High agreement between whole slide imaging and optical microscopy for assessment of HER2 expression in breast cancer: Whole slide imaging for the assessment of HER2 expression

Whole slide imaging (WSI) technology has been used for training, teaching, researching, and remote consultation. Few studies compared HER2 expression using optical microscopy (OM) and WSI evaluations in breast carcinomas. However, no consensus has been achieved comparing both assessments.Material and methodsSections from tissue microarray containing 200 preselected invasive breast carcinomas were submitted to immunohistochemistry applying three anti-HER2 antibodies (HercepTest™, CB11, SP3) and in situ hybridization (DDISH). Slides were evaluated using OM and WSI (Pannoramic MIDI and Viewer, 3DHISTECH). Sensitivity and specificity were calculated comparing the anti-HER2 antibodies and DDISH.ResultsWSI and OM HER2 evaluations agreement was considered good (SP3, k = 0.80) to very good (CB11 and HercepTest™, k = 0.81). WSI evaluation led to higher sensitivity (ranging from 100 of SP3 and HercepTest™ to 97 of CB11) and lower specificity (ranging from 86.4 of SP3 to 89.4 of HercepTest™) compared to OM evaluation (sensitivity ranged from 92.1 of CB11 to 98 of SP3 and specificity ranged from 95.2 of SP3 and HercepTest™ to 97.1 of CB11 and SP3).ConclusionHigh agreement was achieved between WSI and OM evaluations. All three antibodies were highly sensitive and specific using both evaluations. WSI can be considered a useful tool for HER2 immunohistochemical assessment.     

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.     

Back to basics: validation of automated as compared to manual slide staining in the cytopathology laboratory

Regulatory agencies on laboratory accreditation require that a laboratory validate and document an instrument's functionality in its own specific environment, including the capability of the instrument to replace existing processes. Instruments without manufacturer-provided validation protocols must still undergo validation with documentation of the specific method used. This study was performed to validate the Sakura Tissue-Tek DRS 2,000 automated slide stainer.     

Using a web-based system for the continuous distance education in cytopathology

Background

The evolution of information technologies and telecommunications has made the World Wide Web a low cost and easily accessible tool for the dissemination of information and knowledge. Continuous Medical Education (CME) sites dedicated in cytopathology field are rather poor, they do not succeed in following the constant changes and lack the ability of providing cytopathologists with a dynamic learning environment, adaptable to the development of cytopathology. Learning methods including skills such as decision making, reasoning and problem solving are critical in the development of such a learning environment.

Objectives

The objectives of this study are (1) to demonstrate on the basis of a web-based training system the successful application of traditional learning theories and methods and (2) to effectively evaluate users’ perception towards the educational program, using a combination of observers, theories and methods.

Implementation

Trainees are given the opportunity to browse through the educational material, collaborate in synchronous and asynchronous mode, practice their skills through problems and tasks and test their knowledge using the self-evaluation tool. On the other hand, the trainers are responsible for editing learning material, attending students’ progress and organizing the problem-based and task-based scenarios. The implementation of the web-based training system is based on the three-tier architecture and uses an Apache Tomcat web server and a MySQL database server.

Methods

By December 2008, CytoTrainer's learning environment contains two courses in cytopathology: Gynaecological Cytology and Thyroid Cytology offering about 2000 digital images and 20 case sessions. Our evaluation method is a combination of both qualitative and quantitative approaches to explore how the various parts of the system and students’ attitudes work together.

Results

Trainees approved of the course's content, methodology and learning activities. The triangulation of evaluation methods revealed that the training program is suitable for the continuous distance education in cytopathology and that it has improved the trainees’ skills in diagnostic cytopathology.

Conclusions

The web-based training system can be successfully involved in the continuous distance education in cytopathology. It provides the opportunity to access learning material from any place at any time and supports the acquisition of diagnostic knowledge.     

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.     

Adaptive eLearning modules for cytopathology education: A review and approach

Clinical training imposes time and resource constraints on educators and learners, making it difficult to provide and absorb meaningful instruction. Additionally, innovative and personalized education has become an expectation of adult learners. Fortunately, the development of web‐based educational tools provides a possible solution to these challenges. Within this review, we introduce the utility of adaptive eLearning platforms in pathology education. In addition to a review of the current literature, we provide the reader with a suggested approach for module creation, as well as a critical assessment of an available platform, based on our experience in creating adaptive eLearning modules for teaching basic concepts in gynecologic cytopathology. Diagn. Cytopathol. 2016;44:944–951. © 2016 Wiley Periodicals, Inc.     

Utility of whole slide imaging and virtual microscopy in prostate pathology

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.     

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.     

Pericardial cytopathology

Cytopathology diagnosis of three hundred and thirty three pericardial effusions performed between September 1999 and August 2006 were systematically analyzed and compared with the biopsy in 71 cases. We described the clinical circumstances, the etiologies, the cytomorphologic features of the effusions, the role of liquid based cytology and ancillary studies such as immunocytochemistry and the sensitivity of cytopathology compared with histopathology. Among the 57 pericardial tumors, 51 (89%) were metastatic carcinomas--included 42 (73%) adenocarcinomas--, 5 (9%) were malignant lymphomas and one (2%) was a malignant mesothelioma. Cytology of pericardial effusion with ancillary studies enables rapid cytodiagnosis as specific as histodiagnosis provided by biopsy.     

Parathyroid cytopathology

Cytologic criteria for diagnosing parathyroid adenomas and hyperplasia have not been elucidated. This report will present the cytomorphology of parathyroid tissue in the spectrum of normal, hyperplastic, and neoplastic states. We examined clinical needle aspirates from three patients with parathyroid lesions as well as 15 needle aspirations or touch preparations from surgical specimens. The series included three with hyperparathyroidism secondary to chronic renal failure, four with primary chief cell hyperplasia, nine with typical adenomas, and two with atypical adenomas. Normal parathyroid glands were also studied. Most parathyroid lesions could be distinguished from thyroid lesions by frequent thick fragments of cohesive cells with frayed edges and typical nuclear features. In general, the nuclei were small (6-8 mu) and round with regular coarse granular chromatin. Occasional larger nuclei (10-30 mu) with similar chromatin were observed in some cases. Oxyphil cells with abundant granular cytoplasm were present in some cases; one case with mostly oxyphil cells was difficult to differentiate from a thyroid neoplasm. Pseudocolloid was found in seven cases. Criteria for the differentiation between parathyroid hyperplasia and adenomas were not discovered. In addition, the cytology and differential diagnosis of atypical parathyroid adenomas are described and illustrated.     

Pitfalls in pulmonary cytopathology

Lung cancer is the most frequently diagnosed major cancer. Fine‐needle aspiration of lung lesions is a reliable test with a high diagnostic yield, high sensitivity, and high specificity, yet differentiation of reactive pulmonary processes from neoplasms and subclassification of lung neoplasms often poses difficult diagnostic dilemmas. This review outlines potential pitfalls in pulmonary cytology and presents diagnostic tools to assist in the accurate diagnosis. Diagn. Cytopathol. 2011;39:144–154. © 2010 Wiley‐Liss, Inc.     

Diagnostic accuracy in cytopathology

Metastases from pituitary carcinomas are rare lesions that can mimic other tumors on fine-needle aspiration biopsies. Two patients with primary pituitary neoplasms developed cervical lymph node metastases, which were sampled and diagnosed correctly using the fine-needle aspiration biopsy technique. These two cases demonstrate the varied cytologic patterns of pituitary neoplasms, ranging from uniform bland cells to cells with striking anaplastic features. The time period between the onset of symptoms and subsequent metastases is unpredictable as well, underscoring the need for an accurate clinical history before a meaningful cytologic interpretation is made. Diagn Cytopathol 1994; 11:68–73. © 1994 Wiley-Liss, Inc.     

Diagnostic challenges in thyroid cytopathology

Fine needle aspiration (FNA) is a long-standing modality used to obtain diagnostic material from patients with thyroid nodules. However, some common and uncommon situations exist in which diagnostic categorization of an FNA specimen is not straightforward. Diagnostically challenging thyroid lesions are typically either benign entities with cytomorphology that mimics malignancy, or malignant entities with unusual cytomorphology that causes difficulty in classification. Awareness of such diagnostic challenges can help broaden one's differential diagnosis when encountering such lesions on FNA. However, in many instances a definitive diagnosis may not be possible and providing an indeterminate diagnosis is most appropriate.     

Recent advances in pulmonary cytopathology

During the past five years, advances in pulmonary cytopathology have made possible the achievement of several goals, including the diagnosis of pneumonias in immunocompromised hosts, the detection and localization of occult lung cancers in high-risk cigarette smokers, the diagnosis of lesions of the lungs and chest wall by fine-needle aspiration, and the detection of asbestos exposure by sputum cytologic studies. Significant progress has also been made in the application of cell image analysis to the detection of premalignant bronchial epithelial cells in sputum. For the most part, these advances are based on such well-known cytologic procedures as the preparation of thin and evenly distributed smears, prompt fixation, properly controlled and monitored Papanicolaou staining, and thorough screening of slides. Such diligence in laboratory techniques remains the backbone of excellence in pulmonary cytopathology. Cytologic findings should be interpreted with the clinical features of each case in mind, for the practice of pulmonary cytopathology remains an art as well as a science.