Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users should be aware of.A narrative review was performed using online databases such as PubMed, Google Scholar and reference lists of identified papers. Language was limited to English.Errors can be pre-analytical, analytical or post-analytical. Samples should be analysed within 15 min and kept at room temperature and taken at least 15-30 min after changes to inspired oxygen and ventilator settings, for accurate oxygen measurement. Plastic syringes are more oxygen permeable if chilled. Currently, analysers run arterial, venous, capillary and intraosseous samples, but variations in reference intervals may not be appreciated or reported. Analytical issues can arise from interference secondary to drugs, such as spurious hyperchloraemia with salicylate and hyperlactataemia with ethylene glycol, or pathology, such as spurious hypoxaemia with leucocytosis and alkalosis in hypoalbuminaemia. Interpretation is complicated by result adjustment, for example, temperature (alpha-stat adjustment may overestimate partial pressure of carbon dioxide (pCO2) in hypothermia, for example), and inappropriate reference intervals, for example, in pregnancy bicarbonate, and pCO2 ranges should be lowered.Lack of appreciation for patient-specific and circumstance-specific reference intervals, including extremes of age and altitude, and transformation of measurements to standard conditions can lead to inappropriate assumptions. It is vitally important for users to optimise specimen collection, appreciate the analytical methods and understand when reference intervals are applicable to their specimen type, clinical question or patient.
{"title":"Pitfalls in the diagnosis and management of acid-base disorders in humans: a laboratory medicine perspective.","authors":"Henry Carlton, Kate E Shipman","doi":"10.1136/jcp-2024-209423","DOIUrl":"https://doi.org/10.1136/jcp-2024-209423","url":null,"abstract":"<p><p>Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users should be aware of.A narrative review was performed using online databases such as PubMed, Google Scholar and reference lists of identified papers. Language was limited to English.Errors can be pre-analytical, analytical or post-analytical. Samples should be analysed within 15 min and kept at room temperature and taken at least 15-30 min after changes to inspired oxygen and ventilator settings, for accurate oxygen measurement. Plastic syringes are more oxygen permeable if chilled. Currently, analysers run arterial, venous, capillary and intraosseous samples, but variations in reference intervals may not be appreciated or reported. Analytical issues can arise from interference secondary to drugs, such as spurious hyperchloraemia with salicylate and hyperlactataemia with ethylene glycol, or pathology, such as spurious hypoxaemia with leucocytosis and alkalosis in hypoalbuminaemia. Interpretation is complicated by result adjustment, for example, temperature (alpha-stat adjustment may overestimate partial pressure of carbon dioxide (pCO<sub>2</sub>) in hypothermia, for example), and inappropriate reference intervals, for example, in pregnancy bicarbonate, and pCO<sub>2</sub> ranges should be lowered.Lack of appreciation for patient-specific and circumstance-specific reference intervals, including extremes of age and altitude, and transformation of measurements to standard conditions can lead to inappropriate assumptions. It is vitally important for users to optimise specimen collection, appreciate the analytical methods and understand when reference intervals are applicable to their specimen type, clinical question or patient.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: We aimed to evaluate the performances of the Idylla GeneFusion Assay (IGFA) designed to detect, in a single, rapid and fully automated assay, ALK, ROS1, RET, NTRK1, NTRK2 and NTRK3 gene fusions and MET exon 14 skipping in cancer samples.
Methods: Based on a set of tumours enriched in cases with gene fusions, we applied the IGFA to tumour areas of various sizes and tumour cell contents. IGFA results were compared with those obtained with other methods (immunohistochemistry, fluorescent in situ hybridisation, DNA and RNA next-generation sequencing).
Results: We selected 68 tumours: 49 cases with known gene fusions (8 ALK, 8 ROS1, 5 RET, 7 NTRK1, 3 NTRK2 and 6 NTRK3 ones) or MET exon 14 skipping mutations (12 cases) and 19 cases with no fusion and no MET mutation. We performed 128 IGFA tests on distinct tissue areas. The global sensitivity and specificity of the IGFA were, respectively, 62.82% and 99.2% with variations between molecular targets and tissue areas. Of note, 72.5% sensitivity and 98.79% specificity were obtained in 37 tissue areas fulfilling the manufacturer's recommendations (ie, at least 10% of tumour cells in at least 20 mm² of tissue area). The rate of non-conclusive results was higher in small samples with low percentages of tumour cells.
Conclusions: The IGFA could contribute to the rapid detection of targetable gene fusions and mutations, especially in context of rapidly growing cancers requiring urgent therapeutic choices.
{"title":"Performances of the Idylla GeneFusion Assay: contribution to a rapid diagnosis of targetable gene fusions in tumour samples.","authors":"Matthieu Guillard, Charline Caumont, Pascale Marcorelles, Jean-Philippe Merlio, David Cappellen, Arnaud Uguen","doi":"10.1136/jcp-2023-208798","DOIUrl":"10.1136/jcp-2023-208798","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to evaluate the performances of the Idylla GeneFusion Assay (IGFA) designed to detect, in a single, rapid and fully automated assay, <i>ALK</i>, <i>ROS1</i>, <i>RET</i>, <i>NTRK1</i>, <i>NTRK2</i> and <i>NTRK3</i> gene fusions and <i>MET</i> exon 14 skipping in cancer samples.</p><p><strong>Methods: </strong>Based on a set of tumours enriched in cases with gene fusions, we applied the IGFA to tumour areas of various sizes and tumour cell contents. IGFA results were compared with those obtained with other methods (immunohistochemistry, fluorescent in situ hybridisation, DNA and RNA next-generation sequencing).</p><p><strong>Results: </strong>We selected 68 tumours: 49 cases with known gene fusions (8 <i>ALK</i>, 8 <i>ROS1</i>, 5 <i>RET</i>, 7 <i>NTRK1</i>, 3 <i>NTRK2</i> and 6 <i>NTRK3</i> ones) or <i>MET</i> exon 14 skipping mutations (12 cases) and 19 cases with no fusion and no <i>MET</i> mutation. We performed 128 IGFA tests on distinct tissue areas. The global sensitivity and specificity of the IGFA were, respectively, 62.82% and 99.2% with variations between molecular targets and tissue areas. Of note, 72.5% sensitivity and 98.79% specificity were obtained in 37 tissue areas fulfilling the manufacturer's recommendations (ie, at least 10% of tumour cells in at least 20 mm² of tissue area). The rate of non-conclusive results was higher in small samples with low percentages of tumour cells.</p><p><strong>Conclusions: </strong>The IGFA could contribute to the rapid detection of targetable gene fusions and mutations, especially in context of rapidly growing cancers requiring urgent therapeutic choices.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariela Huerta-Rosario, Mariam Mir, Carlos Quispe-Vicuña, Helena Hwang, Venetia Sarode, Yan Peng, Yisheng Fang, Marilyn Leitch, Sunati Sahoo
Aims: Touch preparation (TP) and frozen section (FS) are the two methods routinely used in the intraoperative evaluation (IOE) of sentinel lymph nodes (SLNs) to detect metastases in patients with breast cancer. Both methods are extremely sensitive and specific in the primary surgery (non-neoadjuvant systemic therapy (non-NST)) setting. Since NST introduces unique challenges in the IOE of SLNs, the aim was to determine the accuracy of TP and FS in the IOE of SLNs in the NST setting and compare the results with the non-NST setting and to examine factors that contribute to any differences.
Methods: We analysed 871 SLNs from 232 patients (615 SLNs from NST and 256 SLNs from non-NST settings) between 2016 through 2019.
Results: In the NST group, TP alone (n=366) had a sensitivity of 45.7% and specificity of 99.7%; FS alone (n=90) had a sensitivity of 83.3% and specificity of 100%. When both TP and FS (n=135) were used, the sensitivity was 80.3% and the specificity was 98.6%.In the non-NST group, TP alone (n=193) had a sensitivity of 66.7% and specificity of 100%; FS alone (n=22) had a sensitivity and specificity of 100%; and combined TP and FS (n=34) had a sensitivity and specificity of 100% and 96%, respectively.
Conclusions: Evaluating SLNs intraoperatively in the NST setting can be challenging secondary to therapy-related changes. In the NST setting, FS has higher sensitivity and specificity compared with TP for the IOE of SLNs and should be the preferred method.
{"title":"Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer treated with systemic neoadjuvant therapy.","authors":"Mariela Huerta-Rosario, Mariam Mir, Carlos Quispe-Vicuña, Helena Hwang, Venetia Sarode, Yan Peng, Yisheng Fang, Marilyn Leitch, Sunati Sahoo","doi":"10.1136/jcp-2023-208862","DOIUrl":"10.1136/jcp-2023-208862","url":null,"abstract":"<p><strong>Aims: </strong>Touch preparation (TP) and frozen section (FS) are the two methods routinely used in the intraoperative evaluation (IOE) of sentinel lymph nodes (SLNs) to detect metastases in patients with breast cancer. Both methods are extremely sensitive and specific in the primary surgery (non-neoadjuvant systemic therapy (non-NST)) setting. Since NST introduces unique challenges in the IOE of SLNs, the aim was to determine the accuracy of TP and FS in the IOE of SLNs in the NST setting and compare the results with the non-NST setting and to examine factors that contribute to any differences.</p><p><strong>Methods: </strong>We analysed 871 SLNs from 232 patients (615 SLNs from NST and 256 SLNs from non-NST settings) between 2016 through 2019.</p><p><strong>Results: </strong>In the NST group, TP alone (n=366) had a sensitivity of 45.7% and specificity of 99.7%; FS alone (n=90) had a sensitivity of 83.3% and specificity of 100%. When both TP and FS (n=135) were used, the sensitivity was 80.3% and the specificity was 98.6%.In the non-NST group, TP alone (n=193) had a sensitivity of 66.7% and specificity of 100%; FS alone (n=22) had a sensitivity and specificity of 100%; and combined TP and FS (n=34) had a sensitivity and specificity of 100% and 96%, respectively.</p><p><strong>Conclusions: </strong>Evaluating SLNs intraoperatively in the NST setting can be challenging secondary to therapy-related changes. In the NST setting, FS has higher sensitivity and specificity compared with TP for the IOE of SLNs and should be the preferred method.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: To systematically examine the sample suitability and stability for volatile alcohols (methanol, ethanol and isopropanol with its metabolite acetone) and glycols (ethylene/propylene glycols, EG/PG) in different collection tubes.
Method: Two pools of whole blood were created and spiked with two levels of volatile alcohols and EG/PG. The spiked whole blood was added to six different blood collection tubes and were kept at different storage conditions. An aliquot was prepared from baseline replicates. Concentrations of volatile alcohols and glycols were analysed by gas chromatography.
Results: All blood collection tubes have demonstrated similar performance over different storage conditions, that is, to be statistically insignificant (p>0.05) with the only exception of PG at the high concentration of day 7 at 4°C condition (p<0.05 but clinically insignificant as
Conclusion: Grey/red/lavender, serum separator tube, plasma separator tube and the newly developed Barricor tubes are all suitable for volatile alcohols and EG/PG analysis. Primary samples are stable for 2 days room temperature, 14 days at 4°C and 28 days at -20°C for volatile alcohols, and 2 days room temperature, 7 days at 4°C, and 28 days at -20°C for EG. Aliquoted samples are stable up to 28 days at -20°C for all volatile alcohols and glycols.
{"title":"Sample suitability and stability in different blood collection tubes for methanol, ethanol, isopropanol, acetone and glycols analysis.","authors":"Leonardo Cui, John G Swanwick, Yu Chen","doi":"10.1136/jcp-2022-208649","DOIUrl":"10.1136/jcp-2022-208649","url":null,"abstract":"<p><strong>Aim: </strong>To systematically examine the sample suitability and stability for volatile alcohols (methanol, ethanol and isopropanol with its metabolite acetone) and glycols (ethylene/propylene glycols, EG/PG) in different collection tubes.</p><p><strong>Method: </strong>Two pools of whole blood were created and spiked with two levels of volatile alcohols and EG/PG. The spiked whole blood was added to six different blood collection tubes and were kept at different storage conditions. An aliquot was prepared from baseline replicates. Concentrations of volatile alcohols and glycols were analysed by gas chromatography.</p><p><strong>Results: </strong>All blood collection tubes have demonstrated similar performance over different storage conditions, that is, to be statistically insignificant (p>0.05) with the only exception of PG at the high concentration of day 7 at 4°C condition (p<0.05 but clinically insignificant as <clinical acceptable limit (CAL) of 25%). Compared with the baseline, most volatile alcohols showed statistical significance (p<0.05) but were clinically stable for all storage conditions (biases<CAL). Similarly, compared with day 1, most EG/PG were stable up to 28 days at -20°C. Aliquoted samples were clinically stable up to 28 days at -20°C.</p><p><strong>Conclusion: </strong>Grey/red/lavender, serum separator tube, plasma separator tube and the newly developed Barricor tubes are all suitable for volatile alcohols and EG/PG analysis. Primary samples are stable for 2 days room temperature, 14 days at 4°C and 28 days at -20°C for volatile alcohols, and 2 days room temperature, 7 days at 4°C, and 28 days at -20°C for EG. Aliquoted samples are stable up to 28 days at -20°C for all volatile alcohols and glycols.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9467614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shishun Fan, Huirui Zhang, Zhenyu Meng, Ang Li, Yuqing Luo, Yueping Liu
Aims: This meta-analysis assessed the relative diagnostic accuracy of optical coherence tomography (OCT) versus frozen section (FS) in evaluating surgical margins during breast-conserving procedures.
Methods: PubMed and Embase were searched for relevant studies published up to October 2023. The inclusion criteria encompassed studies evaluating the diagnostic accuracy of OCT or FS in patients undergoing breast-conserving surgery. Sensitivity and specificity were analysed using the DerSimonian and Laird method and subsequently transformed through the Freeman-Tukey double inverse sine method.
Results: The meta-analysis encompassed 36 articles, comprising 16 studies on OCT and 20 on FS, involving 10 289 specimens from 8058 patients. The overall sensitivity of OCT was 0.93 (95% CI: 0.90 to 0.96), surpassing that of FS, which was 0.82 (95% CI: 0.71 to 0.92), indicating a significantly higher sensitivity for OCT (p=0.04). Conversely, the overall specificity of OCT was 0.89 (95% CI: 0.83 to 0.94), while FS exhibited a higher specificity at 0.97 (95% CI: 0.95 to 0.99), suggesting a superior specificity for FS (p<0.01).
Conclusions: Our meta-analysis reveals that OCT offers superior sensitivity but inferior specificity compared with FS in assessing surgical margins in breast-conserving surgery patients. Further larger well-designed prospective studies are needed, especially those employing a head-to-head comparison design.
{"title":"Comparing the diagnostic efficacy of optical coherence tomography and frozen section for margin assessment in breast-conserving surgery: a meta-analysis.","authors":"Shishun Fan, Huirui Zhang, Zhenyu Meng, Ang Li, Yuqing Luo, Yueping Liu","doi":"10.1136/jcp-2024-209597","DOIUrl":"10.1136/jcp-2024-209597","url":null,"abstract":"<p><strong>Aims: </strong>This meta-analysis assessed the relative diagnostic accuracy of optical coherence tomography (OCT) versus frozen section (FS) in evaluating surgical margins during breast-conserving procedures.</p><p><strong>Methods: </strong>PubMed and Embase were searched for relevant studies published up to October 2023. The inclusion criteria encompassed studies evaluating the diagnostic accuracy of OCT or FS in patients undergoing breast-conserving surgery. Sensitivity and specificity were analysed using the DerSimonian and Laird method and subsequently transformed through the Freeman-Tukey double inverse sine method.</p><p><strong>Results: </strong>The meta-analysis encompassed 36 articles, comprising 16 studies on OCT and 20 on FS, involving 10 289 specimens from 8058 patients. The overall sensitivity of OCT was 0.93 (95% CI: 0.90 to 0.96), surpassing that of FS, which was 0.82 (95% CI: 0.71 to 0.92), indicating a significantly higher sensitivity for OCT (p=0.04). Conversely, the overall specificity of OCT was 0.89 (95% CI: 0.83 to 0.94), while FS exhibited a higher specificity at 0.97 (95% CI: 0.95 to 0.99), suggesting a superior specificity for FS (p<0.01).</p><p><strong>Conclusions: </strong>Our meta-analysis reveals that OCT offers superior sensitivity but inferior specificity compared with FS in assessing surgical margins in breast-conserving surgery patients. Further larger well-designed prospective studies are needed, especially those employing a head-to-head comparison design.</p><p><strong>Prospero registration number: </strong>CRD42023483751.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madeleine de Carle, Brooke Macnab, Jenewa Utainrat, Jessica Herkes-Deane, John Attia, Theo de Malmanche, Erdahl Teber, Kerrin Palazzi, Craig Scowen, Alexis Hure
Aims: Identifying and reducing low-value care is a vital issue in Australia, with pathology test ordering a common focus in this field. This study builds on previous research and aimed to quantify the impact of the implementation of an electronic ordering (e-ordering) system on the volume of pathology testing, compared with manual (paper based) ordering.
Methods: An audit and analysis of pathology test data were conducted, using an interrupted time series design to investigate the impact of the e-ordering system on pathology ordering patterns. All medical and surgical adult inpatients at a tertiary referral hospital in Newcastle, Australia, were included over a 3-year period.
Results: Overall, there were no statistically significant differences in the volume of orders due to the implementation of the e-ordering system. There was a slight increase in the aggregated volume (tests per admission and tests per bed day) of tests ordered across the entire study period, reflecting a secular trend.
Conclusions: Despite providing greater visibility and tracking of orders, we conclude that the implementation of an e-ordering system does not, in and of itself, reduce ordering volume. Efforts to identify and reduce low-value care will require intentional effort and specifically designed educational programmes or hard-wired algorithms.
{"title":"Does an electronic pathology ordering system change the volume and pattern of routine testing in hospital? An interrupted time series analysis.","authors":"Madeleine de Carle, Brooke Macnab, Jenewa Utainrat, Jessica Herkes-Deane, John Attia, Theo de Malmanche, Erdahl Teber, Kerrin Palazzi, Craig Scowen, Alexis Hure","doi":"10.1136/jcp-2023-208850","DOIUrl":"10.1136/jcp-2023-208850","url":null,"abstract":"<p><strong>Aims: </strong>Identifying and reducing low-value care is a vital issue in Australia, with pathology test ordering a common focus in this field. This study builds on previous research and aimed to quantify the impact of the implementation of an electronic ordering (e-ordering) system on the volume of pathology testing, compared with manual (paper based) ordering.</p><p><strong>Methods: </strong>An audit and analysis of pathology test data were conducted, using an interrupted time series design to investigate the impact of the e-ordering system on pathology ordering patterns. All medical and surgical adult inpatients at a tertiary referral hospital in Newcastle, Australia, were included over a 3-year period.</p><p><strong>Results: </strong>Overall, there were no statistically significant differences in the volume of orders due to the implementation of the e-ordering system. There was a slight increase in the aggregated volume (tests per admission and tests per bed day) of tests ordered across the entire study period, reflecting a secular trend.</p><p><strong>Conclusions: </strong>Despite providing greater visibility and tracking of orders, we conclude that the implementation of an e-ordering system does not, in and of itself, reduce ordering volume. Efforts to identify and reduce low-value care will require intentional effort and specifically designed educational programmes or hard-wired algorithms.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: Cytokeratin 5 (CK5) is a surrogate maker of progenitor cells and early glandular and myoepithelial cells (MECs) in the breast, and CK5 expression in breast MECs varies from ducts to lobules, and from normal to diseased tissue. However, the mechanisms underlying immunophenotypic alterations of CK5 expression in MECs remain unclear.
Methods: CK5 expression in MECs of 20 normal breast samples, 58 ductal carcinoma in situ (DCIS; including 21 DCIS with extensive lobular involvement), 11 atypical ductal hyperplasia (ADH), 18 non-invasive lobular neoplasia consisting of 11 atypical lobular hyperplasia (ALH) and 7 lobular carcinoma in situ (LCIS), 20 cystic lobules and 10 usual ductal hyperplasia (UDH) involving lobules were observed to evaluate the effects of contact with benign hyperplastic or cancerous luminal cells and pressure of dilated glands on CK5 expression.
Results: CK5 expression in normal ductal MECs was exclusively positive, whereas most normal lobular MECs were negative. In DCIS, cancerous ducts were primarily surrounded by CK5-positive MECs (91.0%), as were lobular acini involved by DCIS (89.2%), while the remaining normal acini maintained CK5-negative. CK5-positive MECs were found in 57.5% of acini in ALH and were more prevalent in LCIS (70.7%). CK5 expression was occasionally positive in both cystic lobules (16.7%) and lobules involved by UDH (14.3%), while an increase of CK5-positive MECs was found in ADH (38.2%).
Conclusions: These results suggest that CK5 expression in lobular MECs may be altered by contact with cancerous luminal cells rather than benign hyperplastic luminal cells or pressure from dilated glands.
{"title":"Altered cytokeratin 5 expression in breast lobular myoepithelial cells.","authors":"Anqi Li, Miao Ruan, Xiaochun Fei, Haimin Xu, Shijie Deng, Rui Bi, Wentao Yang, Lei Dong","doi":"10.1136/jcp-2023-208835","DOIUrl":"10.1136/jcp-2023-208835","url":null,"abstract":"<p><strong>Aims: </strong>Cytokeratin 5 (CK5) is a surrogate maker of progenitor cells and early glandular and myoepithelial cells (MECs) in the breast, and CK5 expression in breast MECs varies from ducts to lobules, and from normal to diseased tissue. However, the mechanisms underlying immunophenotypic alterations of CK5 expression in MECs remain unclear.</p><p><strong>Methods: </strong>CK5 expression in MECs of 20 normal breast samples, 58 ductal carcinoma in situ (DCIS; including 21 DCIS with extensive lobular involvement), 11 atypical ductal hyperplasia (ADH), 18 non-invasive lobular neoplasia consisting of 11 atypical lobular hyperplasia (ALH) and 7 lobular carcinoma in situ (LCIS), 20 cystic lobules and 10 usual ductal hyperplasia (UDH) involving lobules were observed to evaluate the effects of contact with benign hyperplastic or cancerous luminal cells and pressure of dilated glands on CK5 expression.</p><p><strong>Results: </strong>CK5 expression in normal ductal MECs was exclusively positive, whereas most normal lobular MECs were negative. In DCIS, cancerous ducts were primarily surrounded by CK5-positive MECs (91.0%), as were lobular acini involved by DCIS (89.2%), while the remaining normal acini maintained CK5-negative. CK5-positive MECs were found in 57.5% of acini in ALH and were more prevalent in LCIS (70.7%). CK5 expression was occasionally positive in both cystic lobules (16.7%) and lobules involved by UDH (14.3%), while an increase of CK5-positive MECs was found in ADH (38.2%).</p><p><strong>Conclusions: </strong>These results suggest that CK5 expression in lobular MECs may be altered by contact with cancerous luminal cells rather than benign hyperplastic luminal cells or pressure from dilated glands.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9359701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pooja Dhorajiya, Sultan Mahmood, Anne Fabrizio, Vikram Deshpande, Monika Vyas
Aims: A synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications is expected to persist in the foreseeable future. We present a large single institutional series of therapeutic resections from patients for whom ORISE was used for initial endoscopic procedures, highlighting the pitfalls and complications associated with its use.
Methods: All specimens showing lifting agent granulomata (LAGs) associated with the use of ORISE were identified. The H&E slides were reviewed to define the morphological characteristics and extent of LAG in the intestinal wall and other organs. The clinical impression and gross findings were compared with the final pathological diagnosis.
Results: 34 cases (28 resections and 6 repeat endoscopic mucosal resection specimens) showed LAG. On microscopy, 20.5% showed no residual disease, 64.7% also showed residual precursor lesion and 14.7% also showed malignancy. In 64.2% of cases, a mass lesion was seen grossly but no malignancy was identified microscopically. ORISE was present in vascular spaces (n=9), lymph nodes (n=2), other organs such as appendix (n=1) and omentum/peritoneum (n=1). The major discordance between clinical impression (mass/neoplasm) and final pathology (no residual malignancy) was seen in 4/34 (11.8%) cases. LAGs were seen up to 10 months after the use of ORISE in the prior endoscopic procedure.
Conclusion: ORISE deposits may mimic residual/disseminated neoplasm and prompt inadvertent changes in surgical decisions. Awareness of this pitfall is essential to prevent unwarranted surgical resections in patients undergoing follow-up for endoscopically resected lesions.
{"title":"Gone but not forgotten: expanding the spectrum of ORISE (submucosal lifting agent) associated diagnostic pitfalls and complications.","authors":"Pooja Dhorajiya, Sultan Mahmood, Anne Fabrizio, Vikram Deshpande, Monika Vyas","doi":"10.1136/jcp-2024-209419","DOIUrl":"https://doi.org/10.1136/jcp-2024-209419","url":null,"abstract":"<p><strong>Aims: </strong>A synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications is expected to persist in the foreseeable future. We present a large single institutional series of therapeutic resections from patients for whom ORISE was used for initial endoscopic procedures, highlighting the pitfalls and complications associated with its use.</p><p><strong>Methods: </strong>All specimens showing lifting agent granulomata (LAGs) associated with the use of ORISE were identified. The H&E slides were reviewed to define the morphological characteristics and extent of LAG in the intestinal wall and other organs. The clinical impression and gross findings were compared with the final pathological diagnosis.</p><p><strong>Results: </strong>34 cases (28 resections and 6 repeat endoscopic mucosal resection specimens) showed LAG. On microscopy, 20.5% showed no residual disease, 64.7% also showed residual precursor lesion and 14.7% also showed malignancy. In 64.2% of cases, a mass lesion was seen grossly but no malignancy was identified microscopically. ORISE was present in vascular spaces (n=9), lymph nodes (n=2), other organs such as appendix (n=1) and omentum/peritoneum (n=1). The major discordance between clinical impression (mass/neoplasm) and final pathology (no residual malignancy) was seen in 4/34 (11.8%) cases. LAGs were seen up to 10 months after the use of ORISE in the prior endoscopic procedure.</p><p><strong>Conclusion: </strong>ORISE deposits may mimic residual/disseminated neoplasm and prompt inadvertent changes in surgical decisions. Awareness of this pitfall is essential to prevent unwarranted surgical resections in patients undergoing follow-up for endoscopically resected lesions.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eros Qama, Carlos Castrodad Rodriguez, Radhika Sekhri, Chuanyong Lu, John McAuliffe, Amarpreet Bhalla
Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.
{"title":"Rosai-Dorfman Disease of pancreas: rare aetiology mimicking malignancy.","authors":"Eros Qama, Carlos Castrodad Rodriguez, Radhika Sekhri, Chuanyong Lu, John McAuliffe, Amarpreet Bhalla","doi":"10.1136/jcp-2024-209412","DOIUrl":"https://doi.org/10.1136/jcp-2024-209412","url":null,"abstract":"<p><p>Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janice Lee Veronica Reeve, David Housley, Patrick J Twomey
Haemolysis is a preanalytical interference commonly encountered in specimens drawn for laboratory testing.1 2 As haemoglobin moieties absorb light between 300 and 600 nm, haemolysis can cause direct spectrophotometric interference in assays which absorb at similar wavelengths (eg, iron, lipase). Haemolysis itself can increase the concentration of intracellular analytes in serum or plasma (eg, potassium, lactate dehydrogenase and asparate aminotransferase) and conversely dilute extracellular molecules (eg, glucose and sodium).1 Therefore, reliable detection of haemolysis is an important prerequisite to the production of reliable laboratory test results. In some instances, knowing the degree of specimen haemolysis can help rationalise aberrant or unexpected test results. The use of automated, preanalytical processes for the detection of haemolysis (H-index), icteric (I-index) and lipaemia (L-index) in patient specimens has superseded their visual inspection.3 4 This is largely due to advances in instrumentation driven by increased demands on our medical laboratory services. In a high throughput laboratory, it is impossible to physically examine every specimen received. Aside from this, visual inspection of specimens is considered arbitrary at best.3 4 In this case, this New York-based laboratory uses two operators to examine specimens when the automated H-index is elevated.5 Here, the ‘high’ H index is set at >90, corresponding, on Roche instrumentation, to a haemoglobin concentration of 0.9 g/L (56 µmol/L). With a Roche H-index measuring range of 5–1200 mg/dL (~3–745 µmol/L), this cut-off of 90 mg/dL could be perceived as relatively low. The lower this index is set the more frequently ‘haemolysed’ samples will be encountered and the more laboratorian time is required for manual specimen inspection. Ideally, such interferents would not be present in patient serum/plasma, but alas they are. …
{"title":"Some issues to consider with the use of serum indices","authors":"Janice Lee Veronica Reeve, David Housley, Patrick J Twomey","doi":"10.1136/jcp-2024-209422","DOIUrl":"https://doi.org/10.1136/jcp-2024-209422","url":null,"abstract":"Haemolysis is a preanalytical interference commonly encountered in specimens drawn for laboratory testing.1 2 As haemoglobin moieties absorb light between 300 and 600 nm, haemolysis can cause direct spectrophotometric interference in assays which absorb at similar wavelengths (eg, iron, lipase). Haemolysis itself can increase the concentration of intracellular analytes in serum or plasma (eg, potassium, lactate dehydrogenase and asparate aminotransferase) and conversely dilute extracellular molecules (eg, glucose and sodium).1 Therefore, reliable detection of haemolysis is an important prerequisite to the production of reliable laboratory test results. In some instances, knowing the degree of specimen haemolysis can help rationalise aberrant or unexpected test results. The use of automated, preanalytical processes for the detection of haemolysis (H-index), icteric (I-index) and lipaemia (L-index) in patient specimens has superseded their visual inspection.3 4 This is largely due to advances in instrumentation driven by increased demands on our medical laboratory services. In a high throughput laboratory, it is impossible to physically examine every specimen received. Aside from this, visual inspection of specimens is considered arbitrary at best.3 4 In this case, this New York-based laboratory uses two operators to examine specimens when the automated H-index is elevated.5 Here, the ‘high’ H index is set at >90, corresponding, on Roche instrumentation, to a haemoglobin concentration of 0.9 g/L (56 µmol/L). With a Roche H-index measuring range of 5–1200 mg/dL (~3–745 µmol/L), this cut-off of 90 mg/dL could be perceived as relatively low. The lower this index is set the more frequently ‘haemolysed’ samples will be encountered and the more laboratorian time is required for manual specimen inspection. Ideally, such interferents would not be present in patient serum/plasma, but alas they are. …","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141586884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}