Laboratory Investigation最新文献

{"title":"Improved Prognostic Stratification With 2023 International Federation of Gynecology and Obstetrics Staging in Endometrial Cancer Reflecting Poor Prognosis of Aggressive Histological Types and p53 Abnormality","authors":"Miseon Lee ,&nbsp;Heesoo Yoon ,&nbsp;Ujae Kim ,&nbsp;Jun Kang ,&nbsp;Yeon Bi Han ,&nbsp;Keun Ho Lee ,&nbsp;Sung Jong Lee ,&nbsp;Sook Hee Hong ,&nbsp;Dong Hoon Suh ,&nbsp;Kidong Kim ,&nbsp;Jae Hong No ,&nbsp;Yong Beom Kim ,&nbsp;Hyojin Kim ,&nbsp;Ahwon Lee","doi":"10.1016/j.labinv.2025.104189","DOIUrl":"10.1016/j.labinv.2025.104189","url":null,"abstract":"<div><div>This study compares the distribution and prognostic impact of the 2009 and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging systems for endometrial cancer and their impact on the 2022 European Society for Medical Oncology (ESMO) risk classification. Patients were restaged according to the 2009 FIGO staging system, the 2023 FIGO staging system, and the 2023 FIGO staging system with molecular classification. Risk groups were assigned according to the 2022 ESMO guidelines using each staging system. Among 679 patients, 139 (20.5%) experienced stage migration when transitioning from the 2009 FIGO staging system to the 2023 FIGO staging system with molecular classification, with 121 (17.8%) upstaged and 18 (2.7%) downstaged. Most changes were from FIGO stage I to stage II, primarily due to p53 abnormality, aggressive histological type, or extensive/substantial lymphovascular space invasion. Hazard ratios for overall survival, disease-free survival, and event-free survival increased with advancing stage groups in all systems, showing the greatest differences when the 2023 FIGO staging system with molecular classification was used. The newly introduced FIGO stages IC, IIC (both representing aggressive histological types), and IICmp53abn (associated with p53 abnormality) in the 2023 FIGO staging system were associated with worse outcomes, similar to FIGO stage III. The prognostic predictability of the 2022 ESMO risk group was minimally affected by the transition from the 2009 FIGO to the 2023 FIGO staging system, as the factors introduced in the new FIGO system were already incorporated into the 2022 ESMO risk classification. Only 17 (2.5%) patients experienced a change in their assigned risk group. The 2023 FIGO staging system showed improved prognostic stratification over the 2009 FIGO staging system, particularly by reflecting the poor prognosis of aggressive histological types and p53 abnormality.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 9","pages":"Article 104189"},"PeriodicalIF":5.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rigor and Reproducibility of Spatial Transcriptomics Performed on Clinically Sourced Human Tissues","authors":"Kelly D. Smith ,&nbsp;James W. MacDonald ,&nbsp;Xianwu Li ,&nbsp;Emily Beirne ,&nbsp;Galen Stewart ,&nbsp;Theo K. Bammler ,&nbsp;Shreeram Akilesh","doi":"10.1016/j.labinv.2025.104190","DOIUrl":"10.1016/j.labinv.2025.104190","url":null,"abstract":"<div><div>Spatial transcriptomic profiling enables precise quantification of gene expression with simultaneous localization of expression profiles onto tissue structures. Several implementations of these approaches have been released as commercialized platforms that will allow multiple laboratories to improve our understanding of human disease mechanisms. There is also intense interest in applying these methods in clinical trials or as laboratory-developed tests to aid in the diagnosis of disease. However, before these technologies can be broadly deployed in clinical research and diagnostics, it is necessary to thoroughly understand their performance in real-world conditions. In this study, we vet the technical reproducibility, data normalization methods, and assay sensitivity focusing predominantly on one widely used spatial transcriptomics methodology, digital spatial profiling. We also compare its performance with a single molecular imager, a newer platform with single-cell resolution. Using clinically sourced human kidney tissues and biopsies as exemplars, we find that digital spatial profiling exhibits high rigor and reproducibility. We show that normalization approaches can impact the biological interpretation of spatial transcriptomics data. Although there is good concordance between multicellular and single-cell resolution methods, there are tradeoffs in cost, execution time, and sensitivity of detection, which may affect which approach is chosen. Our study lays a practical foundation for the incorporation of spatial transcriptomics methods into clinical workflows.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 9","pages":"Article 104190"},"PeriodicalIF":5.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Analysis of Rectal Cancer Biopsies With the Digital Pathology Segmentation Algorithm QuantCRC Associates With Therapy Response and Recurrence","authors":"Reetesh K. Pai ,&nbsp;Cody Eslinger ,&nbsp;Kenneth Lee ,&nbsp;Lama Farhat Farchoukh ,&nbsp;Daniel Walden ,&nbsp;Oluwadunni Emiloju ,&nbsp;Michael Storandt ,&nbsp;Catherine E. Hagen ,&nbsp;Ashlyn Pfeiffer ,&nbsp;Mohammad Bassam Sonbol ,&nbsp;Daniel Ahn ,&nbsp;Tanios Bekaii-Saab ,&nbsp;Andrew Ness ,&nbsp;Joleen Hubbard ,&nbsp;Christina Wu ,&nbsp;Thomas Westerling-Bui ,&nbsp;Riyue Bao ,&nbsp;Fang-Shu Ou ,&nbsp;Rish K. Pai","doi":"10.1016/j.labinv.2025.104187","DOIUrl":"10.1016/j.labinv.2025.104187","url":null,"abstract":"<div><div>We examined whether QuantCRC, a digital pathology segmentation algorithm, on pretherapy rectal cancer biopsies is associated with pathologic complete response (pCR) to neoadjuvant therapy, recurrence-free survival (RFS), and transcriptomic spatial profiling. QuantCRC was evaluated in an observational cohort of 288 pretherapy biopsies and a separate validation cohort of 37 pretherapy biopsies of rectal adenocarcinoma from patients undergoing neoadjuvant therapy. Associations between QuantCRC features and clinical outcomes, pCR, and RFS were analyzed using multivariable logistic regression and Cox proportional hazards modeling, respectively. QuantCRC variables were also correlated with transcriptomic digital spatial profiling of 37 pretreatment biopsies of cT3N⁺ rectal cancer. QuantCRC-derived lymphocytes per square millimeter of tumor epithelium (tumor-infiltrating lymphocytes [TILs]) was significantly associated with pCR (multivariate odds ratio, 1.05; 95% CI, 1.02-1.10; <em>P</em> = .038). QuantCRC-derived TILs were significantly higher in pretherapy biopsies with pCR (91.3 vs 55.9 lymphocytes/mm²; <em>P</em> = .004). The validation cohort confirmed that only QuantCRC-derived TILs in pretherapy biopsies of rectal cancer were significantly associated with complete response to neoadjuvant therapy. QuantCRC %high tumor grade was independently associated with worse RFS (multivariate hazards ratio, 1.27; 95% CI, 1.09-1.47; <em>P</em> = .002). Patients with ≥10.1% high tumor grade identified by QuantCRC had significantly reduced RFS (5-year RFS 69% vs 83%, log-rank <em>P</em> = .007). Transcriptomic profiling identified high interleukin (IL)-6/JAK/STAT3 signaling within immune cells to be associated with worse RFS (adjusted <em>P</em> = .01). Tumors with low IL-6/JAK/STAT3 expression within immune cells had significantly higher TILs compared with tumors with high expression (median, 152 vs 97 TILs/mm²; <em>P</em> = .039). Biopsy-adapted QuantCRC in pretherapy rectal cancer may be helpful in identifying patients who achieve pCR and are at risk for recurrence.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104187"},"PeriodicalIF":5.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and Genomic Characteristics of Minute Pulmonary Meningothelial-like Nodules","authors":"Haochen Li ,&nbsp;Zhicheng Huang ,&nbsp;Yadong Wang ,&nbsp;Chao Guo ,&nbsp;Xiaoyu Li ,&nbsp;Weixun Zhou ,&nbsp;Sha Wang ,&nbsp;Na Bai ,&nbsp;Hanlin Chen ,&nbsp;Bowen Li ,&nbsp;Daoyun Wang ,&nbsp;Zhibo Zheng ,&nbsp;Zhongxing Bing ,&nbsp;Yang Song ,&nbsp;Yuan Xu ,&nbsp;Guanghua Huang ,&nbsp;Ka Luk Fung ,&nbsp;Lan Song ,&nbsp;Naixin Liang ,&nbsp;Shanqing Li","doi":"10.1016/j.labinv.2025.104188","DOIUrl":"10.1016/j.labinv.2025.104188","url":null,"abstract":"<div><div>Minute pulmonary meningothelial-like nodules (MPMNs) are benign lung lesions with histologic characteristics similar to meningeal epithelium. MPMNs often lead to misdiagnosis for their similar radiologic characteristics to malignant nodules. The pathogenesis of MPMNs remains unclear, and this research primarily focused on mutations in a limited number of genes, lacking a comprehensive analysis of their mutational landscape. We collected 134 MPMNs from 88 patients with pathologic examinations at Peking Union Medical College Hospital in the past 5 years. We performed whole-exome sequencing on 12 MPMNs and 7 adenocarcinoma lesions from 6 patients. In our PUMCH-MPMN cohort, we provided clinical, pathologic, radiologic, and follow-up characteristics of patients with MPMNs. Our study demonstrated the pathologic diagnostic value of 3 classic MPMN diagnostic markers (epithelial membrane antigen, progesterone receptor, and vimentin) and the novel marker somatostatin receptor 2. It also suggested the preoperative differential diagnostic value of positron emission tomography/computed tomography. We also classified MPMNs into 4 types based on different discovery methods and verified the diagnostic value of traditional and novel immunohistochemical markers. We performed whole-exome sequencing and revealed that MPMNs harbor mutations enriched in cell cycle and cytoskeleton assembly pathways. On the other hand, classical meningioma-related mutations, such as <em>NF2</em> mutations, were not detected. These findings provide new evidence for the hypothesis that MPMNs arise from reactive proliferation rather than share a common origin with meningiomas, contributing to a better understanding of MPMNs among clinicians and pathologists, reducing misdiagnosis, and improving patient care.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 9","pages":"Article 104188"},"PeriodicalIF":5.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning–Powered Whole Slide Image Analysis in Cancer Pathology","authors":"Chengrun Dang ,&nbsp;Zhuang Qi ,&nbsp;Tao Xu ,&nbsp;Mingkai Gu ,&nbsp;Jiajia Chen ,&nbsp;Jie Wu ,&nbsp;Yuxin Lin ,&nbsp;Xin Qi","doi":"10.1016/j.labinv.2025.104186","DOIUrl":"10.1016/j.labinv.2025.104186","url":null,"abstract":"<div><div>Pathology is the cornerstone of modern cancer care. With the advancement of precision oncology, the demand for histopathologic diagnosis and stratification of patients is increasing as personalized cancer therapy relies on accurate biomarker assessment. Recently, rapid development of whole slide imaging technology has enabled digitalization of traditional histologic slides at high resolution, holding promise to improve both the precision and efficiency of histopathologic evaluation. In particular, deep learning approaches, such as Convolutional Neural Network, Graph Convolutional Network, and Transformer, have shown great promise in enhancing the sensitivity and accuracy of whole slide image (WSI) analysis in cancer pathology because of their ability to handle high-dimensional and complex image data. The integration of deep learning models with WSIs enables us to explore and mine morphologic features beyond the visual perception of pathologists, which can help automate clinical diagnosis, assess histopathologic grade, predict clinical outcomes, and even discover novel morphologic biomarkers. In this review, we present a comprehensive framework for incorporating deep learning with WSIs, highlighting how deep learning–driven WSI analysis advances clinical tasks in cancer care. Furthermore, we critically discuss the opportunities and challenges of translating deep learning–based digital pathology into clinical practice, which should be considered to support personalized treatment of cancer patients.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104186"},"PeriodicalIF":5.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Receptor–Binding SU(VAR)3-9, Enhancer of Zeste, Trithorax Domain Structural Domain Protein 2 Serves as a Potential Prognostic Biomarker in Mantle Cell Lymphoma","authors":"Yu Zhu ,&nbsp;Binshen Ouyang ,&nbsp;Xuan Wang ,&nbsp;Xu Wang ,&nbsp;Chaofu Wang","doi":"10.1016/j.labinv.2025.104181","DOIUrl":"10.1016/j.labinv.2025.104181","url":null,"abstract":"<div><div>Nuclear receptor–binding SET structural domain protein 2 (NSD2) has been implicated in the pathogenesis of multiple cancers, exhibiting mutations or overexpression that contributes to tumor progression and poor clinical outcomes. In mantle cell lymphoma (MCL), approximately 15% of patients harbor <em>NSD2</em> mutations; however, its clinical significance remains to be fully elucidated. In our study, we analyzed Next Generation Sequencing data from 147 MCL patients and identified <em>NSD2</em> mutations in 8.84% (13/147) of cases, with 92.31% (12/13) demonstrating bone marrow involvement. Immunohistochemical evaluation of NSD2 protein expression in 39 patients revealed that high levels of NSD2 protein expression were associated with higher Mantle Cell Lymphoma International Prognostic Index scores, poorer treatment response, inferior overall survival, and progression-free survival. Furthermore, NSD2 expression is strongly associated with aggressive histologic variants, including elevated c-MYC protein expression and a high Ki-67 proliferation index. Our analysis of the cBioPortal database, encompassing lymphoma patients, uncovered that <em>NSD2</em> mutations are most prevalent in MCL. Specifically, E1099K and T1150A point mutations were linked to poorer prognoses. Additionally, our examination of the Gene Expression Omnibus database (GSE93291) revealed a correlation between <em>NSD2</em> messenger RNA (mRNA) expression levels and <em>MKI67</em>, with elevated <em>NSD2</em> mRNA expression being associated with reduced survival rates. Tumor-infiltrating immune cell analysis with CIBERSORT in GSE93291 revealed the correlation with increased intratumoral regulatory T cells. According to our research, <em>NSD2</em> mutations exhibit extremely aggressive biological behavior, and a worse prognosis is associated with higher levels of NSD2 in both mRNA and protein expression. We believe that NSD2 stands as a valuable prognostic marker and a potential therapeutic target in MCL.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104181"},"PeriodicalIF":5.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maturation-Related and Functional-Associated Phenotypic Profile of Tumor T Cells in Mature/Peripheral T-Cell Neoplasms: Association With the Diagnostic Subtype of the Disease","authors":"F. Javier Morán-Plata ,&nbsp;Noemí Muñoz-García ,&nbsp;Susana Barrena ,&nbsp;Ana Yeguas ,&nbsp;Ana Balanzategui ,&nbsp;Sonia Carretero-Domínguez ,&nbsp;Julio Pozo ,&nbsp;Quentin Lécrevisse ,&nbsp;María González-González ,&nbsp;Paloma Bárcena ,&nbsp;Miguel Alcoceba ,&nbsp;María Herrero-García ,&nbsp;Fernando Solano ,&nbsp;Miriam López-Parra ,&nbsp;Alejandro Martín García-Sancho ,&nbsp;Cristiane de Sá Ferreira-Facio ,&nbsp;Neus Villamor ,&nbsp;Catarina Lau ,&nbsp;Maria Dos Anjos Teixeira ,&nbsp;Vitor Botafogo ,&nbsp;Julia Almeida","doi":"10.1016/j.labinv.2025.104180","DOIUrl":"10.1016/j.labinv.2025.104180","url":null,"abstract":"<div><div>T-cell chronic lymphoproliferative disorders (T-CLPD) are a heterogeneous group of mature T-cell malignancies, the classification of which remains challenging. In this study, we classified tumor cells from 86 patients diagnosed with either T-CLPD (n = 81) or T-cell acute lymphoblastic leukemia (n = 5) into precise functional and maturation-associated compartments, based on their phenotypic similarities with their normal maturation-related and functional associated T-cell counterparts. A database was generated using blood samples from 6 sex- and age-matched healthy donors as a template for normal T-cell subset flow cytometric immunophenotypes, to which tumor cells of individual patients were compared. Except for nodal T follicular–helper cell lymphoma and adult T-cell leukemia/lymphoma, which showed phenotypes overlapping with that of T follicular–helper and T regulatory cells, respectively, all other T-CLPD displayed immunophenotypic profiles consistent with conventional T helper (Th) cells, with different maturation-associated profiles per diagnostic category. These included predominant naive/naive-central memory phenotypes in T-cell prolymphocytic leukemia to terminal effector cytotoxic cellular profiles in T-cell large granular lymphocytic leukemia; other T-CLPD diagnostic categories (mostly Sézary syndrome/mycosis fungoides) resembled the diverse memory T-cell subsets. Interestingly, immunophenotypically less-mature tumor cells (T-cell prolymphocytic leukemia) displayed more heterogeneous Th profiles, whereas those with memory T-cell profiles showed more consistent Th-associated patterns (eg, Th2 or Th17 in Sézary syndrome/mycosis fungoides), and the most mature neoplasms (eg, T-cell large granular lymphocytic leukemia) systematically displayed a Th1-like pattern, reflecting progressively lower plasticity for the more advanced tumor-associated maturation stages. These findings confirm the presence of distinct phenotypic patterns resembling specific maturation-associated and Th-related profiles of normal T cells among distinct diagnostic categories of T-CLPD, which might contribute to a more precise classification of T-CLPD.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104180"},"PeriodicalIF":5.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intelligent Diagnosis of Pancreatic Biopsy From Endoscopic Ultrasound-Guided Fine-Needle Aspiration Via Stimulated Raman Histopathology","authors":"Tao Tan ,&nbsp;Liyang Ma ,&nbsp;Yuheng Guo ,&nbsp;Tianyin Chen ,&nbsp;Lili Meng ,&nbsp;Kuan Luo ,&nbsp;Pinghong Zhou ,&nbsp;Mingyan Cai ,&nbsp;Minbiao Ji ,&nbsp;Hao Hu","doi":"10.1016/j.labinv.2025.104182","DOIUrl":"10.1016/j.labinv.2025.104182","url":null,"abstract":"<div><div>Endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) has become one of the most important preoperative diagnostic methods for pancreatic tumors, but it often faces challenges of redundant sampling from patients and complex tissue processing that hinders timely diagnosis. Intraoperative rapid on-site evaluation is an auxiliary diagnostic technique that helps assess sample quality in real time, but it heavily depends on pathologists and involves subjectivity and complex procedures. Here, we developed a rapid and label-free approach for intraoperative histology on EUS-FNA specimen via deep learning–based stimulated Raman scattering microscopy, aimed at replacing rapid on-site evaluation and providing a more efficient and objective diagnostic approach. Fresh pancreatic EUS-FNA tissues were imaged with stimulated Raman scattering and compared with hematoxylin and eosin staining to identify key histologic features. Using images from 76 patients, a convolutional neural network model was established to identify benign, malignant, and nondiagnostic areas, achieving a validation accuracy &gt;96% on an external test set of 33 cases. Furthermore, gradient-weighted class activation mapping was able to highlight histologic profiles within individual biopsy. Our approach has potential application in efficient intraoperative assessment of pancreatic biopsy through EUS-FNA.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104182"},"PeriodicalIF":5.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Digital Image Analysis for Assessing Cutaneous Fibrosis Correlates With Histopathological Scoring in Patients With Systemic Sclerosis","authors":"Ruben Oganesyan ,&nbsp;Dimitra Pouli ,&nbsp;Bo Shi ,&nbsp;Mary Carns ,&nbsp;Kathleen Dennis-Aren ,&nbsp;Maria E. Teves ,&nbsp;John Varga ,&nbsp;Rosalynn M. Nazarian","doi":"10.1016/j.labinv.2025.104177","DOIUrl":"10.1016/j.labinv.2025.104177","url":null,"abstract":"<div><div>Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by progressive fibrosis of the skin, blood vessels, and internal organs. Accurate assessment of skin fibrosis is essential for disease monitoring and treatment evaluation, yet reliable quantitative methods are lacking. We compared computer-assisted digital image analysis with traditional semiquantitative histopathological scoring. Patients with SSc and healthy controls were identified from a hospital database. Clinical data, modified Rodnan skin score, and hematoxylin and eosin–stained skin biopsies were collected. Biopsies were scored using modified Keyser and Farge criteria. Whole-slide images were analyzed using QuPath open source digital pathology software (v0.5.1) for area annotation, normalized cellularity, and collagen density, whereas collagen alignment was evaluated using CurveAlign (MATLAB) software. Seven SSc and 7 healthy controls (no significant demographic differences) were studied. SSc samples showed significant differences in hyalinized collagen (<em>P</em> &lt; .001), dermal fibroblast cellularity (<em>P</em> = .009), and total histopathological score (<em>P</em> = .007). Quantitative analysis confirmed decreased dermal cellularity (<em>P</em> = .024), increased collagen density (<em>P</em> = .009), and higher collagen alignment, with reduced fiber orientation variability, reflecting extracellular matrix restructuring in SSc. Tools such as QuPath and CurveAlign improve objectivity and reproducibility in SSc skin assessment, correlating well with traditional scores. These findings support the integration of computer-aided quantitative analysis into clinical practice and trials, advancing personalized fibrosis evaluation. Larger, longitudinal studies are needed for further validation.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104177"},"PeriodicalIF":5.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-Based Detection of Colorectal Serrated Lesions: Digital Flatness, a Novel Metric Designed for Whole-Slide Images","authors":"Margherita Mottola ,&nbsp;Costantino Ricci ,&nbsp;Federico Chiarucci ,&nbsp;Caterina Ravaioli ,&nbsp;Alessia Grillini ,&nbsp;Alessandro Gherardi ,&nbsp;Michelangelo Fiorentino ,&nbsp;Alessandro Bevilacqua ,&nbsp;Francesca Ambrosi","doi":"10.1016/j.labinv.2025.104178","DOIUrl":"10.1016/j.labinv.2025.104178","url":null,"abstract":"<div><div>Colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) are characterized by sawtooth or stellate epithelial architecture. Distinguishing between SSLs and HPs is crucial as SSLs are precursors of colorectal carcinomas in 30% of cases, whereas HPs are likely precursors to SSLs. The differentiation of SSL from HP is primarily based on architectural features. Indeed, the hallmark of SSL is a substantial distortion of the typical crypt design and silhouette, which shows horizontal expansion along the muscularis mucosae and enlargement of the crypt base, especially in the lower third of the crypt. The ability to analyze digitized histologic images has led to innovative automated tissue analysis, thereby improving reproducibility and objectivity in pathologists' reports. Some recent studies explored colorectal cancer diagnosis and grading through automated quantitative analysis, but none of them focused on SSL detection. This study aimed to develop an automated method for SSL diagnosis by defining specific metrics to characterize their most common visual features. We developed a processing pipeline involving the automatic segmentation of all the tissue structures required for computing quantitative morphologic and architectural features, which allows detection of SSLs. In particular, we designed a novel metric, digital flatness, which numerically characterizes the parallelism of the gland's contour edges with the muscolaris mucosa profile. In a data set of 759 polyp glands, 41 of which were reported as SSLs by expert pathologists, our novel detection method achieved specificity of 92% and sensitivity of 83%, with accuracy of 92%. Our results represent a first approach to a simple, common, but still debated issue among gastrointestinal pathologists, thus providing valid support for the objective and standardized individuation of SSLs.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 8","pages":"Article 104178"},"PeriodicalIF":5.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}