Histology and histopathology最新文献

{"title":"New insights into solitary bronchial mucosal neuroma: A case report and literature review.","authors":"Dan Gao, Lei Han, Guijie Guan, Weijia Han, Li Shi, Yunshuang Liu, Ying Wu","doi":"10.14670/HH-25-132","DOIUrl":"https://doi.org/10.14670/HH-25-132","url":null,"abstract":"<p><p>Solitary bronchial mucosal neuroma is an exceptionally rare benign neurogenic tumor, with only four cases reported to date. Its etiology remains unclear, and histologically it resembles a traumatic neuroma despite arising in the absence of prior injury or surgery. Here, we present the fourth reported case of solitary bronchial mucosal neuroma and review all documented cases to better characterize its clinicopathological features and pathogenesis. Case Presentation. A 58-year-old man with a history of pulmonary tuberculosis presented with cough, purulent sputum, and hemoptysis. Imaging and bronchoscopy revealed a yellowish-white endobronchial lesion causing luminal stenosis. Histological examination of biopsy specimens demonstrated disorganized nerve bundles beneath the mucosa, comprising S-100-positive Schwann cells and neurofilament-positive axons, with variable epithelial membrane antigen-positive perineurial cells. Screening for multiple endocrine neoplasia type 2B (MEN2B) and other syndromic associations was negative. Wedge resection additionally revealed an incidental 2 mm carcinoid tumorlet. Conclusion. Solitary bronchial mucosal neuroma predominantly affects middle-aged to elderly individuals, often in the context of chronic inflammatory lung disease. It likely represents a traumatic neuroma of autonomic origin, with chronic inflammation playing a contributory role. Solitary bronchial mucosal neuroma should be considered in the differential diagnosis of endobronchial lesions and may coexist with carcinoid tumors. The lesion follows a benign course and is curable with complete resection. Further studies are needed to elucidate its pathogenesis and clinical spectrum.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25132"},"PeriodicalIF":2.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological changes of the diaphragm in heart failure: A scoping review of human and animal studies.","authors":"Mahiro Fukunaga, Akinori Kaneguchi, Takuya Umehara","doi":"10.14670/HH-25-131","DOIUrl":"10.14670/HH-25-131","url":null,"abstract":"<p><p>Diaphragmatic dysfunction, characterized by both impaired strength and endurance, is increasingly recognized as a key contributor to dyspnea and reduced exercise tolerance in heart failure (HF). While histological alterations in limb skeletal muscles have been well characterized, those in the diaphragm have not been systematically synthesized. This scoping review aimed to integrate findings from human and animal studies to characterize histological remodeling of the diaphragm following HF. A comprehensive search across five electronic databases followed by screening identified 20 eligible studies, including 2 in humans and 18 in animal models. The diaphragm exhibited several characteristic trends, including a fast-to-slow muscle type transition, muscle fiber atrophy predominantly affecting Type II fibers, increased capillarization, increased mitochondrial enzyme activity, reduced mitochondrial size, increased connective tissue (fibrosis), and increased apoptosis. Some of these alterations were similar to those observed in limb muscles; however, the fast-to-slow transition, increased capillarization, and increased mitochondrial enzyme activity contrasted with the typical slow-to-fast shift, capillary rarefaction, and reduced mitochondrial enzyme activity seen in limb muscles. Type II fiber-dominant atrophy and fibrosis likely underlie muscle weakness. Importantly, our findings suggest a mismatch between structural adaptations and functional outcomes. Specifically, while histological changes indicate a shift toward an endurance-oriented phenotype, HF is associated with reduced diaphragmatic endurance, suggesting that factors beyond structural remodeling contribute to reduced endurance. Our results provide insight into the mechanisms of diaphragmatic dysfunction in HF and highlight the diaphragm as a potential therapeutic target. Further accumulation of human data is needed to strengthen these findings.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25131"},"PeriodicalIF":2.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of mismatch repair deficiency with histopathological parameters in endometrial carcinoma: A study from the kurdistan region of Iraq.","authors":"Daria Ismail Amin, Hadeel Adnan Yaseen","doi":"10.14670/HH-25-130","DOIUrl":"https://doi.org/10.14670/HH-25-130","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability (MSI) is one of the four molecular classes of endometrial carcinomas (EC) identified by The Cancer Genome Atlas (TCGA), which is associated with an intermediate prognosis. The identification of mismatch deficient (MMRd) tumors has become essential for clinical decision-making and therapeutic management.</p><p><strong>Objectives: </strong>To analyze mismatch repair (MMR) protein expression by immunohistochemistry (IHC) and determine its association with the clinicopathological characteristics of EC, highlighting its potential role as a prognostic factor in clinical practice.</p><p><strong>Materials and methods: </strong>The retrospective observational study was conducted from 100 patient specimens with EC after hysterectomy or dilatation and curettage (D&C), from January 2017 to December 2024 at Hiwa Hematology/Oncology Hospital. Patients' age, surgical type, clinicopathological information, and histopathological characteristics were obtained from the hospital database. Then, the expression of MMR proteins (PMS2, MLH1, MSH2, and MSH6) was assessed in specimens using IHC on formalin-fixed paraffin blocks. Finally, the expression of MMR proteins in relation to clinicopathological parameters was determined.</p><p><strong>Results: </strong>Abnormal expression of MMR proteins was detected in 22 cases, of which 18 showed combined loss of MLH1/PMS2 expression, 3 showed combined loss of MSH2/MSH6, while only one case revealed isolated loss of PMS2.</p><p><strong>Conclusion: </strong>MMRd with predominance of an MLH1/PMS2 loss pattern is significantly linked to endometrioid histological type, tumor grading, and tumor-infiltrating lymphocytes. MMRd serves as a useful molecular biomarker and potential predictor of the immune microenvironment, supporting its role in prognosis and personalized therapy.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25130"},"PeriodicalIF":2.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFA6D expression and localization in renal tubules correlate with epithelial cell attenuation and membrane modifications in unilateral ureteral obstruction in young adult mice.","authors":"Apussara Watthanakitphibun, Suthankamon Khrongyut, Hiroyuki Sakagami, Surang Chomphoo, Hisatake Kondo, Wiphawi Hipkaeo","doi":"10.14670/HH-25-133","DOIUrl":"https://doi.org/10.14670/HH-25-133","url":null,"abstract":"<p><p>In our recent study (Watthanakitphibun et al., 2026), we reported remarkable membrane modifications in the basolateral cell domains of attenuated epithelial cells in dilated distal tubules and collecting ducts in the renal cortex, predominantly in the former, induced by unilateral ureteral obstruction (UUO). These modifications included the disappearance of typical basal infoldings and the appearance of ellipsoidal membrane sacs containing thin cytoplasmic processes along the basolateral cell membranes and within the cellular interior. We thus suggested that they represent a temporal sequence of membrane addition sources to compensate for the increased cell surface area associated with cell attenuation. To support the proposed temporal sequence of these membrane modifications, the present study examined the expression and localization of EFA6D, a molecule that plays a pivotal role in activating Arf6, whose involvement in membrane dynamics is well established, in the renal cortical tubules of adult mice under UUO. While EFA6D was faintly expressed in normal kidneys, western blotting revealed enhanced expression on UUO day 1, with significantly higher levels on days 3 and 5. Double immunofluorescence microscopy showed EFA6D immunoreactivity localized in attenuated cells of dilated distal tubules dominantly and of collecting ducts less dominantly, but not significantly in proximal tubules. In ultrastructure, EFA6D was mainly localized in the ellipsoidal membrane sacs and clusters of small vesicles beneath the apical membranes in the attenuated epithelial cells. Our findings on the expression and cellular interior localization of EFA6D support the proposed temporal sequence of events: disappearance of basal infolding, followed by membrane sac formation, and subsequent membrane addition. This sequence promotes cell surface expansion associated with cell attenuation during tubule/duct dilation induced by UUO.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25133"},"PeriodicalIF":2.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGR1 promotes ferroptosis in endometrial cancer cells by increasing NOX4 transcription.","authors":"Yuan Liu, Yuni Jin, Huiming Guo, Wen Sun, Xiaoning Lu","doi":"10.14670/HH-25-128","DOIUrl":"https://doi.org/10.14670/HH-25-128","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of early growth response 1 (EGR1) in the progression of endometrial cancer (EC) and to elucidate the molecular mechanism by which EGR1 regulates ferroptosis, with a focus on NADPH oxidase 4 (NOX4) as a downstream mediator.</p><p><strong>Methods: </strong>An EC xenograft model was established in nude mice. EGR1 was overexpressed in HEC-1B cells, and cell proliferation and migration were assessed using CCK-8, colony formation, and Transwell assays. Ferroptosis-related indicators (Fe²⁺, MDA, GSH, and lipid ROS) and related proteins (GPX4, SLC7A11, and IREB2) were measured. The ferroptosis inhibitor Fer-1 was used for rescue experiments. Gene and protein expression were analyzed via RT-qPCR, western blotting, and immunohistochemistry. The transcriptional regulation of NOX4 by EGR1 was validated using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays.</p><p><strong>Results: </strong>EGR1 expression was downregulated in EC. Overexpression of EGR1 inhibited the proliferation and migration of HEC-1B cells and suppressed tumor growth <i>in vivo</i>. EGR1 overexpression induced ferroptosis, as evidenced by increased levels of Fe²⁺, MDA, and lipid ROS; decreased GSH levels; downregulation of GPX4 and SLC7A11; and upregulation of IREB2. These effects were reversed by Fer-1. Mechanistically, EGR1 directly bound to the <i>NOX4</i> promoter and increased its transcription, leading to increased ROS production and thereby facilitating ferroptosis.</p><p><strong>Conclusion: </strong>EGR1 inhibits the progression of EC at least in part through transcriptionally activating NOX4, which promotes ROS accumulation and contributes to ferroptosis induction. This study provides a theoretical basis for targeting EGR1 as a potential therapeutic strategy for treating EC.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25128"},"PeriodicalIF":2.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SHCBP1 promotes cisplatin resistance and progression of LSCC through POU2F1-mediated transcriptional activation.","authors":"Mian Dai, Gang Qin, Yundan Bai","doi":"10.14670/HH-25-127","DOIUrl":"https://doi.org/10.14670/HH-25-127","url":null,"abstract":"<p><p>This study aimed to investigate the role of Src homology collagen-binding protein 1 (SHCBP1) in the progression and cisplatin resistance of laryngeal squamous cell carcinoma (LSCC), and to elucidate the underlying regulatory mechanism. LSCC cell lines were used to assess SHCBP1 expression by western blotting and quantitative real-time PCR (qRT-PCR). SHCBP1 knockdown was achieved by siRNA transfection, and its effects on cell proliferation, migration, and cisplatin sensitivity were evaluated through cell viability assays, wound healing assays, and flow cytometry. The transcriptional regulation of SHCBP1 by POU class 2 homeobox 1 (POU2F1) was investigated using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis. <i>In vivo</i>, tumor xenograft models were established to determine the impact of SHCBP1 knockdown on tumor growth and cisplatin responsiveness. SHCBP1 was highly expressed in LSCC cells, and its knockdown significantly inhibited LSCC cell proliferation and migration. Moreover, SHCBP1 silencing enhanced the sensitivity of LSCC cells to cisplatin treatment. Mechanistically, POU2F1 was shown to activate SHCBP1 transcription in LSCC cells. <i>In vivo</i> experiments further confirmed that SHCBP1 knockdown suppressed tumor growth and metastasis and increased cisplatin sensitivity. Overall, SHCBP1 contributes to LSCC cisplatin resistance and progression by promoting POU2F1-mediated transcriptional activation.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25127"},"PeriodicalIF":2.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α falls short, ERCC-1 stands out: Predictive insights in locally advanced cervical cancer.","authors":"Fatma Sert, Gurdeniz Serin, Senem Alanyali, Meltem Ozturk, Mert Delikaya, Osman Zekioglu, Zeynep Ozsaran","doi":"10.14670/HH-25-125","DOIUrl":"https://doi.org/10.14670/HH-25-125","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the association between pretreatment immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α) and excision repair cross-complementation group 1 (ERCC1) and clinical outcomes in patients with locally advanced cervical cancer (LACC) treated with definitive concurrent radiochemotherapy (cRCT).</p><p><strong>Methods: </strong>Eighty-seven patients with histologically confirmed LACC who received definitive cRCT between 2005 and 2015 were retrospectively analyzed. Immunohistochemical staining for HIF-1α and ERCC1 was performed on pretreatment biopsy specimens, and H-scores were calculated semi-quantitatively. Receiver operating characteristic (ROC) curve analysis determined optimal cut-off values: ≤100 and >100 for HIF-1α, and ≤130 and >130 for ERCC1. Overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with Cox regression models.</p><p><strong>Results: </strong>The median age was 57 years (range: 37-85). The five-year OS, LRFS, and DMFS rates were 57.8%, 69.7%, and 69.1%, respectively. In multivariate analysis, incomplete treatment response (<i>p</i><0.001) and high neutrophil-to-lymphocyte ratio (<i>p</i>=0.042) were independent predictors of poor OS. For LRFS, tumor size >4 cm (<i>p</i>=0.048), incomplete response (<i>p</i><0.001), and high ERCC1 expression (<i>p</i>=0.032) were identified as unfavorable prognostic factors. High ERCC1 expression also correlated with increased late toxicity (<i>p</i>=0.038). HIF-1α expression showed no significant association with any survival outcome.</p><p><strong>Conclusions: </strong>High ERCC1 expression was an independent prognostic indicator for poor LRFS, suggesting its potential as a biomarker of radioresistance. In patients with elevated ERCC1, alternative non-platinum agents may be considered. HIF-1α had no predictive or prognostic value in this cohort.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25125"},"PeriodicalIF":2.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAAS attenuates LPS-induced acute lung injury by targeting HMGB1-mediated NF-κB/NLRP3 inflammasome signaling.","authors":"Zhiyu Xie, Chong Liu, Xianhui Hong, Jianwei Shen","doi":"10.14670/HH-25-124","DOIUrl":"https://doi.org/10.14670/HH-25-124","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) induced by lipopolysaccharide (LPS) involves severe inflammation and epithelial damage, necessitating effective therapeutic strategies. This study investigated the protective effects and mechanisms of salvianic acid A sodium (SAAS) against LPS-induced cytotoxicity and ALI.</p><p><strong>Methods: </strong><i>In vitro</i> cytoprotection and anti-inflammatory effects of SAAS (0-60 μM) were assessed in LPS-challenged alveolar type II (AT2) epithelial cells using CCK-8 assays and quantification of inflammatory mediators (NLRP3, ASC, IL-1β, IL-6, TNF-α). <i>In vivo</i> efficacy was evaluated in an LPS-induced murine ALI model treated with SAAS via histopathology, lung wet/dry weight ratio, myeloperoxidase (MPO) activity, serum/lung cytokine levels (ELISA), and immunohistochemistry (IHC). Mechanistic insights were gained through western blot and qPCR analysis of HMGB1 signaling components.</p><p><strong>Results: </strong>SAAS (&#8804;60 μM) exhibited no intrinsic cytotoxicity but dose-dependently attenuated LPS-induced AT2 cell death. It significantly suppressed LPS-triggered expression of NLRP3 inflammasome components (NLRP3, ASC), caspase-1, and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) <i>in vitro</i>. In the ALI model, SAAS administration ameliorated histopathological damage, attenuated pulmonary edema, suppressed MPO activity, and reduced systemic and pulmonary levels of TNF-α, IL-6, IL-18, and IL-1β. Mechanistically, SAAS inhibited LPS-induced HMGB1 upregulation, acetylation, and nuclear-to-cytoplasmic translocation. Consequently, it suppressed downstream NF-κB activation and NLRP3 inflammasome assembly/activation.</p><p><strong>Conclusion: </strong>SAAS confers significant protection against LPS-induced ALI by targeting the HMGB1 signaling axis. It inhibits HMGB1 expression, acetylation, and cytoplasmic translocation, thereby disrupting NF-κB-mediated cytokine production and NLRP3 inflammasome activation. These findings identify SAAS as a promising multi-target therapeutic agent for inflammatory lung injury.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25124"},"PeriodicalIF":2.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF20 relieves high glucose-induced Schwann cell mitochondrial damage through the activation of SIRT1.","authors":"Ya Ning, Yuewei Liang, Youqing Huang","doi":"10.14670/HH-25-129","DOIUrl":"https://doi.org/10.14670/HH-25-129","url":null,"abstract":"<p><strong>Background: </strong>Schwann cell mitochondrial damage plays an important role in diabetic neuropathic pain (DNP). Fibroblast growth factor 20 (FGF20) has been shown to protect nerve cells and regulate neural function, but its function and mechanism in DNP remain unclear.</p><p><strong>Methods: </strong>A DNP mouse model induced by streptozotocin (STZ) and an RSC96 cell model induced by high glucose (HG) were used for experimental studies. The metabolism of the mice was evaluated by measuring body weight and blood glucose levels. Pathological changes in the sciatic nerve were observed by hematoxylin and eosin (HE) staining. The pain sensitivity of the mice was evaluated by the von Frey test and thermal sensitivity test. Cell viability was determined by a cell counting kit-8 (CCK-8) assay. MitoSOX Red staining was performed to detect mitochondrial reactive oxygen species (ROS) levels. 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining was used to measure the mitochondrial membrane potential, and the expression of proteins was detected by western blotting and immunohistochemistry.</p><p><strong>Results: </strong>FGF20 expression was low in DNP mice and HG-induced Schwann cells. Overexpression of FGF20 relieved symptoms in DNP mice, including partial recovery of body weight, a reduction in blood glucose levels, an increase in the tactile response threshold, and a reduction in thermal response delay. In addition, FGF20 overexpression increased the expression of the mitochondrial autophagy proteins PINK1 and Parkin, adenosine triphosphate (ATP) content, and mitochondrial membrane potential levels, and reduced ROS accumulation in RSC96 cells. Molecular mechanisms reveal that sirtuin 1 (SIRT1) expression is downregulated in DNP, and FGF20 upregulates SIRT1 expression, and that SIRT1 knockdown weakened the improvement effect of FGF20 on mitochondrial autophagy and damage.</p><p><strong>Conclusion: </strong>FGF20 may promote mitochondrial autophagy in Schwann cells by upregulating SIRT1 expression, thereby inhibiting mitochondrial damage and thus alleviating DNP.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25129"},"PeriodicalIF":2.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GLI1</i>-Altered neoplasms: From molecular alterations to morphologic and phenotypic features with formal recognition in the upcoming WHO Classification of soft tissue tumors.","authors":"Raquel Rivas-Hernández, Francisco Giner, Elena Prados, Reyes Claramunt, Raquel López, Antonio Fernández, Empar Mayordomo, José Antonio López-Guerrero, Samuel Navarro, Antonio Llombart-Bosch, Isidro Machado","doi":"10.14670/HH-25-123","DOIUrl":"10.14670/HH-25-123","url":null,"abstract":"<p><p><i>GLI1</i>-altered mesenchymal tumors represent a recently defined group of neoplasms molecularly characterized by <i>GLI1</i> gene fusions or amplifications. Although initially thought to share similar molecular alterations, including pericytoma with <i>ACTB::GLI1</i> fusion, plexiform fibromyxoma, and gastroblastoma, these tumors are now recognized as distinct entities with specific clinicopathological features. Histologically, <i>GLI1</i>-altered mesenchymal tumors typically exhibit a multinodular growth pattern composed of relatively uniform epithelioid-to-ovoid cells arranged in nested formations. These nests are supported by a delicate arborizing capillary network and are often embedded in a myxoid stroma. Immunohistochemically, variable positivity for CD56, S100, CD10, smooth muscle actin, cyclin D1, and p16 has been reported. GLI1 immunohistochemistry is both highly sensitive and specific, serving as a valuable diagnostic marker in the appropriate context. Some <i>GLI1</i>-amplified tumors may show co-amplification of neighboring genes, including <i>STAT6, MDM2, CDK4</i>, and <i>DDIT3</i>, which can result in variable immunoreactivity depending on amplicon size. These tumors can arise at a broad range of anatomical sites and occur across all age groups. Although <i>GLI1</i>-altered mesenchymal neoplasms were initially considered indolent, malignant cases with metastatic potential have been reported. Necrosis, high mitotic index, and large tumor size are associated with an increased risk of metastasis. Tumors with <i>GLI1</i> amplification generally demonstrate worse clinical outcomes than those driven by <i>GLI1</i> fusions. Definitive diagnosis requires molecular confirmation via next-generation sequencing and/or fluorescence in situ hybridization. Accurate recognition of <i>GLI1</i>-altered mesenchymal tumors has important diagnostic, prognostic, and therapeutic implications. Herein, we describe the clinicopathologic features of GLI1-altered neoplasms, including their molecular findings and the differential diagnosis with other tumors exhibiting overlapping morphology and immunoprofile.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25123"},"PeriodicalIF":2.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}