Clinical Laboratory Testing Practices in Diffuse Gliomas Prior to Publication of 2021 World Health Organization Classification of Central Nervous System Tumors

CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear. OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors. DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers in gliomas. RESULTS.—: The data provide perspective into the testing practices for diffuse gliomas from a broad group of clinical laboratories in 2020. More than 98% of participating laboratories perform testing for glioma biomarkers recognized as diagnostic for specific subtypes, including IDH. More than 60% of laboratories also use molecular markers to differentiate between astrocytic and oligodendroglial lineage tumors, with some laboratories providing more comprehensive analyses, including prognostic biomarkers, such as CDKN2A/B homozygous deletions. Almost all laboratories test for MGMT promoter methylation to identify patients with an increased likelihood of responding to temozolomide. CONCLUSIONS.—: These findings highlight the state of molecular testing in 2020 for the diagnosis and classification of diffuse gliomas at large academic medical centers. The findings show that comprehensive molecular testing is not universal across clinical laboratories and highlight the gaps between laboratory practices in 2020 and the recommendations in the 2021 World Health Organization Classification of Central Nervous System Tumors

Utility of repeat testing of critical values: A q-probes analysis of 86 clinical laboratories

Context.— A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result.Objectives.— To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test.Design.— Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing.Results.— Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care.Conclusion.— Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.</jats:p

Human Papillomavirus Genotyping Testing Practice In 2014: Results Of A College Of American Pathologists National Survey

Context. - College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratories. Objective. - To investigate human papillomavirus (HPV) genotyping testing practice patterns in laboratories in 2014. Design. - Data were analyzed from the CAP HPV Genotyping Practices Supplemental Questionnaire distributed to 749 laboratories participating in the CAP Human Papillomavirus (High Risk) for Cytology Program. Results. - Six hundred four of 749 laboratories (80.6%) responded to the survey. More laboratories offered HPV genotyping testing and performed in-house HPV genotyping testing as compared to previous surveys. The Roche cobas HPV test was the most commonly used genotyping method (37.0%; 160 of 433), followed by Hologic Aptima HPV16 18/45 (26.1%; 113 of 433) and Hologic Cervista HPV16/18 (14.3%; 62 of 433). Most laboratories (287 of 399; 71.9%) offered HPV genotyping for high-risk HPV cases regardless of Papanicolaou (Pap) test results and patient age; this pattern was more common in laboratories using cobas. The remaining laboratories specifically offered testing to women with a negative Pap test result at age 30 years and older (65.2%, 73 of 112) or all ages (37.5%, 42 of 112). The median reporting rates of HPV16 and/or HPV18 positivity were 20.6%, 25.7%, 21.1%, and 57.4% for women with positive high-risk HPV adjunctive negative Pap results, atypical squamous cells of undermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous lesion, respectively. Conclusions. - Human papillomavirus genotyping testing has increased. Roche cobas and Hologic Aptima genotype methods were the most common, and laboratories using cobas usually offered genotyping regardless of Pap test result and age. The data provide a baseline and trend of HPV genotyping test practices in 2014

Misinterpretation Rates Of High-Grade Squamous Intraepithelial Lesion In The College Of American Pathologists Gynecologic Pap Education And Pap Proficiency Test Program

Context. - Misinterpretation of high-grade squamous intraepithelial lesion (HSIL) is an important problem in daily practice and in the College of American Pathologists (CAP) PAP Proficiency Test (PAP-PT). Objective. - To investigate factors related to misinterpretation of HSIL through responses in a proficiency test versus an educational environment. Design. - We retrospectively evaluated 28 000 responses in the PAP Education Program (PAP-Edu) and 59 140 responses in PAP-PT from 1147 field-validated HSIL slides from 2007 to 2014. The related factors, such as program types, preparation types, participant types, and program years, were evaluated. Results. - Overall, 4.0% (2379 of 59 140) of responses for HSIL slides from PAP-PT were misinterpreted as either low-grade squamous intraepithelial lesion (LSIL) or negative, significantly more than those from PAP-Edu (3.2%; 898 of 28 000). However, the false-negative rate (misinterpreted as negative) was 0.9% (519 of 59 140) for PAP-PT, lower than that for PAP-Edu (1.0%; 266 of 28 000). The misinterpretation rates in PAP-PT trended down with time. Misinterpretation rates did not vary significantly by preparation methods. The misinterpretation rate for HSIL in the pathologists\u27 responses was lower than that in cytotechnologists\u27 responses in PAP-PT. More HSIL was misinterpreted as LSIL than as benign in both programs. Cytotechnologists interpreted HSIL as LSIL twice as much as pathologists. The most common false-negative misinterpretations were negative for intraepithelial lesion or malignancy and reparative change. Conclusions. - The higher LSIL misinterpretation rate by cytotechnologists may be related to the differences in reporting responsibilities and proficiency test grading criteria. The trend of gradually decreasing misinterpretation rates of a reference diagnosis of HSIL in the PAP-PT program may be related to higher test-taking confidence and better preparation through educational programs. The fact that pathologists performed better than cytotechnologists in PAP-PT, but not in PAP-Edu, may reflect a heightened approach and attentiveness in the test-taking environment for pathologists

Performance Characteristics Of Cerebrospinal Fluid Cytology: An Analysis Of Responses From The College Of American Pathologists Nongynecologic Cytopathology Education Program

Context.-Cerebrospinal fluid cytology is a critical diagnostic tool for the diagnosis of many conditions affecting the central nervous system. Objective.-To assess the performance characteristics of cerebrospinal fluid cytology samples by evaluating participant interpretations within the College of American Pathologists Nongynecologic Cytopathology Education program. Design.-Participant interpretations (N 1/4 46 264) evaluated in the College of American Pathologists Nongynecologic Cytopathology Education Program were examined for concordance with the general category and with the reference diagnosis. Two nonlinear mixed models were used to analyze the concordance rates. Results.-The overall concordance rates for the general category and reference diagnosis were 92.1% and 81.0%, respectively. In the malignant category, the concordance rates with the reference diagnosis were lowest for diagnoses of nonhematopoietic small blue round cell tumors (54.8%) and metastatic malignancy (77.5%); the concordance rate with the reference diagnosis was highest for leukemia/ lymphoma (94.0%). In the benign category, the concordance rate was lowest for normal cerebrospinal fluid reference diagnoses (58.6%), followed by acute and chronic inflammation (64.6%), fungal infection (80.8%), and macrophages (85.3%). Significant differences in concordance were uncovered when performance was evaluated by participant type and stain technique. Leukemia/lymphoma was the most common diagnosis for misclassified nonhematopoietic small blue round cell tumor cases and negative or inflammatory cerebrospinal fluid cases. Conclusions.-This study illustrates the difficulties in achieving accurate diagnoses from cerebrospinal fluid specimens, particularly for nonhematopoietic small blue round cell tumors and normal and inflammatory cerebrospinal fluid specimens

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

ContextThe 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.ObjectivesTo 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.DesignConcordance 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.ResultsCytotechnologists 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 &lt; .001) and better performance for each preparation type (P = .003). Concordance initially dropped after the introduction of proficiency testing (P &lt; .001) for conventional and liquid-based (SurePath) preparations by both participant types, followed by quick, parallel improvement.ConclusionsPerformance 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

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 \u3c .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 \u3c .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

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

ContextThe 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.ObjectivesTo 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.DesignConcordance 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.ResultsCytotechnologists 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 &lt; .001) and better performance for each preparation type (P = .003). Concordance initially dropped after the introduction of proficiency testing (P &lt; .001) for conventional and liquid-based (SurePath) preparations by both participant types, followed by quick, parallel improvement.ConclusionsPerformance 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

Rescreening Practices of Negative Papanicolaou Tests With Positive Human Papillomavirus Test Result

CONTEXT.—: The yield of the prospective rescreening process for negative for intraepithelial lesion or malignancy (NILM) Papanicolaou (Pap) tests is higher with the inclusion of a greater proportion of high-risk cases. One of the suggested criteria for classifying a Pap test finding as high risk is recent or concurrent high-risk human papillomavirus (HPV) positivity. OBJECTIVE.—: To evaluate how the results of HPV testing have been incorporated in the prospective rescreening of NILM Pap tests across a wide range of laboratories. DESIGN.—: A questionnaire survey was sent to laboratories participating in the 2019 College of American Pathologists (CAP) Gynecologic Cytology (PAP Education) Program. RESULTS.—: Of the 1507 participating laboratories, 667 (44%) responded to the survey. Most laboratories (59.4%; 396 of 667) had not incorporated HPV test/genotyping results to select NILM Pap tests for rescreening. Amongst the remaining laboratories, for NILM HPV-positive Pap test results, 112 (16.8%) had a policy to rescreen by a cytotechnologist only, 51 (7.6%) by a pathologist only, and 86 (12.9%) by both. Of 264 laboratories, 181 (68.6%) reported the cytology upon availability of the HPV test result and completion of the secondary review. Of 661 laboratories, 145 (21.9%) included consensus-type recommendations in the cytology report for such Pap tests. CONCLUSIONS.—: This CAP survey provides significant information regarding the current trends in the use of HPV test results in prospective rescreening of NILM Pap tests. Future studies on quality improvement can further assist in the standardization of this process across different laboratories