Pathologie (Heidelberg, Germany)最新文献

{"title":"[Pathology and molecular pathology of carcinoma of the penis].","authors":"August Fiegl, Arndt Hartmann, Kerstin Junker, Jan Mink, Robert Stoehr","doi":"10.1007/s00292-024-01402-w","DOIUrl":"https://doi.org/10.1007/s00292-024-01402-w","url":null,"abstract":"<p><p>Penile carcinoma exhibits significant geographic variation in incidence, ranking 30th globally among newly diagnosed cancers with an annual rate of 0.84 cases per 100,000 men. Particularly high incidence rates of up to 2.2 are seen in Latin America, Asia, and Africa, largely due to a high prevalence of HPV, lower circumcision rates, and inadequate hygiene standards.The 2022 WHO classification of urogenital tumors continues to differentiate penile carcinomas based on their HPV status; however, the subdivision of numerous subtypes especially of the HPV(+) carcinomas was abandoned. This article aims to present current knowledge on the carcinogenesis of HPV(+) and HPV(-) penile carcinomas and their precursor lesions as well as updates from the latest WHO classification.Approximately 50% of penile carcinomas are caused by infection with high-risk HPV subtypes, with positive p16 immunohistochemistry serving as a good surrogate marker for HPV(+) tumors. HPV(-) carcinomas frequently show TP53 mutations and are associated with a poorer prognosis.While localized penile carcinomas have a relatively good prognosis, survival rates in metastatic cases remain poor. Neither microsatellite instability nor mismatch-repair deficiency appear to play a role, but up to 62.2% of tumors express PD-L1. Currently, immune checkpoint inhibitors such as Avelumab and Ipilimumab, along with antibody-drug conjugates targeting TROP2 and Nectin‑4, are being tested in clinical trials, potentially leading to the approval of targeted therapies for metastatic penile carcinoma in the future.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clues in dermatopathological diagnostics].","authors":"Almut Böer-Auer","doi":"10.1007/s00292-024-01400-y","DOIUrl":"https://doi.org/10.1007/s00292-024-01400-y","url":null,"abstract":"<p><p>Numerous diagnostic clues are used in routine dermatopathological diagnostics. Ideally, a diagnostic clue can lead directly to a specific diagnosis and save further time-consuming additional diagnostic procedures. This article discusses the concept of \"clues to diagnosis\" starting from its historical beginnings with a review of relevant studies and including current literature. Selected clues to dermatophytosis, psoriasis, and mycosis fungoides are analyzed. In addition, some newer and still little-known dermatopathological clues to inflammatory and infectious skin disease are presented. The aim is to specify the use of clues on the basis of current findings and to draw attention to scientifically sound clues.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Establishment of a German ICCR dataset : Translation and integration of SNOMED CT using the example of TUR-B].","authors":"J Dörenberg, C J Schmidt, T Berlage, R Knüchel-Clarke","doi":"10.1007/s00292-024-01398-3","DOIUrl":"https://doi.org/10.1007/s00292-024-01398-3","url":null,"abstract":"<p><strong>Background: </strong>The structured recording of data from histopathological findings and their interoperability is critical for quality assurance in pathology.</p><p><strong>Materials and methods: </strong>To harmonize the content of the reports, the International Collaboration on Cancer Reporting (ICCR) has defined standardized datasets. These datasets are not yet available in German nationwide. This gap is addressed here using the transurethral bladder resection (TUR-B) dataset as a use case.</p><p><strong>Results: </strong>We describe the process of establishing the datasets by carrying out translation, mapping on SNOMED CT codes, and using SNOMED CTs hierarchy to fill dropdown menus. Furthermore, we identified rules for checking for self-consistency of reports by using the example of the TUR bladder.</p><p><strong>Discussion: </strong>With this article, we have created an example of a German version of the ICCR TUR‑B dataset including mapping to the SNOMED CT terminology. Further activities should include the definition of overarching cancer disease models to further exploit the potential of SNOMED CT.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of a comparative analysis of microsatellite instability and standard mismatch repair protein-deficiency tests in a large cancer cohort.","authors":"András Kiss, Maja L Nádorvári, Janina Kulka, Tamás Barbai, Erzsébet Rásó, István Kenessey, Gábor Lotz, József Tímár","doi":"10.1007/s00292-024-01397-4","DOIUrl":"https://doi.org/10.1007/s00292-024-01397-4","url":null,"abstract":"<p><strong>Background: </strong>Mismatch repair deficiency (dMMR) with microsatellite instability (MSI) is frequent in cancer, particularly in gastrointestinal and endometrial malignancies. The increased tumor mutational burden renders dMMR/MSI tumors suitable targets for immune checkpoint inhibitors-provided the regulatory genetic defect can be detected. dMMR and MSI are considered equally effective predictors of the efficacy of ICIs; however, while dMMR testing is based on detection of missing MMR proteins in immunohistochemistry (IHC), MSI polymerase chain reaction (PCR) testing focuses on the consequences of dMMR at the genomic level.</p><p><strong>Materials and methods: </strong>A retrospective analysis was carried out in a large cancer cohort (n = 1306). dMMR was tested by four IHC reactions (MLH1, PMS2, MSH2, MSH6), and MSI was assessed by pentaplex PCR (BAT-25, BAT-26, MONO-27, NR-21, NR-24) in 703 cases. In 64 cases (5%), technical failures (mostly poor preanalytical fixation) prevented dMMR/MSI testing. Tumors were colorectal (CRC; n: 978), cancer of unknown primary (n: 126), endometrial (n: 39), pancreatic (n: 36), and gastric (n: 33). dMMR was diagnosed as classical, nonclassical, or unusual, depending on IHC.</p><p><strong>Results: </strong>The MSI-high incidence was 12.1% overall and similar in the CRC subcohort. Interestingly, the dMMR incidence was higher in the total cohort (20.3%) and similar in the CRC subcohort. The incidences of proficient MMR (pMMR) and microsatellite stability (MSS) were similar in the total cohort and in the CRC subcohort. A 19.3% discrepancy was found between MMR IHC and MSI PCR for the entire cohort, independent of tumor types. In the case of pMMR, the discrepancy rate for MSS/MSI-low was low (2.0%; entire cohort and the CRC subcohort). However, the discrepancy between dMMR and MSI-high was high within the entire cohort (60.9%) and in the CRC (58.6%) and non-CRC subcohorts (68%). This high discrepancy was not due to tumors with a low T/N ratio. Regarding dMMR phenotypes, classical dMMR had a ~ 60% correlation with MSI-high status, while non-classical dMMR had a much lower and unusual dMMR a very low (< 10%) correlation with MSI-high in the entire cohort and in the CRC subcohort. Overall, the MSI PCR sensitivity for MMR IHC status was very low.</p><p><strong>Conclusion: </strong>dMMR and MSI-high likely result in an increased rate of structurally altered proteins, i.e., neoantigens, and the efficacy of cancer immunotherapies is thus expected to be higher. We compared MMR IHC to MSI PCR in a large cohort of cancer patients to study how PCR test results correlate to MMR IHC. Our data imply that preanalytical factors strongly influence the results of MMR IHC and MSI PCR and may question the current dogma that dMMR phenotype and genetic MSI status are equivalent predictive markers for immunotherapies.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Molecular testing in mesenchymal neoplasms: What, when, and how to test? : A review with a special focus on the value of next-generation immunochemistry as a substitute for molecular testing].","authors":"Abbas Agaimy","doi":"10.1007/s00292-024-01399-2","DOIUrl":"https://doi.org/10.1007/s00292-024-01399-2","url":null,"abstract":"<p><p>With the widespread use of diverse modern molecular testing tools, the last two decades have seen significant advances in the classification of soft tissue neoplasms. Specifically, numerous molecularly defined new entities have been introduced and many established older entities have received more insightful molecular studies that have developed their classification further. The discrepant therapeutic and prognostic implications of this evolving complexity of the nosology of neoplastic diseases make the precise subtyping of soft tissue neoplasms unavoidable. However, these rapid developments of the modern diagnostic molecular pathology did not only offer efficient solutions to many complex classification issues, but they were accompanied by similarly complex and diverse emerging problems. Most importantly, these advances have not only challenged the historical dogma of some phenotypes that were once considered specific, but they also have questioned the value of diagnostic immunohistochemistry compared to emerging modern diagnostic molecular tools. Moreover, the central question of when to test, what to test, and how to test became more confusing. This review addresses the major molecular categories in soft tissue neoplasms, their characteristics, and the criteria to be used for selecting the most appropriate molecular diagnostic tool to be used in individual cases with a special focus on the value of next generation immunohistochemistry as a substitute for molecular testing.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Ecological sustainability of deep learning in pathology : A modeling study].","authors":"Saskia von Stillfried, Peter Boor","doi":"10.1007/s00292-024-01382-x","DOIUrl":"https://doi.org/10.1007/s00292-024-01382-x","url":null,"abstract":"","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstructing 3D histological structures using machine learning (artificial intelligence) algorithms.","authors":"J Báskay, M Kivovics, D Pénzes, E Kontsek, A Pesti, A Kiss, M Szócska, O Németh, P Pollner","doi":"10.1007/s00292-024-01387-6","DOIUrl":"https://doi.org/10.1007/s00292-024-01387-6","url":null,"abstract":"<p><strong>Background: </strong>Histomorphometry is currently the gold standard for bone microarchitectural examinations. This relies on two-dimensional (2D) sections to deduce the spatial properties of structures. Micromorphometric parameters are calculated from these sections based on the assumption of a plate-like 3D microarchitecture, resulting in the loss of 3D structure due to the destructive nature of classical histological processing.</p><p><strong>Materials and methods: </strong>To overcome the limitation of histomorphometry and reconstruct the 3D architecture of bone core biopsy samples from 2D histological sections, bone core biopsy samples were decalcified and embedded in paraffin. Subsequently, 5 µm thick serial sections were stained with hematoxylin and eosin and scanned using a 3DHISTECH PANNORAMIC 1000 Digital Slide Scanner (3DHISTECH, Budapest, Hungary). A modified U‑Net architecture was trained to categorize tissues on the sections. LoFTR feature matching combined with affine transformations was employed to create the histologic reconstruction. Micromorphometric parameters were calculated using Bruker's CTAn software (v. 1.18.8.0, Bruker, Kontich, Belgium) for both histological and microCT datasets.</p><p><strong>Results: </strong>Our method achieved an overall accuracy of 95.26% (95% confidence interval (CI): [94.15%, 96.37%]) with an F‑score of 0.9320 (95% CI: [0.9211, 0.9429]) averaged across all classes. Correlation coefficients between micromorphometric parameters measured on microCT imaging and histological reconstruction showed a strong linear relationship, with Spearman's ρ‑values of 0.777, 0.717, 0.705, 0.666, and 0.687 for bone volume/tissue volume (BV/TV), bone surface/TV, trabecular pattern factor, trabecular thickness, and trabecular separation, respectively. Bland-Altman and mountain plots indicated good agreement between the methods for BV/TV measurements.</p><p><strong>Conclusion: </strong>This method enables examination of tissue microarchitecture in 3D with an even higher resolution than microcomputed tomography (microCT), without losing information on cellularity. However, the limitation of this procedure is its destructive nature, which precludes subsequent mechanical testing of the sample or any further secondary measurements. Furthermore, the number of histological sections that can be created from a single sample is limited.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key considerations when implementing new diagnostic technologies in routine practice.","authors":"Jochen Lennerz","doi":"10.1007/s00292-024-01396-5","DOIUrl":"https://doi.org/10.1007/s00292-024-01396-5","url":null,"abstract":"<p><strong>Background: </strong>The field of pathology is evolving with the integration of advanced and artificial-intelligence-powered diagnostic technologies. However, there remains a significant gap in clearly outlining the key considerations for the effective implementation of these innovations into clinical care.</p><p><strong>Objectives: </strong>The aim of this review was to identify and address the essential aspects required to bridge the implementation gap of new diagnostic technologies in pathology.</p><p><strong>Material and methods: </strong>This review synthesizes key elements from relevant scientific journals, organizational websites, and practical examples from pathology practice. The findings are presented as a structured framework of six key elements, supported by an infographic and illustrative cases from clinical settings.</p><p><strong>Results: </strong>The key elements are: (1) Innovation depends more on the people driving it than on the work it demands, highlighting the importance of team collaboration and communication; (2) in-depth knowledge of the delivery system emphasizing the importance of care, IT, and administrative layers is crucial; (3) data-driven decision-making in healthcare transformation is central, with an emphasis on the process of converting real-world data (RWD) into actionable real-world evidence (RWE); (4) a proven approach for practice transformation uses a structured (utilization management strategy, UMS) framework; (5) a balanced approach toward financial sustainability, including local and systemic financial strategies, is important; and (6)  ensuring safe and effective progress requires a new, collaborative definition of regulatory science, aligning innovation with regulatory oversight to support technological advancements.</p><p><strong>Conclusion: </strong>These key aspects offer a foundational framework for integrating new technologies into healthcare. Although not exhaustive, overlooking them would miss a significant opportunity to enhance patient care.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Microsatellite instability-What should be considered in routine examinations?]","authors":"Wolfgang Dietmaier, Daniela Hirsch, Josef Rüschoff","doi":"10.1007/s00292-024-01392-9","DOIUrl":"10.1007/s00292-024-01392-9","url":null,"abstract":"","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Centers for experimental animal pathology still occupy a small but valuable niche in translational medicine-time for change?]","authors":"Tanja Poth, Peter Schirmacher","doi":"10.1007/s00292-024-01383-w","DOIUrl":"10.1007/s00292-024-01383-w","url":null,"abstract":"<p><p>Since CRISPR/Cas systems can be easily used to establish new genetically engineered mouse models, application of these models in the translational research field to explore predictive and therapeutic approaches for human diseases is rising.Integrative centers for experimental animal pathology, such as the CMCP in Heidelberg and the CEP in Munich, link the veterinary and human pathology discipline and contribute substantially to meaningful study results by combining the technical, research, and diagnostic expertise for phenotyping, evaluating, and interpretating complex animal models in the context of human pathology. They provide high-quality tissue processing in a broad spectrum of standard and specialized tissue-based technologies. The histopathology platform enables animal model evaluation including phenotyping, scoring, and detecting species-specific \"background lesions.\" By providing essential prerequisites for high-quality, reproducible, and sustainable research in translational medicine, facilities for experimental animal pathology optimally fulfill the requirements for publications in top-class professional journals, contribute to the implementation of the 3R principle for animal welfare, and help to reduce costs in the preclinical research.The importance of animal models reflecting human diseases will increase in the future but the requirements for high-quality tissue processing and comparative pathology/morphological phenotyping cannot be met by single facilities in a niche position. To cover the existing gap and expected rising demand in the German and European translational research landscape, further facilities for experimental animal pathology that are integrated in the human pathology environment should be established.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}