing preparation types, modified Giemsa-stained smears showed the lowest overall concordance (46.8%). Modified Giemsa-stained smears with SCCs were the least likely to be accurately subcategorized (36.4%). Conclusions.-Participants are proficient at interpreting NSCLCs as malignant by FNA but are less successful at subcategorization with cytomorphology alone. During the study period, a statistically significant trend was confirmed toward greater accuracy of subcategorization of adenocarcinomas, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and therapy.

Room for improvement: initial experience with anal cytology: observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology.

CONTEXT: Anal cytology is being used more frequently for anal cancer screening, yet many cytologists are unfamiliar with it. OBJECTIVE: To describe the performance of anal cytology in the College of American Pathologists' Interlaboratory Comparison Program in Non-Gynecologic Cytology (CAP NGC) educational slide program during a 6-year time span, from 2006 to 2011, using participant responses (pathologist, cytotechnologist, and laboratory). DESIGN: Concordance rates for the target diagnosis and general category for each slide challenge were analyzed. Four main factors were included in the analysis: (1) general category or specific responses, (2) program year from 2006 to 2011, (3) participant type (pathologist, cytotechnologist, or overall laboratory), and (4) preparation type (liquid-based or conventional). RESULTS: Participants most frequently correctly classified negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesion, and herpes simplex virus infection, with concordance rates of 78.8%, 85%, and 80.2%, respectively. Performance on challenges with target diagnoses of high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, and ameba was poor, with concordance rates of 57.1%, 56.2%, and 41.5%, respectively. Significant improvement during the 6 years was seen in the concordance rates of participants' responses for low-grade squamous intraepithelial lesion challenges but not for HSIL. There was no significant difference in performance by slide preparation type. CONCLUSIONS: The poor performance on anal cytology in the CAP NGC program, especially with regard to correct identification of HSIL and squamous cell carcinoma, indicates that there is a need for continued education about anal cytology.

Implementation of the Bethesda System for Reporting Thyroid Cytopathology: observations from the 2011 thyroid supplemental questionnaire of the College of American Pathologists.

CONTEXT: Although information about the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely disseminated since its inception in 2007, the extent of its implementation and impact on daily practice has not been formally evaluated. OBJECTIVES: To assess the extent of uptake of TBSRTC across pathology laboratories and to evaluate its impact on daily practice by collating participant responses to the 2011 supplemental thyroid questionnaire of the College of American Pathologists. DESIGN: A questionnaire was designed to gather information about various aspects of TBSRTC and mailed in June 2011 to 2063 laboratories participating in the College of American Pathologists cytopathology interlaboratory comparison program. The participating laboratories' answers were collated and summarized. RESULTS: Seven hundred and seventy-seven laboratories (37.6%) returned the survey. Although 60.9% (n = 451) and 17.1% (n = 127) of laboratories reported using TBSRTC or planning to use it in the near future, respectively, 22% (n = 163) had no plans to implement TBSRTC. Of the latter, 32% (n = 70) stated that they were unaware of this classification system. The majority (78.3%, n = 343) of the laboratories used TBSRTC as published in the Thyroid Bethesda System atlas, whereas 21.7% (n = 95) used it with minor modifications. Most reported that the use of TBSRTC had caused either no change (n = 67, 15.2%) or only minor changes (n = 353, 80.2%) in the terminology and diagnostic criteria previously used in their laboratories. CONCLUSIONS: According to the collected data, TBSRTC is generally well implemented in pathology laboratories. However, because approximately a third of those not using this terminology are not aware of it, additional educational efforts regarding TBSRTC are warranted.

Cytology of spontaneous nipple discharge--is it worth it? Performance of nipple discharge preparations in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: The usefulness of spontaneous nipple discharge analysis is controversial. Nipple discharge preparations are rare in clinical practice and malignant cases are exceptional. The College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology has included nipple discharge preparations since its inception. OBJECTIVES: To evaluate participant responses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology to assess the accuracy of cytologic interpretation of nipple discharge preparation. DESIGN: General diagnostic category (benign, suspicious, malignant), participant type (pathologist, cytotechnologist), stain (Papanicolaou, modified Giemsa), and program year (2005-2009) were analyzed using χ(2) and a nonlinear mixed model for slide factor correlation structure. RESULTS: Of 2506 responses, 1280 (51%) were malignant, 171 (7%) were papillary, and 1055 (42%) were benign. There were 222 discordant general category responses with a false-positive/suspicious rate of 12.8% and a false-negative rate of 3.4%. The most common false-negative diagnosis was mastitis/abscess (125 of 1272 responses; 9.8%). The most common false-positive response was papillary lesion (26 of 457 responses; 5.7%). There were no differences between stains or years. Cytotechnologists performed better than pathologists; pathologists had a higher false-negative rate than cytotechnologists (15.3% versus 7.9%, P < .001). CONCLUSIONS: There is poor accuracy in evaluating nipple discharge preparation in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. If the findings in the program parallel clinical practice, nipple discharge preparations may adversely impact patient care. A benign nipple discharge cytologic diagnosis does not exclude malignancy, and the false-positive/suspicious rate requires confirmation of a malignant nipple discharge prior to definitive patient management.

Identification of Trichomonas vaginalis in different Papanicolaou test preparations: trends over time in the College of American Pathologists educational Interlaboratory Comparison Program.

CONTEXT: The College of American Pathologists' Interlaboratory Comparison Program in Gynecologic Cytology has seen an increase in enrollment in liquid-based Papanicolaou test challenges with a decrease for conventional Papanicolaou tests. Trichomonas vaginalis can be difficult to identify in all preparation types. OBJECTIVES: To evaluate 20 years of participant results from the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology for Trichomonas to ascertain whether performance has changed because of the introduction of liquid-based Papanicolaou and proficiency testing. DESIGN: Concordance rates for the target diagnosis of Trichomonas vaginalis were evaluated for 167,956 participant responses (1990-2010). A nonlinear mixed model was fit with participant type, preparation type, and a 2-level program year (1990-2005 and 2006-2010) reflecting before and after proficiency testing began. A repeated-measures component allowed modeling of the slide-specific performance to ensure that the overall results were not based on the performance of a few slides. RESULTS: Cytotechnologists had higher concordance with the target diagnosis than did pathologists (89.8% [72,992 of 81,319] versus 83.4% [72,271 of 86,637], P < .001) and better performance for each preparation type (P = .003). Concordance initially dropped after the introduction of proficiency testing (P < .001) for conventional and liquid-based (SurePath) preparations by both participant types, followed by quick, parallel improvement. CONCLUSIONS: Performance is high in the detection of Trichomonas vaginalis in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology. Liquid-based Papanicolaou and proficiency testing minimally affected participant performance. Cytotechnologists performed better over time and across preparation types than did pathologists, although pathologists showed performance results parallel to that of the cytotechnologists. Awareness of the performance differences by pathologists and cytotechnologists, as well as their difference in proficiency among liquid-based techniques, may help ensure accurate results in clinical practice.

Accuracy and false-positive rate of the cytologic diagnosis of follicular cervicitis: observations from the College of American Pathologists Pap Educational Program.

CONTEXT: Follicular cervicitis is usually easily identifiable on Papanicolaou (Pap) tests; however, historically, follicular cervicitis is reported to lead to false-positive diagnoses of epithelial cell abnormalities. OBJECTIVES: To assess participant responses in the College of American Pathologists (CAP) Pap educational program (CAP-PAP) to determine the accuracy and false-positive rate of follicular cervicitis cases. Design.-We performed a retrospective review of 4914 participant responses for gynecologic cytology challenges with the reference diagnosis of follicular cervicitis during 11 years (2000-2010) from CAP-PAP. Reference diagnosis category, false-positive rates by participant type (laboratory, cytotechnologist, pathologist), and preparation type (conventional smears, ThinPrep) were analyzed. RESULTS: Of the total 4914 general category responses, 4368 (88.9%) were benign while 546 (11.1%) responses were epithelial cell abnormalities (false positives). Of benign responses, only 2026 (46.4%) were an exact match to follicular cervicitis. Adenocarcinoma and high-grade squamous intraepithelial lesion were the most common diagnoses chosen as a false-positive interpretation (42.3% and 20.1%, respectively). Participant type was significantly associated with false-positive interpretations (laboratory: 19.2%; cytotechnologist: 11.1%; pathologist: 7.9%; P < .001). ThinPrep was also significantly associated with false-positive results as compared to conventional smears (12.2% versus 3.6%; P < .001). CONCLUSIONS: In an interlaboratory comparison educational program, follicular cervicitis is difficult to interpret accurately and represents an important cause of false-positive responses. Follicular cervicitis may mimic adenocarcinoma or high-grade squamous intraepithelial lesion, particularly in liquid-based preparations. The diagnostic difficulty most likely arises from the lymphocytes being less conspicuous in the background as well as their tendency to aggregate in ThinPrep as compared to conventional smears.

The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories.

CONTEXT: The College of American Pathologists (CAP) Human Papillomavirus (High-Risk) Survey for Cytopathology and Other Laboratories (CHPV) meets the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) requirements for 5 proficiency testing challenges analyzed 3 times per year. This study reports laboratory performance for CHPV from 2008 through 2010. OBJECTIVE: To identify trends in proficiency testing performance for subscribers to the CAP CHPV. DESIGN: CHPV responses were evaluated by using a nonlinear mixed model (significance level of .05) with a 2-factor interaction term and repeated measures component, comparing year, media, method, and intended response. Media types included Digene transport, SurePath, ThinPrep media, or a mixture of media types. Proficiency testing challenges validated at 80% consensus. RESULTS: All challenges validated; 476 laboratories submitted 14 911 responses with 14 620 correct responses (98%). There were no differences between positive or negative challenges, or rate of correct responses; significant differences existed between media types by year and methods. Digene and ThinPrep media performed better than SurePath (P < .001; P = .03). There was a statistically significant difference between methods (P < .001); "other commercial kits," "other (noncommercial)" tests, and Third Wave performed more poorly than others. CONCLUSIONS: Laboratories performed well when testing for human papillomavirus in CHPV during a period of 3 years. All challenges performed to the 80% threshold. Significant differences were found between methods and media. The CAP CHPV survey provides useful information for laboratories choosing human papillomavirus testing methods.

Quality improvement opportunities in gynecologic cytologic-histologic correlations: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 4.

CONTEXT: Cytopathology experts, interested stakeholders, and representatives from the College of American Pathologists, the Centers for Disease Control and Prevention, the American Society of Cytopathology, the Papanicolaou Society of Cytopathology, the American Society for Clinical Pathology, and the American Society of Cytotechnology convened the Gynecologic Cytopathology Quality Consensus Conference to present preliminary consensus statements developed by working groups, including the Cytologic-Histologic Correlations Working Group 4, using results from surveys and literature review. Conference participants voted on statements, suggested changes where consensus was not achieved, and voted on proposed changes. OBJECTIVES: To document existing practices in gynecologic cytologic-histologic correlation, to develop consensus statements on appropriate practices, to explore standardization, and to suggest improvement in these practices. DATA SOURCES: The material is based on survey results from 546 US laboratories, review of the literature from 1988 to 2011, and the College of American Pathologists Web site for consensus comments and additional survey questions. CONCLUSIONS: Cytologic-histologic correlations can be performed retrospectively, during initial case review, or both. At minimum, all available slides should be reviewed for a high-grade squamous intraepithelial lesion Papanicolaou test with negative biopsies. The preferred monitor for correlations is the positive predictive value of a Papanicolaou test. Laboratories should design cytologic-histologic correlation programs to explore existing or perceived quality deficiencies.

Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology.

CONTEXT: Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs). OBJECTIVE: To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. DESIGN: Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hürthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed. RESULTS: The 47, 076 thyroid FNA slide responses, between 2001 and 2009, included 44, 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P < .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P < .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p <.001). CONCLUSIONS: LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described.