Background: Tumor programmed death-ligand 1 (PD-L1) status is useful in determining which patients may benefit from programmed death-1 (PD-1)/PD-L1 inhibitors. However, little is known about the association between PD-L1 status and tumor histopathological patterns. Using deep learning, we predicted PD-L1 status from hematoxylin and eosin (H and E) whole-slide images (WSIs) of nonsmall cell lung cancer (NSCLC) tumor samples. Materials and Methods: One hundred and thirty NSCLC patients were randomly assigned to training (n = 48) or test (n = 82) cohorts. A pair of H and E and PD-L1-immunostained WSIs was obtained for each patient. A pathologist annotated PD-L1 positive and negative tumor regions on the training samples using immunostained WSIs for reference. From the H and E WSIs, over 145,000 training tiles were generated and used to train a multi-field-of-view deep learning model with a residual neural network backbone. Results: The trained model accurately predicted tumor PD-L1 status on the held-out test cohort of H and E WSIs, which was balanced for PD-L1 status (area under the receiver operating characteristic curve [AUC] =0.80, P << 0.01). The model remained effective over a range of PD-L1 cutoff thresholds (AUC = 0.67–0.81, P ≤ 0.01) and when different proportions of the labels were randomly shuffled to simulate interpathologist disagreement (AUC = 0.63–0.77, P ≤ 0.03). Conclusions: A robust deep learning model was developed to predict tumor PD-L1 status from H and E WSIs in NSCLC. These results suggest that PD-L1 expression is correlated with the morphological features of the tumor microenvironment.

Objective: Digital pathology is today a widely used technology, and the digitalization of microscopic slides into whole slide images (WSIs) allows the use of machine learning algorithms as a tool in the diagnostic process. In recent years, “deep learning” algorithms for image analysis have been applied to digital pathology with great success. The training of these algorithms requires a large volume of high-quality images and image annotations. These large image collections are a potent source of information, and to use and share the information, standardization of the content through a consistent terminology is essential. The aim of this project was to develop a pilot dataset of exhaustive annotated WSI of normal and abnormal human tissue and link the annotations to appropriate ontological information. Materials and Methods: Several biomedical ontologies and controlled vocabularies were investigated with the aim of selecting the most suitable ontology for this project. The selection criteria required an ontology that covered anatomical locations, histological subcompartments, histopathologic diagnoses, histopathologic terms, and generic terms such as normal, abnormal, and artifact. WSIs of normal and abnormal tissue from 50 colon resections and 69 skin excisions, diagnosed 2015-2016 at the Department of Clinical Pathology in Linköping, were randomly collected. These images were manually and exhaustively annotated at the level of major subcompartments, including normal or abnormal findings and artifacts. Results: Systemized nomenclature of medicine clinical terms (SNOMED CT) was chosen, and the annotations were linked to its codes and terms. Two hundred WSI were collected and annotated, resulting in 17,497 annotations, covering a total area of 302.19 cm², equivalent to 107,7 gigapixels. Ninety-five unique SNOMED CT codes were used. The time taken to annotate a WSI varied from 45 s to over 360 min, a total time of approximately 360 h. Conclusion: This work resulted in a dataset of 200 exhaustive annotated WSIs of normal and abnormal tissue from the colon and skin, and it has informed plans to build a comprehensive library of annotated WSIs. SNOMED CT was found to be the best ontology for annotation labeling. This project also demonstrates the need for future development of annotation tools in order to make the annotation process more efficient.

Background: Digital pathology has progressed over the last two decades, with many clinical and nonclinical applications. Transplantation pathology is a highly specialized field in which the majority of practicing pathologists do not have sufficient expertise to handle critical needs. In this context, digital pathology has proven to be useful as it allows for timely access to expert second-opinion teleconsultation. The aim of this study was to review the experience of the application of digital pathology to the field of transplantation. Methods: Papers on this topic were retrieved using PubMed as a search engine. Inclusion criteria were the presence of transplantation setting and the use of any type of digital image with or without the use of image analysis tools; the search was restricted to English language papers published in the 25 years until December 31, 2018. Results: Literature regarding digital transplant pathology is mostly about the digital interpretation of posttransplant biopsies (75 vs. 19), with 15/75 (20%) articles focusing on agreement/reproducibility. Several papers concentrated on the correlation between biopsy features assessed by digital image analysis (DIA) and clinical outcome (45/75, 60%). Whole-slide imaging (WSI) only appeared in recent publications, starting from 2011 (13/75, 17.3%). Papers dealing with preimplantation biopsy are less numerous, the majority (13/19, 68.4%) of which focus on diagnostic agreement between digital microscopy and light microscopy (LM), with WSI technology being used in only a small quota of papers (4/19, 21.1%). Conclusions: Overall, published studies show good concordance between digital microscopy and LM modalities for diagnosis. DIA has the potential to increase diagnostic reproducibility and facilitate the identification and quantification of histological parameters. Thus, with advancing technology such as faster scanning times, better image resolution, and novel image algorithms, it is likely that WSI will eventually replace LM.

Background: Pathology report defects refer to errors in the pathology reports, such as transcription/voice recognition errors and incorrect nondiagnostic information. Examples of the latter include incorrect gender, incorrect submitting physician, incorrect description of tissue blocks submitted, report formatting issues, and so on. Over the past 5 years, we have implemented computational algorithms to identify and correct these report defects. Materials and Methods: Report texts, tissue blocks submitted, and other relevant information are retrieved from the pathology information system database. Two complementary algorithms are used to identify the voice recognition errors by parsing the gross description texts to either (i) identify previously encountered error patterns or (ii) flag sentences containing previously-unused two-word sequences (bigrams). A third algorithm based on identifying conflicting information from two different sources is used to identify tissue block designation errors in the gross description; the information on actual block submission is compared with the block designation information parsed from the gross description text. Results: The computational algorithms identify voice recognition errors in approximately 8%–10% of the cases and block designation errors in approximately 0.5%–1% of all the cases. Conclusions: The algorithms described here have been effective in reducing pathology report defects. In addition to detecting voice recognition and block designation errors, these algorithms have also be used to detect other report defects, such as wrong gender, wrong provider, special stains or immunostains performed but not reported, and so on.

Background: The introduction of digital pathology into clinical practice has led to the development of clinical workflows with digital images, in connection with pathology reports. Still, most of the current work is time-consuming manual analysis of image areas at different scales. Links with data in the biomedical literature are rare, and a need for search based on visual similarity within whole slide images (WSIs) exists. Objectives: The main objective of the work presented is to integrate content-based visual retrieval with a WSI viewer in a prototype. Another objective is to connect cases analyzed in the viewer with cases or images from the biomedical literature, including the search through visual similarity and text. Methods: An innovative retrieval system for digital pathology is integrated with a WSI viewer, allowing to define regions of interest (ROIs) in images as queries for finding visually similar areas in the same or other images and to zoom in/out to find structures at varying magnification levels. The algorithms are based on a multimodal approach, exploiting both text information and content-based image features. Results: The retrieval system allows viewing WSIs and searching for regions that are visually similar to manually defined ROIs in various data sources (proprietary and public datasets, e.g., scientific literature). The system was tested by pathologists, highlighting its capabilities and suggesting ways to improve it and make it more usable in clinical practice. Conclusions: The developed system can enhance the practice of pathologists by enabling them to use their experience and knowledge to control artificial intelligence tools for navigating repositories of images for clinical decision support and teaching, where the comparison with visually similar cases can help to avoid misinterpretations. The system is available as open source, allowing the scientific community to test, ideate and develop similar systems for research and clinical practice.