American Pathologists Research Articles

A-146 A Review of RDW-CV and RDW-SD Measurements in Patients With Iron Deficiency Anemia in an Acute Care Hospital in Singapore

Abstract Background Red Cell Distribution Width (RDW) is a routinely available parameter on automated haematology analysers. This parameter is often used to help in the diagnosis of iron deficiency anaemia. RDW quantitatively measures the degree of anisocytosis of the red blood cells. The more common way of reporting RDW is RDW-CV, which is based on the coefficient of variation of the red blood cell distribution volume and is calculated using mean red cell volume. RDW can also be presented as RDW-SD, which is a direct measurement of the width of the red blood cell distribution curve and is not influenced by mean red cell volume. Conventionally, laboratories report RDW-CV as part of the red blood cell indices in full blood count (FBC) reports. However, it has been proposed that RDW-SD is a better indicator of iron deficiency anaemia compared to RDW-CV. The authors seek to review and assess the clinical utility of both RDW measurements in patients with iron deficiency anaemia in an acute care hospital in Singapore. Methods RDW data of samples from 271 unique individuals from Sysmex XN-9000 (Sysmex, Japan) automated haematology analysers over a period of two months were reviewed. These individuals were selected as they had plasma iron measured in the same blood collection. The individuals were sorted into two groups based on the plasma iron measurement: with iron deficiency (80%) and without iron deficiency (20%). The correlation of RDW-CV and RDW-SD with the plasma iron concentration of the individuals was studied. The RDW-CV reference range used were established for the local population by an in-house reference range validation study while that of the RDW-SD is from a recent Participant Summary Report for a College of American Pathologists (CAP) Hematology Automated Differential survey (FH9-B 2022). The sensitivity, specificity, predictive values, and overall efficiency of RDW-CV and RDW-SD were calculated and compared using the data collected. Results The sensitivity and specificity of RDW-CV in detecting iron deficiency anaemia are 45.2% and 68.5%. The positive and negative predictive values for RDW-CV are 85.2% and 23.7% respectively. The sensitivity and specificity of RDW-SD in detecting iron deficiency are 33.2% and 64.8%. The positive and negative predictive value of RDW-SD are 79.1% and 19.4% respectively. The overall efficiency of RDW-CV is 49.8%, significantly higher than 39.4% of RDW-SD. Conclusion This retrospective study suggested that RDW-CV is still a better blood cell index than RDW-SD in the differential diagnosis of iron deficiency anaemia in a predominantly Asian population. However, the use of RDW-SD reference range that is appropriate for the local population may improve the clinical utility of the RDW-SD.

A-377 The Selection and Implementation of POC Illicit Drug Toxicology Testing in Hamad Medical Corporation - Doha, Qatar

Abstract Background In 2013, Qatar launched the National Mental Health Strategy which is further supported by National Health Strategy 2018–2022 and Qatar National Vision 2030, where the mental health has been identified as a priority area of development. In doing so, the Ministry of Public Health worked closely with the Ministry of Interior in providing the appropriate treatment rehabilitation. With all considerable advantages of point-of-care testing (POCT) in rapid diagnosis, POC toxicological test has been implemented and used in screening of patients for drugs of abuse. In this study, we highlighted the challenges in selection and implementation process of POC toxicological test in Hamad Medical Corporation (HMC). Methods Due to unavailability of all required drug panels, it had to be customized and tested for the verification purpose before starting the evaluation process. Maintaining HMC procurements regulations and Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologist (CAP) standards for POC toxicology tests, two POC illicit drug toxicology screening tests has been evaluated, comparison study has been performed against the HMC central laboratory. POCT team conducted training session ensuring the appropriate practice in place. The Extendable Laboratory Information System (LIS) functionality has been utilized for seamless data management and reporting for the automated analyzer. Results QUIDEL triage meter pro is an automated drug testing analyzer which detects Amphetamines, Barbiturates, Benzodiazepines, Cannabinoids, Methadone Metabolite, Methamphetamine, Opiates, Tricyclic and Cocaine Metabolites, while the customized manual testing kit FASTEP detects Tramadol (TRA), Methylenedioxymeth-amphetamine (MDMA), Phencyclidine (PCP), Buprenorphine (BUP), Oxycodone (OXY), Fentanyl (FYL), Ethyl Glucuronide (EtG), Cotinine (COT), Pregabalin (PGB) and Gamma Hydroxybutyrate (GHB). Both analytical performances were verified. Rapid bedside testing performed for more than 100 patients in last 8 months during admission, observation, and pre- discharge process. There is An Obvious improvement observed in testing turnaround time compared to the laboratory, easy results interpretation and reporting as well as cost-effective. Conclusion The implementation of POC illicit drug toxicology testing in HMC aligned with core pillars of the Qatar vision 2030 to deliver the right treatment at the right time and place. Its enhancing patient outcomes and overall Satellite health care sector in Qatar.

A-181 Comparison of POCT Accreditation Between TJC and CAP: Which Way to Go?

Abstract Background Point-of-care testing (POCT) at UW Health University Hospital is accredited by the Joint Commission (TJC) while the main laboratory is accredited by the College of American Pathologists (CAP). Consolidating to a single accrediting agency would eliminate the burden of maintaining two separate accreditation programs, and reduce related expenses. In consideration of consolidation, we compared the accreditation requirements between the two agencies for POCT. Methods CAP standards in the All Common (n = 84), POC (n = 62), and Lab General checklists (n = 98) were evaluated for non-waived testing requirements in accordance to the POC test menu. The POC test menu includes the following non-waived tests: activated clotting time, blood gases, urine specific gravity by refractometry, and Tzanck smear; and provider performed microscopy (PPM): wet mount (skin or hair), wet prep, and fern test. A gap analysis was conducted to distinguish differences between CAP and TJC standards and further investigation was initiated when needed. Results The majority of CAP checklist standards aligned with the current processes under TJC. From the CAP All Common checklist, 5 out of 84 standards flagged as a potential gap. One notable difference was found for CAP COM.04250Comparability of Instruments and Methods—Nonwaived testing where comparison studies are required only for instruments and methods under the same CAP number. In contrast, the TJC requires instrument and method comparisons across the entire organization, regardless of separate CLIA certificates or sites. Shifting POC nonwaived tests to CAP would eliminate the need to perform comparisons across different sites, which in our hands has been labor intensive and of little clinical value. From CAP POC checklist, 10 out of 62 standards flagged as potential gaps. Specifically, CAP POC.03800Problem Resolution where the ability to provide prompt resolution for POC issues for all shifts in which POC testing is performed is demonstrated. From the CAP Lab General checklist, 4 out of 98 standards flagged as a potential gap. Specifically, CAP GEN.40470Specimen Collection Training where additional discussion with nursing education would be needed to assess collection training records. The other key difference was with CAP GEN.23584Interim Self-Inspection where self-inspection is required during the interim year. Conclusion Overall, our assessment is that moving non-waived POC testing to CAP will align the requirements for this set of largely hospital based POC tests, where the considerable effort saved from eliminating organization wide instrument/method comparisons could be more effectively applied to expanding our existing CAP mandated interim self-inspections to include nonwaived POCT. Because the vast majority of the waived testing performed at our organization occurs at ambulatory sites under CMS oversight, leaving waived POC tests under TJC oversight was felt to align better. Overall, the POCT requirements under CAP checklists were similar to TJC with minor, but potentially impactful, differences. In our situation, moving nonwaived POC testing to CAP accreditation and keeping waived POC testing under TJC accreditation provided the best balance between quality/patient safety and regulatory administrative effort.

Reporting and Establishment of Reference Intervals for Antiphospholipid Antibody Immunoassays: A Survey of Participants in the College of American Pathologists Proficiency Testing Program.

Misdiagnosis of antiphospholipid syndrome can occur owing to the wide diversity of antiphospholipid (aPL) assays and a lack of international calibrators and harmonized reference intervals. To assess laboratory practices regarding reporting and establishing reference intervals for immunoglobulin (Ig) G/IgM anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (anti-β2GPI) assays. Supplemental questions related to reporting and establishing reference ranges for aPL assays were sent as part of the Antiphospholipid Antibody (ACL)-B 2019 College of American Pathologists (CAP) proficiency testing survey. The response rate and methods assessment details were determined, as well as qualitative and quantitative results for 3 test samples. The number of participants reporting results for IgG aCL (n = 489), IgM aCL (n = 476), IgG anti-β2GPI (n = 354), and IgM anti-β2GPI (n = 331) varied by antibody type. The enzyme-linked immunosorbent assay (ELISA) (up to 58.6%, 260 of 444) was the most used method; others included multiplex (from 18.9% to 23.9%), fluorescence enzyme immunoassay (14.4%-17.6%), and chemiluminescence immunoassay (6.5%-9.0%). More respondents reported quantitative than qualitative results, and manufacturer cutoff ranges were used by 92.9% and 94.2% of respondents for aCL and anti-β2GPI, respectively. Despite variation in the use of semiquantitative ranges, qualitative negative/positive reporting of the test samples achieved almost 100% consensus. Qualitative consensus was met in contrast to the wide range of quantitative results obtained for each analyte across different kits. ELISA remains the most used method for detecting aPL antibodies, with most laboratories reporting quantitative results based on manufacturers' suggested reference ranges. The categorization of quantitative results as equivocal, weak positive, or positive for responders using kits from the same manufacturer was variable.

Creation of a Quality Payment Program Measure for Mismatch Repair or Microsatellite Instability Biomarker Testing Status in Colorectal, Endometrial, Gastroesophageal, or Small Bowel Carcinoma.

Quality measures that are supported by evidence-based clinical practice guidelines are preferred for assessing the quality of pathologists' practices. Careful testing of a measure ensures that scores obtained by that measure reflect the quality of a pathologist's practice. To specify a new quality measure and to demonstrate through testing that it is suitable for measuring pathologists' appropriate incorporation of information regarding microsatellite instability (MSI) and/or mismatch repair (MMR) status in pathology reports for colorectal, endometrial, gastroesophageal, and small bowel carcinoma. The College of American Pathologists collaborated with the American Gastroenterological Association to specify and test the new measure. Face validity testing was used to investigate the validity of the measure. Feasibility testing was conducted to understand if data elements required by the measure specification were readily accessible. Signal-to-noise analysis was used to characterize the measure's reliability. Guideline recommendations for MSI and/or MMR testing supported specifications for the measure. Face validity testing indicated that the measure could distinguish the quality of care provided. Data elements required by the measure specification were found to be accessible, which supported the measure's feasibility. Reliability testing showed that differences in measure score were attributable to real differences in performance rather than random variation in scoring. The Mismatch Repair or Microsatellite Instability Biomarker Testing Status in Colorectal Carcinoma, Endometrial, Gastroesophageal, or Small Bowel Carcinoma measure was appropriately specified, and testing demonstrated that it is well suited for characterizing the quality of pathologists' communication of MMR and/or MSI status.

Pancreaticobiliary Cytology Practice in 2021: Results of a College of American Pathologists Survey.

The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice. To investigate pancreaticobiliary cytology practice in domestic and international laboratories in 2021. We analyzed data from the CAP Pancreaticobiliary Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2021 CAP Nongynecologic Cytopathology Education Program. Ninety-three percent (567 of 612) of respondent laboratories routinely evaluated pancreaticobiliary cytology specimens. Biliary brushing (85%) was the most common pancreaticobiliary cytology specimen evaluated, followed by pancreatic fine-needle aspiration (79%). The most used sampling methods reported by 235 laboratories were 22-gauge needle for fine-needle aspiration (62%) and SharkCore needle for fine-needle biopsy (27%). Cell block was the most used slide preparation method (76%), followed by liquid-based cytology (59%) for pancreatic cystic lesions. Up to 95% (303 of 320) of laboratories performed rapid on-site evaluation (ROSE) on pancreatic solid lesions, while 56% (180 of 320) performed ROSE for cystic lesions. Thirty-six percent (193 of 530) of laboratories used the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology in 2021. Among all institution types, significant differences in specimen volume, specimen type, ROSE practice, and case sign-out were identified. Additionally, significant differences in specimen type, slide preparation, and ROSE practice were found. This is the first survey from the CAP to investigate pancreaticobiliary cytology practice. The findings reveal significant differences among institution types and between domestic and international laboratories. These data provide a baseline for future studies in a variety of practice settings.

Improving the Customer Experience: Physician Feedback Program for Clinical Laboratories.

Clinician feedback is an important source of information for laboratory quality improvement programs. To pilot a program for nearly real-time solicitation and analysis of physician feedback regarding clinical laboratory services. Laboratories distributed either electronic or paper survey forms to physicians. Results were tabulated by College of American Pathologists staff. Free-text comments were shared promptly with the participating laboratories to facilitate follow-up. Forty-seven clinical laboratories participated in the study and submitted results for 987 physician surveys, including both paper and electronic forms. Of 694 responses submitted electronically within the study period, 460 (66.3%) included at least 1 free-text entry, for a total of 951 free-text comments. Point-of-service solicitation of physician feedback regarding clinical laboratory services is feasible and can provide a substantial quantity of potentially useful information regarding laboratory performance from the customer perspective.

Interpretable HER2 scoring by evaluating clinical guidelines through a weakly supervised, constrained deep learning approach.

The evaluation of the Human Epidermal growth factor Receptor-2 (HER2) expression is an important prognostic biomarker for breast cancer treatment selection. However, HER2 scoring has notoriously high interobserver variability due to stain variations between centers and the need to estimate visually the staining intensity in specific percentages of tumor area. In this paper, focusing on the interpretability of HER2 scoring by a pathologist, we propose a semi-automatic, two-stage deep learning approach that directly evaluates the clinical HER2 guidelines defined by the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP). In the first stage, we segment the invasive tumor over the user-indicated Region of Interest (ROI). Then, in the second stage, we classify the tumor tissue into four HER2 classes. For the classification stage, we use weakly supervised, constrained optimization to find a model that classifies cancerous patches such that the tumor surface percentage meets the guidelines specification of each HER2 class. We end the second stage by freezing the model and refining its output logits in a supervised way to all slide labels in the training set. To ensure the quality of our dataset's labels, we conducted a multi-pathologist HER2 scoring consensus. For the assessment of doubtful cases where no consensus was found, our model can help by interpreting its HER2 class percentages output. We achieve a performance of 0.78 in F1-score on the test set while keeping our model interpretable for the pathologist, hopefully contributing to interpretable AI models in digital pathology.

Reviewers for the College of American Pathologists 2023 Annual Meeting (CAP23) Abstract Program

Reviewers for the College of American Pathologists 2023 Annual Meeting (CAP23) Abstract Program

Abstracts and Case Studies From the College of American Pathologists 2023 Annual Meeting (CAP23)

Abstracts and Case Studies From the College of American Pathologists 2023 Annual Meeting (CAP23)

Significant Variability in the Identification and Reporting of Band Neutrophils by Participants Enrolled in the College of American Pathologists Proficiency Testing Program: Time for a Change.

Increased band neutrophils in blood smear differential counts ("bandemia") are entrenched in medicine as a flag for sepsis. However, laboratory hematology experts have long advocated for discontinuation of reporting bands separately from segmented neutrophils because of poor sensitivity and specificity, poor interobserver agreement, and availability of alternative biomarkers for sepsis. To describe band neutrophil reporting practices and reproducibility of band classification among laboratories participating in the College of American Pathologists (CAP) proficiency testing (PT) program. A survey questionnaire was distributed to hematology PT participants. A subsequent morphologic challenge included 12 preselected cell identifications of segmented neutrophils, bands, and metamyelocytes, and a 100-cell manual differential count of a digitally scanned blood smear. Among laboratories that reported manual differentials, most respondents reported bands (4554 of 5268; 86.4%). Only 3222 of 4412 respondents (73.0%) provided band reference ranges. Though participants classified "easy" band neutrophils well (78.0%-98.3%), categorization of cell identifications for "moderate" and "difficult" bands was poor (3.1%-39.0% of laboratories), with classification instead as segmented neutrophils. This pattern was seen regardless of laboratory demographic characteristics. Marked variability in band counts was observed on the 100-cell differential count for both CAP PT participants and CAP Hematology and Clinical Microscopy Committee (HCMC) members (coefficients of variation, 55.8% and 32.9%, respectively). Variability was significantly improved when segmented and band neutrophils were grouped together (coefficients of variation, 6.2% and 5.0%, respectively). Most CAP PT-participating laboratories report band counts, many without reference ranges. The survey confirms significant interlaboratory variability of band enumeration when bands are separately identified from segmented neutrophils. This study reaffirms the CAP Hematology and Clinical Microscopy Committee's strong recommendation to group segmented and band neutrophils together in manual differential counts.

The Implementation of Nongynecologic Reporting Systems in Cytopathology Laboratories Is Highly Variable: Analysis of Data From a 2020 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

In recent years, several reporting systems have been developed by national and international cytopathology organizations to standardize the evaluation of specific cytopathology specimen types. To assess the current implementation rates, implementation methods, and barriers to implementation of commonly used nongynecologic reporting systems in cytopathology laboratories. Data were analyzed from a survey developed by the College of American Pathologists Cytopathology Committee and distributed to participants in the College of American Pathologists Nongynecologic Cytopathology Education Program mailing. Nongynecologic reporting systems with the highest rate of adoption were the Bethesda System for Reporting Thyroid Cytopathology, 2nd edition (74.1%; 552 of 745); the Paris System for Reporting Urinary Cytology (53.9%; 397 of 736); and the Milan System for Reporting Salivary Gland Cytopathology (29.1%; 200 of 688). The most common reason given for not adopting a reporting system was satisfaction with a laboratory's current system. Implementation varied among laboratories with regard to which stakeholders were involved in deciding to implement a system and the amount of education provided during the implementation process. The implementation of nongynecologic reporting systems in cytopathology laboratories was highly variable.

A Primer on Gene Editing.

Gene editing-based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions. To educate pathologists about gene editing technologies, inform them of potential indications and risks, outline regulatory and practical issues that could affect hospital-based practice and laboratory testing, and advocate that pathologists need to be present at discussions among industry and regulators pertaining to gene editing-based therapies. A Gene Editing Workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop an educational paper to serve as a stimulus to increase pathologist involvement and inquiry in gene editing therapeutic and diagnostic implementation. Through multiple discussions and literature review, the workgroup identified potential gaps in pathologists' knowledge of gene editing. Additional topics that could impact pathology and laboratory medicine were also identified and summarized in order to facilitate pathologists as stakeholders in gene editing therapy administration and monitoring and potential use in diagnostics. Gene editing therapy is a complex but potentially transformative area of medicine. This article serves as an introduction to pathologists to assist them in future discussions with colleagues and potentially identify and alter pathology practices that relate to gene editing.

Relevance of shrinkage versus fragmented response patterns in rectal cancer.

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. 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. 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.

Pathologic tumor response to neoadjuvant therapy in resected pancreatic cancer: does it affect prognosis?

Neoadjuvant therapy (NAT) + surgical resection for pancreatic cancer (PC) has gained consensus in recent years. Pathological response (PR) is generally assessed according to the College of American Pathologists grading system, ranging from 0 (complete response) to 3 (no response). The aim of our study is to evaluate the PR in a series of resections for PC after NAT and its prognostic implication. 112 patients undergone NAT and resection for PC between 2011 and 2020 were retrospectively evaluated. PR was 0/1, 2 and 3 in 18 (15%), 79 (61%) and 29 (24%) cases, respectively. Chemotherapy regimens different from FOLFIRINOX and gemcitabine + nab-paclitaxel (OR 11.61 (2.53-53.36), p = 0.002) and lymphovascular invasion (OR 11.28 (1.89-67.23), p = 0.008) were associated to PR-3. Median follow-up was 25.8 (3.6-130.5) months. For PR-0/1, PR-2 and PR-3, median DFS was 45.8, 11.5, 4.6months (p < 0.0001), respectively, while median OS was not reached, 27.1 and 17.5months (p = 0.0006), respectively. At univariate analysis, PR-0/1 was significantly associated to better DFS and OS (HR 0.33 (0.17-0.67), p = 0.002; HR 0.20 (0.07-0.54), p = 0.002, respectively). At multivariate analysis, pancreaticoduodenectomy (HR 0.50 (0.30-0.84), p = 0.009), LNR (HR 27.14 (1.21-608.9), p = 0.038) and lymphovascular invasion (HR 1.99 (1.06-3.76), p = 0.033) were independently associated to DFS; pre-treatment CA 19.9 value (HR 1.00 (1.00-1.00), p = 0.025), post-treatment resectability status (HR 0.51 (0.28-0.95), p = 0.035), pancreaticoduodenectomy (HR 0.56 (0.32-0.99), p = 0.050), severe morbidity (2.99 (1.22-7.55), p = 0.017), LNR (HR 56.8 (2.08-1548.3), p = 0.017), lymphovascular invasion (HR 2.18 (1.08-4.37), p = 0.029) were independently associated to OS. PR did not reach statistical significance at multivariate analysis. A favorable PR is observed only in a limited number of cases. The prognostic role of PR, despite being promising, remains unclear and further multicentric studies are needed.

The Significance of Recognition of Human Epidermal Growth Factor 2 Low in Breast Cancer Therapy.

In response to recent clinical trials that demonstrate the clinical benefit of antibody-drug conjugate drug therapy in breast cancer (BC) with human epidermal growth factor 2 (HER2) immunohistochemical scores of 1+ or 2+ and negative in situ hybridization results, a new concept of "HER2-low BC" has emerged to describe this newly relevant therapeutic category of BC. Clinical recognition of HER2-low BC has caused a paradigm shift in the therapeutic landscape and management of patients with BC and resulted in rapid changes in clinical practice guidelines. In addition the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recently updated their HER2 Guidelines Recommendations to specifically address HER2-low BC. A literature search in PubMed of peer-reviewed articles, regulatory communications, and relevant practice guidelines pertaining to HER2-low BC was conducted. In this review, we have summarized current published knowledge regarding the clinicopathologic and molecular features, diagnostic criteria, and most current guideline recommendations regarding HER2-low BC, and also highlight ongoing practical and diagnostic challenges when identifying HER2-low BC in routine clinical practice.

Imaging lymph node regression can predict the pathological tumor regression grade in gastric cancer after neoadjuvant treatment

BackgroundNeoadjuvant chemotherapy has become the standard treatment for locally advanced gastric cancer. The tumor regression grade system is an effective and widely used tool for the evaluation of treatment response to neoadjuvant chemotherapy. However, whether tumor regression grade could be predicted using clinical characteristics is uncertain. MethodsA total of 287 locally advanced gastric cancer patients from 2014 to 2021 were retrospectively included. According to the College of American Pathologists' tumor regression grade system, patients were classified into response group (tumor regression grade 0–1) and non-response group (tumor regression grade 2–3). Associations between clinical characteristics and neoadjuvant chemotherapy response were performed by the logistic regression model. The Kaplan–Meier method was used to estimate the survival. A prediction scoring system was constructed based on the β coefficients of multivariate analysis. The receiver operating characteristic curve and decision curve analysis were used to evaluate the performance of the predictive scoring system. ResultsSurvival analysis showed that patients with tumor regression grades 0 to 1 had significantly better disease-free survival and overall survival than the tumor regression grades 2 to 3. Tumor differentiation, ycT stage, immunotherapy, and lymph node regression were independent predictors of pathological response to neoadjuvant chemotherapy. We further developed a scoring system to predict the tumor regression grade. The receiver operating characteristic and decision curve analysis showed good predictive performance of the scoring system. ConclusionLymph node regression could be used as a predictor for pathological response. We developed a scoring system to predict the treatment response of patients with gastric cancer receiving neoadjuvant chemotherapy. The scoring system based on the predictors could provide guidance for making clinical decisions.

Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection. We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM- (residual tumor >1mm from the CRM), CRM-close (residual tumor >0 to 1mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per the Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications. Of the 519 patients included, 351 (68%) had CRM-, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival [DFS; CRM+ vs. CRM-: hazard ratio (HR), 1.53 [95% CI, 1.03-2.28]; P =0.034] and overall survival (OS; CRM+ vs. CRM-: HR, 1.97 [95% CI, 1.32-2.95]; P <0.001). Survival was not significantly different between CRM-close and CRM-. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP-: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P =0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P =0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P =0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P =0.11). CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM- were similar.

Standardized Clinical Annotation of Digital Histopathology Slides at the Point of Diagnosis

As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist’s regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides.

RNA Sequencing for Solid Tumor Fusion Gene Detection: Proficiency Testing Practice and Performance Comparison.

Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays. To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B). CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed for correct identification of the fusion event, associated performance variables, and laboratory practices. Overall, the 4-year program detection rate (sensitivity) was 95.5% (1486 of 1556 results). False-negative rates were 3.6% (53 of 1463) and 18.3% (17 of 93) for fusion gene and intragenic rearrangement/exon-skipping events, respectively. Only 19 false-positive results were reported among the 8 PT mailings, and most were likely the result of preanalytical or postanalytical errors. There were no practice characteristics (eg, instrumentation, sequencing method) significantly associated with the fusion detection results. These data reveal a high overall sensitivity and specificity for fusion gene detection by participating laboratories using clinical RNA sequencing. Performance was comparable across all laboratories, regardless of methodology. The fraction of false-negative results for intragenic rearrangement/exon-skipping events was greater than that for the chimeric fusion genes. False-negative results could not be attributed to any specific practice characteristics.