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.     

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.     

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.     

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.     

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.     

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.     

Whole-slide imaging in cytopathology: state of the art and future directions

Whole slide imaging (WSI) has been increasingly adopted for digital evaluation of surgical pathology specimens. Unlike histological slides, cytological preparations frequently display a heterogeneous distribution of cells throughout slides in different focal planes sometimes admixed with obscuring material, therefore requiring multiple scanning planes which significantly lengthens image acquisition and evaluation times. Although examination of digital images can be more advantageous than conventional glass slides, the challenges of focusing, scanning and screening cytological specimens and the associated increase in scan times and data storage needs have limited the routine application of WSI in cytopathology practice. Emerging digital systems designed to overcome image acquisition obstacles coupled with artificial intelligence algorithms augmenting screening of digital cytology slides offer innovative solutions to address these limitations. The aim of this review is to critically address the potential benefits and pitfalls of employing WSI in cytopathology practice and to introduce promising state-of-the-art solutions on the horizon.     

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 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.     

Whole-specimen histopathology: a method to produce whole-mount breast serial sections for 3-D digital histopathology imaging

AIMS: To develop a method for preparing diagnostic-quality, whole-mount serial sections of breast specimens while preserving 3-D conformation. This required supporting the fresh specimen prior to breadloafing and refining the conventional tissue processing method. The overall goal is to use digital images of whole-specimen histopathology to improve the estimation of extent of disease. METHODS AND RESULTS: To maintain a 3-D conformation, the specimen is suspended in 3.5% agar at 55 degrees C. The block is sliced at 5-mm intervals. Sectioning is performed after extended fixation in 4% formaldehyde from paraformaldehyde in 0.1 m Millonig's buffer, followed by paraffin processing using a non-routine schedule and extended paraffin infiltration. Whole-mount serial breast sections are produced with features of equal or superior quality to that which can be achieved using conventional methods. The method is compatible with some immunohistochemical stains but requires further optimization for others. CONCLUSIONS: The technique is currently suitable for research applications. With the reduction in processing time achievable with microwave-assisted processing, there is the potential for its use as a routine clinical method. This tool may improve the accuracy of margin estimates and identification of multifocality in breast cancer; further evaluation is necessary.     

Virtual microscopy and digital pathology in training and education

Traditionally, education and training in pathology has been delivered using textbooks, glass slides and conventional microscopy. Over the last two decades, the number of web-based pathology resources has expanded dramatically with centralized pathological resources being delivered to many students simultaneously. Recently, whole slide imaging technology allows glass slides to be scanned and viewed on a computer screen via dedicated software. This technology is referred to as virtual microscopy and has created enormous opportunities in pathological training and education. Students are able to learn key histopathological skills, e.g. to identify areas of diagnostic relevance from an entire slide, via a web-based computer environment. Students no longer need to be in the same room as the slides. New human-computer interfaces are also being developed using more natural touch technology to enhance the manipulation of digitized slides. Several major initiatives are also underway introducing online competency and diagnostic decision analysis using virtual microscopy and have important future roles in accreditation and recertification. Finally, researchers are investigating how pathological decision-making is achieved using virtual microscopy and modern eye-tracking devices. Virtual microscopy and digital pathology will continue to improve how pathology training and education is delivered.     

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.     

Low-contact and high-interconnectivity pathology (LC&HI Path): post-COVID19-pandemic practice of pathology

The COVID-19 pandemic situation may be viewed as an opportunity to accelerate some of the ongoing transformations in modern pathology. This refers primarily to the digitalisation of the practice of tissue and cellular pathology diagnostics. However, it is also an opportunity to analyse the modus operandi of a discipline that has been practised in a similar manner for more than 100 years. The challenge is to define the next generation of interconnectivity tools that would be necessary to achieve a new operational model that, while ensuring low face-to-face interaction between the main players of the diagnostic pipeline, allows maximum interconnectivity to serve our patients and the immediate teaching and research needs associated with clinical tissue/cellular samples. This viewpoint aims to describe what this new paradigm, a low-contact and high-interconnectivity pathology (LC&HC Path) operation, may require in the near future.     

Evaluation of immunohistochemical staining using whole-slide imaging for HER2 scoring of breast cancer in comparison with real glass slides

Whole‐slide imaging (WSI) has been used for education and histological image preservation, and several studies have also reported its validity for practical pathological diagnosis. However, such studies employed materials stained with hematoxylin‐eosin (HE), and very few attempts have been made to use immunohistochemically stained materials for diagnostic purposes. In the present study, we investigated the availability of WSI diagnosis for immunohistochemically stained materials in place of routine glass slides. Thirty pathologists participated in a trial of HER2 expression diagnosis using WSI and compared the results with those obtained by light microscopy. The validity of WSI diagnosis (interobserver agreement) was rated as ‘substantial’ in comparison with glass slide diagnosis (κ‐value = 0.719). There was a tendency for observers to assign higher scores with WSI than with glass slides, probably because WSI requires slides to be scanned into a computer and observed via a monitor. Although we were able to demonstrate the potential utility of WSI for diagnosing immunostained materials, it must be borne in mind that there are some differences in visualization between WSI and glass slides.     

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.