Understanding the financial aspects of digital pathology: A dynamic customizable return on investment calculator for informed decision-making.

Background: The adoption of digital pathology has transformed the field of pathology, however, the economic impact and cost analysis of implementing digital pathology solutions remain a critical consideration for institutions to justify. Digital pathology implementation requires a thorough evaluation of associated costs and should identify and optimize resource allocation to facilitate informed decision-making. A dynamic cost calculator to estimate the financial implications of deploying digital pathology systems was needed to estimate the financial effects on transitioning to a digital workflow. Methods: A systematic approach was used to comprehensively assess the various components involved in implementing and maintaining a digital pathology system. This consisted of: (1) identification of key cost categories associated with digital pathology implementation; (2) data collection and analysis of cost estimation; (3) cost categorization and quantification of direct and indirect costs associated with different use cases, allowing customization of each factor based on specific intended uses and market rates, industry standards, and regional variations; (4) opportunities for savings realized by digitization of glass slides and (5) integration of the cost calculator into a unified framework for a holistic view of the financial implications associated with digital pathology implementation. The online tool enables the user to test various scenarios specific to their institution and provides adjustable parameters to assure organization specific relatability. Results: The Digital Pathology Association has developed a web-based calculator as a companion tool to provide an exhaustive list of the necessary concepts needed when assessing the financial implications of transitioning to a digital pathology system. The dynamic return on investment (ROI) calculator successfully integrated relevant cost and cost-saving components associated with digital pathology implementation and maintenance. Considerations include factors such as digital pathology infrastructure, clinical operations, staffing, hardware and software, information technology, archive and retrieval, medical-legal, and potential reimbursements. The ROI calculator developed for digital pathology workflows offers a comprehensive, customizable tool for institutions to assess their anticipated upfront and ongoing annual costs as they start or expand their digital pathology journey. It also offers cost-savings analysis based on specific user case volume, institutional geographic considerations, and actual costs. In addition, the calculator also serves as a tool to estimate number of required whole slide scanners, scanner throughput, and data storage (TB). This tool is intended to estimate the potential costs and cost savings resulting from the transition to digital pathology for business plan justifications and return on investment calculations. Conclusions: The digital pathology online cost calculator provides a comprehensive and reliable means of estimating the financial implications associated with implementing and maintaining a digital pathology system. By considering various cost factors and allowing customization based on institution-specific variables, the calculator empowers pathology laboratories, healthcare institutions, and administrators to make informed decisions and optimize resource allocation when adopting or expanding digital pathology technologies. The ROI calculator will enable healthcare institutions to assess the financial feasibility and potential return on investment on adopting digital pathology, facilitating informed decision-making and resource allocation.

Automated imaging analysis of Ki-67 immunohistochemistry on whole slide images of cell blocks from pancreatic neuroendocrine neoplasms.

INTRODUCTION: Accurate grading of pancreatic neuroendocrine tumors (PanNETs) relies on the assessment of Ki-67 immunohistochemistry (IHC). While digital imaging analysis (DIA) has been employed for Ki-67 IHC assessment in surgical specimens, its applicability to cytologic specimens remains underexplored. This study aimed to evaluate an automated DIA for assessing Ki-67 IHC on PanNET cell blocks. MATERIALS AND METHODS: The study included 61 consecutive PanNETs and 5 pancreatic neuroendocrine carcinomas. Ki-67 IHC slides from cell blocks were digitally scanned into whole slide images using Philips IntelliSite Scanners and analyzed in batches using the Visiopharm Ki-67 App in a digital workflow. Ki-67 scores obtained through DIA were compared to pathologists' manual scores. RESULTS: The Pearson correlation coefficient of the percentage of Ki-67-stained nuclei between DIA reads and the originally reported reads was 0.9681. Concordance between DIA Ki-67 grades and pathologists' Ki-67 grades was observed in 92.4% (61/66) of cases with the calculated Cohen's Kappa coefficient of 0.862 (almost perfect agreement). Discordance between DIA and pathologists' consensus reads occurred in 5 PanNET cases which were upgraded from G1 to G2 by DIA due to contaminated Ki-67-stained inflammatory cells. CONCLUSIONS: DIA demonstrated excellent concordance with pathologists' assessments, with only minor grading discrepancies. However, the essential role of pathologists in confirming results is emphasized to enhance overall accuracy.

Comparing Accuracy of Helicobacter pylori Identification Using Traditional Hematoxylin and Eosin-Stained Glass Slides With Digital Whole Slide Imaging.

With advancements in the field of digital pathology, there has been a growing need to compare the diagnostic abilities of pathologists using digitized whole slide images against those when using traditional hematoxylin and eosin (H&E)-stained glass slides for primary diagnosis. One of the most common specimens received in pathology practices is an endoscopic gastric biopsy with a request to rule out Helicobacter pylori (H. pylori) infection. The current standard of care is the identification of the organisms on H&E-stained slides. Immunohistochemical or histochemical stains are used selectively. However, due to their small size (2-4 µm in length by 0.5-1 µm in width), visualization of the organisms can present a diagnostic challenge. The goal of the study was to compare the ability of pathologists to identify H. pylori on H&E slides using a digital platform against the gold standard of H&E glass slides using routine light microscopy. Diagnostic accuracy rates using glass slides vs digital slides were 81% vs 72% (P = .0142) based on H&E slides alone. When H. pylori immunohistochemical slides were provided, the diagnostic accuracy was significantly improved to comparable rates (96% glass vs 99% digital, P = 0.2199). Furthermore, differences in practice settings (academic/subspecialized vs community/general) and the duration of sign-out experience did not significantly impact the accuracy of detecting H. pylori on digital slides. We concluded that digital whole slide images, although amenable in different practice settings and teaching environments, does present some shortcomings in accuracy and precision, especially in certain circumstances and thus is not yet fully capable of completely replacing glass slide review for identification of H. pylori. We specifically recommend reviewing glass slides and/or performing ancillary stains, especially when there is a discrepancy between the degree of inflammation and the presence of microorganisms on digital images.

Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists.

CONTEXT.­: Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice. Currently there are no formal guidelines to assist pathology laboratories in verification and/or validation of such systems. These recommendations are being proposed for the evaluation of machine learning systems in the clinical practice of pathology. OBJECTIVE.­: To propose recommendations for performance evaluation of in vitro diagnostic tests on patient samples that incorporate machine learning as part of the preanalytical, analytical, or postanalytical phases of the laboratory workflow. Topics described include considerations for machine learning model evaluation including risk assessment, predeployment requirements, data sourcing and curation, verification and validation, change control management, human-computer interaction, practitioner training, and competency evaluation. DATA SOURCES.­: An expert panel performed a review of the literature, Clinical and Laboratory Standards Institute guidance, and laboratory and government regulatory frameworks. CONCLUSIONS.­: Review of the literature and existing documents enabled the development of proposed recommendations. This white paper pertains to performance evaluation of machine learning systems intended to be implemented for clinical patient testing. Further studies with real-world clinical data are encouraged to support these proposed recommendations. Performance evaluation of machine learning models is critical to verification and/or validation of in vitro diagnostic tests using machine learning intended for clinical practice.

Comparison of four different displays for identification of select pathologic features extracted from whole slide images of surgical pathology cases.

BACKGROUND: The establishment of minimum standards for display selection for the whole slide image (WSI) interpretation has not been fully defined. Recently, pathologists have increasingly preferred using remote displays for clinical diagnostics. Our study aims to assess and compare the performance of three fixed work displays and one remote personal display in accurately identifying ten selected pathologic features integrated into WSIs. DESIGN: Hematoxylin and eosin-stained glass slides were digitized using Philips scanners. Seven practicing pathologists and three residents reviewed ninety WSIs to identify ten pathologic features using the LG, Dell, and Samsung and an optional consumer-grade display. Ten pathologic features included eosinophils, neutrophils, plasma cells, granulomas, necrosis, mucin, hemosiderin, crystals, nucleoli, and mitoses. RESULTS: The accuracy of the identification of ten features on different types of displays did not significantly differ among the three types of "fixed" workplace displays. The highest accuracy was observed for the identification of neutrophils, eosinophils, plasma cells, granuloma, and mucin. On the other hand, a lower accuracy was observed for the identification of crystals, mitoses, necrosis, hemosiderin, and nucleoli. Participant pathologists and residents preferred the use of larger displays (>30″) with a higher pixel count, resolution, and luminance. CONCLUSION: Most features can be identified using any display. However, certain features posed more challenges across the three fixed display types. Furthermore, the use of a remote personal consumer-grade display chosen according to the pathologists' preference showed similar feature identification accuracy. Several factors of display characteristics seemed to influence pathologists' display preferences such as the display size, color, contrast ratio, pixel count, and luminance calibration. This study supports the use of standard "unlocked" vendor-agnostic displays for clinical digital pathology workflow rather than purchasing "locked" and more expensive displays that are part of a digital pathology system.

New digital confocal laser microscopy may boost real-time evaluation of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from solid pancreatic lesions: Data from an international multicenter study.

BACKGROUND: Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens. METHODS: This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis. FINDINGS: Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement. INTERPRETATION: Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors. FUNDING: This study was not supported by any funding source.

Integrating and validating automated digital imaging analysis of estrogen receptor immunohistochemistry in a fully digital workflow for clinical use.

Background: The Visiopharm automated estrogen receptor (ER) digital imaging analysis (DIA) algorithm assesses digitized ER immunohistochemistry (IHC) by segmenting tumor nuclei and detecting stained nuclei automatically. We aimed to integrate and validate this algorithm in a digital pathology workflow for clinical use. Design: The study cohort consisted of a serial collection of 97 invasive breast carcinoma specimens including 73 biopsies and 24 resections. ER IHC slides were scanned into Philips Image Management System (IMS) during our routine digital workflow and digital images were directly streamed into Visiopharm platform and analyzed using automated ER algorithm to obtain the positively stained tumor nuclei and staining intensity. ER DIA scores were compared with pathologists' manual scores. Results: The overall concordance between pathologists' reads and DIA reads was excellent (91/97, 93.8%). Pearson Correlation Coefficient of the percentage of ER positive nuclei between the original reads and VIS reads was 0.72. Six cases (3 ER-negative and 3 ER-positive) had discordant results. All 3 false negative cases had very weak ER staining and no more than 10% positivity. The causes for false positive DIA were mainly pre-analytic/pre-imaging and included intermixed benign glands in tumor area, ductal carcinoma in-situ (DCIS) components, and tissue folding. Conclusions: Automated ER DIA demonstrates excellent concordance with pathologists' scores and accurately discriminates ER positive from negative cases. Furthermore, integrating automated biomarker DIA into a busy clinical digital workflow is feasible and may save time and labor for pathologists.

Types and frequency of whole slide imaging scan failures in a clinical high throughput digital pathology scanning laboratory.

Digital workflow transformation continues to sweep throughout a diversity of pathology departments spanning the globe following catalyzation of whole slide imaging (WSI) adoption by the SARS-CoV-2 (COVID-19) pandemic. The utility of WSI for a litany of use cases including primary diagnosis has been emphasized during this period, with WSI scanning devices gaining the approval of healthcare regulatory bodies and practitioners alike for clinical applications following extensive validatory efforts. As successful validation for WSI is predicated upon pathologist diagnostic interpretability of digital images with high glass slide concordance, departmental adoption of WSI is tantamount to the reliability of such images often predicated upon quality assessment notwithstanding image interpretability but extending to quality of practice following WSI adoption. Metrics of importance within this context include failure rates inclusive of different scanning errors that result in poor image quality and the potential such errors may incur upon departmental turnaround time (TAT). We sought to evaluate the impact of WSI implementation through retrospective evaluation of scan failure frequency in archival versus newly prepared slides, types of scanning error, and impact upon TAT following commencement of live WSI operation in May 2017 until the present period within a fully digitized high-volume academic institution. A 1.19% scan failure incidence rate was recorded during this period, with re-scanning requested and successfully executed for 1.19% of cases during the reported period of January 2019 until present. No significant impact upon TAT was deduced, suggesting an outcome which may be encouraging for departments considering digital workflow adoption.

Dissecting the Business Case for Adoption and Implementation of Digital Pathology: A White Paper from the Digital Pathology Association.

We believe the switch to a digital pathology (DP) workflow is imminent and it is essential to understand the economic implications of conversion. Many aspects of the adoption of DP will be disruptive and have a direct financial impact, both in short term costs, such as investment in equipment and personnel, and long term revenue potential, such as improved productivity and novel tests. The focus of this whitepaper is to educate pathologists, laboratorians and other stakeholders about the business and monetary considerations of converting to a digital pathology workflow. The components of a DP business plan will be thoroughly summarized, and guidance will be provided on how to build a case for adoption and implementation as well as a roadmap for transitioning from an analog to a digital pathology workflow in various laboratory settings. It is important to clarify that this publication is not intended to list prices although some financials will be mentioned as examples. The authors encourage readers who are evaluating conversion to a DP workflow to use this paper as a foundational guide for conducting a thorough and complete assessment while incorporating in current market pricing. Contributors to this paper analyzed peer-reviewed literature and data collected from various institutions, some of which are mentioned. Digital pathology will change the way we practice through facilitating patient access to expert pathology services and enabling image analysis tools and assays to aid in diagnosis, prognosis, risk stratification and therapeutic selection. Together, they will result in the delivery of valuable information from which to make better decisions and improve the health of patients.

Digital Pathology Initiatives and Experience of a Large Academic Institution During the Coronavirus Disease 2019 (COVID-19) Pandemic.

CONTEXT.­: Pathology practices have begun integrating digital pathology tools into their routine workflow. During 2020, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic, causing a global health crisis that significantly affected the world population in several areas, including medical practice, and pathology was no exception. OBJECTIVE.­: To summarize our experience in implementing digital pathology for remote primary diagnosis, education, and research during this pandemic. DESIGN.­: We surveyed our pathologists (all subspecialized) and trainees to gather information about their use of digital pathology tools before and during the pandemic. Quality assurance and slide distribution data were also examined. RESULTS.­: During the pandemic, the widespread use of digital tools in our institution allowed a smooth transition of most clinical and academic activities into remote with no major disruptions. The number of pathologists using whole slide imaging (WSI) for primary diagnosis increased from 20 (62.5%) to 29 (90.6%) of a total of 32 pathologists, excluding renal pathology and hematopathology, during the pandemic. Furthermore, the number of pathologists exclusively using whole slide imaging for primary diagnosis also increased from 2 (6.3%) to 5 (15.6%) during the pandemic. In 35 (100%) survey responses from attending pathologists, 21 (60%) reported using whole slide imaging for remote primary diagnosis following the Centers for Medicare and Medicaid Services waiver. Of these 21 pathologists, 18 (86%) responded that if allowed, they will continue using whole slide imaging for remote primary diagnosis after the pandemic. CONCLUSIONS.­: The pandemic served as a catalyst to pathologists adopting a digital workflow into their daily practice and realizing the logistic and technical advantages of such tools.

Contemporary Whole Slide Imaging Devices and Their Applications within the Modern Pathology Department: A Selected Hardware Review.

Digital pathology (DP) has disrupted the practice of traditional pathology, including applications in education, research, and clinical practice. Contemporary whole slide imaging (WSI) devices include technological advances that help address some of the challenges facing modern pathology, such as increasing workloads with fewer subspecialized pathologists, expanding integrated delivery networks with global reach, and greater customization when working up cases for precision medicine. This review focuses on integral hardware components of 43 market available and soon-to-be released digital WSI devices utilized throughout the world. Components such as objective lens type and magnification, scanning camera, illumination, and slide capacity were evaluated with respect to scan time, throughput, accuracy of scanning, and image quality. This analysis of assorted modern WSI devices offers essential, valuable information for successfully selecting and implementing a digital WSI solution for any given pathology practice.

Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association.

The advent of whole-slide imaging in digital pathology has brought about the advancement of computer-aided examination of tissue via digital image analysis. Digitized slides can now be easily annotated and analyzed via a variety of algorithms. This study reviews the fundamentals of tissue image analysis and aims to provide pathologists with basic information regarding the features, applications, and general workflow of these new tools. The review gives an overview of the basic categories of software solutions available, potential analysis strategies, technical considerations, and general algorithm readouts. Advantages and limitations of tissue image analysis are discussed, and emerging concepts, such as artificial intelligence and machine learning, are introduced. Finally, examples of how digital image analysis tools are currently being used in diagnostic laboratories, translational research, and drug development are discussed.

Significance of the epithelioid granuloma in biopsies of Crohn's colitis.

BACKGROUND: The relevance of granulomas in biopsy specimens from patients with Crohn's disease is largely unknown. Most previous studies have been performed on small samples and have produced conflicting results. This study was designed to compare the demographic, clinical, and histopathologic characteristics of a large cohort of documented patients with Crohn's disease with and without epithelioid granulomas. METHODS: Data of all patients with Crohn's disease were extracted from a computerized database of 1.3 million subjects who underwent colonoscopy and had their biopsy specimens diagnosed by a single group of gastrointestinal pathologists. The influence of age, gender, patient symptoms, and histopathologic finding on the presence of granuloma was analyzed. RESULTS: There were 10,456 patients with Crohn's disease: 952 (9%) patients harbored granulomas (cases) and 9504 (91%) patients (controls) had none. Cases were significantly younger than controls: 42.4 ± 17.9 versus 48.0 ± 16.4 years (P < 0.0001). Cases presented with more symptoms than controls (odds ratio, 95% confidence interval): diarrhea (2.29, 2.28-2.31), anemia (2.06, 2.02-2.10), vomiting (2.13, 2.07-2.19), abdominal pain (1.75, 1.72-1.78), hematochezia (1.97, 1.94-2.00), and weight loss (3.94, 3.93-3.94). In a multivariate logistic regression analysis, younger age, presence of chronic active colitis, and symptoms of weight loss remained independent statistically significant predictors for the presence of granulomas. CONCLUSIONS: In colonic biopsies from patients with Crohn's disease, granulomas constitute a rare finding. Presence of granulomas is associated with younger patient age, more severe histopathologic expression of the underlying disease, and more clinical symptoms.

Gastric heterotopia in the proximal oesophagus ("inlet patch"): Association with adenocarcinomas arising in Barrett mucosa.

BACKGROUND: The prevalence of inlet patches and their association with other conditions of the gastrointestinal tract have been studied prospectively in tertiary care facilities; little is known about practice patterns in private outpatient clinics and endoscopy centres. AIMS: To assess prevalence, demographic determinants, and associated clinicopathologic features of inlet patches in patients who had oesophagogastroduodenoscopy in outpatient settings throughout the United States. METHODS: Retrospective analysis of the clinicopathologic records of 487,229 unique patients who had oesophagogastroduodenoscopy with biopsies between January 2008 and December 2010. RESULTS: There were 870 patients with inlet patches with a prevalence of 0.18%. Significant associations included male gender (OR 1.68), dysphagia (OR 1.34), upper respiratory complaints (OR 2.81), globus (OR 5.39) Barrett oesophagus (OR 1.55), and adenocarcinomas arising in Barrett mucosa (OR 5.64). CONCLUSIONS: The prevalence of inlet patches in a tertiary care setting (0.18%) was considerably lower than reported in prospective studies (3.7% on average). Inlet patches were significantly associated with male gender, dysphagia, upper respiratory complaints, globus, Barrett mucosa, and adenocarcinomas arising in Barrett oesophagus. Further studies will be needed to determine if patients with inlet patches and Barrett mucosa benefit from increased surveillance.

Primary retroperitoneal teratoma presenting as an adrenal tumor in an adult.

Primary teratomas in the retroperitoneum are rare in adults. Most teratomas in this region are secondary to germ cell tumors of the testes or ovaries. We describe a case of mature cystic teratoma that was clinically suggestive of an adrenal myelolipoma. Resection was attempted using laparoscopy but was converted to open adrenalectomy to ensure complete resection. Because of the risk of malignancy, follow-up radiographic studies were performed to ensure the oncologic efficacy of resection. The patient has been free of recurrence for longer than 18 months.

Myoepithelial carcinoma arising in a pleomorphic adenoma of the parotid gland: report of a case with cytopathologic findings.

BACKGROUND: Carcinoma arising in a mixed tumor, or carcinoma ex pleomorphic adenoma (CEPA), is an uncommon primary salivary gland neoplasm. Among the various types of carcinomas that can be seen histologically in a CEPA, myoepithelial carcinoma is one of the rarest forms. CASE: A 76-year-old woman presented with an incidental parotid/parapharyngeal mass. Computed tomography-guide fine needle aspiration (FNA) showed a biphasic neoplasm with epithelial and stromal components consistent with pleomorphic adenoma (PA). However, in addition, a distinct population of discohesive atypical and pleomorphic cells with high nuclear/cytoplasmic ratio was noted in the background. In the cytopathologic diagnosis a suspicion was raised about a possible CEPA. Subsequent resection of the parotid mass confirmed the presence of low grade myoepithelial carcinoma arising in a PA. CONCLUSION: Although uncommon, CEPA should be suspected on FNA when atypical cytomorphologic characteristics are observed. In rare cases a myoepithelial carcinoma also arises in a preexisting PA, necessitating an accurate interpretation for more definitive therapy.