Journal of Pathology Clinical Research最新文献

{"title":"Development of a prognostic risk model for clear cell renal cell carcinoma by systematic evaluation of DNA methylation markers: an update after ISUP/WHO 2022 classification","authors":"Selena Odeh,&nbsp;Iryna Samarska,&nbsp;Andres Matoso,&nbsp;Marcella MLL Baldewijns,&nbsp;Christina A Hulsbergen-van de Kaa,&nbsp;Axel Zur Hausen,&nbsp;Manon van Engeland,&nbsp;Leo J Schouten,&nbsp;Kim M Smits","doi":"10.1002/2056-4538.70030","DOIUrl":"10.1002/2056-4538.70030","url":null,"abstract":"<p>Although several prognostic models have been developed for clear cell renal cell carcinoma (ccRCC), these are still suboptimal and there is a need to identify additional prognostic biomarkers. Previously, we developed a prognostic model containing five DNA methylation markers (<i>NEFH</i>, <i>NEURL</i>, <i>GATA5</i>, <i>GREM1</i>, and <i>LAD1</i>) and clinicopathological characteristics based on the TNM 3rd edition and Fuhrman grading system. Here, we evaluated the effect of the recent ISUP/ 2022 WHO revisions on our previous prognostic model by incorporating the new ISUP/WHO standards, TNM 8th edition, and several novel prognostic factors (necrosis, lymphovascular invasion, sarcomatoid and rhabdoid features). Data from 308 ccRCC cases from the Netherlands Cohort Study were included for this study. Clinicopathological factors, novel prognostic factors, and the five methylation markers were analyzed for their individual and combined prognostic value using Kaplan–Meier analyses and Cox proportional hazard models. To compare models, the Akaike information criterion (AIC) and c-statistic were used. All evaluated factors were statistically significantly associated with cause-specific survival. The clinical model using the ISUP and TNM 8th edition performed similarly when compared to the Fuhrman/TNM 3rd edition model (AIC 592, c-statistic 0.63 and AIC 595, c-statistic 0.62, respectively). After addition of the five DNA methylation markers to the ISUP/TNM 8th model, this model was slightly improved (AIC 584, c-statistic 0.70). The addition of necrosis and lymphovascular invasion (LVI) did not further improve these results (AIC 586, c-statistic 0.71 and AIC 588, c-statistic 0.71, respectively). Despite the individual prognostic significance of necrosis, LVI, the presence of sarcomatoid and/or rhabdoid differentiation, ISUP, and TNM 8th edition, these factors did not influence the performance of our prognostic model. The model including the five DNA methylation markers, age at diagnosis, sex, TNM stage (8th edition), ISUP grading, and tumor size was the best performing model, thereby highlighting the potential importance of molecular markers.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchronous endometrial/cervical and ovarian/fallopian tube carcinoma: a genome-wide mutation analysis","authors":"Lihong Li,&nbsp;Mengfei Yao,&nbsp;Luyuan Li,&nbsp;Susheng Shi,&nbsp;Yan Song","doi":"10.1002/2056-4538.70040","DOIUrl":"10.1002/2056-4538.70040","url":null,"abstract":"<p>In this study, we explored the genomic underpinnings of synchronous endometrial and ovarian/fallopian tube carcinoma (SEOC) and synchronous cervical and ovarian/fallopian tube carcinoma (SCOC), focusing on their clonal relationships to discern whether these malignancies represent dual primary tumors (DPTs) or have metastatic origins. We established a cohort comprising 54 SEOC patients and 7 SCOC patients. After selection, 17 patients (12 SEOC and 5 SCOC) underwent comprehensive analysis via whole-exome sequencing. The study encompassed a diverse array of histological subtypes, including high-grade serous carcinoma (HGSC) or uterine serous carcinoma (USC), endometrioid carcinoma exhibiting papillary/mucinous features, dedifferentiated carcinoma (DC), clear cell carcinoma (CCC), HPV-associated cervical squamous cell carcinoma, and HPV-independent cervical adenocarcinoma. Analysis revealed that 58.3% (7 of 12) of SEOC cases and all SCOC cases demonstrated shared mutations. This suggests a clonal relationship and supports a metastatic origin for these tumors. Notably, metastatic SEOC instances included co-occurrences of USC and HGSC in both the endometrium and the ovaries/fallopian tubes, endometrial and ovarian CCC, concurrent endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) with mucinous metaplasia, as well as cases of endometrial DC with ovarian CCC, and both EEC and ovarian DC. Among the SEOC cases classified as metastatic, patients with high-grade tumors and advanced ovarian stage succumbed to their disease, whereas the remainder survived without relapse. In the SCOC cohort, one patient died from the disease. The favorable survival outcomes across varied histotypes suggest that a stage upgrade may not be warranted. Given the favorable clinical outcomes observed, the term ‘trans-tubal spread’ may be more appropriate than ‘metastasis’ in this context to prevent potential overtreatment. Directionality analysis revealed a bidirectional pattern of trans-tubal spread between the uterus/cervix and ovary/fallopian tubes. The presence of dedifferentiated carcinoma confirms the manifestation of dedifferentiation during spread. These findings lend support to the trans-tubal implantation hypothesis and contribute novel insights into the molecular mechanisms underlying tumor dissemination in SEOC and SCOC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages: potential role in skeletal involvement in classic Hodgkin lymphoma","authors":"Maja Dam Andersen,&nbsp;Katharina Wolter,&nbsp;Marie Hairing Enemark,&nbsp;Mette Abildgaard Pedersen,&nbsp;Lars Christian Gormsen,&nbsp;Kristina Lystlund Lauridsen,&nbsp;Jørn Starklint,&nbsp;Stephen Jacques Hamilton-Dutoit,&nbsp;Francesco d'Amore,&nbsp;Maja Ludvigsen,&nbsp;Peter Kamper","doi":"10.1002/2056-4538.70038","DOIUrl":"10.1002/2056-4538.70038","url":null,"abstract":"<p>The biology of tumor spread to bone is poorly understood, not least in classic Hodgkin lymphoma (cHL). We used gene expression profiling and immunohistochemistry to characterize the nodal tumor microenvironment of cHL cases with and without skeletal involvement at diagnosis. Gene expression profiling of 66 pretreatment lymphoma samples revealed that lymph nodes from patients with skeletal cHL (s-cHL) exhibited a higher abundance of cells expressing macrophage markers, particularly M2-like markers, than nodal-only cHL (n-cHL). These markers included <i>CD163</i>, <i>MRC1</i> (<i>CD206</i>), <i>MARCO</i>, and <i>SIGLEC1</i>. Additionally, there was a notable downregulation of genes encoding B-cell-associated markers such as <i>MS4A1</i> (<i>CD20</i>), <i>CD19</i>, <i>PAX5</i>, and <i>CD79A/B</i>. We further evaluated the protein expression of macrophage markers (CD68, CD163, and CD206) and the B-cell marker CD20 in 193 pretreatment lymphoma samples using immunohistochemistry. Our analysis revealed significantly higher expression levels of all three macrophage markers in s-cHL samples compared to n-cHL samples (<i>p</i> &lt; 0.001). Conversely, the expression level of CD20 was significantly lower in s-cHL compared with n-cHL (<i>p</i> &lt; 0.001). All three macrophage markers correlated positively with Ann Arbor stage, indicating their potential involvement in the dissemination of cHL in general. Our findings suggest a potential role for tumor-associated macrophages in the dissemination of cHL to bone.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which descriptor should spread through air spaces (STAS) be incorporated into? T descriptor versus residual tumor classification","authors":"Yedong Mi,&nbsp;Donglai Chen,&nbsp;Zhangqiang Chen,&nbsp;Yue Li,&nbsp;Xiaoxiao Dai,&nbsp;Shanshan Shen,&nbsp;Jian Shu,&nbsp;Yongzhong Li,&nbsp;Lijie Tan,&nbsp;Yiming Mao,&nbsp;Qifeng Ding,&nbsp;Yongbing Chen","doi":"10.1002/2056-4538.70039","DOIUrl":"10.1002/2056-4538.70039","url":null,"abstract":"<p>It has not been determined which descriptor spread through air spaces (STAS) should be incorporated into the context of the ninth Tumor, Node and Metastasis (TNM) staging system: the T or the uncertain resection [R(un)] category. A multicenter retrospective cohort of 807 patients with pathological stage I lung adenocarcinoma was included in this study to assess the feasibility of incorporating STAS into the T descriptor or the R(un) category by analyzing recurrence-free survival (RFS) and overall survival (OS). Decision curve analysis (DCA) was performed to evaluate the standardized net benefit of the proposed T (nT) and that of the proposed residual tumor classification (nR) versus the current staging systems. Log-rank tests indicated that patients with pT1/STAS-positive lung adenocarcinoma had similar RFS and OS to patients with pT2a disease irrespective of R status. Regarding STAS as an indicator for upgrading R0 to R(un), comparable survival was observed between pT1-2a/STAS-positive patients undergoing R0 segmentectomy and pT1-2a patients undergoing R(un) segmentectomy. We further assessed the effects of the combination of STAS with either T or R category on survival in a validation cohort. Subgroup analyses stratified by surgical procedures further identified the consistency of the nT category in discriminating RFS and OS. However, the separation of nR0 and nR(un) disease in pT2a tumors treated by lobectomy or segmentectomy was not sufficiently distinguished. DCA further corroborated a greater predictive capability of nT versus the current T category. In conclusion, STAS might be preferentially considered as an indicator for upgrading pT1 disease into pT2a in the future TNM staging system.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of peritoneal high-grade serous carcinoma after risk-reducing surgery: a systematic review","authors":"Tamar A Gootzen,&nbsp;Anouk B Bouwmeester,&nbsp;Joanne A de Hullu,&nbsp;Jurgen MJ Piek,&nbsp;Jeroen AWM van der Laak,&nbsp;Michiel Simons,&nbsp;Miranda P Steenbeek","doi":"10.1002/2056-4538.70037","DOIUrl":"10.1002/2056-4538.70037","url":null,"abstract":"<p>Germline <i>BRCA1/2</i> pathogenic variant carriers have an increased risk for high-grade serous carcinoma (HGSC) and are therefore advised to have risk-reducing salpingo-oophorectomy around the age of 40. However, a risk of 0.9% to develop peritoneal HGSC remains in these women, which increases to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected. The pathophysiological mechanism that leads to the development of peritoneal HGSC after salpingectomy or salpingo-oophorectomy is still largely unknown. In this systematic review, we aim to provide insights into the pathogenic pathways of peritoneal HGSC after salpingectomy or salpingo-oophorectomy. Therefore, we performed a systematic search for studies investigating pathophysiological mechanisms related to peritoneal HGSC in PubMed and EMBASE. A total of 49 articles were included in this study. Most evidence was found on mechanisms following a tubal origin, such as clonality between STIC and peritoneal HGSC as well as molecular similarities between fallopian tube (FT) epithelium and peritoneal HGSC. Additionally, FT epithelium was shown to adhere to the ovary and could therefore stay present after isolated salpingectomy. There might be a role for the endometrium, as it was observed that serous endometrial intraepithelial carcinoma (SEIC) has a clonal relationship with extra-uterine HGSC. The role of the ovary seems limited, although some mouse models show a role for follicular fluid in the dissemination of malignant cells on the peritoneum. In conclusion, different mechanisms might be responsible for peritoneal HGSC development after bilateral salpingectomy or salpingo-oophorectomy. Most available evidence supports the dissemination of precursor cells originating in the FT. Also, a possible role for the endometrium was found. An ovarian origin seems less likely; however, execution of oophorectomy does not seem obsolete in clinical practice as follicular fluid might promote dissemination and residual tubal tissue can be present on the ovary after salpingectomy.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated tumor-stroma ratio estimation for improved prognostic stratification of squamous cell carcinoma of the oral tongue","authors":"Lixiao Wang,&nbsp;Katrine Sörensen,&nbsp;Philip J Coates,&nbsp;Xiaolian Gu,&nbsp;Nicola Sgaramella,&nbsp;Mustafa Magan Barre,&nbsp;Karin Nylander","doi":"10.1002/2056-4538.70036","DOIUrl":"10.1002/2056-4538.70036","url":null,"abstract":"<p>Squamous cell carcinoma of the oral tongue (SCCOT) represents an aggressive malignancy characterized by high metastatic potential and significant heterogeneity in its tumor microenvironment. The tumor-stroma ratio (TSR) has emerged as a prognostic biomarker, with higher stromal content frequently correlating with worse survival outcomes. Traditional approaches using the standard 50% TSR cutoff may not be optimal for SCCOT, and visual TSR estimation introduces variability during TSR region annotation. This study aimed to develop and validate a dedicated TSR estimation model for SCCOT by incorporating representative TSR regions from the invasive tumor front of whole slide images and to determine the optimal TSR threshold for prognostic stratification. Using hematoxylin and eosin-stained images from The Cancer Genome Atlas as a discovery cohort and whole slide images from Norrland's University Hospital Umea, Sweden (NUS) as a validation cohort, we developed a computational model to estimate TSR. The model demonstrated a high correlation with pathologist-based TSR estimation in both discovery (<i>R</i> = 0.848, <i>p</i> &lt; 0.01) and validation (<i>R</i> = 0.783, <i>p</i> &lt; 0.01) cohorts. The optimal 55% cutoff identified by the model improved prognostic accuracy over the traditional 50% threshold, with patients having high stroma within the tumor invasive front showing worse overall (log-rank <i>p</i> = 0.006) and disease-specific (log-rank <i>p</i> = 0.016) survival. Our computational TSR model for SCCOT demonstrates that automated TSR estimation enhances prognostic accuracy at an optimal cutoff of 55%, contributing to more precise risk stratification and potentially enabling personalized treatment strategies in SCCOT management.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronan accumulation is associated with reduced hyaluronidase expression in renal cell carcinoma, with CD44, HAS1, and HYAL2 emerging as prognostic markers","authors":"Otto Jokelainen,&nbsp;Teemu Rintala,&nbsp;Satu Remes,&nbsp;Sanna Pasonen-Seppänen,&nbsp;Timo K Nykopp,&nbsp;Reijo Sironen","doi":"10.1002/2056-4538.70035","DOIUrl":"10.1002/2056-4538.70035","url":null,"abstract":"<p>Hyaluronan (HA), a large extracellular matrix glycosaminoglycan, is associated with malignant features in several human cancers. The accumulation of HA in renal cell carcinomas (RCC) correlates with unfavorable outcomes, higher tumor grade, and more advanced disease stages. However, the mechanisms responsible for HA buildup in these neoplasms remain unclear, and studies on the expression of hyaluronan-metabolizing and -degrading enzymes are either lacking or conflicting. This study aims to address this knowledge gap. Formalin-fixed paraffin-embedded (FFPE) RCC samples of various histological subtypes from 315 patients were immunohistochemically stained for CD44 (the main receptor of HA), hyaluronan-synthesizing enzymes HAS1–3, and degrading enzymes HYAL1–2. Protein expression levels were correlated with clinicopathological variables and their prognostic significance was evaluated. Additionally, the mRNA expression levels of these proteins were examined using RNA extracted from the same samples and publicly available data from the cancer genome atlas (TCGA). CD44 protein expression was associated with increased tumoral HA content, poor prognosis, higher tumor grade, advanced stage, and sarcomatoid/rhabdoid changes. HYAL1 and HYAL2 protein levels were reduced in HA-positive tumors, and low HYAL2 expression predicted worse prognosis. Elevated HAS2 protein expression was associated with poor differentiation, while low HAS1 protein levels were associated with reduced survival. mRNA levels of <i>CD44</i> and <i>HYAL2</i> correlated with their respective protein expression levels, and <i>CD44</i> mRNA expression was also associated with HA content. In RCC, HA accumulation appears to be primarily driven by decreased degradation. HAS1 and HYAL2 were identified as novel prognostic biomarkers. These findings provide new insights into HA metabolism in RCC and open potential avenues for better understanding and management of these tumors.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging deep learning to discover interpretable cellular spatial biomarkers for prognostic predictions based on hepatocellular carcinoma histology","authors":"Huijuan Hu,&nbsp;Tianhua Tan,&nbsp;Yerong Liu,&nbsp;Wei Liang,&nbsp;Wei Zhang,&nbsp;Jinsong Zhang,&nbsp;Ju Cui,&nbsp;Jinghai Song,&nbsp;Xuefei Li","doi":"10.1002/2056-4538.70033","DOIUrl":"10.1002/2056-4538.70033","url":null,"abstract":"<p>The spatial structure of various cell types in the tumour microenvironment (TME) can provide valuable insights into disease progression. However, identifying the spatial organization of diverse cell types that significantly correlates with patient prognosis remains challenging. In this study, enabled by deep learning-based cell segmentation and recognition, we developed a computational pipeline to systematically quantify the spatial distribution features of tumour cells, stromal cells, and lymphocytes in haematoxylin and eosin (H&amp;E)-stained pathological images of hepatocellular carcinoma (HCC). We identified six cellular spatial features that consistently and significantly correlated with the overall survival of patients in two independent HCC patient cohorts, The Cancer Genome Atlas Program cohort and the Beijing Hospital cohort. Each threshold for patient stratification was the same for both cohorts, and the six features independently served as prognostic indicators when individually analysed alongside clinical variables. Furthermore, the combination of features such as the mean value of cellular diversity around stromal cells (StrDiv-M), the median distance between all cells (CellDis-MED), and the median value of variation coefficient of the distance around stromal cells and their neighbours (CvStrDis-MED) could further stratify the patient prognosis. In addition, incorporating cell spatial features with another clinical feature, microvascular invasion improved prognostic stratification efficacy for patients from both cohorts. In conclusion, by quantifying the cellular spatial organization features in the HCC TME, we discovered novel biomarkers for evaluating tumour prognosis. These findings could promote mechanistic studies of the cellular spatial organization within the HCC TME and potentially guide future clinical treatment.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entropy and expertise: assessing changes in pathologists' language over time using the UK Liver Pathology External Quality Assessment scheme","authors":"Jonathan P Callaghan,&nbsp;Katrina Z Freimane,&nbsp;Rachel M Brown,&nbsp;Alyn L Cratchley,&nbsp;Timothy J Kendall","doi":"10.1002/2056-4538.70032","DOIUrl":"10.1002/2056-4538.70032","url":null,"abstract":"<p>External Quality Assessment (EQA) schemes are an important quality assurance tool and aim to ensure consistency among histopathologists. In this study, we use Shannon entropy as a novel metric to evaluate linguistic variability in the UK Liver Pathology EQA scheme. Analysing free-text responses by participants over a decade, we aimed to quantify language trends in morphological assessments and clinicopathological diagnoses. Accounting for an increasing word count and when pathologists joined the scheme, our findings reveal a significant increase in entropy of morphological assessments over time, indicating growing linguistic diversity that may reflect the increasing complexity of liver pathology. Entropy of clinicopathological diagnoses over the same period did not provide clear evidence for convergent diagnostic language. High entropy corresponded to cases that elicited more diverse responses and could be considered more challenging, highlighting the utility of this method to identify potential areas for targeted education. We demonstrate entropy as a novel tool to analyse pathologist language and enhance quality assurance in the evolving pathology landscape.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quantitative tumor-wide analysis of morphological heterogeneity of colorectal adenocarcinoma","authors":"Mihnea P Dragomir,&nbsp;Vlad Popovici,&nbsp;Simon Schallenberg,&nbsp;Martina Čarnogurská,&nbsp;David Horst,&nbsp;Rudolf Nenutil,&nbsp;Fred Bosman,&nbsp;Eva Budinská","doi":"10.1002/2056-4538.70034","DOIUrl":"10.1002/2056-4538.70034","url":null,"abstract":"<p>The intertumoral and intratumoral heterogeneity of colorectal adenocarcinoma (CRC) at the morphologic level is poorly understood. Previously, we identified morphological patterns associated with CRC molecular subtypes and their distinct molecular motifs. Here we aimed to evaluate the heterogeneity of these patterns across CRC. Three pathologists evaluated dominant, secondary, and tertiary morphology on four sections from four different FFPE blocks per tumor in a pilot set of 22 CRCs. An AI-based image analysis tool was trained on these tumors to evaluate the morphologic heterogeneity on an extended set of 161 stage I–IV primary CRCs (<i>n</i> = 644 H&amp;E sections). We found that most tumors had two or three different dominant morphotypes and the complex tubular (CT) morphotype was the most common. The CT morphotype showed no combinatorial preferences. Desmoplastic (DE) morphotype was rarely dominant and rarely combined with other dominant morphotypes. Mucinous (MU) morphotype was mostly combined with solid/trabecular (TB) and papillary (PP) morphotypes. Most tumors showed medium or high heterogeneity, but no associations were found between heterogeneity and clinical parameters. A higher proportion of DE morphotype was associated with higher T-stage, N-stage, distant metastases, AJCC stage, and shorter overall survival (OS) and relapse-free survival (RFS). A higher proportion of MU morphotype was associated with higher grade, right side, and microsatellite instability (MSI). PP morphotype was associated with earlier T- and N-stage, absence of metastases, and improved OS and RFS. CT was linked to left side, lower grade, and better survival in stage I–III patients. MSI tumors showed higher proportions of MU and TB, and lower CT and PP morphotypes. These findings suggest that morphological shifts accompany tumor progression and highlight the need for extensive sampling and AI-based analysis. In conclusion, we observed unexpectedly high intratumoral morphological heterogeneity of CRC and found that it is not heterogeneity <i>per se</i>, but the proportions of morphologies that are associated with clinical outcomes.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}