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Primary Screening in Semi-Automated Gynecologic Cytology is an Insensitive Method of Identifying Epithelial Cell Abnormality in HPV-Positive Patients Based on Cases Flagged for Full Manual Review
Abstracts
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Individual Cytopathologists’ Rates of Atypia Diagnoses (%ATY) and Atypia to Positive Ratios (ATY/POS) Diagnoses in Non-Gynecologic Cytology (NgyCy): A Potential Focus for Continuous Quality Improvement (CQI)
Clinical Mutation Detection in Small Biopsies and Fine Needle Aspirations Including Bone Metastases Using a Next Generation Sequencing Assay
Stefan Pambuccian, MD, Guliz Barkan, MD, Swati Mehrotra, MD, Mohammed Atieh, DO, Eva Wojcik, MD, MIAC Loyola University Medical Center, Maywood, Illinois Introduction: For gynecologic cytopathology (GyCy), individual pathologists’ %ATY and their rates of ATY/POS, i.e. the ASC/SIL ratio, have been the focus of successful CQI activities during the last two decades. The aim of this study was to study the value of monitoring %ATY and ATY/ POS in NGyCy specimens, as part of the cytopathology laboratory’s CQI program. Materials and Methods: For the 16 year interval (2000-2015), we calculated each cytopathologist’s %ATY and ATY/POS ratio in GyCy, exfoliative cytopathology (ExCy) and fine needle aspiration (FNA) specimens. For each specimen type, %ATY and ATY/POS ratios were calculated for each cytopathologist, and compared to the laboratory average (LA) and standard deviation (SD). Pearson correlations between %ATY and ATY/POS ratios and the cytopathologist’s years of experience and total number of cases examined were calculated for GCy, FNA and ExCy, as were correlations between %ATY and ATY/POS ratios in GCy, FNA and ExCy. Results: 11 board-certified cytopathologists with 2-20 years (mean 86) of experience diagnosed 1,187 to 26,825 cytology cases each (total 96,913 cases, including 35,803 GyCy, 38,983 ExCy, and 22,127 FNA) (Figure 1). Two cytopathologists had %ATY or ATY/POS ratios >2SD in GyCy and ExCy. No significant correlations were found between the cytopathologists’ experience or case volume and their %ATY or ATY/POS ratios. There was a significant correlation between cytopathologists’ %ATY in GyCy and ExCy cases (rZ0.80, pZ0.003) and ATY/POS ratios in GyCy and ExCy (rZ0.88, p <0.0001), but not between FNA and GyCy or ExCy cases. Conclusion: Since our results show a significant correlation between cytopathologists’ GyCy and ExCy %ATY and ATY/POS ratios, CQI measures similar to those successfully applied for GyCy could be applied to ExCy. Our laboratory will implement monitoring ExCy % ATY and ATY/POS ratios as part of our ongoing quality improvement process.
Gang Zheng, MD, PhD, Ming-Tseh Lin, MD, Christopher Gocke, MD, James Eshleman, MD, PhD, Peter Illei, MD The Johns Hopkins Medical Institutions, Baltimore, Maryland Introduction: Next generation sequencing (NGS) provides information for management of cancer. In this retrospective study of a 50 gene cancer hotspot NGS assay, we evaluated factors that may affect the success rate of NGS tests. Materials and Methods: A total of 1,121 formalin-fixed paraffin-embedded (FFPE) tissues were submitted to the Johns Hopkins Molecular Diagnostics Laboratory between April 2013 and October 2014. Results: Mutations were detected in 702 specimens, 381 specimens were “negative for mutation” and 38 specimens (3.4%) were reported as “no result” due to failure of the NGS assay. Lowest failure rate was in CRC panel (3/312, 1.0%) followed by lung cancer panel (26/623, 4.2%, P < 0.01) and melanoma panel (8/168, 4.8%, P Z 0.02). Referred specimens from other hospitals showed a higher failure rate (15/301, 5.0%) as compared to specimens taken and processed at the Johns Hopkins Hospital (14/795, 1.8%) (P < 0.01). Biopsy specimens (20/347, 5.8%, P < 0.001) and FNA specimens (4/128, 3.1%, P Z 0.04) also showed a higher failure rate as compared to the resection/excision specimens (4/587, 0.7%). Successful NGS results were obtained from all 30 aspiration specimens of effusions. Higher failure rate was observed in referred specimens (5.0% vs. 1.8%), biopsy specimens (5.8%) and fine needle aspiration specimens (3.1%), as compared to the resection/excision specimens (0.7%). Bone metastasis specimens showed an overall 36% failure rate. However, biopsy bone specimens with no or short decalcification had a lower failure rate (3/16, 23%) than resection bone specimens with a prolonged decalcification process (5/9, 55%). Conclusion: CRC panel showed a lower failure rate than the lung cancer or melanoma panel. Resection specimens provided a higher success rate for the NGS assay, but biopsy or FNA is better testing bone metastases. Effusions are excellent specimens for NGS testing.
135 Primary Screening in Semi-Automated Gynecologic Cytology is an Insensitive Method of Identifying Epithelial Cell Abnormality in HPVPositive Patients Based on Cases Flagged for Full Manual Review Louis Vaickus, MD1, David Wilbur, MD1, Brenda Sweeney, SCT (ASCP), MB1, Andrew Renshaw, MD2 1 Massachusetts General Hospital, Boston, Massachusetts 2 Baptist Hospital of Miami, Miami, Florida
Figure 1.
Atypia in GYN, exfoliative and FNA cytol
Introduction: Negative gynecological cytology (NILM) cases in laboratories using semi-automated guided screening devices with slide stratification (i.e. BD-FocalPoint), are manually reviewed by two methods: Immediate full slide review after fields of view analysis (FOV+FSR) and QA/high-risk quintile directed full manual review (FMR). For FOV+FSR, current FDA approvals and guidelines require/recommend rescreening negatives at a rate of at least 15% or twice the epithelial cell abnormality (ECA) rate, respectively. No requirements exist for FMR. The effectiveness of the current manual review system is unknown. Materials and Methods: Gynecological cytology cases from 2009-2014 were analyzed. The data comprised 93,169 patients, 194,656 specimens and 50,413 HPV tests. Results: FMR and FOV+FSR rates ranged from 10-20% and 30-45%, respectively. In FMR, the ECA-rate was correlated with HPV-positive
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rate (r2Z0.86, YZ0.24X+0.04); both ECA-rate and HPV-rate decreased with age (Figure 1 and 2). For FOV+FSR, ECA-rate was also related to HPV-positive rate (r2Z0.75, YZ1.3X+0.16) and both rates decreased with age (Figure 1 and 2). HPV-positive patients were much more likely to have ECA than HPV-negative patients (63% vs 12%). Of FMR cases with cytologically evident ECA (which were designated as NILM after primary screening), 27% (of those with HPV testing results) were HPV-positive, compared to an HPV-positive rate of 7% in FOV+FSR ECA cases. Conclusion: Primary screening with only 30-45% of cases undergoing FOV+FSR is an insensitive method of identifying ECA in HPV-positive cases flagged as FMR eligible. Although the purpose of FMR is to add a second potential layer of screening for these high-risk cases, cytotechnologists have a non-zero false negative rate (w2.8%). Therefore, the progression of a significant number of HPV-positive ECA cases from primary screening to FMR increases the risk of false negative diagnosis. For this reason, the number of HPV-positive cases advancing to FMR should be minimized by devoting additional FOV+FSR/manual screening resources to HPV-positive patients.
Figure 1.
136 Review of Cytology Cases with Improper Patient and/or Specimen Identification Maryna Tarbunova, MD, Jinous Saremian, MD University of Florida College of Medicine, Jacksonville, Florida Introduction: Proper patient identification and specimen labeling is required to protect patients from adverse consequences of errors. The same patient-specific identifiers must be directly associated with the individual and with the specimen containers. The aim of this study is to review cytology cases with improper patient and/or specimen identification and analyze the most common errors. Materials and Methods: This is a retrospective review of cytology cases with improper patient and/or specimen identification during a 5 year period (December 2009 e December 2014) received in the Department of Pathology at UF Health Jacksonville. Results: We reviewed 337 cytology cases with improper patient and/or specimen identification. Registration error (RE), which includes improper patient registration like misspelled first or last name, error in the date of birth(DOB) or patient gender upon registration or failure of timely registration was identified in 211 (62 %) cases. Unlabeled specimen containers, mismatch in the name, gender, DOB or laterality on the container and requisition sheet was identified in 117 (35 %) cases and attributes to a submitting error (SE). Unlabeled specimen container was found to be the most common submitting error (55 out of 117 cases or 47%). Nine (9) cases (3% of all the cases) were mislabeled by a cytotechnologist during the specimen processing and designated as a processing error (PE). Forty two (42) out of 337 or 12% of cases were rejected due to failure of appropriate identification, all of which were due to SE. Conclusion: The analysis of all cases with improper patient and/or specimen identification during a 5 year period revealed RE to be the most common error (62% of cases). Submitting error was found to be the more significant, as 42 out of 117 of these cases (35%) were rejected due to failure of appropriate identification (Figure 1). There was no impact in patient care in any of these cases.
Epithelial cell abnormality rates
Figure 1 Figure 2.
HPV-positive rates
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134
Individual Cytopathologists’ Rates of Atypia Diagnoses (%ATY) and Atypia to Positive Ratios (ATY/POS) Diagnoses in Non-Gynecologic Cytology (NgyCy): A Potential Focus for Continuous Quality Improvement (CQI)
Clinical Mutation Detection in Small Biopsies and Fine Needle Aspirations Including Bone Metastases Using a Next Generation Sequencing Assay
Stefan Pambuccian, MD, Guliz Barkan, MD, Swati Mehrotra, MD, Mohammed Atieh, DO, Eva Wojcik, MD, MIAC Loyola University Medical Center, Maywood, Illinois Introduction: For gynecologic cytopathology (GyCy), individual pathologists’ %ATY and their rates of ATY/POS, i.e. the ASC/SIL ratio, have been the focus of successful CQI activities during the last two decades. The aim of this study was to study the value of monitoring %ATY and ATY/ POS in NGyCy specimens, as part of the cytopathology laboratory’s CQI program. Materials and Methods: For the 16 year interval (2000-2015), we calculated each cytopathologist’s %ATY and ATY/POS ratio in GyCy, exfoliative cytopathology (ExCy) and fine needle aspiration (FNA) specimens. For each specimen type, %ATY and ATY/POS ratios were calculated for each cytopathologist, and compared to the laboratory average (LA) and standard deviation (SD). Pearson correlations between %ATY and ATY/POS ratios and the cytopathologist’s years of experience and total number of cases examined were calculated for GCy, FNA and ExCy, as were correlations between %ATY and ATY/POS ratios in GCy, FNA and ExCy. Results: 11 board-certified cytopathologists with 2-20 years (mean 86) of experience diagnosed 1,187 to 26,825 cytology cases each (total 96,913 cases, including 35,803 GyCy, 38,983 ExCy, and 22,127 FNA) (Figure 1). Two cytopathologists had %ATY or ATY/POS ratios >2SD in GyCy and ExCy. No significant correlations were found between the cytopathologists’ experience or case volume and their %ATY or ATY/POS ratios. There was a significant correlation between cytopathologists’ %ATY in GyCy and ExCy cases (rZ0.80, pZ0.003) and ATY/POS ratios in GyCy and ExCy (rZ0.88, p <0.0001), but not between FNA and GyCy or ExCy cases. Conclusion: Since our results show a significant correlation between cytopathologists’ GyCy and ExCy %ATY and ATY/POS ratios, CQI measures similar to those successfully applied for GyCy could be applied to ExCy. Our laboratory will implement monitoring ExCy % ATY and ATY/POS ratios as part of our ongoing quality improvement process.
Gang Zheng, MD, PhD, Ming-Tseh Lin, MD, Christopher Gocke, MD, James Eshleman, MD, PhD, Peter Illei, MD The Johns Hopkins Medical Institutions, Baltimore, Maryland Introduction: Next generation sequencing (NGS) provides information for management of cancer. In this retrospective study of a 50 gene cancer hotspot NGS assay, we evaluated factors that may affect the success rate of NGS tests. Materials and Methods: A total of 1,121 formalin-fixed paraffin-embedded (FFPE) tissues were submitted to the Johns Hopkins Molecular Diagnostics Laboratory between April 2013 and October 2014. Results: Mutations were detected in 702 specimens, 381 specimens were “negative for mutation” and 38 specimens (3.4%) were reported as “no result” due to failure of the NGS assay. Lowest failure rate was in CRC panel (3/312, 1.0%) followed by lung cancer panel (26/623, 4.2%, P < 0.01) and melanoma panel (8/168, 4.8%, P Z 0.02). Referred specimens from other hospitals showed a higher failure rate (15/301, 5.0%) as compared to specimens taken and processed at the Johns Hopkins Hospital (14/795, 1.8%) (P < 0.01). Biopsy specimens (20/347, 5.8%, P < 0.001) and FNA specimens (4/128, 3.1%, P Z 0.04) also showed a higher failure rate as compared to the resection/excision specimens (4/587, 0.7%). Successful NGS results were obtained from all 30 aspiration specimens of effusions. Higher failure rate was observed in referred specimens (5.0% vs. 1.8%), biopsy specimens (5.8%) and fine needle aspiration specimens (3.1%), as compared to the resection/excision specimens (0.7%). Bone metastasis specimens showed an overall 36% failure rate. However, biopsy bone specimens with no or short decalcification had a lower failure rate (3/16, 23%) than resection bone specimens with a prolonged decalcification process (5/9, 55%). Conclusion: CRC panel showed a lower failure rate than the lung cancer or melanoma panel. Resection specimens provided a higher success rate for the NGS assay, but biopsy or FNA is better testing bone metastases. Effusions are excellent specimens for NGS testing.
135 Primary Screening in Semi-Automated Gynecologic Cytology is an Insensitive Method of Identifying Epithelial Cell Abnormality in HPVPositive Patients Based on Cases Flagged for Full Manual Review Louis Vaickus, MD1, David Wilbur, MD1, Brenda Sweeney, SCT (ASCP), MB1, Andrew Renshaw, MD2 1 Massachusetts General Hospital, Boston, Massachusetts 2 Baptist Hospital of Miami, Miami, Florida
Figure 1.
Atypia in GYN, exfoliative and FNA cytol
Introduction: Negative gynecological cytology (NILM) cases in laboratories using semi-automated guided screening devices with slide stratification (i.e. BD-FocalPoint), are manually reviewed by two methods: Immediate full slide review after fields of view analysis (FOV+FSR) and QA/high-risk quintile directed full manual review (FMR). For FOV+FSR, current FDA approvals and guidelines require/recommend rescreening negatives at a rate of at least 15% or twice the epithelial cell abnormality (ECA) rate, respectively. No requirements exist for FMR. The effectiveness of the current manual review system is unknown. Materials and Methods: Gynecological cytology cases from 2009-2014 were analyzed. The data comprised 93,169 patients, 194,656 specimens and 50,413 HPV tests. Results: FMR and FOV+FSR rates ranged from 10-20% and 30-45%, respectively. In FMR, the ECA-rate was correlated with HPV-positive
S60
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rate (r2Z0.86, YZ0.24X+0.04); both ECA-rate and HPV-rate decreased with age (Figure 1 and 2). For FOV+FSR, ECA-rate was also related to HPV-positive rate (r2Z0.75, YZ1.3X+0.16) and both rates decreased with age (Figure 1 and 2). HPV-positive patients were much more likely to have ECA than HPV-negative patients (63% vs 12%). Of FMR cases with cytologically evident ECA (which were designated as NILM after primary screening), 27% (of those with HPV testing results) were HPV-positive, compared to an HPV-positive rate of 7% in FOV+FSR ECA cases. Conclusion: Primary screening with only 30-45% of cases undergoing FOV+FSR is an insensitive method of identifying ECA in HPV-positive cases flagged as FMR eligible. Although the purpose of FMR is to add a second potential layer of screening for these high-risk cases, cytotechnologists have a non-zero false negative rate (w2.8%). Therefore, the progression of a significant number of HPV-positive ECA cases from primary screening to FMR increases the risk of false negative diagnosis. For this reason, the number of HPV-positive cases advancing to FMR should be minimized by devoting additional FOV+FSR/manual screening resources to HPV-positive patients.
Figure 1.
136 Review of Cytology Cases with Improper Patient and/or Specimen Identification Maryna Tarbunova, MD, Jinous Saremian, MD University of Florida College of Medicine, Jacksonville, Florida Introduction: Proper patient identification and specimen labeling is required to protect patients from adverse consequences of errors. The same patient-specific identifiers must be directly associated with the individual and with the specimen containers. The aim of this study is to review cytology cases with improper patient and/or specimen identification and analyze the most common errors. Materials and Methods: This is a retrospective review of cytology cases with improper patient and/or specimen identification during a 5 year period (December 2009 e December 2014) received in the Department of Pathology at UF Health Jacksonville. Results: We reviewed 337 cytology cases with improper patient and/or specimen identification. Registration error (RE), which includes improper patient registration like misspelled first or last name, error in the date of birth(DOB) or patient gender upon registration or failure of timely registration was identified in 211 (62 %) cases. Unlabeled specimen containers, mismatch in the name, gender, DOB or laterality on the container and requisition sheet was identified in 117 (35 %) cases and attributes to a submitting error (SE). Unlabeled specimen container was found to be the most common submitting error (55 out of 117 cases or 47%). Nine (9) cases (3% of all the cases) were mislabeled by a cytotechnologist during the specimen processing and designated as a processing error (PE). Forty two (42) out of 337 or 12% of cases were rejected due to failure of appropriate identification, all of which were due to SE. Conclusion: The analysis of all cases with improper patient and/or specimen identification during a 5 year period revealed RE to be the most common error (62% of cases). Submitting error was found to be the more significant, as 42 out of 117 of these cases (35%) were rejected due to failure of appropriate identification (Figure 1). There was no impact in patient care in any of these cases.
Epithelial cell abnormality rates
Figure 1 Figure 2.
HPV-positive rates