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Context.--The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. Objective.--To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. Methods.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Results.--Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Conclusions.--Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens. doi: 10.5858/arpa.2020-0119-CP, With the advances in minimally invasive sampling techniques, the ability to provide a diagnosis and perform multiple ancillary studies on limited-volume tissue samples, including small biopsy and cytology specimens, has [...]

* 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.doi: 10.5858/arpa.2018-0003-CP), The College of American Pathologists (CAP) Cytopathology Committee maintains and administers the PAP Education (PAP Ed) program, which provides 2 mailings of 5 glass slide Papanicolaou (Pap) tests annually to [...]

Context.--Adenocarcinoma in situ (AIS) is difficult to correctly interpret on Papanicolaou (Pap) cytology slides and false-negative interpretations of AIS can cause significant problems in daily practice. Objective.--To investigate the false-negative interpretation rate of AIS and the factors related to false-negative interpretation through responses in an educational environment. Design.--We retrospectively evaluated 11 337 responses in the PAP Education Program (PAP-Edu) from 173 AIS slides from 2011 to 2015. The false-negative interpretation rate, most common false-negative interpretations, and related other factors were evaluated. Results.--The overall false-negative rate was 6.9% (784 of 11 337). Respondents correctly interpreted AIS 50.0% (5667 of 11 337) of the time; high-grade intraepithelial lesion (HSIL) and malignancies (adenocarcinoma, squamous cell carcinoma, and other carcinomas) accounted for 42.7% (4842 of 11 337) and low-grade intraepithelial lesion accounted for 0.4% (44 of 11 337) of responses. Overall, 92.7% (10 509 of 11 337) of responses were HSIL and above. Among 784 false-negative responses, negative for intraepithelial lesion or malignancy was the most common (61.5% [482 of 784]), followed by reparative changes (24.1% [189 of 784]) and atrophic vaginitis (7.7% [60 of 784]). Overall, pathologists' responses showed a significantly higher false-negative rate than cytotechnologists' responses (8.3%, 403 of 4835 versus 5.7%, 275 of 4816; P < .001). The false-negative response rates were not statistically different among preparation types. Conclusions.--The low correct interpretation rate and higher false-negative rate for AIS demonstrate the difficulty in interpreting AIS on Pap cytology, which may cause clinical consequences. The higher false-negative rate with pathologists than with cytotechnologists suggests cytotechnologists' higher screening sensitivity for AIS or cautious interpretation to avoid false-positive results by pathologists. (Arch Pathol Lab Med. 2017;141:666-670; doi: 10.5858/arpa.2016-0234-CP), Cervical glandular neoplasia, including adenocarcinoma in situ (AIS) and invasive adenocarcinoma, is less common than squamous neoplasia. However, the relative proportion of glandular neoplasia has increased from 5% to 25% [...]

* 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. (Arch Pathol Lab Med. 2016;140:1364-1370; doi: 10.5858/arpa.2016-0061-CP), Results of the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study established the role of high-risk human papillomavirus (HR-HPV) testing as a cost-effective [...]

* Context.--Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. Objectives.--To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. Design.--Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. Results.--In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media--ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)--was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms--Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)--outperformed laboratory-developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). Conclusions.--Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests. (Arch Pathol Lab Med. 2016;140:1371-1374; doi: 10.5858/arpa.2015-0526-CP), Laboratories that are licensed to test for high-risk human papillomavirus (HPV) in patient samples are required by the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) to participate in annual [...]

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 PAPPT, 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' responses was lower than that in cytotechnologists' 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. (Arch Pathol Lab Med. 2016;140:1221-1224; doi: 10.5858/arpa.2015-0446-CP), Since 1988, the College of American Pathologists (CAP) has been providing educational gynecologic cytology glass slide challenges through its Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP program). (1) In 2005, [...]

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. (Arch Pathol Lab Med. 2015;139:757-761; doi: 10.5858/arpa.2014-0393-CP), The College of American Pathologists (CAP) has used survey questionnaires to assess practice patterns in cervicovaginal cytology since 1994. These surveys have documented the widespread implementation of the first 2 [...]

Abstract Low and high-grade ductal carcinoma in-situ (DCIS) are known to be highly disparate by a multitude of parameters, including progression potential, immunophenotype, gene expression profile and DNA ploidy. In this study, we analyzed a group of intermediate and high-grade DCIS cases to determine how well the core biopsy predicts the maximal pathology in the associated excisions, and to determine if there are any core biopsy morphologic features that may predict a close (≤ 0.2 cm) or positive margin in the subsequent excision. Forty-nine consecutive paired specimens [core biopsies with a maximal diagnosis of DCIS, and their corresponding excisions, which included 20 and 29 specimens from mastectomies and breast conserving surgeries respectively] were evaluated in detail. In 5 (10%) of 49 cases, no residual carcinoma was found in the excision. In another 4 cases, the changes were diagnostic only of atypical ductal hyperplasia. There were 4 and 3 respective cases of invasive and microinvasive carcinoma out of the 49 excision specimens, for an overall invasion frequency of 14%. In 28 cases where a sentinel lymph node evaluation was performed, only 1 was found to be positive. Among the 40 cases with at least residual DCIS in the excision, there were 5 cases in which comedo-pattern DCIS was present in the excision but not in the core biopsy, attributed to the lower maximal nuclear grade in the biopsy proliferation in 4 cases and the absence of central necrosis in the 5th. For the other main histologic patterns, in 8 (20%) of 40 cases, there were more patterns identified in the core biopsy than in the corresponding excision. For the other 32 cases, 100%, 66%, 50%, 33% and 25% of the number of histologic patterns in the excisions were captured in 35%, 5%, 17.5%, 15% and 7.5% of the preceding core biopsies respectively. Therefore, the core biopsy reflected at least half of the non-comedo histologic patterns in 77.5% of cases. In 6(15%) of the 40 cases, the maximum nuclear grade of the excision (grade 3) was higher than that seen in the core biopsy (grade 2). Overall, however, the maximum nuclear grade in the excision was significantly predicted by maximum nuclear grade in the core biopsy (p = 0.028), with a Phi of 0.347, indicating a moderately strong association. At a size threshold of 2.7 cm, there was no significant association between lesional size and core biopsy features. Furthermore, the clear margin width of the cases with lesional size ≤ 2.7 cm (mean 0.69 cm) was not significantly different (p = 0.4) from the cases with lesional size > 2.7 cm (mean 0.56 cm). Finally, among a variety of core biopsy features that were evaluated, including maximum nuclear grade, necrosis, cancerization of lobules, number of tissue cores with DCIS, number of DCIS ducts per tissue core, total DCIS ducts, or comedo-pattern, only necrosis was significantly associated with a positive or close (≤ 0.2 cm) margin on multivariate analysis (Phi of 0.350). It is concluded that a significant change [to invasive disease (14%) or to no residual disease (10%)] is seen in approximately 24% of excisions that follow a core biopsy diagnosis of intermediate or high-grade DCIS. Core biopsy features are of limited value in predicting a close or positive margin in these lesions.

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. [ABSTRACT FROM AUTHOR]

* 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 PAPPT, 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' responses was lower than that in cytotechnologists' 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context.--Adenocarcinoma in situ (AIS) is difficult to correctly interpret on Papanicolaou (Pap) cytology slides and false-negative interpretations of AIS can cause significant problems in daily practice. Objective.--To investigate the false-negative interpretation rate of AIS and the factors related to false-negative interpretation through responses in an educational environment. Design.--We retrospectively evaluated 11 337 responses in the PAP Education Program (PAP-Edu) from 173 AIS slides from 2011 to 2015. The false-negative interpretation rate, most common false-negative interpretations, and related other factors were evaluated. Results.--The overall false-negative rate was 6.9% (784 of 11 337). Respondents correctly interpreted AIS 50.0% (5667 of 11 337) of the time; high-grade intraepithelial lesion (HSIL) and malignancies (adenocarcinoma, squamous cell carcinoma, and other carcinomas) accounted for 42.7% (4842 of 11 337) and low-grade intraepithelial lesion accounted for 0.4% (44 of 11 337) of responses. Overall, 92.7% (10 509 of 11 337) of responses were HSIL and above. Among 784 false-negative responses, negative for intraepithelial lesion or malignancy was the most common (61.5% [482 of 784]), followed by reparative changes (24.1% [189 of 784]) and atrophic vaginitis (7.7% [60 of 784]). Overall, pathologists' responses showed a significantly higher false-negative rate than cytotechnologists' responses (8.3%, 403 of 4835 versus 5.7%, 275 of 4816; P, .001). The false-negative response rates were not statistically different among preparation types. Conclusions.--The low correct interpretation rate and higher false-negative rate for AIS demonstrate the difficulty in interpreting AIS on Pap cytology, which may cause clinical consequences. The higher false-negative rate with pathologists than with cytotechnologists suggests cytotechnologists' higher screening sensitivity for AIS or cautious interpretation to avoid false-positive results by pathologists. [ABSTRACT FROM AUTHOR]