Pathology Practice Research Articles

The Modified Barium Swallow Study and Esophageal Screening: A Survey of Clinical Practice Patterns

Modified barium swallow study (MBSS) is a videofluoroscopic evaluation of oropharyngeal swallowing. Views of esophageal bolus flow during MBSS are permitted under speech-language pathology practice guidelines. However, controversy exists over its implementation. Poor consensus and limited practice guidance may lead to clinical practice variations. Aims of the investigation were to (a) describe current practice patterns of speech-language pathologist visualizing bolus flow through the esophagus during the MBSS, (b) understand areas of variation when incorporating esophageal visualization during the MBSS, and (c) determine clinicians' willingness to modify MBSS procedures to include esophageal imaging. A web-based survey (Qualtrics XM) consisting of 26 questions was distributed via web posting and e-mail to members of the American Speech-Language-Hearing Association Special Interest Group 13 and Dysphagia Café. The survey was open for 3 months. Descriptive and associative statistics were completed. Field-testing was performed prior to dissemination of the survey to address content validity. A total of 321 individuals participated; 265 responses were used for analysis. Ninety-three percent of respondents viewed the esophagus during the MBSS. Twelve percent followed to the proximal esophagus, 15% to the mid esophagus, 66% to the lower esophagus, and 6% to varied levels. Variability was also reported in contrast type, volume administered, and nomenclature used. Interestingly, few people (3.61%) disagreed that esophageal visualization should be performed during MBSS. Speech-language pathology respondents in this study visualize contrast flow through the esophagus and are enthusiastic about expanding the standard MBSS. However, results of the survey demonstrate a lack of uniformity in assessment practices. Unfortunately, this may impact the diagnostic accuracy and clinical utility when adding esophageal visualization to the MBSS. This study highlights the need for a standardized protocol and identifies current barriers and controversies that may prevent expanding the MBSS to more comprehensively evaluate individuals with dysphagia.

Abstract P6-04-07: Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader Study

Abstract Objective This study aimed to clinically validate the use of an AI-based solution by pathologists for the primary diagnosis of breast core needle biopsies as compared with the gold standard practice (review on the microscope). Methods A two-arm prospective reader study comparing the performance of pathologists using an AI-based solution with pathologists using a microscope was performed at two sites (different staining and digital scanners). Both arms were compared to ground truth (GT) established by the consensus of two breast pathologists. Rates of major discrepancies between each arm and GT, as determined by an adjudicating pathologist, were compared. Results Eight pathologists participated in the study and reported on 385 cases (442 HES and 330 H&E slides), each case being reported twice, once in each study arm. Pathologists first reviewed only H&E/HES slides, if requested and available, they were provided with IHCs, while the AI results were on H&E/HES only. The major discrepancy rates of the microscope arm and of the AI arm against GT were 4.42% and 3.12%, respectively, demonstrating a 29.4% reduction in major discrepancies. Pathologists with AI demonstrated very high accuracy for the detection of invasive carcinoma with sensitivity and specificity of 100% for both, as well as for DCIS/ADH with sensitivity of 92.4% and specificity of 97.8%. Conclusions This multi-site reader study reports diagnostic accuracy improvements by pathologists performing diagnosis and reporting with the support of a first read AI solution for breast biopsies. The AI solution performed accurately and generalized well for different staining platforms and different scanners. Thus, AI solutions could be used as significant aiding tools for pathologists in clinical decision-making in routine pathology practice, enhancing the quality and reproducibility of diagnosis. Citation Format: Anne Salomon, Alona Nudelman, Joanna Cyrta, Marina Maklakovski, Anat Albrecht Shach, Geraldine Sebag, Giuseppe Mallel, Ira Krasnitsky, Tali Feinberg, Manuela Vecsler, Judith Sandbank. Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-07.

Multicenter automatic detection of invasive carcinoma on breast whole slide images.

Breast cancer is one of the most prevalent cancers worldwide and pathologists are closely involved in establishing a diagnosis. Tools to assist in making a diagnosis are required to manage the increasing workload. In this context, artificial intelligence (AI) and deep-learning based tools may be used in daily pathology practice. However, it is challenging to develop fast and reliable algorithms that can be trusted by practitioners, whatever the medical center. We describe a patch-based algorithm that incorporates a convolutional neural network to detect and locate invasive carcinoma on breast whole-slide images. The network was trained on a dataset extracted from a reference acquisition center. We then performed a calibration step based on transfer learning to maintain the performance when translating on a new target acquisition center by using a limited amount of additional training data. Performance was evaluated using classical binary measures (accuracy, recall, precision) for both centers (referred to as "test reference dataset" and "test target dataset") and at two levels: patch and slide level. At patch level, accuracy, recall, and precision of the model on the reference and target test sets were 92.1% and 96.3%, 95% and 87.8%, and 73.9% and 70.6%, respectively. At slide level, accuracy, recall, and precision were 97.6% and 92.0%, 90.9% and 100%, and 100% and 70.8% for test sets 1 and 2, respectively. The high performance of the algorithm at both centers shows that the calibration process is efficient. This is performed using limited training data from the new target acquisition center and requires that the model is trained beforehand on a large database from a reference center. This methodology allows the implementation of AI diagnostic tools to help in routine pathology practice.

A Scoping Review of Auditory Dysfunction After Childhood Traumatic Brain Injury.

The purpose of this scoping review was to gain an understanding of the evidence available on auditory dysfunction after childhood traumatic brain injury (TBI) and identify limitations, clinical implications, and future directions for speech-language pathology and audiology practice and research. This scoping review of the literature followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A total of eight articles met inclusion for this scoping review. All studies were observational studies (n = 4 with controls, n = 4 without controls). Age at injury, injury severity, time postinjury, and age at time of study varied across the included studies. Three major topics related to childhood TBI were addressed among the included studies: (a) prevalence of auditory dysfunction (n = 5), (b) functional outcomes and biological markers related to auditory processing (n = 2), and (c) clinical presentation of auditory dysfunction (n = 2). This review highlights the particular lack of experimental evidence related to risk and protective factors and assessment and management strategies related to auditory dysfunction after childhood TBI. There is a major need for more research and research of higher rigor to be conducted with individuals who experienced a childhood TBI to support audiologists' and speech-language pathologists' evidence-based decision making to improve long-term functional outcomes for children with TBI.

Inflammatory Conditions of the Pancreatobiliary Tree.

The Pancreatobiliary Pathology Society (PBPS) would like to thank Alain C. Borczuk, MD, and the Archives of Pathology & Laboratory Medicine for again highlighting our society by publishing 3 review articles based on the presentations at the PBPS companion society symposium, which was held at the 2021 United States and Canadian Academy of Pathology (USCAP) meeting. As always, PBPS's mission remains the education of surgical pathologists and cytopathologists about the importance of recent advances in this complex field, which will hopefully transform the way we practice pancreatobiliary pathology. The PBPS fosters excellence and international collaboration in education, research, and the global practice of pancreatobiliary pathology. PBPS became an official society in 2016 and a USCAP companion society in 2018. However, the sharing of knowledge, enthusiasm, and ideas in pancreatobiliary pathology actually began more than 20 years ago as an annual “Pancreas Club” luncheon, held during the annual USCAP meeting, which grew over the years and eventually became the PBPS. The first advisory council members of the Pancreas Club were Volkan Adsay, MD; Ralph Hruban, MD; David Klimstra, MD; Günter Klöppel, MD; and Giuseppe Zamboni, MD. Thanks to their continued dedication to pancreatobiliary pathology and contagious enthusiasm, many other pathologists interested in the field were attracted to join and motivated its transformation into the official 501c3 society that it is today (PBPath.org).Because of the COVID-19 pandemic, the 2021 annual USCAP meeting (and by extension the PBPS companion society meeting) was held virtually. The theme of the 2021 PBPS Companion Society Symposium was “Inflammatory Conditions of the Pancreatobiliary Tree.” It featured 1.5 hours of on-demand educational content provided by 4 invited speakers, as well as a live 30-minute question-and-answer session with the speakers and moderators, Michelle Reid, MD, MS, and Rondell Graham, MBBS. The theme of the 2021 meeting was updates on acute and chronic inflammatory conditions of the pancreatobiliary tree, and it featured 4 outstanding presentations by experts in the field (Barbara Centeno, MD, Vikram Deshpande, MD, Dr Klöppel, and Dr Zamboni) entitled (1) “Cytopathology of Inflammatory Lesions of the Pancreatobiliary Tree” (Centeno), (2) “IgG4-Related (Autoimmune) Pancreatitis” (Deshpande), (3) “Acute and Alcoholic Pancreatitis” (Klöppel), and (4) “Paraduodenal Pancreatitis” (Zamboni).All 4 presentations from the 2021 companion meeting have been converted into review articles and are featured in this issue of Archives of Pathology & Laboratory Medicine. In the first article, “Cytopathology of Inflammatory Lesions of the Pancreatobiliary Tree,” Dr Centeno reviews the cytopathology of inflammatory lesions of the pancreas and bile duct, including the different types of pancreatitis. The cytologic criteria useful for differentiating reactive ductal atypia from adenocarcinoma and other malignant mimics are also discussed, and the application of ancillary techniques for this differential diagnosis is emphasized. In addition, Dr Centeno reviews pertinent and best pathology practices in the application of ancillary immunohistochemical and molecular studies for the differential diagnosis of benign from malignant processes in the bile duct. The second article is entitled “Navigating the Challenges Associated With a Diagnosis of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis” and is written by Dr Deshpande, along with his colleagues Osman Yilmaz, MD, and Karen Pinto, MBBS, DNB, FRCPath. In this article Drs Yilmaz, Pinto, and Deshpande examine the clinicopathologic features of type 1 and 2 autoimmune pancreatitis and immunoglobulin G4–related sclerosing cholangitis. They emphasize the use of a multimodal approach (clinical, radiographic, serologic, histopathologic, and immunohistochemical correlation) and highlight the distinctive overlapping qualities that can aid in diagnosing these entities and distinguishing them from other fibroinflammatory and/or neoplastic mimics. The authors also discuss diagnostic pitfalls and differential diagnoses and offer an approach to the interpretation of needle biopsies, including ampullary biopsies. The third article is entitled “Acute and Chronic Alcoholic Pancreatitis, Including Paraduodenal Pancreatitis.” It combines the talks of our third and fourth speakers, Dr Klöppel and Dr Zamboni. In this combined article, Drs Klöppel and Zamboni present the current state of pathology and pathogenesis of alcohol-associated pancreatitis, including paraduodenal pancreatitis. In the context of the most important epidemiologic, clinical, and radiologic features, the role of alcohol overconsumption and related macroscopic changes and histopathologic characteristics are addressed. Pathologic findings that distinguish mild from severe pancreatitis, as well as a histologic staging system for chronic pancreatitis, are emphasized. The morphologic features of paraduodenal pancreatitis as well as the anatomic peculiarities associated with it are also described.We are extremely proud of our society and the continued contributions of its members to the field of pancreatobiliary pathology. We hope that you will enjoy these review articles highlighting the experts' perspectives on inflammatory conditions of the pancreatobiliary tree.

Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions by p16 and p53 Immunohistochemistry: Considerations, Caveats, and an Algorithmic Approach

There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV−/p53wt), or HPV-independent/p53 abnormal (HPV−/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53. Noncomplementary p16 and p53 patterns were resolved by repeating p53 IHC and HPV RNA in situ hybridization (ISH) on whole sections, and sequencing for TP53. Of 82 p16-positive VSCC, 73 (89%) had complementary p16 and p53 patterns and were classified into the HPV+ group, 4 (4.9%) had wild-type p53 staining, positive HPV ISH and were classified into the HPV+ group, whereas 5 (6.1%) had p53 abnormal IHC patterns (1 null, 4 overexpression), negativity for HPV ISH, and harbored TP53 mutations (1 splice site, 4 missense); they were classified as HPV−/p53abn. Of 143 p16-negative VSCC, 142 (99.3%) had complementary p53 and p16 patterns: 115 (80.4%) HPV−/p53abn and 27 (18.9%) HPV−/p53wt. One had a basal-sparing p53 pattern, positivity for HPV ISH and was negative for TP53 mutations—HPV+ category. The use of IHC also led to revised diagnoses—HSIL to dVIN (3/43), dVIN to vaVIN (8/34), and dVIN to HSIL (3/34). Overall, 215/225 VSCC (95.6%) could be easily classifiable into 3 groups with p16 and p53 IHC. We identified several caveats, with the major caveat being that “double-positive” p16/p53 should be classified as HPV−/p53abn. We propose an algorithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice.

A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score

Background and objectiveIn recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated. Materials and methodsIn our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied. ResultsThe patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS 1 and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an independent risk factor for DFS (HR: 2.144 (95 % CI: 1.219–3.77) p: 0.008), but not an independent risk factor for OS. ConclusionCMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis.

Qualifications, professional roles and service practices of nurses, occupational therapists and speech-language pathologists in the management of adults with oropharyngeal dysphagia: a Nordic survey

Purpose To identify the qualifications, professional roles and service practices of nurses, occupational therapists (OTs) and speech-language pathologists (SLPs) in the management of adults with oropharyngeal dysphagia (OD) in the Nordic countries. Methods A web-based survey was developed that consisted of 50 questions on respondent demographics, education, experience, roles and service practices provided for adults with OD. The survey was distributed to practicing nurses, OTs, and SLPs in five Nordic countries via professional associations, social media, online networks and snowballing. Results Data from 396 nurses, OTs and SLPs whom provided services for adults with OD revealed that the majority of respondents worked in acute care and inpatient rehabilitation facilities. Most respondents had minimal undergraduate education and practical clinical training in OD. Notable variances in roles and service practices in OD between professions and countries were found. OTs were the primary service provider for OD management in Denmark, while SLPs had this role in the other Nordic countries. Nurses were mainly involved in screening and some compensatory treatments in most Nordic countries. Limited use of evidence-based screening, non-instrumental or instrumental clinical assessments and rehabilitative therapeutic methods was evident. Conclusions Study results highlight challenges in education and training of professionals responsible for the management of adults with OD in the Nordic countries. Increased use of evidence-based assessment and exercise-based treatments to improve swallowing are warranted. Adherence to European and international clinical practice guidelines for the management of adults with OD is recommended.

Improving sarcoma classification by using RNA hybridisation capture sequencing in sarcomas of uncertain histogenesis of young individuals

Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens. Successful sequencing was obtained in 12 of 21 samples (57%), two of which (16.6%) harboured translocations. A novel NEAT1::GLI1 fusion, not previously reported in the literature, presented in a young patient with a tumour in the retroperitoneum, which displayed low grade epithelioid cells. The second case, a localised lung metastasis in a young male, demonstrated a EWSR1::NFATC2 translocation. No targeted fusions were identified in the remaining 83.4% (n=10) of cases. Forty-three per cent of the samples failed sequencing as a result of RNA degradation. RNA-based sequencing is an important tool, which helps to redefine the classification of unclassified or partly classified sarcomas of young adults by identifying pathogenic gene fusions in up to 16.6% of the cases. Unfortunately, 43% of the samples underwent significant RNA degradation, falling below the sequencing threshold. As CaptureSeq is not yet available in routine pathology practice, increasing awareness of the yield, failure rate and possible aetiological factors for RNA degradation is fundamental to maximise laboratory procedures to improve RNA integrity, allowing the potential identification of significant gene alterations in solid tumours.

HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role.

Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.

Computational pathology in 2030: a Delphi study forecasting the role of AI in pathology within the next decade

Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. Perspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analysed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. Consensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI's role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. This systematic consensus study details the expected short-to-mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI's successful clinical implementation. No specific funding was provided for this study.

Significance of postmortem biomarkers and multimarker strategy in sudden cardiac death

The most common cause in the etiology of sudden cardiac death (SCD) is ischemic heart disease due to atherosclerosis. Postmortem diagnosis can be made by histopathological examinations, but routine histopathological examinations are limited, especially in the early period of postmortem ischemia. For this reason, many methods are being investigated for the postmortem diagnosis of ischemia, and postmortem biochemical studies are promising. In our study, we evaluated the biochemical markers; hs-cTnT, NT-proBNP, H-FABP, pentraxin-3, copeptin, ischemic modified albumin (IMA), and PAPP-A in postmortem serums. In forensic pathology practice, it was investigated whether it would be useful to go to the diagnosis by measuring more than one marker in a single biological fluid in SCD cases. The study included 35 sudden cardiac death cases and 24 control cases and as a result of our study, hs-cTnT, NT-proBNP, and H-FABP values were found to be significantly higher in the SCD group than in the control group. Within the scope of the multi-marker strategy, models were tried to be developed in which the markers were used together, and it was concluded that the model consisting of the myocardial ischemia marker hs-cTnT, the myocardial stress marker NT-proBNP, and the inflammation marker pentraxin 3 was the most accurate combination by correctly classifying the cases at a rate of 94.9%. As a result, it was thought that it would be appropriate to use the multi-marker strategy which is widely used in clinical applications, also in forensic medicine applications.

Visual interstitial fibrosis assessment as continuous variable in protocol renal transplant biopsies.

In current renal transplant pathology practice interstitial fibrosis is visually assessed in categories according to the Banff classification. As this has a moderate reproducibility, which is little ameliorated by morphometric analysis, we investigated whether visual renal fibrosis assessment is feasible on a continuous scale, i.e. as percentage affected area of the cortex. Protocol renal biopsies taken at transplantation (n=125), three (n=73) and twelve months (n=88) after transplantation were visually scored in categories (Banff), and percentages for interstitial fibrosis (ci). Interobserver variation (ICC and weighted κ) was assessed, and morphometric analysis on Sirus Red stained sections was performed. Correlations between the different methods and their association with donor age and eGFR 1 year and 5 year post transplant were analyzed using Pearson's or Spearman's rho. Interobserver agreement was equivalent for Banffci and %ci (κ0.713 vs. ICC 0.792), and for BanffIF/TA and %IF/TA (κ0.615 vs. ICC 0.743). Both Banffci and %ci were associated with Sirius Red morphometry in three and twelve month. With all three methods, a significant correlation was found between donor age and fibrosis in the implantation biopsy, and between fibrosis in the 12 month biopsy and eGFR at 1 and 5 years (eGFR at 1 year: Sirius Red ρ-0.487, %ci ρ-0.393, Banffci ρ-0.413, all p<0.01, eGFR at 5 years: Sirius Red ρ-0.392, %ci ρ-0.333, Banffci ρ-0.435, all p<0.01. Interstitial fibrosis assessment on a continuous scale can be used next to scoring in categories according to the Banff classification in protocol renal transplant biopsies.

The Evolution of Ki-67 and Breast Carcinoma: Past Observations, Present Directions, and Future Considerations.

The 1983 discovery of a mouse monoclonal antibody-the Ki-67 antibody-that recognized a nuclear antigen present only in proliferating cells represented a seminal discovery for the pathologic assessment of cellular proliferation in breast cancer and other solid tumors. Cellular proliferation is a central determinant of prognosis and response to cytotoxic chemotherapy in patients with breast cancer, and since the discovery of the Ki-67 antibody, Ki-67 has evolved as an important biomarker with both prognostic and predictive potential in breast cancer. Although there is universal recognition among the international guideline recommendations of the value of Ki-67 in breast cancer, recommendations for the actual use of Ki-67 assays in the prognostic and predictive evaluation of breast cancer remain mixed, primarily due to the lack of assay standardization and inconsistent inter-observer and inter-laboratory reproducibility. The treatment of high-risk ER-positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer with the recently FDA-approved drug abemaciclib relies on a quantitative assessment of Ki-67 expression in the treatment decision algorithm. This further reinforces the urgent need for standardization of Ki-67 antibody selection and staining interpretation, which will hopefully lead to multidisciplinary consensus on the use of Ki-67 as a prognostic and predictive marker in breast cancer. The goals of this review are to highlight the historical evolution of Ki-67 in breast cancer, summarize the present literature on Ki-67 in breast cancer, and discuss the evolving literature on the use of Ki-67 as a companion diagnostic biomarker in breast cancer, with consideration for the necessary changes required across pathology practices to help increase the reliability and widespread adoption of Ki-67 as a prognostic and predictive marker for breast cancer in clinical practice.

From morbid anatomy to molecular analysis: the evolution of anatomical pathology in Australia

The practice of anatomical pathology in Australia has evolved rapidly in the past two centuries, from the morbid anatomy performed in the early 1800s to the highly specialised histological, immunohistochemical and even molecular analysis of tissues performed today. While some literature exists on the development of anatomical pathology as a specialty worldwide, there is minimal formal literature on the history of this specialty in Australia. This poster examines key events that have shaped modern Australian anatomical pathology. Against the backdrop of global advances in medicine, we discuss the transition from macroscopic to microscopic observation forming the basis of the pathologist’s daily work, the significance of the establishment of a college, and the economic forces that have influenced the growth of anatomical pathology. In doing so, we elucidate the origin of contemporary issues facing the specialty, and to explore the implications of such developments as digital pathology for its future.

Ruptured interstitial pregnancy: a case report of a sudden maternal death in the late second trimester from a rare cause

Introduction: Interstitial pregnancy is a rare type of tubal ectopic pregnancy that occurs when implantation takes place in the interstitial segment of the fallopian tube. It remains one of the most difficult gestations to diagnose clinically and sonographically, hence a higher risk of rupture and catastrophic haemorrhage because of delayed diagnosis as the gestation progresses. We report a case of sudden maternal death from a ruptured interstitial pregnancy involving a woman at 27 weeks of pregnancy who was mistakenly thought to have a normal intrauterine pregnancy antenatally. Case description: A 40-year-old woman, normally conceived gravida 7, para 4, abortus 2 at 25 weeks of pregnancy by date, was dead on arrival at the hospital after experiencing sudden abdominal pain. A forensic autopsy revealed more than 2100 ml of hemoperitoneum. The uterine cavity was empty, and the right uterine fundus had an asymmetric cystic bulge found to be a ruptured interstitial pregnancy with a 27-week-old male fetus. Discussion and conclusion: The pathology of interstitial pregnancy and the distinction between this entity and the similar but distinct angular and cornual pregnancies will be described. This case report highlights a type of ectopic pregnancy rarely encountered in forensic pathology practice.

PathNarratives: Data annotation for pathological human-AI collaborative diagnosis.

Pathology is the gold standard of clinical diagnosis. Artificial intelligence (AI) in pathology becomes a new trend, but it is still not widely used due to the lack of necessary explanations for pathologists to understand the rationale. Clinic-compliant explanations besides the diagnostic decision of pathological images are essential for AI model training to provide diagnostic suggestions assisting pathologists practice. In this study, we propose a new annotation form, PathNarratives, that includes a hierarchical decision-to-reason data structure, a narrative annotation process, and a multimodal interactive annotation tool. Following PathNarratives, we recruited 8 pathologist annotators to build a colorectal pathological dataset, CR-PathNarratives, containing 174 whole-slide images (WSIs). We further experiment on the dataset with classification and captioning tasks to explore the clinical scenarios of human-AI-collaborative pathological diagnosis. The classification tasks show that fine-grain prediction enhances the overall classification accuracy from 79.56 to 85.26%. In Human-AI collaboration experience, the trust and confidence scores from 8 pathologists raised from 3.88 to 4.63 with providing more details. Results show that the classification and captioning tasks achieve better results with reason labels, provide explainable clues for doctors to understand and make the final decision and thus can support a better experience of human-AI collaboration in pathological diagnosis. In the future, we plan to optimize the tools for the annotation process, and expand the datasets with more WSIs and covering more pathological domains.

Formulation of the final clinical, pathological, forensic diagnosis, selection and coding according to ICD-10 of the original cause of death in lethal outcomes associated with pathology of transplanted organs

Introduction. When compiling the final clinical, pathoanatomical and forensic diagnoses, as well as choosing and coding according to ICD-10 the initial cause of death in patients after organ transplantation, difficulties often arise due to the lack of unified recommendations.Materials and methods. We analyzed 60 protocols of post-mortem autopsies of lethal outcomes in patients after organ transplantation at the Sklifosovsky Research Institute of Emergency Medicine, Moscow for 7 years (from 2016 to 2022).Results. Based on the results of the analysis, taking into account the literature data, recommendations were formulated on the formulation of the final clinical, pathoanatomical and forensic diagnoses, selection and coding according to ICD-10 of the initial cause of death in patients after solid organ transplantation.Findings. The developed recommendations on the formulation of the final clinical, pathoanatomical and forensic diagnoses in cases of death of patients after solid organ transplantation can be used in the daily practice of clinical doctors, pathologists and forensic experts.

Impact of the COVID-19 pandemic on pathological autopsy practices in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.

Impact of COVID-19 on Ophthalmic Pathology

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains a significant concern to the public and a major challenge to healthcare workers. Although vaccination programs are generally regarded as successful, recent reports have shown that vaccine effectiveness is decreasing gradually, particularly as booster uptakes are low. The next pandemic is unpredictable and inevitable. Therefore, understanding the impact of COVID-19 on different aspects of healthcare will aid in adaptation to life with pandemics and enable prioritization of medical treatment. The SARS-CoV-2 outbreak significantly changed all sectors of healthcare. Ocular oncology and pathology practices were adapted to adjust to the many new challenges the COVID-19 pandemic presented. This review highlights laboratory modifications and shows how the number, type, and histology of eye oncology cases were impacted during the pandemic.