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Nature Communications Oct 2023Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure....
Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure. Determining the tumor types directly from whole-slide images (WSIs) is of great value for glioma diagnosis. This study presents an integrated diagnosis model for automatic classification of diffuse gliomas from annotation-free standard WSIs. Our model is developed on a training cohort (n = 1362) and a validation cohort (n = 340), and tested on an internal testing cohort (n = 289) and two external cohorts (n = 305 and 328, respectively). The model can learn imaging features containing both pathological morphology and underlying biological clues to achieve the integrated diagnosis. Our model achieves high performance with area under receiver operator curve all above 0.90 in classifying major tumor types, in identifying tumor grades within type, and especially in distinguishing tumor genotypes with shared histological features. This integrated diagnosis model has the potential to be used in clinical scenarios for automated and unbiased classification of adult-type diffuse gliomas.
Topics: Adult; Humans; Brain Neoplasms; Deep Learning; Neuropathology; Glioma
PubMed: 37821431
DOI: 10.1038/s41467-023-41195-9 -
Seminars in Cancer Biology Jul 2021Deep Learning (DL) algorithms are a set of techniques that exploit large and/or complex real-world datasets for cross-domain and cross-discipline prediction and... (Review)
Review
Deep Learning (DL) algorithms are a set of techniques that exploit large and/or complex real-world datasets for cross-domain and cross-discipline prediction and classification tasks. DL architectures excel in computer vision tasks, and in particular image processing and interpretation. This has prompted a wave of disruptingly innovative applications in medical imaging, where DL strategies have the potential to vastly outperform human experts. This is particularly relevant in the context of histopathology, where whole slide imaging (WSI) of stained tissue in conjuction with DL algorithms for their interpretation, selection and cancer staging are beginning to play an ever increasing role in supporting human operators in visual assessments. This has the potential to reduce everyday workload as well as to increase precision and reproducibility across observers, centers, staining techniques and even pathologies. In this paper we introduce the most common DL architectures used in image analysis, with a focus on histopathological image analysis in general and in breast histology in particular. We briefly review how, state-of-art DL architectures compare to human performance on across a number of critical tasks such as mitotic count, tubules analysis and nuclear pleomorphism analysis. Also, the development of DL algorithms specialized to pathology images have been enormously fueled by a number of world-wide challenges based on large, multicentric image databases which are now publicly available. In turn, this has allowed most recent efforts to shift more and more towards semi-supervised learning methods, which provide greater flexibility and applicability. We also review all major repositories of manually labelled pathology images in breast cancer and provide an in-depth discussion of the challenges specific to training DL architectures to interpret WSI data, as well as a review of the state-of-the-art methods for interpretation of images generated from immunohistochemical analysis of breast lesions. We finally discuss the future challenges and opportunities which the adoption of DL paradigms is most likely to pose in the field of pathology for breast cancer detection, diagnosis, staging and prognosis. This review is intended as a comprehensive stepping stone into the field of modern computational pathology for a transdisciplinary readership across technical and medical disciplines.
Topics: Breast Neoplasms; Computational Biology; Deep Learning; Diagnostic Imaging; Female; Humans; Image Processing, Computer-Assisted; Pathology, Clinical
PubMed: 32818626
DOI: 10.1016/j.semcancer.2020.08.006 -
Turk Patoloji Dergisi 2023In Turkey, autopsy performers, namely forensic medicine practitioners, are neither pathologists nor have properly received pathology training during residency in...
OBJECTIVE
In Turkey, autopsy performers, namely forensic medicine practitioners, are neither pathologists nor have properly received pathology training during residency in contrast to the Anglo-Saxon model of forensic medicine practices, since the current curriculum of forensic medicine residency lacks adequate training in post-mortem histopathology. Likewise, pathologists lack a specific post-mortem pathology clerkship. In this study, we intended to determine whether forensic physicians in Turkey find themselves competent in post-mortem histopathology or were adequately trained during their residencies.
MATERIAL AND METHOD
Turkish forensic medicine practitioners were administered an online questionnaire whereby self-evaluations of their histopathology knowledge and their views on histopathology training during forensic medicine residency were assessed. The 151 physicians who completed the questionnaire made up the study group.
RESULTS
It was found out that the majority of Turkish forensic medicine practitioners (85.4%) did not find the histopathology training during their residency adequate. Similarly, 85.4% of the participants indicated their incompetence in histopathological examination of post-mortem tissue of any kind, and showed their willingness for further training in pathology. 66.9% strongly agreed that post-mortem histopathology requires training that is distinct from surgical pathology. In case of providing post-mortem histopathology training within the scope of forensic medicine residency, topics such as microscopic morphology of post-mortem changes, histological changes related to injuries, and estimation of wound age are expected to be beneficial to 88.7% 83.4%, and 83.4% of the participants respectively.
CONCLUSION
The current curriculum should be revised in a way that the surgical pathology clerkship meets forensic physicians' needs, so that they can then refer more difficult, non-routine histopathological consultations to pathologists who are also well-trained in postmortem histopathology. Consideration should also be given to establishing a subspecialty training - a master's or doctoral degree programs in forensic pathology.
Topics: Humans; Autopsy; Forensic Medicine; Pathologists; Pathology, Surgical; Turkey
PubMed: 35102540
DOI: 10.5146/tjpath.2022.01569 -
Analytical Chemistry Oct 2019Fourier transform-infrared spectroscopy (FT-IR) represents an attractive molecular diagnostic modality for translation to the clinic, where comprehensive chemical... (Review)
Review
Fourier transform-infrared spectroscopy (FT-IR) represents an attractive molecular diagnostic modality for translation to the clinic, where comprehensive chemical profiling of biological samples may revolutionize a myriad of pathways in clinical settings. Principally, FT-IR provides a rapid, cost-effective platform to obtain a molecular fingerprint of clinical samples based on vibrational transitions of chemical bonds upon interaction with infrared light. To date, considerable research activities have demonstrated competitive to superior performance of FT-IR strategies in comparison to conventional techniques, with particular promise for earlier, accessible disease diagnostics, thereby improving patient outcomes. However, amidst the changing healthcare landscape in times of aging populations and increased prevalence of cancer and chronic disease, routine adoption of FT-IR within clinical laboratories has remained elusive. Hence, this perspective shall outline the significant clinical potential of FT-IR diagnostics and subsequently address current barriers to translation from the perspective of all stakeholders, in the context of biofluid, histopathology, cytology, microbiology, and biomarker discovery frameworks. Thereafter, future perspectives of FT-IR for healthcare will be discussed, with consideration of recent technological advances that may facilitate future clinical translation.
Topics: Bacterial Infections; Biomarkers; Body Fluids; Humans; Pathology, Clinical; Precision Medicine; Spectroscopy, Fourier Transform Infrared; Translational Research, Biomedical
PubMed: 31503460
DOI: 10.1021/acs.analchem.9b02280 -
Expert Review of Molecular Diagnostics 2023Invasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly... (Review)
Review
BACKGROUND
Invasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly sensitive and specific molecular assays that can differentiate between colonized and pathogenic organisms from different clinical specimens.
AREAS COVERED
We reviewed the literature evaluating the current state of molecular diagnostics for invasive fungal infections, focusing on current and novel molecular tests such as polymerase chain reaction (PCR), digital PCR, high-resolution melt (HRM), and metagenomics/next generation sequencing (mNGS).
EXPERT OPINION
PCR is highly sensitive and specific, although performance can be impacted by prior/concurrent antifungal use. PCR assays can identify mutations associated with antifungal resistance, non-Aspergillus mold infections, and infections from endemic fungi. HRM is a rapid and highly sensitive diagnostic modality that can identify a wide range of fungal pathogens, including down to the species level, but multiplex assays are limited and HRM is currently unavailable in most healthcare settings, although universal HRM is working to overcome this limitation. mNGS offers a promising approach for rapid and hypothesis-free diagnosis of a wide range of fungal pathogens, although some drawbacks include limited access, variable performance across platforms, the expertise and costs associated with this method, and long turnaround times in real-world settings.
Topics: Humans; Antifungal Agents; Mycoses; Pathology, Molecular; Fungi; Invasive Fungal Infections; Sensitivity and Specificity
PubMed: 37801397
DOI: 10.1080/14737159.2023.2267977 -
Der Pathologe Feb 2020For lung carcinomas with certain molecular genetic alterations of the ALK, BRAF or EGFR gene, there are targeted therapies that are also approved as first-line therapy.... (Review)
Review
For lung carcinomas with certain molecular genetic alterations of the ALK, BRAF or EGFR gene, there are targeted therapies that are also approved as first-line therapy. Often, only limited sample material from biopsies is available for molecular pathological testing. In some cases, biopsies with standard and immunohistochemical staining have no or too low tumor content to be used for PCR-based examinations or fluorescence in situ hybridization (FISH) analyses. In such cases, cytological preparations such as bronchus brush smears, transbronchial needle aspiration (TBNA), bronchial lavage, puncture smears from lymph node or peripheral metastases, pleural effusion, ascites, and pericardial effusion can be used. Standard stainings such as HE, Pappenheim, and Papanicolaou as well as immunohistological preparations can be used after morphological analysis and confirmatory diagnosis in order to extract DNA from them or to use them for FISH analysis. A cytopathologist marks the tumor cell areas on the slide beforehand. It is only possible to dissect these areas and extract DNA if the proportion of tumor cells is sufficiently high. In order to carry out a FISH analysis with the cytological preparations, the cytopathologist must draw in areas as small as possible with more than 100 tumor cells. Already stained sections are destained before the hybridization reaction. The aim is to achieve comprehensive diagnostics even with limited starting material and to avoid re-biopsies. Between 2016 and July 2019, 1711 next generation sequencing (NGS) and FISH analyses were performed on cytological preparations at the Department of Pathology of the University Hospital of Cologne. The success rate of 85.9% for NGS examinations was slightly higher than the success rate of 82.8% for FISH analyses.
Topics: Biomarkers, Tumor; Biopsy, Fine-Needle; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Pathology, Molecular
PubMed: 31932945
DOI: 10.1007/s00292-019-00733-3 -
American Journal of Clinical Pathology May 2022The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology.... (Review)
Review
OBJECTIVES
The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center.
METHODS
A review of consultation cases at our institution was performed by searching our laboratory information system. The contributing institution's diagnosis was compared with that rendered by the reviewing cytopathologist to assess major and/or minor diagnostic discrepancies.
RESULTS
In total, 928 cases were reviewed with the following distribution: fine-needle aspiration (FNA, 79.4%), exfoliative nongynecologic cytology (18.3%), and cases with both FNA and nongynecologic cytology (2.3%). There were 379 (40.8%) true consults and 549 (59.2%) confirming consults. A total of 586 (63.1%) cases were in agreement with the outside pathologist, 78 (8.4%) cases had major discrepancies, and 264 (28.4%) cases had minor discrepancies. Major discrepancies were most common for pancreas (38.5%), lymph node (11.5%), and soft tissue sites (9.0%).
CONCLUSIONS
Of the cases, 8.4% had major diagnostic discrepancies between the original diagnosis and the consultation diagnosis, which is consistent with reported values in surgical pathology consultation studies. The findings support the importance of second-opinion consultation in cytopathology to guide patient care.
Topics: Biopsy, Fine-Needle; Cytodiagnosis; Humans; Pancreas; Pathology, Surgical; Referral and Consultation
PubMed: 34724037
DOI: 10.1093/ajcp/aqab182 -
Pathologie (Heidelberg, Germany) Jul 2024In recent decades, nephropathology has developed worldwide as a subspeciality of pathology, which requires special methodological and technical equipment to process the... (Review)
Review
In recent decades, nephropathology has developed worldwide as a subspeciality of pathology, which requires special methodological and technical equipment to process the material and specific clinical and pathological expertise to interpret the findings. These special requirements mean that nephropathology is not available at all pathology institutes, but is carried out on a large scale in a few highly specialised centres. The history of nephropathology, or in a narrower sense the specialised histopathological examination of kidney biopsies, began in 1958 with the first use or performance of a kidney biopsy [1]. It thus replaced the practice of urinalysis, which had been common since the Middle Ages, as a diagnostic tool for kidney diseases. Specialised techniques such as immunofluorescence or immunohistology but also electron microscopy are required to assess specific renal changes, for which the examination of renal biopsies is one of the few remaining routine applications today. In Germany and German-speaking countries, the discipline developed thanks to the work of outstanding people in the field of pathology who were primarily involved in this discipline and had the necessary technical and human resources in their laboratories to ensure that these biopsies could be analysed.
Topics: Humans; Kidney Diseases; Biopsy; Kidney; Pathology; Nephrology; Germany
PubMed: 38512473
DOI: 10.1007/s00292-024-01310-z -
Advances in Anatomic Pathology Jul 2020Quantitative biomarkers are key prognostic and predictive factors in the diagnosis and treatment of cancer. In the clinical laboratory, the majority of biomarker... (Review)
Review
Quantitative biomarkers are key prognostic and predictive factors in the diagnosis and treatment of cancer. In the clinical laboratory, the majority of biomarker quantitation is still performed manually, but digital image analysis (DIA) methods have been steadily growing and account for around 25% of all quantitative immunohistochemistry (IHC) testing performed today. Quantitative DIA is primarily employed in the analysis of breast cancer IHC biomarkers, including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu; more recently clinical applications have expanded to include human epidermal growth factor receptor 2/neu in gastroesophageal adenocarcinomas and Ki-67 in both breast cancer and gastrointestinal and pancreatic neuroendocrine tumors. Evidence in the literature suggests that DIA has significant benefits over manual quantitation of IHC biomarkers, such as increased objectivity, accuracy, and reproducibility. Despite this fact, a number of barriers to the adoption of DIA in the clinical laboratory persist. These include difficulties in integrating DIA into clinical workflows, lack of standards for integrating DIA software with laboratory information systems and digital pathology systems, costs of implementing DIA, inadequate reimbursement relative to those costs, and other factors. These barriers to adoption may be overcome with international standards such as Digital Imaging and Communications in Medicine (DICOM), increased adoption of routine digital pathology workflows, the application of artificial intelligence to DIA, and the emergence of new clinical applications for DIA.
Topics: Humans; Image Processing, Computer-Assisted; Pathology, Clinical
PubMed: 32467397
DOI: 10.1097/PAP.0000000000000263 -
Seminars in Diagnostic Pathology Sep 2019From a technical perspective, specimen identity determination in surgical pathology over the last several decades has primarily focused on analysis of repetitive DNA... (Review)
Review
From a technical perspective, specimen identity determination in surgical pathology over the last several decades has primarily focused on analysis of repetitive DNA sequences, specifically microsatellite repeats. However, a number of techniques have recently been developed that have similar, if not greater, utility in surgical pathology, most notably analysis of single nucleotide polymorphism (SNPs) and gene panels by next generation sequencing (NGS). For cases with an extremely limited sample or a degraded sample, sequence analysis of mitochondrial DNA continues to be the method of choice. From a diagnostic perspective, interest in identity determination in surgical pathology is usually centered on resolving issues of specimen provenance due to specimen labeling/accessioning deficiencies and possible contamination, but is also frequently performed in cases for which the patient's clinical course following definitive therapy is remarkably atypical, in cases of an unexpected diagnosis, and by patient request for "peace of mind". However, the methods used for identity determination have a much broader range of applications in surgical pathology beyond tissue provenance analysis. The methods can be used to provide ancillary information for cases in which the histomorphology is not definitively diagnostic, as for example for tumors that have a virtually identical microscopic appearance but for which the differential diagnosis includes synchronous/metachronous tumors versus a metastasis, and for the diagnosis of hydropic early gestations versus hydatidiform molar pregnancies. The methods also have utility in several other clinical settings, for example to rule out a donor-transmitted malignancy in a transplant recipient, to monitor bone marrow transplant engraftment, and to evaluate natural chimerism.
Topics: High-Throughput Nucleotide Sequencing; Humans; Pathology, Surgical
PubMed: 31196743
DOI: 10.1053/j.semdp.2019.06.001