Laboratory Investigation最新文献

{"title":"Leptin Receptor–Expressing (LepR+) Fibroblasts Activated by BMP Signaling Promote Bone Resorption in Developmental Odontogenic Cysts","authors":"Hetian Bai ,&nbsp;Jinyong Li ,&nbsp;Yeting Tu ,&nbsp;Chongyun Bao","doi":"10.1016/j.labinv.2025.104239","DOIUrl":"10.1016/j.labinv.2025.104239","url":null,"abstract":"<div><div>Cystic lesions are more prevalent in jawbones than in other bones. Odontogenic cysts are typically painless and asymptomatic and often reach significant sizes before detection. Unlike odontogenic cysts of inflammatory origin, understanding of the mechanisms of pathogenesis and progression of developmental odontogenic cysts remains incomplete. This study aimed to elucidate the cause and mechanisms of bone resorption in developmental odontogenic cysts. First, single-cell RNA sequencing was conducted for one of the most common developmental odontogenic cysts, dentigerous cysts (DCs), and the obtained data were compared with those of dental follicles of embedded teeth. Most DEGs in DCs and dental follicles were associated with immunoglobulin secretion, and an activated immunoglobulin-secreting plasma cell subtype was confirmed. Cell-to-cell interaction analysis revealed strong interactions between the activated plasma cells and leptin receptor–expressing (LepR⁺) fibroblasts via a “bone morphogenetic protein 6 and its receptor type 2\" interaction. These LepR⁺ fibroblasts constituted the majority of fibroblasts in DCs. And these fibroblasts highly expressed genes were related to osteoclastogenesis, such as <em>CSF1</em>, <em>IL6</em>, and <em>IL34</em>. Mouse bone marrow–derived monocytes and bone marrow mesenchymal stem cells were treated with culture supernatants of the LepR⁺ fibroblasts. The treatment led to osteoclast formation and bone resorption, and inhibition of bone morphogenetic protein signaling suppressed the osteoclastogenesis effect. Thus, the LepR⁺ fibroblasts distinguished developmental odontogenic cysts from benign follicles; such cells interacted with activated plasma cell through the bone morphogenetic protein signaling pathway. And the LepR⁺ fibroblasts were crucial in osteoclast induction and bone resorption in DCs. This study confirmed a novel LepR⁺ fibroblast–induced bone erosion mechanism in developmental odontogenic cysts, which may inspire future pharmacological or surgical therapies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104239"},"PeriodicalIF":4.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065219","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":"Exploring Molecular Characteristics and Therapeutic Strategies for Primary Sinonasal Mucosal Melanoma With Distant Metastasis","authors":"Dong Ren ,&nbsp;Chenchen Niu ,&nbsp;Nyein Htun ,&nbsp;Xin Zhang ,&nbsp;Jiadi He ,&nbsp;Ronggang Li ,&nbsp;Qiongru Liu ,&nbsp;Vincent Lee ,&nbsp;Robert A. Edwards ,&nbsp;Grace G. Zhou ,&nbsp;Brandon M. Lehrich ,&nbsp;Derek H. Liu ,&nbsp;Angie Nguyen ,&nbsp;Jeff Chan ,&nbsp;Nicholas R. Pannunzio ,&nbsp;Edward C. Kuan ,&nbsp;Beverly Y. Wang","doi":"10.1016/j.labinv.2025.104238","DOIUrl":"10.1016/j.labinv.2025.104238","url":null,"abstract":"<div><div>Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy of the sinonasal tract. Due to its advanced clinical presentation and frequent late-stage diagnosis, the 5-year survival rate is &lt;30%, with an even worse prognosis in patients with distant metastasis (SNMM-M). Therefore, characterizing the molecular landscape of SNMM may provide novel therapeutic targets for SNMM-M. This study aimed to decipher the histopathological and molecular landscape of SNMM-M and yields novel insights into potential therapeutic approaches using targeted DNA and RNA next-generation sequencing, immunohistochemistry, and fluorescence in situ hybridization. SNMM-M cases were characterized by epithelioid-predominant morphology, frequent tumor necrosis, minimal pleomorphism, and sparse tumor-infiltrating lymphocytes (TILs). A significant association between the absence of brisk TILs and metastasis in SNMM was noted. Moreover, the presence of lymphovascular invasion and absence of brisk TILs were both significantly associated with poorer overall survival in patients with SNMM. Both DNA and RNA sequencing identified no gene fusions, whereas DNA sequencing revealed 304 genomic alterations across 186 genes, including 9 multihit genes. Notably, missense mutations in structure-specific endonuclease subunit (<em>SLX4</em>), a key homologous recombination repair scaffold protein, were exclusively detected in SNMM-M, and patients with <em>SLX4</em> mutations exhibited significantly worse survival (median, 9.9 vs 41.2 months without <em>SLX4</em> mutations; <em>P</em> &lt; .0001). A comparative analysis of genomic alterations and copy number variations of clinically actionable genes between SNMM-M and SNMM without distant metastasis (SNMM-nM) revealed that <em>CDK4</em> gains/amplifications were commonly seen in SNMM-M cases, whereas receptor tyrosine kinase and homologous recombination repair gene alterations were highly enriched in SNMM-nM cases. Additionally, PD-L1 was more commonly expressed in SNMM-nM. These exploratory findings suggest that <em>SLX4</em> mutation may serve as a potential prognostic biomarker and that CDK4 inhibitors could represent promising therapeutic options for SNMM-M. However, given the limited sample size, further validation in larger studies is essential to confirm these findings.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 12","pages":"Article 104238"},"PeriodicalIF":4.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008311","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":"Tenascin-C Expression in Relation to Tumor-Stroma Interaction in Ameloblastoma","authors":"Satoko Sumi ,&nbsp;Shohei Yoshimoto ,&nbsp;Kanako Suyama ,&nbsp;Masahide Taguchi ,&nbsp;Hiromitsu Morita ,&nbsp;Akimitsu Hiraki ,&nbsp;Kyoko Oka","doi":"10.1016/j.labinv.2025.104237","DOIUrl":"10.1016/j.labinv.2025.104237","url":null,"abstract":"<div><div>Ameloblastoma (AM) is a benign epithelial odontogenic tumor that occurs in the jawbone. Although benign, AM can exhibit aggressive features, including locally invasive growth. In addition, local recurrence or distant metastasis may occur. Therefore, understanding the mechanisms underlying AM-cell migration is essential for improving clinical therapy. The role of the tumor microenvironment in disease progression has been extensively studied in various tumors. In the microenvironment, it has been reported that the extracellular matrix plays many roles. Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is highly expressed during tissue development and remodeling. In this study, we investigated the involvement of TN-C in AM progression. Immunohistochemical analysis of AM specimens revealed high TN-C protein expression in the stroma, particularly at the invasive front. In contrast, RNA in situ hybridization demonstrated that <em>TNC</em> was localized within tumor cells, suggesting that the TN-C protein in the stroma is secreted by tumor cells rather than produced by stromal cells. In in vitro analyses, TN-C expression was significantly upregulated in cocultures of the AM cell line, AM-1, and primary human periodontal ligament fibroblasts, indicating that tumor-stroma interactions enhance tumor-derived TN-C expression. Functionally, TN-C stimulation promoted AM-cell migration, whereas <em>TNC</em> knockdown suppressed it. Spatial transcriptomics revealed elevated <em>TNC</em> expression in regions undergoing malignant transformation. Our results demonstrate that tumor-derived TN-C promotes AM progression. The expression of TN-C at the invasive front and in malignant regions suggests its potential as both a prognostic marker and a therapeutic target in tumor progression.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104237"},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006405","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":"Telepathology for Consultation in the Military Health System: An Evaluation of Pathologists’ Impressions of Facilitators and Barriers Prior to Implementation","authors":"Victoria Mahar,&nbsp;Zachary Colburn,&nbsp;Joshua Sakai","doi":"10.1016/j.labinv.2025.104236","DOIUrl":"10.1016/j.labinv.2025.104236","url":null,"abstract":"<div><div>Challenging pathology case consultations require the shipment of irreplaceable patient materials to the consultants’ location for evaluation. In the military, consultants and generalists span geographically diverse locations. Shipped cases risk diagnostic delays, loss, and irreparable damage in transit over extensive distances. Using digital pathology for consultation eliminates these risks. Digital pathology implementation efforts in the Military Health System have been unsuccessful; however, triservice pathologists’ attitudes toward this innovation have never been investigated. Our explanatory mixed-methods study used a web-based needs assessment and interviews to understand pathologists’ facilitators and barriers to using digital pathology for consultation. We believe that understanding their perceptions is critical if further implementation efforts are to be successful. Analyses showed that pathologists were receptive to enterprise-wide implementation, especially if it improved turnaround time and allowed immediate subspecialist feedback. Future implementation efforts may benefit from comprehensive technical support combined with a consolidated digital pathology program office for implementation and sustainment guidance.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104236"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000987","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":"Association of the BRAFV600E Mutation With Morphology and Heterogeneity in Melanoma","authors":"Ya-ting Qiu ,&nbsp;Long-feng Ke ,&nbsp;Wen-wen Zhang ,&nbsp;Shu-yi Lu ,&nbsp;Chen-yu Wu ,&nbsp;Yun-li Xie ,&nbsp;Yu Chen ,&nbsp;Gang Chen ,&nbsp;Yan-ping Chen","doi":"10.1016/j.labinv.2025.104235","DOIUrl":"10.1016/j.labinv.2025.104235","url":null,"abstract":"<div><div>The <em>BRAFV600E</em> mutation test for melanoma patients has become the key to precision therapy. In this study, we compared the concordance of immunohistochemistry (IHC), quantitative real-time PCR (qPCR), and next-generation sequencing (NGS) in detecting the <em>BRAFV600E</em> mutation in a Chinese melanoma patient population. In addition, this study evaluated the <em>BRAFV600E</em> mutation heterogeneity between primary and metastatic melanoma sites, as well as within the same lesion, and investigated the association between <em>BRAFV600E</em> mutation status and tumor cell morphology. A total of 880 samples from 555 patients diagnosed with malignant melanoma were collected, and IHC for <em>BRAFV600E</em> was conducted. Of these, 385 were subjected to qPCR and 115 to NGS concurrently. Inter and intratumor heterogeneities of <em>BRAFV600E</em> mutations were compared. Hematoxylin and eosin (H&amp;E) stain was performed, and the cell morphologies were reviewed. The IHC and qPCR results were discordant in 14 cases, yielding a concordance rate of 96.36%. IHC and NGS results showed a concordance rate of 97.39%. The sensitivity and specificity of BRAFV600E detection by IHC were 96.95% and 99.46%, with an overall concordance rate of 98.80%. One of 130 patients (0.77%) showed intertumor heterogeneity, and 3 of 880 samples (0.34%) showed intratumor heterogeneity. VE1 staining patterns significantly differed across cell morphologies (<em>P</em> &lt; .01). Compared with qPCR and NGS, VE1 IHC offers high sensitivity, specificity, and consistency in detecting the <em>BRAFV600E</em> mutation in melanomas. The <em>BRAFV600E</em> mutation in melanoma exhibits low intertumor and intratumor heterogeneities and is significantly associated with tumor cell morphology; tumors with epithelioid cell morphology are most likely to harbor the <em>BRAFV600E</em> mutation.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104235"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000891","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":"Comprehensive Analysis of Neurogenic Differentiation Factor 1 (NEUROD1), Achaete-Scute Homolog 1 (ASCL1), POU Class 2 Homeobox 3 (POU2F3), and Yes-Associated Protein 1 (YAP1) Expression Signatures Reveals Unique Large-Cell Neuroendocrine Carcinoma (LCNEC) Subgroups With Potential Therapeutic Implications","authors":"Frank W.J. Heijboer ,&nbsp;Jules L. Derks ,&nbsp;Dana A.M. Mustafa ,&nbsp;Nicole Rijnsburger ,&nbsp;Bregtje C.M. Hermans ,&nbsp;Lisa M. Hillen ,&nbsp;PALGA-Group ,&nbsp;Ernst-Jan M. Speel ,&nbsp;Anne-Marie C. Dingemans ,&nbsp;Jan H. von der Thüsen","doi":"10.1016/j.labinv.2025.104234","DOIUrl":"10.1016/j.labinv.2025.104234","url":null,"abstract":"<div><div>Large-cell neuroendocrine carcinoma (LCNEC) can be genomically subtyped into small-cell lung cancer (SCLC) and non-SCLC–like. Neurogenic differentiation 1 (NEUROD1), achaete-scute homolog 1 (ASCL1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1 (YAP1) (NEUROD1, ASCL1, POU2F3, and YAP1 [NAPY]) subtypes have been reported for SCLC. We immunohistochemically evaluated NAPY in LCNEC alongside relevant protein expression data. Tissue microarrays from 133 stage I-III resected LCNEC were reviewed and immunostained for NAPY, protein retinoblastoma (pRb), delta-like ligand 3 (DLL3), cMYC, and thyroid transcription factor 1. An H-score of &gt;10 was considered positive (+), and &gt;50, dominant. Unsupervised clustering and spatial immune RNA profiling using GeoMx Digital Spatial Profiling (NanoString Technology) were performed. Clinical data were obtained from the Netherlands Cancer Registry. ASCL1 was dominant in 26% and NEUROD1 in 18% of LCNEC. pRb loss was observed in 75%, and DLL3+, cMYC+, and thyroid transcription factor 1+ in 66%, 26%, and 70%, respectively. Unsupervised clustering identified 5 expression-based subgroups: NEUROD1^high-ASCL1^high (10%), ASCL1^high (22%), POU2F3^high (5%), YAP1^high (11%), and NAPY^low (51%). Both ASCL1^high subgroups correlated with DLL3^high and high neuroendocrine (NE) marker expression. YAP1^high was enriched for pRb+. POU2F3^high and YAP1^high subgroups were NE marker low and DLL3^low. GeoMX Digital Spatial Profiling identified 4 upregulated genes involved in immune system and/or tumor development in the NEUROD1^high-ASCL1^high-POU2F3^high- group. In this comprehensive evaluation of NAPY markers in LCNEC, we observed 5 expression-based subgroups: NEUROD1^high-ASCL1^high, ASCL1^high, POU2F3^high, YAP1^high, and NAPY^low. The NE subgroups (NEUROD1^high-ASCL1^high and ASCL1^high) were recognized with DLL3^high expression. Compared with the proportion known in SCLC, more NAPY^low and YAP1^high and fewer POU2F3^high cases were identified. Application of NAPY in LCNEC provides a more modest discrimination of subgroups compared with SCLC. Further research on potential drug targets is warranted, ie, differences in DLL3 and YAP1 expression could guide personalized treatment strategies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104234"},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992935","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":"Cover","authors":"","doi":"10.1016/S0023-6837(25)00140-0","DOIUrl":"10.1016/S0023-6837(25)00140-0","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 9","pages":"Article 104230"},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094920","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":"Validation and Prospective Testing of a High-Sensitivity, Quantitative Analytic Assay for HER2 on Histopathology Slides","authors":"Nay N.N. Chan ,&nbsp;Patricia Gaule ,&nbsp;Julia Benanto ,&nbsp;Liam Scott ,&nbsp;Charles J. Robbins ,&nbsp;Mengni He ,&nbsp;Katherine Bates ,&nbsp;Revekka Khaimova ,&nbsp;Daniel C. Liebler ,&nbsp;Regan Fulton ,&nbsp;David L. Rimm","doi":"10.1016/j.labinv.2025.104233","DOIUrl":"10.1016/j.labinv.2025.104233","url":null,"abstract":"<div><div>The recent approval of antibody-drug conjugates targeting human epidermal growth factor receptor 2 (HER2) (such as trastuzumab deruxtecan [T-DXd]) has led to challenges for the immunohistochemical (IHC) companion diagnostic test because the test was optimized for gene-amplified levels of HER2. Here, we develop and validate an objective test for low-level HER2 expression toward more accurate selection of patients for T-DXd. We validated the high-sensitivity HER2 assay using a mix of the requirements for an IHC assay and that of a ligand-binding assay. Then, we prospectively tested it on 316 core biopsy specimens received by the Yale Pathology Laboratories from August 2022 to August 2023. Using a 40-case breast cancer tissue validation set, we find very high accuracy and precision with a coefficient of variation &lt;10% and define a reportable range for the assay in attomoles per square millimeter. These prospective cases not only show the dynamic range of HER2 expression but also the discordance of Yale Pathology Labs staff pathologist scores with quantitative measurements, especially in the low range of HER2. We find that 6% of the cohort was below the limit of detection of this more sensitive assay, whereas 71% of the IHC 0 cases were above the limit of quantification. Efforts are underway to determine a possible threshold expression level required for T-DXd response. In summary, this assay validation study provides a method for accurate, objective measurement of HER2 and has the potential to improve selection of patients for T-DXd or similarly targeted antibody-drug conjugate therapies in future.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 12","pages":"Article 104233"},"PeriodicalIF":4.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959187","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":"Heterogeneous Distribution of Human Papillomavirus (HPV) Integration Sites in Cervical Precancers Compromises the Diagnostic Accuracy of Integrant-Specific PCR","authors":"Lydia Kirsche ,&nbsp;Lars Jansen ,&nbsp;Annett Petzold ,&nbsp;Petra Reinecke ,&nbsp;Peter Behrens ,&nbsp;Carol Geppert ,&nbsp;Nikolaus Gaßler ,&nbsp;Matthias Dürst","doi":"10.1016/j.labinv.2025.104232","DOIUrl":"10.1016/j.labinv.2025.104232","url":null,"abstract":"<div><div>Human papillomavirus (HPV) DNA integration into the host genome is a frequent event in cervical carcinogenesis and may drive clonal expansion of the affected cells. Based on viral cellular junction (vcj) sequences, highly specific vcj-PCRs can be designed to detect viral integrants in DNA from cervical cell scrapes or tissue samples. In a recent study, such patient-specific vcj-PCR assays were employed for the detection of recurrent high-grade squamous intraepithelial lesions (HSIL) during postoperative surveillance. Although the specificity of vcj-PCR was 100%, only 50% of the recurrences were detected using this approach. The focus of the current study was to analyze the cause of this limited sensitivity. Using chemical microdissection and subsequent vcj-PCR analysis, we could demonstrate that the majority of lesions have a heterogeneous integrant pattern. Only 2 of 16 cones showed a homogeneous distribution of the respective integrants throughout the entire lesion. The other lesions displayed clonal outgrowths harboring the integrant in a background HPV16/18 DNA-positive HSIL tissue. In 4 cases, the respective integrant was undetectable in the lesion. These findings indicate that vcj-PCR has limited sensitivity for the detection of recurrent disease owing to intralesional heterogeneity. The observed heterogeneous integrant pattern may thus reflect the multifocal nature of most large HSIL. Alternatively, the possibility that HPV integration may be a late event in the carcinogenic process also needs to be considered.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104232"},"PeriodicalIF":4.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959191","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":"Fatty Pancreas Disease: An Integrated Study on Frozen Tissues Shows Distinct Compartments of Interlobular/Intralobular, Intra-Acinar, and Intra-Islet Fat Deposition","authors":"Claudio Luchini ,&nbsp;Carlotta Franzina ,&nbsp;Federico Caldart ,&nbsp;Nicolò De Pretis ,&nbsp;Manola Crestani ,&nbsp;Massimo Donadelli ,&nbsp;Paola Mattiolo ,&nbsp;Alessandra Fiore ,&nbsp;Federica Danzi ,&nbsp;Riccardo De Robertis ,&nbsp;Michele Bevere ,&nbsp;Roberto Baldan ,&nbsp;Laura Tommasi ,&nbsp;Nicolò Vianini ,&nbsp;Paolo Bernardi ,&nbsp;Mirco Galiè ,&nbsp;Antonio Pea ,&nbsp;Rachele Ciccocioppo ,&nbsp;Mirko D’Onofrio ,&nbsp;Roberto Salvia ,&nbsp;Luca Frulloni","doi":"10.1016/j.labinv.2025.104214","DOIUrl":"10.1016/j.labinv.2025.104214","url":null,"abstract":"<div><div>Obesity-related diseases and perturbations of fat metabolism represent some of the most common health challenges. In this complex scenario, recent evidence has suggested the emergence of a condition related to fat accumulation in the pancreas, which is generally referred to as fatty pancreas disease. This study aimed to clarify the different compartments of intrapancreatic fat deposition. The study cohort is represented by 100 patients who underwent pancreatic surgical resection. The pancreatic neck margin was analyzed with hematoxylin and eosin for evaluating tissue composition and with Oil Red O, a fat-specific histochemical staining, highlighting lipid droplets as red signals, for evaluating the presence of intracellular fat. Two cases were also analyzed with electron microscopy as cross-sectional validation. Regarding tissue composition, the most prevalent component was normal pancreatic parenchyma (mean value, 71.8%), followed by fibrosis (17.3%) and interlobular/intralobular fat (10.9%). Regarding intracellular fat deposition, Oil Red O–positive intracytoplasmic lipid droplets were present in most patients. The tissue areas with the highest levels of fat deposition were Langerhans’ islets, with neuroendocrine/insular cells showing more commonly a diffuse pattern of fat accumulation (&gt;75% of cells). Electron microscopy confirmed the presence of intracytoplasmic lipid vacuoles in neuroendocrine/insular cells. Our findings showed the presence of different compartments of intrapancreatic fat deposition, both in terms of tissue composition and intracellular compartmentalization. Understanding the mechanisms of fat deposition in the pancreas is crucial toward improving the general knowledge on fatty pancreas disease, also opening new perspectives for the study of lipid metabolism and the treatment of fat-related diseases.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 11","pages":"Article 104214"},"PeriodicalIF":4.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959249","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}