Many studies have examined the diagnostic concordance of whole slide imaging (WSI) and light microscopy (LM) for surgical pathology. In cytopathology, WSI use has been more limited, mainly because of ...technical issues. The aim of this study was to review the literature and determine the overall diagnostic concordance of WSI and LM in cytopathology. A systematic search of PubMed, Scopus, and the Cochrane Library was performed, with data extracted from the included articles. A quality assessment of studies was performed with a modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. The primary outcome was concordance for the diagnoses rendered by WSI and LM as shown by the concordance rate with the original diagnosis, intra‐observer and interobserver concordance with the κ coefficient, or a percentage. Secondary outcomes included the time taken to reach a diagnosis and the quality and perception of WSI. A descriptive survey was provided. Among 1867 publications, a total of 19 studies (1%) were included. Overall, the concordance between WSI and the original diagnosis was 84.1%, the intra‐observer concordance between WSI and LM was 92.5% with a κ coefficient of 0.66, and the interobserver κ coefficient was 0.69. The time to reach a diagnosis was longer with WSI in all studies. The quality of WSI was good, but diagnostic confidence and cytologist preference were higher for LM. In conclusion, the concordance of WSI with LM is acceptable and in line with systematic reviews in surgical pathology. However, the time required for scanning and technical issues represent barriers to complete adoption. It is foreseeable that technical advances and rigorous validation study design will help to improve the diagnostic concordance of WSI with LM in cytopathology.
The diagnostic concordance of whole slide imaging with light microscopy in cytopathology as measured with the intra‐observer κ coefficient is comparable to that of surgical pathology. Some limitations due to the scan time and the time to render a diagnosis can be still barriers to the widespread adoption of whole slide imaging in cytopathology.
One of the most relevant prognostic factors in cancer staging is the presence of lymph node (LN) metastasis. Evaluating lymph nodes for the presence of metastatic cancerous cells can be a lengthy, ...monotonous, and error-prone process. Owing to digital pathology, artificial intelligence (AI) applied to whole slide images (WSIs) of lymph nodes can be exploited for the automatic detection of metastatic tissue. The aim of this study was to review the literature regarding the implementation of AI as a tool for the detection of metastases in LNs in WSIs. A systematic literature search was conducted in PubMed and Embase databases. Studies involving the application of AI techniques to automatically analyze LN status were included. Of 4584 retrieved articles, 23 were included. Relevant articles were labeled into three categories based upon the accuracy of AI in evaluating LNs. Published data overall indicate that the application of AI in detecting LN metastases is promising and can be proficiently employed in daily pathology practice.
Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology ...samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1‐associated protein 1 (BAP1), methylthioadenosine (MTAP), 5‐hydroxymethylcitosine (5‐hmC), glucose transporter 1 (GLUT1), insulin like‐growth factor II messenger RNA–binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin‐dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta‐analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy‐one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval CI, 0.59‐0.71) and a specificity of 0.99 (CI, 0.93‐1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38‐0.57) and 0.62 (CI, 0.53‐0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78‐0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70‐0.90) and 0.65 (CI, 0.41‐0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68‐0.77) and a specificity of 0.90 (CI, 0.84‐0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
The diagnostic biomarkers BAP1 and MTAP by immunohistochemistry and CDKN2A (p16) by fluorescence in situ hybridization (FISH) are reliable markers with superb specificity (close to 1.00) for distinguishing malignant mesothelial cells from reactive mesothelial cells, but none of them are sufficient when used alone because of only moderate sensitivity (0.40‐0.60). The diagnostic power is markedly improved when 2 of the contemporary biomarkers are used, such as a combination of BAP1 loss by immunohistochemistry and CDKN2A (p16) homozygous deletion by FISH. A combined analysis of BAP1 and MTAP loss by immunohistochemistry is also promising.
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of ...PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable.
The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data ...concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04–2.56,
p
= 0.03, I
2
68%, τ
2
0.19 and HR 1.90, CI 1.33–2.70,
p
< 0.001, I
2
0%, τ
2
0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and
BRAFV600E
mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.
Objective
Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption ...remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.
Methods
A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all validation studies designed to evaluate the feasibility of WSI for diagnostic clinical use in pathology. Technical and diagnostic problems encountered with WSI in these studies were recorded.
Results
A total of 45 studies were identified in which technical issues were reported in 15 (33%), diagnostic issues in 8 (18%), and 22 (49%) reported both. Key technical problems encompassed slide scan failure, prolonged time for pathologists to review cases, and a need for higher image resolution. Diagnostic challenges encountered were concerned with grading dysplasia, reliable assessment of mitoses, identification of microorganisms, and clearly defining the invasive front of tumors.
Conclusion
Despite technical advances with WSI technology, some critical concerns remain that need to be addressed to ensure trustworthy clinical diagnostic use. More focus on the quality of the pre-scanning phase and training of pathologists could help reduce the negative impact of WSI technical difficulties. WSI also seems to exacerbate specific diagnostic tasks that are already challenging among pathologists even when examining glass slides with conventional light microscopy.
Kidney transplantation is the best treatment for end-stage renal disease since it offers the greatest survival benefit compared to dialysis. The gap between the number of renal transplants performed ...and the number of patients awaiting renal transplants leads to a steadily increasing pressure on the scientific community. Kidney preimplantation biopsy is used as a component of the evaluation of organ quality before acceptance for transplantation. However, the reliability and predictive value of biopsy data are controversial. Most of the previously proposed predictive models were not associated with graft survival, but what has to be reaffirmed is that histologic examination of kidney tissue can provide an objective window on the state of the organ that cannot be deduced from clinical records and renal functional studies. The balance of evidence indicates that reliable decisions about donor suitability must be made based on the overall picture. This work discusses recent trends that can reduce diagnostic timing and variability among players in the decision-making process that lead to kidney transplants, from the pathologist's perspective.
Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is ...an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death‐ligand 1 (PD‐L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD‐L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta‐analysis we demonstrate a lack of prognostic significance of PD‐L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD‐L1 evaluation and discuss future opportunities such as leveraging digital pathology.
Digital pathology world tour Rizzo, Paola Chiara; Caputo, Alessandro; Maddalena, Eddy ...
DIGITAL HEALTH,
01/2023, Letnik:
9
Book Review, Journal Article
Recenzirano
Odprti dostop
Objective
Digital pathology (DP) is currently in the spotlight and is rapidly gaining ground, even though the history of this field spans decades. Despite great technological progress, the adoption ...of DP for routine clinical diagnostic use remains limited.
Methods
A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all published studies that encompassed any application of DP.
Results
Of 4888 articles retrieved, 4041 were included. Relevant articles were categorized as “diagnostic” (147/4041, 4%) where DP was utilized for routine diagnostic workflow and “non-diagnostic” (3894/4041, 96%) for all other applications. The “non-diagnostic” articles were further categorized according to DP application including “artificial intelligence” (33%), “education” (5%), “narrative” (17%) for reviews and editorials, and “technical” (45%) for pure research publications.
Conclusion
This manuscript provided temporal and geographical insight into the global adoption of DP by analyzing the published scientific literature.
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