Whole-slide imaging: widening the scope of cytopathology

Whole slide imaging (WSI) is broadening the scope of cytopathology. Whole slide images are being used for telecytology, quality assurance activities (e.g. proficiency testing) and teaching (e.g. digital teaching sets and online virtual atlases). Progress in WSI technology that permits high resolution scanning, z-stacking, and hybrid robotic devices has encouraged the use of this imaging modality for cytology practice, education and research. However, widespread adoption in cytology still depends on overcoming barriers unrelated to cytology and challenges directly related to digitizing cytopathology slides. The aim of this article is to review WSI technology, applications and limitations specific to cytopathology.     

Fibrocartilaginous mesenchymoma of bone: a single‐institution experience with molecular investigations and a review of the literature

Whole slide imaging is being used increasingly in research applications and in frozen section, consultation and external quality assurance practice. Digital pathology, when integrated with other digital tools such as barcoding, specimen tracking and digital dictation, can be integrated into the histopathology workflow, from specimen accession to report sign‐out. These elements can bring about improvements in the safety, quality and efficiency of a histopathology department. The present paper reviews the evidence for these benefits. We then discuss the challenges of implementing a fully digital pathology workflow, including the regulatory environment, validation of whole slide imaging and the evidence for the design of a digital pathology workstation.     

International telecytology: Current applications and future potential

International telecytology can improve patient care by increasing access to regional and international expertise in cytopathology. The majority of international telecytology studies published to date have been based on static telepathology platforms. Overall concordance rates for these studies ranged from 71% to 93%. This is comparable to the concordance rates published for other studies comparing diagnoses made by digital still images to reference glass slides, which vary from 80% to 95%. Static telepathology systems are relatively cheap and easy to use, and have the potential to increase access to international experts in developing countries with limited resources. In contrast, resource‐rich academic and private medical centers can use whole slide digital imaging (WSI) for telecytology consultation, though few studies have been published addressing this topic. International telepathology consultation services with digital whole slide image capabilities have been established at several academic medical centers including the University of Pittsburgh Medical Center (UPMC) and the University of California at Los Angeles (UCLA), through the UCLA Center for Telepathology and Digital Pathology. In a small series of 20 telecytology cases submitted to UCLA from 2014 to 2017 (10 gynecologic and 10 fine needle aspiration cases), a meaningful diagnosis was rendered for 100% of cases, with 100% concordance between the submitting institution, versus consultation diagnosis provided by UCLA. These limited results are promising, and in the future both WSI and static telecytology consultation may have a place serving clinical needs in different practice settings.     

Applications and implications of whole-slide imaging in breast pathology

Technological advances in whole slide imaging (WSI) technology and artificial intelligence (AI) applications in recent years have resulted in increasing adoption of this paradigm shift technology. This brings with it many advantages, new challenges, and potential adaptations to the microscopic assessment of specimens that pathologists need to be aware of. This article describes the applications and implications of WSI within the context of the reporting of breast pathology specimens. Challenging diagnostic entities in digital breast pathology are presented and the key areas in which AI could be useful in breast pathology are highlighted.     

Virtual reality microscope versus conventional microscope regarding time to diagnosis: an experimental study

Aims: To create and evaluate a virtual reality (VR) microscope that is as efficient as the conventional microscope, seeking to support the introduction of digital slides into routine practice. Methods and results: A VR microscope was designed and implemented by combining ultra‐high‐resolution displays with VR technology, techniques for fast interaction, and high usability. It was evaluated using a mixed factorial experimental design with technology and task as within‐participant variables and grade of histopathologist as a between‐participant variable. Time to diagnosis was similar for the conventional and VR microscopes. However, there was a significant difference in the mean magnification used between the two technologies, with participants working at a higher level of magnification on the VR microscope. Conclusions: The results suggest that, with the right technology, efficient use of digital pathology for routine practice is a realistic possibility. Further work is required to explore what magnification is required on the VR microscope for histopathologists to identify diagnostic features, and the effect on this of the digital slide production process.     

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.     

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.     

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.     

The management of implementing a digital pathology workflow

More and more departments are implementing a digital workflow. This overview is intended to provide a high-level rational management approach to navigating some of the major issues that one is likely to encounter. Key stake holder engagement from the main domains: hospital administration, IT and laboratory management and leadership is essential. A business case taking into account local needs is the first step. The impact of a “disruptive” technology on working habits and work flow needs to be assessed and changes need to be resourced and catered for. Choice of scanner and software depends on local needs and also ability for seamless integration in the laboratory information system. Service contracts and redundancy in the eventuality of scanner failure/breakdown is critical and needs to be planned for. Pathologist management should be phased with formal validation and monitoring.     

Digital Pathology: A Tool for 21st Century Neuropathology

Digital pathology represents an electronic environment for performing pathologic analysis and managing the information associated with this activity. The technology to create and support digital pathology has largely developed over the last decade. The use of digital pathology tools is essential to adapt and lead in the rapidly changing environment of 21st century neuropathology. The utility of digital pathology has already been demonstrated by pathologists in several areas including consensus reviews, quality assurance (Q/A), tissue microarrays (TMAs), education and proficiency testing. These utilities notwithstanding, interface issues, storage and image formatting all present challenges to the integration of digital pathology into the neuropathology work environment. With continued technologic improvements, as well as the introduction of fluorescent side scanning and multispectral detection, future developments in digital pathology offer the promise of adding powerful analytic tools to the pathology work environment. The integration of digital pathology with biorepositories offers particular promise for neuropathologists engaged in tissue banking. The utilization of these tools will be essential for neuropathologists to continue as leaders in diagnostics, translational research and basic science in the 21st century.     

Digital pathology: current status and future perspectives

During the last decade pathology has benefited from the rapid progress of image digitizing technology. The improvement in this technology had led to the creation of slide scanners which are able to produce whole slide images (WSI) which can be explored by image viewers in a way comparable to the conventional microscope. The file size of the WSI ranges from a few megabytes to several gigabytes, leading to challenges in the area of image storage and management when they will be used routinely in daily clinical practice. Digital slides are used in pathology for education, diagnostic purposes (clinicopathological meetings, consultations, revisions, slide panels and, increasingly, for upfront clinical diagnostics) and archiving. As an alternative to conventional slides, WSI are generally well accepted, especially in education, where they are available to a large number of students with the full possibilities of annotations without the problem of variation between serial sections. Image processing techniques can also be applied to WSI, providing pathologists with tools assisting in the diagnosis-making process. This paper will highlight the current status of digital pathology applications and its impact on the field of pathology.     

A validation study of whole slide imaging for primary diagnosis of lymphoma

Whole slide imaging (WSI) is being increasingly used worldwide. Although previous studies have asserted the validity of WSI diagnosis, they have primarily targeted only small specimens and excluded cases requiring immunohistochemistry or special staining, such as lymphoma. The purpose of this study was to evaluate the accuracy of WSI diagnosis of lymphoma, for which 240 biopsies and resections of lymphoma cases were selected from the study set of lymphomas. All slides including H&E, immunohistochemical and special staining were digitized using a WSI image scanner. An experienced pathologist performed the WSI diagnoses, which were compared with original diagnoses based on light microscopic examinations. Discrepancy between the two interpretations were classified into three categories: concordance, minor discrepancy (no clinical significance), and major discrepancy (with clinical significance). Overall concordance between the light microscopic and WSI diagnosis was found in 223 cases (92.92%; 95%CI = 88.90–95.82), minor discrepancy in fifteen (6.25%; 95%CI = 3.54–10.10), and major discrepancy in two (0.83%; 95%CI = 0.10–2.98). Diagnosis of lymphoma using WSI appeared to be mostly accurate, suggesting that WSI may be a reliable technology for the diagnosis of lymphoma.     

Medicolegal and regulatory aspects of whole slide imaging-based telepathology

Telepathology is lauded for its potential to overcome geographic barriers and bring expert diagnostic opinions to underserved regions. However, the legal and regulatory aspects governing its use in the United States and abroad are disparate and incomplete. In addition, there is essentially no case law that specifically addressed telepathology. Important issues to consider for the implementation and practice of telepathology, including state and regional licensure requirements, credentialing and privileging, liability and medical malpractice coverage, privacy and security, medical device regulation, and reimbursement for services are reviewed here for several regions, including the United States, Canada, the European Union, and China.     

Integration of digital pathology in multidisciplinary breast site group rounds

Whole slide scanning and digitizing an entire glass slide technology opens multiple opportunities for integration in clinical practice. Clinical applications other than primary diagnosis include the use of digitized slides in multidisciplinary rounds. Integration of this emerging technology requires not only adaptation by pathologists but also investment in infrastructure for hardware and software components, electronic storage solutions, support from clinicians and hospital administration as well as training personal. The process of replacing conventional glass with digitized slides in pathology case presentation in multidisciplinary rounds is discussed highlighting the strengths and weaknesses of this transition. Successful implementation relies heavily on careful preliminary workflow process design and support from leaders within Anatomic Pathology and the cancer center.