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.     

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.     

Fibrocartilaginous mesenchymoma of the distal femur: case report and literature review

A case of a 9-year-old boy with fibrocartilaginous mesenchymoma located in the distal femur is presented. Fibrocartilaginous mesenchymoma is a rare tumor. There have been 17 cases reported since 1984. The presenting complaint was pain and local discomfort. Radiological examination showed lytic and sclerotic lesions located in the distal femur. Magnetic resonance imaging showed that there was no soft tissue expansion. Differential diagnosis included fibrocartilaginous dysplasia, dedifferentiated chondrosarcoma, desmoplastic fibroma, fibrosarcoma and low-grade osteosarcoma. The diagnosis of the tumor in a state hospital would not have been possible. Wide resection of the tumor and resection arthrodesis with an intramedullary nail has yielded good results. The patient has been disease free for 4 years. Pathological diagnosis of this very rare tumor may be challenging; the treatment should be wide resection of the tumor.     

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.     

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.     

Pathological aspects of mucinous cholangiocarcinoma: A single‐center experience and systematic review

Cholangiocarcinoma is a malignant neoplasm originating from the biliary epithelium. Its incidence is highest in Southeast Asia, especially in Thailand. Mucinous intrahepatic cholangiocarcinoma (mucinous iCCA), characterized by an abundant extracellular mucin pool accounting for at least 50% of total tumor volume, is an extremely rare variant of such malignancy and is notorious for rapid progression and dismal prognosis. We conducted an 11‐year retrospective analysis of resected mucinous iCCAs from our institution with a systematic review on mucinous iCCAs and combined hepatocellular‐mucinous cholangiocarcinoma (cHCC‐mCCA). There were four resected mucinous iCCA specimens at our institution (prevalence = 0.5%). Most of the patients were male. The clinicopathological characteristics were variable. The diagnosis of mucinous iCCAs could not be rendered without pathological evaluation. Either intraductal papillary neoplasm or biliary intraepithelial neoplasia was present in three out of four cases. One patient passed away at 11 months following liver resection. A total of 19 mucinous iCCAs and four cHCC‐mCCAs from previously published literature were analyzed. The 1‐year mortality rate of mucinous iCCAs from our series and published literature is 35%. The present study confirmed that mucinous iCCA is an exceedingly uncommon variant of iCCA. The differential diagnoses include metastatic carcinoma with mucinous component and cHCC‐mCCA.     

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.     

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.     

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.     

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.     

Therapy‐related B‐lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature

Therapy related acute lymphoblastic leukemia (t‐ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t‐B‐ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t‐B‐ALL cases with a pre‐B cell immunophenotype. Ph + t‐B‐ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t‐B‐ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t‐B‐ALL have been described in the literature. In the current study, three of four cases with Ph + t‐B‐ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t‐B‐ALL and prior radiation exposure.     

Diagnostic telepathology: long-term experience of a single institution

Objectives The paper reviews the development of the application of telepathology in a department of surgical pathology between 1991 and 2003. The goal of the efforts during this time was to give up the concept of programming a single application, available only between two fixed workstations with sophisticated devices and special software, and to find the virtual largest common denominator for implementing as many different applications as possible with the same basic system.Methods A new telepathology system was designed as a client–server system with a relational database at its centre. The clients interact together by transferring the questions (texts and images) to a record (case) in the database on the server and by transferring the answers to the same record on the database.Results The new open telepathology system iPath () has been very well accepted by many groups around the world. The main application fields are: consultations between pathologists and medical institutions without a pathologist (e.g. for frozen section diagnoses or for surgical diagnoses in hospitals in South Asia or Africa), tumour boards, field studies and distance education ().Conclusions Having observed that with iPath we have succeeded in satisfying all our telepathology needs, we are inclined to put the emphasis on the nature of the tasks being performed, as opposed to the methods or technical means for performing a given task. The three organisation models proposed by Weinstein et al. (2001) [24] can be reduced to only two models: the model of discussion groups and the model of expert groups (virtual institutes).     

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.