Whole Slide Imaging: Technology and Applications Hanna, Matthew G; Parwani, Anil; Sirintrapun, Sahussapont Joseph
Advances in anatomic pathology,
2020-July, Volume:
27, Issue:
4
Journal Article
Peer reviewed
Pathology has benefited from advanced innovation with novel technology to implement a digital solution. Whole slide imaging is a disruptive technology where glass slides are scanned to produce ...digital images. There have been significant advances in whole slide scanning hardware and software that have allowed for ready access of whole slide images. The digital images, or whole slide images, can be viewed comparable to glass slides in a microscope, as digital files. Whole slide imaging has increased in adoption among pathologists, pathology departments, and scientists for clinical, educational, and research initiatives. Worldwide usage of whole slide imaging has grown significantly. Pathology regulatory organizations (ie, College of American Pathologists) have put forth guidelines for clinical validation, and the US Food and Drug Administration have also approved whole slide imaging for primary diagnosis. This article will review the digital pathology ecosystem and discuss clinical and nonclinical applications of its use.
Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require ...pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3–42 in.; resolution, 1280 × 800–3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.
Laboratory medicine has reached the era where promises of artificial intelligence and machine learning (AI/ML) seem palpable. Currently, the primary responsibility for risk-benefit assessment in ...clinical practice resides with the medical director. Unfortunately, there is no tool or concept that enables diagnostic quality assessment for the various potential AI/ML applications. Specifically, we noted that an operational definition of laboratory diagnostic quality - for the specific purpose of assessing AI/ML improvements - is currently missing.
A session at the 3rd Strategic Conference of the European Federation of Laboratory Medicine in 2022 on "
prompted an expert roundtable discussion. Here we present a conceptual diagnostic quality framework for the specific purpose of assessing AI/ML implementations.
The presented framework is termed diagnostic quality model (DQM) and distinguishes AI/ML improvements at the test, procedure, laboratory, or healthcare ecosystem level. The operational definition illustrates the nested relationship among these levels. The model can help to define relevant objectives for implementation and how levels come together to form coherent diagnostics. The affected levels are referred to as scope and we provide a rubric to quantify AI/ML improvements while complying with existing, mandated regulatory standards. We present 4 relevant clinical scenarios including multi-modal diagnostics and compare the model to existing quality management systems.
A
is essential to navigate the complexities of clinical AI/ML implementations. The presented diagnostic quality framework can help to specify and communicate the key implications of AI/ML solutions in laboratory diagnostics.
The establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization ...provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope.
Four slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen's Kappa and determined "true" MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity.
In the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly "substantial" or greater (Kappa = 0.594-0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p = 0.002, 0.012, and 0.001).
This study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy.
Multilocular cystic renal cell carcinoma has been recently excluded from clear cell renal cell carcinoma (CCRCC) category and re-designated as multilocular cystic renal neoplasm of low malignant ...potential (MCRNLMP) due to its uniformly good outcomes. While strict distinction between MCRNLMP from predominantly cystic CCRCC (pc-CCRCC) is being emphasized, the significance of extensive true cystic component in CCRCC has not been investigated. Herein, we analyzed 57 MCRNLMP, 69 pc-CCRCC, and 46 non-cystic CCRCC. There were no statistically significant differences between the three subtypes in age, gender, and laterality. ISUP grades were 1 (73%) or 2 (27%) for MCRNLMP; for pc-CCRCC were 1 (31%), 2 (60%), and 3 (9%); and for non-cystic CCRCC were 1 (9%), 2 (52%), 3 (26%), and 4 (13%). MCRNLMP were either pT stage 1 (91%) or 2 (9%), pT stages for pc-CCRCC were 1 (92.5%), 2 (1.5%), and 3 (6%) and for non-cystic CCRCC were 1 (58.7%), 2 (6.5%), and 3 (34.8%). None of MCRNLMP patients developed recurrences or metastases, and only 1 contralateral kidney tumor and 1 metastasis developed in pc-CCRCC. In contrast, 19 patients with non-cystic CCRCC developed metastases (5-year PFS 58%, CI 38.3–73.5%), and 1 patient died of disease. Monosomy 3 was common in both MCRNLMP (3/3) and pc-CCRCC (6/7). This large series of MCRNLMP confirms its indolent behavior, shows that pc-CCRCC has significantly better prognosis than non-cystic CCRCC and may define the lower grade spectrum of CCRCC. We recommend that the presence and extent of CCRCC cystic component should be documented in the pathology report.
Background: The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle ...aspirations and core biopsies, required rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this technical article, we present a detailed description of our implementation of robotic TC. Methods: Pathology devised the remote robotic TC solution after acknowledging that it would not be cost effective to staff cytotechnologists on-site at the satellite location. Sakura VisionTek was selected as our robotic TC solution. In addition to configuration of the dynamic robotic TC solution, pathology realized integrating the technology solution into operations would require a multidisciplinary effort and reevaluation of existing staffing and workflows. Results: Extensively described are the architectural framework and multidisciplinary process re-design, created to navigate the constraints of our technical, cultural, and organizational environment. Also reviewed are the benefits and challenges associated with available desktop sharing solutions, particularly accounting for information security concerns. Conclusions: Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. Our goal is providing an extensive perspective of the implementation process, particularly technical, cultural, and operational constraints. Through this perspective, our template can serve as an extensible blueprint for other centers interested in implementing robotic TC without on-site cytotechnologists.
Accurate pathologic assessment in placental pathology is mostly dependent on a complete clinical history provided by a clinical team. However, often, the necessary clinical information is lacking, ...and electronic order sets (EOSs), if implemented correctly, create an opportunity for entering consistent and accurate clinical data. In this viewpoint piece, we describe a framework for synoptic EOS in placental pathology. We outline the necessary data and create optional clinical data that get entered as a dropdown menu of free text. While EOSs are the best way to approach and diagnose placenta and other nonneoplastic pathologic specimens, the barriers for implementation include paper requisitions and a cultural mindset resistance. The aspiration for our synoptic EOS is to become an effective tool for communication between proceduralists and pathologists for proper diagnosis of placental specimens. Through our EOS, the appropriate and complete clinical context is conveyed from the clinical teams to the pathologist. The pathologist can easily and rapidly extract the necessary information to render an accurate and precise diagnosis. The captured data likewise become a valuable research resource.
Percutaneous radiofrequency ablation is increasingly used for curative treatment of primary cancers of the kidney. We reviewed our experience of percutaneous sampling performed under computed ...tomographic guidance with fine needle aspiration biopsy (FNAB) and core biopsy (CB), and we report on the complementary roles of these 2 techniques in a series of 351 consecutive patients undergoing radiofrequency ablation for renal neoplasms. Both FNAB and CB were obtained in 290 cases, of which 156 patients (54%) were positive for neoplasm in both specimens, and 27 (9%) were negative for tumor in both specimens. In 58 (20%) patients, the FNABs were positive, but the CBs were negative, and the reverse occurred in 11 patients (4%). When suspicious interpretations by FNAB and CB are included as positives in the calculations, both their complementary nature and the relative higher diagnostic yield of FNAB persisted. In 25 cases with FNABs positive for neoplasm, the CB allowed a more specific tumor classification. The 19 cases of FNAB which were read as negative/benign had corresponding CBs that were also negative/benign in 13 cases; yet, 6 were diagnostic of renal cell carcinoma not otherwise specified (1 case), renal cell carcinoma clear cell/conventional (4 cases), and non-Hodgkin lymphoma (1 case). These and additional findings illustrate the complementary value of the combination of the 2 biopsy methods for a reliable pretherapy morphologic confirmation of specific renal neoplasms. FNAB has relatively greater sensitivity and utility for on-site evaluation, whereas CB provides an additional sample for more specific subclassification and additional studies.
Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology ...departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago. This experience and the large-scale scan operations led to the identification of required framework components of digital pathology operations. The cost of these components for the 2021 digital pathology operations at MSK were studied and calculated to enable an understanding of the operation and benchmark the accompanying costs.
This paper describes the unique infrastructure cost and the costs associated with the digital pathology clinical operation use cases in a large, tertiary cancer center. These calculations can serve as a blueprint for other institutions to provide the necessary concepts and offer insights towards the financial requirements for digital pathology adoption by other institutions.
Background: The use of minimally invasive procedures to obtain material for diagnostic purposes has become more prevalent in recent years. As such, there is increased demand for immediate cytologic ...adequacy assessment of minimally invasive procedures. The array of different locations in which rapid on-site evaluation (ROSE) is expected requires an ever-increasing number of cytology personnel to provide support for adequacy assessment. In our study, we describe the implementation process of a telecytology (TC) system in a high case volume setting and evaluate the performance of this activity. Methods: We performed retrospectively an analysis of all consecutive remote TC ROSE evaluations obtained for 15 months. The specimens were evaluated using a TC system. The ROSE adequacy assessment obtained at the time of the procedure was compared to the final cytopathologist-rendered adequacy assessment when all the material was available for review, including the alcohol-fixed preparations. Results: A total of 8106 distinct cases were analyzed. TC-assisted preliminary adequacy assessment was highly concordant with the final cytopathologist-rendered adequacy assessment. Perfect concordance or accuracy was at 93.1% (7547/8106). The adequacy upgrade rate (inadequate specimen became adequate) was 6.8% (551/8106), and the initial adequacy downgrade (adequate specimen became inadequate) was <0.1% (8/8106). Conclusions: The TC outcome demonstrates high concordance between the initial adequacy assessment and final cytopathologist-rendered adequacy assessment. Adequacy upgrades were minor but, more importantly, our results demonstrate a minimal adequacy downgrade. The process implemented effectively eliminated the need for an attending pathologist to be physically present onsite during a biopsy procedure.
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