Digital breast pathology: validation and training for primary digital practice

Digital pathology is a technology which is transforming the way in which breast histopathology specimens are assessed, reported and reviewed. Large scale clinical laboratory deployments of whole slide imaging systems are occurring in diagnostic pathology departments across the world, requiring laboratory and diagnostic staff to navigate new skills and workflows. Transferring from conventional light microscopy assessment of breast specimens to the use of whole slide images (WSI) can be a challenging experience. This article describes an approach to training and validation for breast consultant histopathologists, which has been used and adapted at a number of sites. Examples of types of case that are suitable for training, and some of the potential “pitfalls” of digital reporting for the novice are described, and practical advice regarding clinical digital breast workflow is shared.     

Modern imaging technologies in toxicologic pathology: An overview

Modern imaging technology, now utilized in most biomedical research areas (bioimaging), enables the detection and visualization of biological processes at various levels of the molecule, organelle, cell, tissue, organ and/or whole body. In toxicologic pathology, the impact of modern imaging technology is becoming apparent from digital histopathology to novel molecular imaging for in vivo studies. This overview summarizes recent progresses in digital microscopy imaging and newly developed digital slide techniques. Applications of virtual microscopy imaging are discussed and compared to traditional optical microscopy reading. New generation digital pathology approaches, including automatic slide inspection, digital slide databases and image management are briefly introduced. Commonly used in vivo preclinical imaging technologies are also summarized. While most of these new imaging techniques are still undergoing rapid development, it is important that toxicologic pathologists embrace and utilize these technologies as advances occur.     

Being fully digital: perspective of a Dutch academic pathology laboratory

The introduction of fast and robust whole slide scanners has facilitated the implementation of ‘digital pathology’ with various uses, the final challenge being full digital diagnostics. In this article, we describe the implementation process of a fully digital workflow for primary diagnostics in 2015 at the University Medical Centre in Utrecht, The Netherlands, as one of the first laboratories going fully digital with a future‐proof complete digital archive. Furthermore, we evaluated the experience of the first 2 years of working with the system by pathologists and residents. The system was successfully implemented in 6 months, including a European tender procedure. Most pathologists and residents had high confidence in working fully digitally, the expertise areas lagging behind being paediatrics, haematopathology, and neuropathology. Reported limitations concerned recognition of microorganisms and mitoses. Neither the age of respondents nor the number of years of pathology experience was correlated with the confidence level regarding digital diagnostics. The ergonomics of digital diagnostics were better than those of traditional microscopy. In this article, we describe our experiences in implementing our fully digital primary diagnostics workflow, describing in depth the implementation steps undertaken, the interlocking components that are required for a fully functional digital pathology system (laboratory management, hospital information systems, data storage, and whole slide scanners), and the changes required in workflow and slide production.     

A whole-slide imaging based workflow reduces the reading time of pathologists

Even though entirely digitized microscopic tissue sections (whole slide images, WSIs) are increasingly being used in histopathology diagnostics, little data is still available on the effect of this technique on pathologists' reading time. This study aimed to compare the time required to perform the microscopic assessment by pathologists between a conventional workflow (an optical microscope) and digitized WSIs. WSI was used in primary diagnostics at the Laboratory for Pathology Eastern Netherlands for several years (LabPON, Hengelo, The Netherlands). Cases were read either in a traditional workflow, with the pathologist recording the time required for diagnostics and reporting, or entirely digitally. Reading times were extracted from image management system log files, and the digitized workflow was fully integrated into the laboratory information system. The digital workflow saved time in the majority of case categories, with prostate biopsies saving the most (68% time gain). Taking into account case distribution, the digital workflow produced an average gain of 12.3%. Using WSI instead of conventional microscopy significantly reduces pathologists' reading times. Pathologists must work in a fully integrated environment to fully reap the benefits of a digital workflow.     

Digital microscopy imaging and new approaches in toxicologic pathology

Digital microscopy, a comprehensive integration of digital imaging and light microscopy, can assist the pathologist to observe, acquire, record, share, analyze, and manage pathology image data. To lead the activity for establishing new generation digital microscopy capacity, novel concepts and strategies of digital pathology information flow and digital pathology platform were designed to integrate personal digital pathology microscopy workstations and other pathology imaging modalities with centralized data storage/management. In addition, a strategy for Web-enabled interactive telepathology that would permit global capacity was designed. A novel concept of high content pathology was also created to develop an automated tissue microscopy imaging and screening approach. These new concepts, strategies, and approaches guided the development and implementation of a digital pathology platform, a telepathology platform, and automated tissue slide imaging capacity. Digital microscopy photography is now able to replace photographic film in toxicologic pathology. Digital pathology and telepathology platforms can provide a networked environment for multisite, global team participation. Our practice also ascertained the central value of digital microscopy which can provide innovative quantitative pathology information and data mining capability with various imaging biomarkers via advanced digital image processing and pathology informatics; these are now the focus of ongoing development.     

Colour in digital pathology: a review

Colour is central to the practice of pathology because of the use of coloured histochemical and immunohistochemical stains to visualize tissue features. Our reliance upon histochemical stains and light microscopy has evolved alongside a wide variation in slide colour, with little investigation into the implications of colour variation. However, the introduction of the digital microscope and whole‐slide imaging has highlighted the need for further understanding and control of colour. This is because the digitization process itself introduces further colour variation which may affect diagnosis, and image analysis algorithms often use colour or intensity measures to detect or measure tissue features. The US Food and Drug Administration have released recent guidance stating the need to develop a method of controlling colour reproduction throughout the digitization process in whole‐slide imaging for primary diagnostic use. This comprehensive review introduces applied basic colour physics and colour interpretation by the human visual system, before discussing the importance of colour in pathology. The process of colour calibration and its application to pathology are also included, as well as a summary of the current guidelines and recommendations regarding colour in digital pathology.     

Digital workflow management for quality assessment in pathology

Information systems (IS) are well established in the multitude of departments and practices of pathology. Apart from being a collection of doctor's reports, IS can be used to organize and evaluate workflow processes. We report on such a digital workflow management using IS at the Department of Pathology, University Hospital Magdeburg, Germany, and present an evaluation of workflow data collected over a whole year. This allows us to measure workflow processes and to distinguish the effects of alterations in the workflow for quality assessment. Moreover, digital workflow management provides the basis for the integration of diagnostic virtual microscopy.     

Whole-slide imaging: routine pathologic diagnosis

Digital pathology systems offer pathologists an alternate, emerging mechanism to manage and interpret information. They offer increasingly fast and scalable hardware platforms for slide scanning and software that facilitates remote viewing, slide conferencing, archiving, and image analysis. Deployed initially and validated largely within the research and biopharmaceutical industries, WSI is increasingly being implemented for direct patient care. Improvements in image quality, scan times, and imageviewing browsers will hopefully allow pathologists to more seamlessly convert to digital pathology, much like our radiology colleagues have done before us. However, WSI creates both opportunities and challenges. Although niche applications of WSI technology for clinical, educational, and research purposes are clearly successful, it is evident that several areas still require attention and careful consideration before more widespread clinical adoption of WSI takes place. These include regulatory issues, development of standards of practice and validation guidelines, workflow modifications, as well as defining situations where WSI technology will really improve practice in a cost-effective way. Current progress on these and other issues, along with improving technology, will no doubt pave the way for increased adoption over the next decade, allowing the pathology community as a whole to harness the true potential of WSI for patient care. The digital decade will likely redefine how pathology is practiced and the role of the pathologist.     

Digital pathology and artificial intelligence as the next chapter in diagnostic hematopathology

Digital pathology has a crucial role in diagnostic pathology and is increasingly a technological requirement in the field. Integration of digital slides into the pathology workflow, advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond the microscopic slide and enable true integration of knowledge and expertise. There is clear potential for artificial intelligence (AI) breakthroughs in pathology and hematopathology.In this review article, we discuss the approach of using machine learning in the diagnosis, classification, and treatment guidelines of hematolymphoid disease, as well as recent progress of artificial intelligence in flow cytometric analysis of hematolymphoid diseases. We review these topics specifically through the potential clinical applications of CellaVision, an automated digital image analyzer of peripheral blood, and Morphogo, a novel artificial intelligence-based bone marrow analyzing system. Adoption of these new technologies will allow pathologists to streamline workflow and achieve faster turnaround time in diagnosing hematological disease.     

Telepathology: current status and future prospects in diagnostic histopathology

Telepathology is the process of diagnostic histopathology performed on digital images viewed on a display screen rather than by conventional glass slide light microscopy. The technology of telepathology has radically improved over the past 5 years so that it is no longer the limiting factor in the diagnostic process. This review looks at the resources needed for dynamic and static telepathology, including image quality, computers and software interfaces, means of transmission and human resources. It critically analyses 32 published trials of telepathology, including some large prospective studies, in all areas of diagnostic histopathology including intraoperative frozen sections, routine and referral cases. New developments, including internet solutions and virtual microscopy, are described and there is analysis of the economics of telepathology within health care systems. The review concludes that all the necessary technology for telepathology is available, there is strong published evidence for a diagnostic accuracy comparable with glass slide diagnosis, in many contexts there is a clear-cut economic argument in favour of telepathology, and that the technique should now be integrated into mainstream diagnostic histopathology.     

Digital Pathology Consultations—a New Era in Digital Imaging, Challenges and Practical Applications

Digital pathology has grown dramatically in the last 10 years and has created opportunities to not only support the triaging of difficult cases among specialists within an organization, but also enable remote pathology consultations with external organizations across the world. This study investigated one organization's need for a vendor agnostic Digital Pathology Consultation workflow solution that overcomes the challenges associated with the transfer of large studies across a local area network or across the Internet. The organization investigated is a large multifacility healthcare organization that consists of 20 hospitals spread across a wide geographical area. The organization has one of the largest academic pathology departments in the USA, with more than 100 diagnostic anatomic pathologists. This organization developed a set of web-based tools to support the workflow of digital pathology consultations and allow the viewing of whole slide images. The challenges and practical implementations of two different use cases are addressed: the occasional end user (professional or patient) requesting a second opinion and the external laboratory or hospital looking for an established consultative relationship with a large volume of cases. The solution presented in this study addresses the challenges associated with the distribution of large images and the lack of established imaging standards, while providing for a convenient and secure portal for pathologist report entry and distribution.     

Anatomic pathology laboratory information systems: a review

The modern anatomic pathology laboratory depends on a reliable information infrastructure to register specimens, record gross and microscopic findings, regulate laboratory workflow, formulate and sign out report(s), disseminate them to the intended recipients across the whole health system, and support quality assurance measures. This infrastructure is provided by the Anatomical Pathology Laboratory Information Systems (APLIS), which have evolved over decades and now are beginning to support evolving technologies like asset tracking and digital imaging. As digital pathology transitions from "the way of the future" to "the way of the present," the APLIS continues to be one of the key effective enablers of the scope and practice of pathology. In this review, we discuss the evolution, necessary components, architecture and functionality of the APLIS that are crucial to today's practicing pathologist and address the demands of emerging trends on the future APLIS.     

Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies

By imaging large numbers of slides automatically at high resolution, modem automated whole slide imaging (WSI) systems have the potential to become useful tools in pathology practice. This article describes a pilot validation study for use of automated high-speed WSI systems for surgical pathology quality assurance (QA). This was a retrospective comparative study in which 24 full genitourinary cases (including 47 surgical parts and 391 slides) were independently reviewed with traditional microscopy and whole slide digital images. Approximately half the cases had neoplasia in the diagnostic line. At the end of the study, diagnostic discrepancies were evaluated by a pathology consensus committee. The study pathologists felt that the traditional and WSI methods were comparable for case review. They reported no difference in perceived case complexity or diagnostic confidence between the methods. There were 4 clinically insignificant discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI review. Of the 2 discrepancies reported by the WSI method, the committee agreed with the reviewer once and the original report once. At the end of the study, the participants agreed that automated WSI is a viable potential modality for surgical pathology QA, especially in multifacility health systems that would like to establish interfacility QA. The participants felt that major issues limiting the implementation of WSI-based QA did not involve image acquisition or quality but rather image management issues such as the pathologist's interface, the hospital's network, and integration with the laboratory information system.     

The virtual case: a new method to completely digitize cytological and histological slides

The purpose of this study was to present a new method for handling histological/cytological cases. Thanks to the introduction of information technology in pathology, including the amenities afforded by robotic microscopes and digital imaging, tissue slides can be represented and evaluated using digital techniques in order to construct virtual cases through completely automated procedures. A virtual case (VC) is composed of a collection of digital images representing a histological/cytological slide at all magnification levels together with all relevant clinical data. In the present study, we describe an automated system to manage robotic microscope and image acquisition for the proper construction of VCs. These can then be viewed on a computer by means of an interface ("user-friendly") that allows one to select the more appropriate fields and to examine them at different magnifications, rapidly going from panoramic views to high resolution and vice versa. In comparison with glass slides, VCs have several advantages arising from their digital nature and can be considered a common platform for a wide range of applications such as teleconsultation, education, research, and quality control and proficiency tests.     

Primary histologic diagnosis using automated whole slide imaging: a validation study

Background  

Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution.     

Critical comparison of 31 commercially available digital slide systems in pathology

Advances in new technologies for complete slide digitization in pathology have allowed the appearance of a wide spectrum of technologic solutions for whole-slide scanning, which have been classified into motorized microscopes and scanners. This article describes technical aspects of 31 different digital microscopy systems. The most relevant characteristics of the scanning devices are described, including the cameras used, the speed of digitization, and the image quality. Other aspects, such as the file format, the compression techniques, and the solutions for visualization of digital slides, (including diagnosis-aided tools) are also considered. Most of the systems evaluated allow a high-resolution digitization of the whole slide within about 1 hour using a x40 objective. The image quality of the current virtual microscopy systems is suitable for clinical, educational, and research purposes. The efficient use of digital microscopy by means of image analysis systems can offer important benefits to pathology departments.     

Concordance between whole-slide imaging and light microscopy for routine surgical pathology

The use of high-resolution digital images of histopathology slides as a routine diagnostic tool for surgical pathology was investigated. The study purpose was to determine the diagnostic concordance between pathologic interpretations using whole-slide imaging and standard light microscopy. Two hundred fifty-one consecutive surgical pathology cases (312 parts, 1085 slides) from a single pathology service were included in the study after cases had been signed out and reports generated. A broad array of diagnostic challenges and tissue sources were represented, including 52 neoplastic cases. All cases were digitized at ×20 and presented to 2 pathologists for diagnosis using whole-slide imaging as the sole diagnostic tool. Diagnoses rendered by the whole-slide imaging pathologists were compared with the original light microscopy diagnoses. Overall concordance between whole-slide imaging and light microscopy as determined by a third pathologist and jury panel was 96.5% (95% confidence interval, 94.8%-98.3%). Concordance between whole-slide imaging pathologists was 97.7% (95% confidence interval, 94.7%-99.2%). Five cases were discordant between the whole-slide imaging diagnosis and the original light microscopy diagnosis, of which 2 were clinically significant. Discordance resulted from interpretive criteria or diagnostic error. The whole-slide imaging modality did not contribute to diagnostic differences. Problems encountered by the whole-slide imaging pathologists primarily involved the inability to clearly visualize nuclear detail or microscopic organisms. Technical difficulties associated with image scanning required at least 1 slide be rescanned in 13% of the cases. Technical and operational issues associated with whole-slide imaging scanning devices used in this study were found to be the most significant obstacle to the use of whole-slide imaging in general surgical pathology.     

Digital imaging in pathology: theoretical and practical considerations, and applications

Digital imaging is rapidly replacing photographic prints and Kodachromes for pathology reporting and conference purposes. Advanced systems linked to computers allow greater versatility and speed of turn-around as well as lower costs, allowing the incorporation of macroscopic and microscopic pictures into routine pathology reports and publications. Digital images allow transmission to remote sites via the Internet for primary diagnosis, consultation, quality assurance and educational purposes and can be stored and disseminated in CD-ROMs. Total slide digitisation is now a reality and has the potential to replace glass slides to a large extent. There are extensive applications of digital images in education and research, allowing more objective and automated quantitation of a variety of morphological and immunohistological parameters. Three-dimensional images of gross specimens can be developed and posted on websites for interactive educational programs and preliminary reports indicate that medical vision systems are a reality and can provide for automated computer generated histopathological diagnosis and quality assurance.     

Whole slide images for primary diagnostics of gastrointestinal tract pathology: a feasibility study

During the last decade, whole slide images have been used in many areas of pathology such as teaching, research, digital archiving, teleconsultation, and quality assurance testing. However, whole slide images have as yet not much been used for up-front diagnostics because of the lack of validation studies. The aim of this study was, therefore, to test the feasibility of whole slide images for diagnosis of gastrointestinal tract specimens, one of the largest areas of diagnostic pathology. One hundred gastrointestinal tract biopsies and resections that had been diagnosed using light microscopy 1 year before were rediagnosed on whole slide images scanned at ×20 magnification by 5 pathologists (all reassessing their own cases), having the original clinical information available but blinded to their original light microscopy diagnoses. The original light microscopy and whole slide image-based diagnoses were compared and classified as concordant, slightly discordant (without clinical consequences), and discordant. The diagnoses based on light microscopy and the whole slide image-based rediagnoses were concordant in 95% of the cases. Light microscopy and whole slide image diagnosis in the remaining 5% of cases were slightly discordant, none of these were with clinical or prognostic implications. Up-front histopathologic diagnosis of gastrointestinal biopsies and resections can be done on whole slide images.