OBJECTIVE: The digital transformation of the pathology laboratory is being continuously sustained by the introduction of innovative technologies promoting whole slide image (WSI)-based primary diagnosis. Here, we proposed a real-life benchmark of a pathology-dedicated medical monitor for the primary diagnosis of renal biopsies, evaluating the concordance between the \'traditional\' microscope and commercial monitors using WSI from different scanners.
METHODS: The College of American Pathologists WSI validation guidelines were used on 60 consecutive renal biopsies from three scanners (Aperio, 3DHISTECH and Hamamatsu) using pathology-dedicated medical grade (MG), professional grade (PG) and consumer-off-the-shelf (COTS) monitors, comparing results with the microscope diagnosis after a 2-week washout period.
RESULTS: MG monitor was faster (1090 vs 1159 vs 1181 min, delta of 6-8%, p<0.01), with slightly better performances on the detection of concurrent diseases compared with COTS (κ=1 vs 0.96, 95% CI=0.87 to 1), but equal concordance to the commercial monitors on main diagnosis (κ=1). Minor discrepancies were noted on specific scores/classifications, with MG and PG monitors closer to the reference report (r=0.98, 95% CI=0.83 to 1 vs 0.98, 95% CI=0.83 to 1 vs 0.91, 95% CI=0.76 to 1, κ=0.93, 95% CI=077 to 1 vs 0.93, 95% CI=0.77 to 1 vs 0.86, 95% CI=0.64 to 1, κ=1 vs 0.50, 95% CI=0 to 1 vs 0.50, 95% CI=0 to 1, for IgA, antineutrophilic cytoplasmic antibody and lupus nephritis, respectively). Streamlined Pipeline for Amyloid detection through congo red fluorescence Digital Analysis detected amyloidosis on both monitors (4 of 30, 13% cases), allowing detection of minimal interstitial deposits with slight overestimation of the Amyloid Score (average 6 vs 7).
CONCLUSIONS: The digital transformation needs careful assessment of the hardware component to support a smart and safe diagnostic process. Choosing the display for WSI is critical in the process and requires adequate planning.

UNASSIGNED: The use of standardized structured reports (SSR) and suitable terminologies like SNOMED-CT can enhance data retrieval and analysis, fostering large-scale studies and collaboration. However, the still large prevalence of narrative reports in our laboratories warrants alternative and automated labeling approaches. In this project, natural language processing (NLP) methods were used to associate SNOMED-CT codes to structured and unstructured reports from an Italian Digital Pathology Department.
UNASSIGNED: Two NLP-based automatic coding systems (support vector machine, SVM, and long-short term memory, LSTM) were trained and applied to a series of narrative reports.
UNASSIGNED: The 1163 cases were tested with both algorithms, showing good performances in terms of accuracy, precision, recall, and F1 score, with SVM showing slightly better performances as compared to LSTM (0.84, 0.87, 0.83, 0.82 vs 0.83, 0.85, 0.83, 0.82, respectively). The integration of an explainability allowed identification of terms and groups of words of importance, enabling fine-tuning, balancing semantic meaning and model performance.
UNASSIGNED: AI tools allow the automatic SNOMED-CT labeling of the pathology archives, providing a retrospective fix to the large lack of organization of narrative reports.

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E) stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E stained tissue images for malignant lymphoma.

Identifying organs within histology images is a fundamental and non-trivial step in toxicological digital pathology workflows as multiple organs often appear on the same whole slide image (WSI). Previous works in automated tissue classification have investigated the use of single magnifications, and demonstrated limitations when attempting to identify small and contiguous organs at low magnifications. In order to overcome these shortcomings, we present a multi-magnification convolutional neural network (CNN), called MMO-Net, which employs context and cellular detail from different magnifications to facilitate the recognition of complex organs. Across N=320 WSI from 3 contract research organization (CRO) laboratories, we demonstrate state-of-the-art organ detection and segmentation performance of 7 rat organs with and without lesions: liver, kidney, thyroid gland, parathyroid gland, urinary bladder, salivary gland, and mandibular lymph node (AUROC=0.99-1.0 for all organs, Dice≥0.9 except parathyroid (0.73)). Evaluation takes place at both inter- and intra CRO levels, suggesting strong generalizability performance. Results are qualitatively reviewed using visualization masks to ensure separation of organs in close proximity (e.g., thyroid vs parathyroid glands). MMO-Net thus offers organ localization that serves as a potential quality control tool to validate WSI metadata and as a preprocessing step for subsequent organ-specific artificial intelligence (AI) use cases. To facilitate research in this area, all associated WSI and metadata used for this study are being made freely available, forming a first of its kind dataset for public use.

UNASSIGNED: Deep learning methods have demonstrated remarkable performance in pathology image analysis, but they are computationally very demanding. The aim of our study is to reduce their computational cost to enable their use with large tissue image datasets.
UNASSIGNED: We propose a method called Network Auto-Reduction (NAR) that simplifies a Convolutional Neural Network (CNN) by reducing the network to minimize the computational cost of doing a prediction. NAR performs a compound scaling in which the width, depth, and resolution dimensions of the network are reduced together to maintain a balance among them in the resulting simplified network. We compare our method with a state-of-the-art solution called ResRep. The evaluation is carried out with popular CNN architectures and a real-world application that identifies distributions of tumor-infiltrating lymphocytes in tissue images.
UNASSIGNED: The experimental results show that both ResRep and NAR are able to generate simplified, more efficient versions of ResNet50 V2. The simplified versions by ResRep and NAR require 1.32× and 3.26× fewer floating-point operations (FLOPs), respectively, than the original network without a loss in classification power as measured by the Area under the Curve (AUC) metric. When applied to a deeper and more computationally expensive network, Inception V4, NAR is able to generate a version that requires 4× lower than the original version with the same AUC performance.
UNASSIGNED: NAR is able to achieve substantial reductions in the execution cost of two popular CNN architectures, while resulting in small or no loss in model accuracy. Such cost savings can significantly improve the use of deep learning methods in digital pathology. They can enable studies with larger tissue image datasets and facilitate the use of less expensive and more accessible graphics processing units (GPUs), thus reducing the computing costs of a study.

OBJECTIVE: Deep learning methods have demonstrated remarkable performance in pathology image analysis, but they require a large amount of annotated training data from expert pathologists. The aim of this study is to minimize the data annotation need in these analyses.
METHODS: Active learning (AL) is an iterative approach to training deep learning models. It was used in our context with a Tumor Infiltrating Lymphocytes (TIL) classification task to minimize annotation. State-of-the-art AL methods were evaluated with the TIL application and we have proposed and evaluated a more efficient and effective AL acquisition method. The proposed method uses data grouping based on imaging features and model prediction uncertainty to select meaningful training samples (image patches).
RESULTS: An experimental evaluation with a collection of cancer tissue images shows that: (i) Our approach reduces the number of patches required to attain a given AUC as compared to other approaches, and (ii) our optimization (subpooling) leads to AL execution time improvement of about 2.12×.
CONCLUSIONS: This strategy enabled TIL based deep learning analyses using smaller annotation demand. We expect this approach may be used to build other analyses in digital pathology with fewer training samples.

We believe the switch to a digital pathology (DP) workflow is imminent and it is essential to understand the economic implications of conversion. Many aspects of the adoption of DP will be disruptive and have a direct financial impact, both in short term costs, such as investment in equipment and personnel, and long term revenue potential, such as improved productivity and novel tests. The focus of this whitepaper is to educate pathologists, laboratorians and other stakeholders about the business and monetary considerations of converting to a digital pathology workflow. The components of a DP business plan will be thoroughly summarized, and guidance will be provided on how to build a case for adoption and implementation as well as a roadmap for transitioning from an analog to a digital pathology workflow in various laboratory settings. It is important to clarify that this publication is not intended to list prices although some financials will be mentioned as examples. The authors encourage readers who are evaluating conversion to a DP workflow to use this paper as a foundational guide for conducting a thorough and complete assessment while incorporating in current market pricing. Contributors to this paper analyzed peer-reviewed literature and data collected from various institutions, some of which are mentioned. Digital pathology will change the way we practice through facilitating patient access to expert pathology services and enabling image analysis tools and assays to aid in diagnosis, prognosis, risk stratification and therapeutic selection. Together, they will result in the delivery of valuable information from which to make better decisions and improve the health of patients.

OBJECTIVE: This article presents an automatic image processing framework to extract quantitative high-level information describing the micro-environment of glomeruli in consecutive whole slide images (WSIs) processed with different staining modalities of patients with chronic kidney rejection after kidney transplantation.
METHODS: This four-step framework consists of: 1) approximate rigid registration, 2) cell and anatomical structure segmentation 3) fusion of information from different stainings using a newly developed registration algorithm 4) feature extraction.
RESULTS: Each step of the framework is validated independently both quantitatively and qualitatively by pathologists. An illustration of the different types of features that can be extracted is presented.
CONCLUSIONS: The proposed generic framework allows for the analysis of the micro-environment surrounding large structures that can be segmented (either manually or automatically). It is independent of the segmentation approach and is therefore applicable to a variety of biomedical research questions.
CONCLUSIONS: Chronic tissue remodelling processes after kidney transplantation can result in interstitial fibrosis and tubular atrophy (IFTA) and glomerulosclerosis. This pipeline provides tools to quantitatively analyse, in the same spatial context, information from different consecutive WSIs and help researchers understand the complex underlying mechanisms leading to IFTA and glomerulosclerosis.

The subtype of the papillary thyroid carcinoma tall-cell variant has a worse prognosis than does the conventional papillary type (papillary thyroid carcinoma). The new World Health Organization 2017 classification defines a tall-cell variant as a tumour consisting of over 30% of cells that are two or three times as tall as they are wide. However, thresholds have differed. Our aim was to study how tall cells affect the prognosis of papillary thyroid carcinoma patients and to determine, for such cells, a cut-off percentage. Our cohort included 65 papillary thyroid carcinoma patients who underwent surgery at Helsinki University Hospital between 1973 and 1996: originally, 36 otherwise-matched patient pairs, eventually comprising 34 patients with an adverse outcome plus 31 who had recovered. All samples were digitally scanned and scored by two investigators based on tall cell composition. The cohort was analysed with four tall cell thresholds: 10%, 30%, 50% and 70% with a median follow-up of 22 years. In survival analysis, only the 70% threshold showed a correlation with reduced overall survival, disease-specific survival and relapse-free survival. A correlation also emerged with death from papillary thyroid carcinoma. In multivariate analysis, a 70% cut-off and age at diagnosis significantly affected DSS. Increasing tall cell score correlated with increasing age and extrathyroidal extensions. A tall cell composition of 10%, 30% or 50% showed no correlation with adverse outcome and suggests that the choice of pathologists reporting tall-cell variant should be a 70% threshold.

Diagnostic histopathology departments are experiencing unprecedented economic and service pressures, and many institutions are now considering digital pathology as part of the solution. In this document, a follow on to our case for adoption report, we provide information and advice to help departments create their own clear, succinct, individualised business case for the clinical deployment of digital pathology.