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We present GeneBe, an online platform streamlining the automated application of American College of Medical Genetics and Genomics (ACMG), Association for Molecular Pathology (AMP), and the College of American Pathologists (CAP) criteria for assessment of pathogenicity of genetic variants. GeneBe utilizes automated algorithms that evaluate 17 criteria from 28, closely aligning with current guidelines and leveraging data from diverse sources, including ClinVar. The user‐friendly web interface enables manual refinement of assignments for specific criteria based on site‐collected data. Our algorithm demonstrates a high correlation (r = 0.90) of assigned pathogenicity scores compared to expert assessments from the ClinGen Evidence Repository and substantial concordance with ClinVar verdict assignments (κ = 0.69). Comparative analysis with other published tools reveals that GeneBe performs similarly to VarSome while being superior over TAPES and InterVar. In contrast to some other tools, GeneBe's web implementation is tracker‐free and third‐party request‐free, safeguarding user privacy. Additionally, GeneBe offers an Application Programming Interface (API) for enhanced flexibility and integration into existing workflows and is provided free of charge for research purposes. GeneBe is available at https://genebe.net. [ABSTRACT FROM AUTHOR]

Mesothelioma is a rare disease with an historically poor prognosis. Over the past decade, a grading system has been developed that is a powerful prognostic tool in epithelioid mesothelioma. Grading of epithelioid mesothelioma is now required or strongly recommended by expert consensus, the College of American Pathologists, the World Health Organization, and the International Mesothelioma Interest Group. The original nuclear grading system for epithelioid mesothelioma, developed in the United States, split epithelioid mesotheliomas into three prognostic groups with marked differences in survival. Now, this three‐tiered nuclear grading system has been combined with the presence or absence of necrosis to form the currently recommended two‐tiered grading system of low‐ and high‐grade epithelioid mesothelioma. This review will focus on the development of this grading system in mesothelioma, the grading system's shortcomings, and the application of the grading system to cytology specimens and other extra‐pleural sites. Lastly, this review will briefly discuss alternative grading systems and future considerations. [ABSTRACT FROM AUTHOR]

Aims: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. Methods and results: The study included a test (n = 197) and a validation cohort (n = 218) of post‐CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three‐step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II‐IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19–3.50, P = 0.008) and disease‐free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23–5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. Conclusions: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response. [ABSTRACT FROM AUTHOR]

Introduction: Digital cytopathology is being progressively implemented in centres worldwide, but impediments such as the three‐dimensionality of specimens and the size of scanned images have prevented its use from becoming widespread. This study aimed to validate the use of digital whole slide image scanning of cytopathology samples for routine sign‐out. Methods: Specimens were scanned using the Leica Aperio GT 450 System. The following sample types were used: liquid‐based cytology, direct conventional smears from fine needle aspirates and cytospins. Cases were validated by the same pathologist who originally rendered the conventional diagnosis, with a washout of at least 3 months. Final digital diagnoses were compared to the original analogical diagnoses, and cases were considered concordant up to a one‐degree difference between the original and digital diagnoses. Reasons for the unsuccessful scanning of slides were also noted. The technical procedures followed the College of American Pathologists' guidelines for digital pathology validation. Results: A total of 730 slides from 383 cases (337 female, 51 male; median age 42) were successfully scanned. These cases consisted of the following sample types: 81 (21.1%) conventional smears, 240 (62.7%) liquid‐based cytology samples and 62 (16.2%) cytospins. There were only five discordant cases, with a 98.7% agreement between original and digital diagnoses using the difference rate of up to one degree. Seventy‐seven slides (10.5%) had to be rescanned due to technical problems. The main reasons for unsuccessful scanning were paucicellular samples (44; 57.1%), the thickness of the smears (18; 23.4%) and issues with the coverslip (15; 19.5%). Conclusion: Cytological specimens can be successfully scanned and used for digital pathology, with excellent agreement with the original diagnoses. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has become increasingly studied and implemented in some pathology departments; but how might AI models help change medicine? While technology leaders are calling for a pause on developing AI systems until there is greater confidence "that their effects will be positive and their risks will be manageable," (Pause Giant AI Experiments: An Open Letter. March 22, 2023. https://futureoflife.org/open-letter/pause-giant-ai-experiments/) could breakthrough innovations in AI make medicine and physicians better? (There's One Hard Question My Fellow Doctors and I Will Need to Answer Soon. July 6, 2023. https://www.nytimes.com/2023/07/06/opinion/artificial-intelligence-medicine-healthcare.html) This discussion will provide an overview of AI, its current role in pathology practice, what pathologists need to know, and what the College of American Pathologists is doing for pathologists in this area. [ABSTRACT FROM AUTHOR]

Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guideline includes three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been beyond the scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology. A systematic search was carried out in PubMed‐MEDLINE and Embase databases up to November 2021 to identify all publications regarding validation of WSI in cytology. Each article was reviewed to determine if SRs and/or GPSs recommended by the CAP guideline were adequately satisfied. Of 3963 retrieved articles, 25 were included. Only 4/25 studies (16%) satisfied all three SRs, with only one publication (1/25, 4%) fulfilling all three SRs and nine GPSs. Lack of a suitable validation dataset was the main missing SR (16/25, 64%) and less than a third of the studies reported intra‐observer variability data (7/25, 28%). Whilst the CAP guideline for WSI validation in clinical practice helped the widespread adoption of digital pathology, more evidence is required to routinely employ WSI for diagnostic purposes in cytopathology practice. More dedicated validation studies satisfying all SRs and/or GPSs recommended by the CAP are needed to help expedite the use of WSI for primary diagnosis in cytopathology. [ABSTRACT FROM AUTHOR]

Background: Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. Methods: Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015–2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. Results: A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). Conclusion: Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in ovarian clear cell carcinoma (OCCC) by using two antibodies and two scoring guidelines in correlation with HER2 amplification and clinicopathological features. Methods and results: A tissue microarray was constructed by use of a total of 71 OCCC cases for IHC (the A0485 antibody and the 4B5 antibody) and dual‐colour silver in‐situ hybridisation (DISH). Two pathologists independently scored the IHC according to the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) breast cancer guidelines (breast guidelines) and the 2016 ASCO/CAP gastro‐oesophageal adenocarcinoma guidelines (gastric guidelines). IHC concordances between A0485 and 4B5 were 87.3–93.0%. Three to 16 (4.2–22.5%) cases had an IHC score of 2+/3+ with frequent basolateral/lateral membranous staining. The 4B5 antibody yielded fewer IHC 2+ cases than the A0485 antibody (n = 2–6 versus n = 5–12). Five (7.0%) cases had HER2 amplification as determined with DISH. Cases with papillary‐predominant growth patterns were significantly more likely to have HER2 amplification (P = 0.0051). In predicting DISH results, IHC scored according to the gastric guidelines yielded 100%/100% sensitivity and 83.3–95.5%/98.2–100% specificity, and IHC scored according to the breast guidelines yielded 60–80%/33.3–66.7% sensitivity and 95.5–100%/100% specificity (including/excluding IHC 2+ cases). One case had intratumoral heterogeneity, with discordant results between primary and metastatic tumour specimens. Conclusion: We demonstrated HER2 amplification in 7% of OCCC cases, and the molecular change is significantly associated with papillary‐predominant growth patterns. In predicting HER2 amplification, a combination of 4B5 IHC and gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoral heterogeneity, assessment of HER2 status on whole tissue sections and on both primary and metastatic tumour specimens is recommended. [ABSTRACT FROM AUTHOR]

Human Epidermal Growth Factor Receptor 2 (HER2), a routinely tested breast cancer marker, is associated with worse prognosis yet increased sensitivity to targeted neoadjuvant therapy (NAT) in breast cancer patients. The presence of HER2 in breast carcinoma can be detected with either immunohistochemistry (IHC) or in situ hybridization (ISH). In this study, we examine the relationship between clinicopathological features, HER2 detection method (IHC vs ISH), and prognostic outcomes in NAT‐treated HER2‐positive breast cancer patients. We included 99 HER2‐positive patients from three academic institutions following 2018 HER2 testing updates and conducted a retrospective correlational study. Seventy‐one (72%) were HER2‐positive by IHC and 28 (28%) were positive following reflexive ISH. Multivariate analysis showed biomarker status to be significantly associated with pathologic complete response (pCR) (p = 0.003), Residual Cancer Burden (RCB) (p = 0.007), and tumor size downstaging (p = 0.002) and HER2 detection method of IHC to be significantly associated with pCR (p = 0.05), RCB (p = 0.004), and nodal downstaging (p= 0.03). In conclusion, HER2 detection method and biomarker subtype allow for further prognostic stratification of HER2‐positive patients when 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline updates are applied. [ABSTRACT FROM AUTHOR]

Aims: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the testing guideline in 2018 to address issues arising from uncommon human epidermal growth factor receptor 2 (HER2) fluorescence in‐situ hybridisation (FISH) results according to the 2013 guideline. Next‐generation sequencing (NGS) may be used to better classify patients. The aim of this study was to assess the ERBB2 amplification status of invasive breast carcinoma with equivocal HER2 immunohistochemistry (IHC) results by using NGS, focusing on Group 4 (HER2/CEP17 ratio of <2.0; average HER2 signals/cell of ≥4.0 and <6.0). Methods and results: We retrospectively reviewed HER2 FISH and NGS data of HER2 IHC‐equivocal breast carcinomas at our centre between January 2009 and September 2019, wherein all three assays were performed on the same tissue block, and compared HER2 FISH results, according to the 2018 ASCO/CAP guideline, and the ERBB2 amplification status determined with NGS. A total of 52 HER2 FISH and NGS results from 51 patients with HER2 IHC‐equivocal breast carcinomas were reviewed. The cohort included eight cases classified as 2018 ASCO/CAP in‐situ hybridisation Group 1, three classified as Group 2, three classified as Group 3, 14 classified as Group 4, and 24 classified as Group 5. Thirteen of 14 (92.9%) Group 4 (HER2‐negative) cases were classified as ERBB2‐non‐amplified by the use of NGS; the discordant case was later classified as Group 1 with alternative sample FISH testing. NGS revealed no significant difference in somatic mutations or copy number alterations between Groups 4 and 5. Conclusions: Our NGS findings support the reclassification of HER2 FISH‐equivocal cases as HER2‐negative under the 2018 ASCO/CAP guideline. [ABSTRACT FROM AUTHOR]

Background: Therapeutic phlebotomy (TP) is a well‐established medical intervention that evolved from the historical practice of bloodletting. Methods: Patients who require TP are not infrequently told by their health‐care providers to "just go donate blood," but TP should always be offered in the context of a prescribed course of therapy. Providers can prescribe a course of TP for a number of indications, including hereditary hemochromatosis, polycythemia vera, iron overload, and testosterone replacement therapy. Results: A course of prescribed TP specifies that patients can be phlebotomized more frequently than volunteer blood donors and reassures patients that TP is being performed per the orders of their provider. Prescribed TP also facilitates two‐way communication between the referring provider and the transfusion medicine (TM) physician overseeing the TP. The College of American Pathologists TM checklist describes several requirements regarding the documentation and performance of TP, and electronic medical record systems can be used to demonstrate compliance with these requirements. Conclusions: TM physicians should discuss the advantages of prescribing TP with providers who mutually care for patients requiring this intervention. [ABSTRACT FROM AUTHOR]

Background: The AABB (American Association of Blood Banks) and the College of American Pathologists (CAP) regulations call on blood banks to address the risk of misidentification of a patient's blood type, which can result in transfusion of a mismatched product. Transfusion of mismatched blood product is potentially fatal due to acute hemolytic transfusion reaction and is considered a preventable event. CAP regulations outline options to reduce risk of mistransfusion by either documenting the ABO group of the intended recipient on a second sample collected at a separate phlebotomy, or utilizing a mechanical barrier system or electronic identification verification system that ensures the patient from whom the pretransfusion specimen was collected is the same patient who is about to be transfused. Study Design and Methods: An electronic or barrier system was not available for implementation at our institution, therefore we developed a protocol for a two‐sample verification system. The first determination is performed on a current sample and the second by one of the following methods: (a) comparison with previous laboratory records, (b) testing a second sample collected at a time different from the first sample (i.e., laboratory specimen available with a different timestamp, or a new blood sample). Results: We improved our transfusion process and implemented a policy to require a second sample to confirm a patient's blood type. We also implemented workflows to obtain blood type confirmation from history of a second blood type result from previous laboratory records, including a policy to accept previous blood type records from an outside laboratory. Conclusions: We describe a practice change for two‐sample verification for type and screen in a large‐scale pediatric hospital. We outline specific workflows for pre‐operative and emergency transfusion scenarios, and pediatric‐specific challenges. [ABSTRACT FROM AUTHOR]

In the nationwide cancer genome screening project SCRUM‐Japan GI‐SCREEN, 2590 archival formalin‐fixed paraffin‐embedded (FFPE) tumor tissues from 19 institutions were analyzed with two tissue‐based next‐generation sequencing (NGS) panels at the Clinical Laboratory Improvement Amendments (CLIA)‐certified College of American Pathologists (CAP)‐accredited central laboratory. The Oncomine Cancer Research Panel (OCP; 143 genes) succeeded in producing validated results for only 68.3% of the samples (%OCP‐success). CE‐IVD (25 genes) succeeded in 45.9% of the OCP‐failed samples, leading to an overall NGS success (%combined‐success) rate as high as 82.9%. Among 2573 samples, the DNA‐integrity (ΔCt)‐high (ΔCt < 4.4, n = 1253) samples showed significantly higher %OCP‐ and %combined‐success rates (90.2% and 97.4%, respectively) than the DNA‐integrity‐intermediate (4.4 < ΔCt < 6.3, n = 911; 68.9% and 88.7%) and DNA‐integrity‐low ones (ΔCt > 6.3 or polymerase chain reaction‐failed, n = 409; 5.6% and 24.7%). Other factors associated with NGS success included the FFPE‐sample storage period (<4 years), the specimen type (surgical) and the primary tumor site (colorectal). Multivariable analysis revealed DNA integrity as the factor with the strongest independent association with NGS success, although it was suggested that other institution‐specific factors contribute to the discordance of inter‐institutional NGS success rates. Our results emphasize the importance of DNA quality in FFPE samples for NGS tests and the impact of DNA integrity on quality monitoring of pathology specimens for achieving successful NGS. [ABSTRACT FROM AUTHOR]

Introduction: The American Society of Clinical Oncology (ASCO)‐endorsed College of American Pathologists guideline recommends high‐risk human papillomavirus (HPV) testing for metastatic squamous cell carcinoma (SCC) of lymph nodes level II/III of unknown primary. Herein, the performance of HPV‐RNA in situ hybridisation (ISH) in detection of HPV‐related SCC is evaluated implementing the ASCO guideline recommendations. Methods: Eighty head and neck (HN) SCC fine needle aspirations, which utilized HPV‐RNA ISH/P16, were evaluated at Johns Hopkins Hospital (2015‐2018) to investigate their performance and concordance with histology. The results were compared to a prior study of 59 HNSCCs, which HPV‐DNA ISH. Results: Of the 80 reviewed fine needle aspirations, 65 (50 male, 15 female) were included. The mean age was 63.2 ± 14.0 years. The most common site was neck lymph nodes (47, 72.3%). Fifty‐five cases (84.6%) were accompanied by concurrent core biopsy, and 48 cases (59.4%) had surgical follow‐ups. HPV‐RNA ISH was positive in 44 (67.7%), and P16 was strongly positive in 46 (70.8%). The HPV‐RNA ISH/ P16 concordance rate was 92.3% on cytology material. The cytology/surgical concordance rate for HPV‐RNA ISH was 88.9% (16/18). There was a discordance between the results in five cases (7.7%; HPV‐RNA ISH‐/P16+). Conclusion: HPV‐RNA ISH is a robust and reliable method for detecting HPV‐related HNSCC on cytology material showing concordance rate of 92.3% between HPV‐RNA ISH and P16, which is a sensitive but non‐specific marker. Compared to HPV‐DNA ISH, HPV‐RNA ISH reproducibly identifies HPV‐related HNSCC with fewer discrepancies between cytology and histology. The findings of this study are in agreement with the ASCO recommendations. HPV‐RNA ISH is a robust and reliable method for detecting head and neck squamous cell carcinoma (HNSCC) of unknown primary on metastatic lymph nodes (levels II and III) or neck masses on cytology. Cytology material provides sufficient material for HPV RNA ISH and P16 testing which is in agreement with the ASCO guideline recommendations on HNSCC of unknown primary. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER‐2) is an established prognostic and predictive biomarker for breast cancer. To ensure accuracy and uniformity for HER‐2 testing, ASCO/CAP published guidelines in 2007 which were updated in 2013 and recently in 2018. In this first study from Indian Oncology center, we evaluated the impact of 2018 ASCO/CAP guidelines. We found a substantial decrease in equivocal IHC cases (P‐value <.00001). On reclassification, a total of 5.6% cases from equivocal and positive categories (2013 guidelines) shifted to the negative FISH result category (P‐value <.0001), with adoption of 2018 guidelines and eliminated the double equivocal cases. [ABSTRACT FROM AUTHOR]

Background: The Accreditation Council for Graduate Medical Education requires milestone reporting of the Six General Core Competencies. Additionally, Graduate Medical Education (GME) is transitioning to adopt competency-based education methodologies including entrustable professional activities (EPAs) for objective, observable, and measurable milestone progression. The College of American Pathologists published 19 EPAs, including one for transfusion-related adverse events. This survey study includes developing EPAs for transfusion reaction evaluation and assessing residents before and after implementing these EPAs.Study Design and Methods: Three transfusion reaction EPAs were developed and implemented in July 2018 for the Postgraduate Year (PGY) 2 pathology residents. An online, anonymous survey was sent to all 21 pathology trainees before and one year after EPA implementation. In July 2018 and August 2019, each survey included the same six multiple-choice, single-response, confidence questions, with a rating scale of extremely, very, slightly, or not at all confident. This study was approved by the hospital's Institutional Review Board for Health Sciences Research and GME Committee.Results: Analysis was performed on PGY2-4 residents. In 2018, 13 of 20 participants were analyzed. In 2019, 15 of 19 participants were analyzed. Number and percentage of responses were reported. The results showed an increase in trainee confidence, with the greatest improvement among the first class to use the EPAs.Conclusion: EPAs provide an effective framework for objective and measurable progression of trainees. One year after the implementation of transfusion reaction EPAs at our site, the trainees showed enhanced confidence levels in handling Blood Bank and Transfusion Medicine Services coverage. [ABSTRACT FROM AUTHOR]

The International Collaboration on Cancer Reporting (ICCR) is a not‐for‐profit organisation sponsored by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists in association with the Canadian Partnership Against Cancer, the European Society of Pathology, the American Society of Clinical Pathology and the Faculty of Pathology, Royal College of Physicians of Ireland. Its goal is to produce standardised, internationally agreed‐upon, evidence‐based datasets for cancer pathology reporting throughout the world. This paper describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of carcinoma of the urethra in urethrectomy specimens. The dataset is composed of 'required' (mandatory) and 'recommended' (non‐mandatory) elements, which are based on a review of the most recent evidence and supported by explanatory commentary. Fourteen required elements and eight recommended elements were agreed by the international dataset authoring committee to represent the essential/required (core) and recommended (non‐core) information for the reporting of carcinoma of the urethra in urethrectomy specimens. Use of an internationally agreed, structured pathology dataset for reporting carcinoma of the urethra (in urethrectomy specimens) will provide the necessary information for optimal patient management, will facilitate consistent data collection and will provide valuable data for research and international benchmarking. The dataset will be valuable for those countries and institutions that are not in a position to develop their own datasets. [ABSTRACT FROM AUTHOR]

This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. We conducted a literature review for methods used to measure Hb in clinical laboratories and field settings. We described methods to measure Hb and factors influencing results. Automated hematology analyzer (AHA) was reference for all Hb comparisons using evaluation criteria of ±7% set by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Capillary fingerprick blood usually produces higher Hb concentrations compared with venous blood. Individual drops produced lower concentrations than pooled capillary blood. Compared with the AHA: (1) overall cyanmethemoglobin (1.0−8.0  g/L), WHO Colour Scale (0.5−10.0  g/L), paper‐based devices (5.0−7.0  g/L), HemoCue® Hb‐201 (1.0−16.0  g/L) and Hb‐301 (0.5−6.0  g/L), and Masimo Pronto® (0.3−14.0  g/L) overestimated concentrations; (2) Masimo Radical®‐7 both under‐ and overestimated concentrations (0.3−104.0  g/L); and (3) other methods underestimated concentrations (2.0−16.0  g/L). Most mean concentration comparisons varied less than ±7% of the reference. Hb measurements are influenced by several analytical factors. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high‐quality methods in all settings are necessary to ensure the accuracy of Hb measurements.This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high‐quality methods in all settings are necessary to ensure the accuracy of Hb measurements. [ABSTRACT FROM AUTHOR]

Aims: The International Collaboration on Cancer Reporting (ICCR) has provided detailed data sets based upon the published reporting protocols of the Royal College of Pathologists, the Royal College of Pathologists of Australasia and the College of American Pathologists. Methods and results: The data set for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use, and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the fourth edition of the World Health Organisation Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are required and recommended components of the report. Required elements are: specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are: preoperative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). Conclusions: It is anticipated that the implementation of this data set in routine clinical practice will inform patient treatment as well as provide standardised information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. [ABSTRACT FROM AUTHOR]

In breast cancer, human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and/or in situ hybridization. Oncotype DX also reports HER2 status by an rt-PCR-based assay. Assay concordance between IHC and fluorescent in situ hybridization (FISH) (including alternative probe HER2 FISH) vs Oncotype DX HER2 rt-PCR has not been described in the post-2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guideline revision setting. We performed a retrospective review of HER2 equivocal invasive breast carcinoma from 2014 to 2016 with the Oncotype DX HER2 result. Fifteen patients with HER2 equivocal invasive breast cancer had Oncotype DX performed. Of these, 13 underwent alternative probe HER2 FISH yielding 4 negative, 6 equivocal and 3 positive results. All 15 cases were classified as HER2 negative by Oncotype DX rt-PCR, including the three cases which were positive by alternative probe HER2 FISH, yielding a discordance rate for Oncotype DX rt-PCR HER2 of 20% (3/15). All three patients with HER2- positive breast cancer on the basis of alternative probe HER2 FISH received anti- HER2-targeted therapy. Treatment decisions based on HER2 status should utilize the IHC/FISH result as Oncotype DX results may incorrectly disqualify some patients from being eligible for anti-HER2 therapy based on the current 2013 ASCO/CAP HER2 Guidelines. [ABSTRACT FROM AUTHOR]

One nucleotide substitution in codon 217 of HLA‐DRB1*09:31:01 results in a novel allele HLA‐DRB1*09:31:02. [ABSTRACT FROM AUTHOR]

Several reports have demonstrated the use of whole-slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy- and WSI-based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI- and microscopy-based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy-based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI-based primary diagnosis of biopsies and small surgeries in routine daily practice. [ABSTRACT FROM AUTHOR]

Aims The 2013 American Society of Clinical Oncology and the College of American Pathologists ( ASCO/ CAP) HER2 guidelines recommend testing all invasive breast cancers for HER2, typically with immunohistochemistry ( IHC) followed by in-situ hybridization ( ISH) when IHC is equivocal. As well-differentiated breast cancers are rarely HER2-positive, we assessed the value of routine reflex HER2 ISH testing for this subset of breast cancers. Methods and results We collected HER2 IHC 2+ cases and fluorescence in-situ hybridization ( FISH) data from primary breast cancers with well-differentiated tumour types (grade 1 ductal carcinomas, classic lobular carcinomas, tubular, cribriform and pure mucinous carcinomas) at our centre from 2010 to 2015. Haematoxylin and eosin (H&E) and IHC slides were reviewed to confirm tumour type, grade and IHC score based on ASCO/ CAP 2013 guidelines and their recent revisions. Of 4633 invasive carcinomas, 1133 had a well-differentiated tumour type; 177 of these were HER2 IHC equivocal, three of which were low-level amplified by FISH (0.3% of all well-differentiated tumours). One amplified case was classic invasive lobular carcinoma and two were invasive ductal carcinomas, grade 1. One amplified case had chromosome 17 monosomy, and one was rescored as HER2 IHC 1+ upon review. 'Basolateral' staining was noted in one amplified case and in 65 of 174 (37.4%) non-amplified cases. This incomplete membranous staining pattern was observed in the majority of invasive ductal carcinomas that were rescored as 1+ according to the revised 2013 guidelines. Conclusions The rate of HER2 amplification among well-differentiated breast cancers is very low. Basolateral staining in well-differentiated tumours may be overinterpreted as HER2 IHC 2+, but is rarely associated with HER2 amplification. [ABSTRACT FROM AUTHOR]

Aims The recent American Society of Clinical Oncology/College of American Pathologists guidelines for human epidermal growth factor receptor 2 ( HER2) testing in breast cancer recommend repeat testing based on tumour grade, tumour type, and hormone receptor status. The aim of this study was to test the value of these criteria. Methods and results HER2 status was concordant in the core biopsies and excision specimens in 392 of 400 invasive carcinomas. The major reasons for discordance were amplification around the cut-off for positivity and tumour heterogeneity. Of 116 grade 3 carcinomas that were HER2-negative in the core biopsy, four were HER2-positive in the excision specimen. Three of these four either showed borderline negative amplification in the core biopsy or were heterogeneous. None of the 55 grade 1 carcinomas were HER2-positive. Review of repeat testing of HER2 in routine practice suggested that it may also be of value for multifocal tumours and if recommended by the person assessing the in-situ hybridization. Conclusions Mandatory repeat HER2 testing of grade 3 HER2-negative carcinomas is not appropriate. This is particularly true if repeat testing is performed after borderline negative amplification in the core biopsy or in HER2-negative heterogeneous carcinomas. [ABSTRACT FROM AUTHOR]

Aims: The updated 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/ CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines include changes to HER2 in-situ hybridization (ISH) interpretation criteria. We conducted a retrospective review of a consecutive cohort of primary breast carcinomas to assess the impact of updated guidelines on HER2 classification and laboratory resource utilization, and to characterize the pathobiology of HER2 equivocal tumours. Methods and results: A total of 904 dual-probe HER2/ chromosome enumeration probe (CEP17) FISH tests on invasive breast carcinomas were studied. Eighty-five (9.4%) cases had a classification change with the updated guidelines; 66 (7.3%) went from HER2-negative to -equivocal, 15 cases (1.7%) were reclassified as HER2-positive and four cases from HER2-equivocal to - negative. A subset of primary breast cancers, reported initially as HER2-negative but -equivocal by 2013 guidelines, was identified. Traditional pathological factors of this subset were compared to HER2-negative and -positive control cases. The three HER2 groups demonstrated statistically significant differences with respect to prognostic factors, including tumour size, grade and nodal involvement. Conclusions: The updated HER2 testing guidelines will result in the reclassification of approximately 9.4% of primary breast cancers with uncertainty regarding the clinical impact of this reclassification in the majority of cases. Resource utilization will increase as a result of the recommendation for retesting. [ABSTRACT FROM AUTHOR]

We reviewed the 2010 Asbestosis Committee's update on the diagnostic criteria for pathologic asbestosis. We must respectfully disagree with many of the criteria set forth therein, especially for recognizing asbestosis at its earliest stages; with statements focusing on the number of asbestos bodies needed in order to make a pathologic diagnosis of asbestosis; and regarding the benefits and pitfalls of relying on fiber analysis for diagnostic purposes, especially where chrysotile asbestos is concerned, including the methodology used for fiber determination. This critique has become even more relevant with the 2014 Helsinki criteria publication, which adopted the 2010 CAP/PPS criteria. Based on our review of these newer criteria and our experience in this field, we find that the CAP-NIOSH 1982 criteria is still the most acceptable method for the pathologic diagnosis and grading of asbestosis, which can be described as pulmonary fibrosis caused by inhalation of asbestos fibers. Am. J. Ind. Med. 58:1034-1039, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on how to manage Rh typing in obstetric patients and reference of a 30-year-old G2P1 female with 12 weeks pregnant is presented. Topics discussed include results of serologic weak D phenotype revealed by the College of American Pathologists (CAP), evaluation for the need of prophylaxis to prevent hemolytic disease of the fetus and newborn (HDFN), and determining the risk of formation of antigen-D in patients.

The author discusses the results of a survey regarding the procedures for testing serologic weak D phenotype and administration of Rh immune globulin (RhIG) reported by the Transfusion Medicine Resource Committee (TMRC) and College of American Pathologists (CAP). Topics discussed include role of RhD typing in protecting RhD-negative persons from inadvertent alloimmunization, performing of RHD genotyping with the detection of serologic weak D, and selection of blood components for transfusion.

BACKGROUND Several changes were made to bladder cancer staging guidelines between the 6th and 7th editions of the American Joint Committee on Cancer (AJCC) Staging Manual. Also, Collaborative Stage (CS) Data Collection System version 2 (CSv2) implemented for 2010 Surveillance, Epidemiology, and End Results (SEER) cases involved collection of 3 new site-specific factors (SSFs): World Health Organization/International Society of Urological pathology grade (SSF1), size of metastasis in regional lymph nodes (SSF2), and extranodal extension (SSF3). Our objective was to evaluate these new SSFs to assist researchers in their use/interpretation and to describe data quality issues to be addressed moving forward. METHODS Staging trends were assessed for invasive and noninvasive bladder cancer cases from 2004 to 2010. Among 2010 cases, staging was compared using the AJCC 6th and 7th edition guidelines, and evaluation of completeness/quality of the SSFs was performed in relevant subgroups. RESULTS Age-adjusted incidence rates and proportions of cases by stage remained steady from 2004 to 2010. Changes from the AJCC 6th to 7th editions caused no substantial movement between stages. SSF1 had a known value in 82% of cases, which was higher than the traditional SEER grade/differentiation variable. SSF2 and SSF3 were less complete, with 41% and 37% having known values, respectively, among cases with lymph node involvement (according to CS lymph node variable). CONCLUSIONS SSF1 was more complete and straightforward to interpret than the traditional grade/differentiation variable. SSF2 and SSF3 were less complete, may be associated with data quality issues, and should only be used among cases with known lymph node involvement Cancer 2014;120(23 suppl):3815-25. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

The American Society of Clinical Oncology and the College of American Pathologists have issued joint updated comprehensive guideline recommendations for human epidermal growth factor receptor 2 ( HER2) testing in breast cancer. The update not only provides guidelines for the test performance parameters, with the aim of improving test accuracy, reproducibility, and precision, but also provides comprehensive recommendations on the post-analytical interpretation of the results, and requires improved communication among healthcare providers. The updated guidelines are targeted at testing laboratories, pathologists, oncologists, surgeons, and, indirectly, other healthcare providers. Although the guidelines contribute to the improved analytical validity and clinical utility of laboratory assays required for successful molecularly targeted therapy in the era of personalized medicine, the implications of such recommendations have to be acknowledged. Certain recommendations, particularly those related to repeating the test and pathological concordance, have lower levels of supportive evidence than existing key recommendations, and the associated workload implications will be challenging to support in most healthcare systems. In this commentary, we critically address the key updated recommendations and their impact on service provision and patient care. [ABSTRACT FROM AUTHOR]

The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer ( IASLC)/ College of American Pathologists ( CAP) guidelines and the ALK Atlas. The IASLC/ CAP guidelines recommend that tumors from patients with non-small cell lung cancer ( NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor ( EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors. [ABSTRACT FROM AUTHOR]

Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have been compared. We also discussed the potential consequences in our pathological practice.Material andMethodology. 189 HER2 fluorescence in situ hybridisation (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP recommendations. Results.The 2013 version decreased false-negative IHC (3/118 versus 1/54, P= ns) and created more 2+ IHC (40/186 versus 89/186, P = 0.001) or more 3+ IHC (9/186 versus 39/186, P = 0.001). One false-positive IHC was described for the 2013 version (0/9 versus 1/39, P = ns). Equivocal FISH was reduced (8/186 versus 2/186, P = ns). An estimation based on our data for 1000 patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for the 2007 version versus 274 tests for the 2013 version or FISHwork overflowis +52%) and for the control of 2+/3+ IHC(300 for the 2007 version versus 475 for the 2013 version or FISH work overflow is +58%). Conclusions.The new 2013 ASCO/CAP guidelines have detected more HER2 positive cases but have increased the number of FISH tests. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted by Transfusion Medicine Resource Committee of College of American Pathologists (CAP) in the U.S. in 2012. The study found the need of improved laboratory assays for fetomaternal hemorrhage for Rhesus factor (Rh) immunoprophylaxis. It mentions that the quantitative laboratory assays for determining the volume of the fetomaternal hemorrhage (FMH) is a critical step for performing postpartum Rh immunoprophylaxis.

OBJECTIVE • To evaluate whether current nephrectomy pathology reports are sufficient to allow clinicians to use prognostic nomograms, tailor surveillance, enroll patients into adjuvant trials and select systemic therapy for renal cell carcinoma (RCC). PATIENTS AND METHODS • Nephrectomy pathology reports were obtained from the LA County Tumor Registry. Key reporting elements identified by the College of American Pathology (CAP) and utilized in RCC prognostic models were abstracted. Hospital type was coded as community, teaching or cancer centre. • Reporting quality was assessed across hospital type and year. RESULTS • A total of 317 of 344 sampled reports (92.2%) met the inclusion criteria. Tumour size and margin status were commonly reported. Some 90.2% and 84.2% of reports provided data on histology and Fuhrman grade. Tumour classification was omitted in 27.8%. • Microvascular invasion and necrosis were infrequently reported (44.5% and 25.6%, respectively). Only 59.9% of reports met CAP guidelines for tumour classification, margin, size, histology and grade. • Two prognostic nomograms (Stage, Size, Grade and Necrosis system and Kattan) could rarely be utilized (15.8% and 12.3%, respectively), whereas the UCLA Integrated Staging System could be used frequently (65.6%). There were discrepancies satisfying CAP guidelines between community, teaching and cancer centre hospitals, with 54.7%, 70.5% and 75% of reports meeting CAP criteria ( P = 0.0102). CONCLUSIONS • Current RCC pathology reporting fails to satisfy CAP guidelines, does not permit the use of prognostic systems, and may hinder enrollment into adjuvant trials and the selection of systemic therapy. Important reporting discrepancies exist between hospital types, with cancer centres performing best. • Quality improvement initiatives to encourage consistent, comprehensive and clinically relevant pathology reports would improve the quality of RCC patient care. [ABSTRACT FROM AUTHOR]

This study was performed to determine the incidence of 'wrong blood in tube' (WBIT)-type errors at our institution during the past 5 years, to analyse their root cause and to evaluate the efficacy of preventive measures that have been implemented since 2006. All reports of mislabelled and miscollected specimens detected between January 2005 and December 2009 were reviewed. Of these, WBIT-type errors were further analysed as they represent a major risk for mistransfusion. Between 2005 and 2009, 59 373 type and screens were performed at our institution and a total of 26 major errors (WBIT) were identified. Of the errors, eight were detected by discrepant typing results (in comparison with historic blood type), six were discovered by the clinical service and 12 were identified in the blood bank by other means. Our estimated 'raw' WBIT rate (1 in 2283 samples) is comparable to that (1:2262) in the published literature. Since 2006, our nursing policy mandates that 'all type, screen and cross will have two witnesses to the correct ID of the patient and labeling is done at the bedside at the time of the draw.' This has reduced (from 11 in 2006 to 5 in 2007), but did not eliminate, our WBIT problem that persisted into 2008 and 2009 (three and seven incidents, respectively). Since 2009, we also require a second, independently drawn sample in previously un-typed patients who are likely to be transfused. We conclude that WBITs continue to represent a leading cause of potential mistransfusions at our institution. Changes in nursing (two witnesses to correct ID) and/or blood bank policy (check-type with a second specimen) may reduce, but not eliminate, this persistent problem. Clearly, additional safety measures are required to prevent WBIT-type errors. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigated the effect of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas using fluorescent in situ hybridization (FISH) methods. The definition of HER2-positive tumors according to the American Society of Clinical Oncology/College of American Pathologists guidelines is cited. Carcinomas considered for the study included invasive ductal carcinomas of no particular type, mucinous carcinomas, metastatic breast carcinomas, invasive lobular carcinoma and mammary Paget disease.

The article presents a study on the characterization of oral tongue cancer as recommended by the College of American Pathologists (CAP). Patients who were diagnosed with oral tongue cancer and underwent tumor resection were included in the study. Assessment of the pathology report of the depth of invasion (DI), lymphovascular invasion (LVI), and perineural invasion (PNI) was also conducted. Results show the importance of tumor invasion characteristics reporting for oral tongue cancer diagnosis.

Accurate and complete information in pathology reporting is essential since most breast cancer treatment decisions are based on pathologic findings. The College of American Pathologists (CAP) has guidelines for breast cancer reporting; however, pathology reports remain variable. Data were collected on 91 consecutive breast cancer excisional biopsies from “outside slide review” (OSR) cases for a 2-year period to determine the variability in pathology reports in gross and microscopic examinations from 50 different outside community and university hospitals located primarily in the southwestern United States. From the gross pathology report, the following items were analyzed: measurement and weight of specimens, orientation provided by surgeons, number of blocks submitted, designation of margins, and whether margins were indicated as “shaved” or “perpendicular” in relation to the breast tissue at the time of grossing. From the final diagnoses, the following items were analyzed: type and size of tumor, and surgical margins. The results show that 100% of the reports documented the measurement of specimen size, and 30% documented the specimen weight. Surgeons provided orientation of the breast specimens in 65% of cases. Surgical margins were inked in 58%, while only 18% described how margins were submitted (either shaved or perpendicular to the mass). Only 30% of specimens were submitted in toto, 1% were submitted with an unknown amount of tissue, and 69% were submitted in representative sections with an average of 13 blocks for lumpectomies. In the final diagnoses, all reports had documentation of the tumor type and size of the invasive cancer; 26% of the final diagnoses had ductal carcinoma in situ (DCIS) and just 5% of those reports documented the size of the DCIS. The surgical margin status was reported in only 76% of the final diagnoses. This study shows that the pathology reports were heterogeneous with respect to reporting gross and microscopic final diagnoses from the variable hospitals. [ABSTRACT FROM AUTHOR]

The article presents a study that aims to validate whole slide imaging (WSI), a technology in which histopathological slides are optically scanned to produce digital images. The guidelines supporting the implementation of WSI for diagnostic purposes has been released by College of American Pathologists. Overall, WSI assessment of laryngeal premalignancies showed interobserver agreement comparable to that obtained with glass slides.

We identified a novel DQB1*0326 allele from a proficiency test sample provided by the College of American Pathologists (CAP) medical society. This novel DQB1 allele was unexpectedly discovered by sequence-based typing method in an attempt to resolve a discrepant typing result between the CAP survey report and our laboratory report. This novel DQB1 allele is most similar to DQB1*030302 and DQB1*0311. DQB1*0326 has a nucleotide substitution resulting an amino acid change when compared with DQB1*030302 (M to L) and it differs from DQB1*0311 by one nucleotide variation causing an amino acid replacement (A to D). [ABSTRACT FROM AUTHOR]

One nucleotide substitution at residue 25 of HLA-DRB1*09:01:02:01 results in a novel allele, HLA-DRB1*09:31. [ABSTRACT FROM AUTHOR]

The article comments on a study which claimed that there is a scarcity of information about human epidermal growth receptor (HER)-2 testing in clinical practice. The study is based on the data on the effect of trastuzumab on breast cancer, the validity of which is questioned because of a new HER-2 testing guidelines released by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP). It is recommended that the authors of the study comply with the guidelines.

The article discusses the guidelines relevant for molecular testing and the elements of a successful proficiency-testing programs in the U.S. It highlights the standards of various institutions in molecular assay including the American College of Medical Genetics (ACMG) Standards and Guidelines, the Clinical and Laboratory Standards Institute and the College of American Pathologists (CAP). It cites the principles offered by the Clinical Laboratory Improvement Amendment about proficiency tests.