Search Results (2,901)

Objectives: To examine the clinical, pathologic, and molecular features of mixed and mixed feature endometrial carcinomas and compare them to pure serous carcinoma and pure endometrioid carcinoma. Methods: The study analyzed the clinical characteristics, histologic composition, and molecular genetic profiles of mixed and mixed feature endometrial cancers, with a focus on shared and distinct mutations. Patient demographics, disease-free survival, and molecular alterations, including in TP53, PIK3CA, TERT, MAP2K1 genes, and ERBB2 gene amplifications, were assessed and compared to pure serous and pure endometrioid carcinomas. Results: Patients with mixed and mixed-feature carcinomas were older (median age: 73 years) and had worse disease-free survival (median: 23 months) than those with pure endometrioid carcinoma (median: 48 months). Mixed and mixed-feature carcinomas were histologically high-grade, most commonly comprising serous and endometrioid components. Molecular profiling supported a clonal origin of these tumors, with identical TP53 and PIK3CA gene mutations between the two histologic components in each case. There were additional gene mutations (e.g., TERT and MAP2K1) found in higher-grade components. ERBB2 amplifications were more frequent in the mixed carcinomas groups (33%) compared to pure serous (11%) and pure endometrioid carcinomas (0%). Some of the mixed and mixed-feature carcinomas also showed FBXW7 mutations, not seen in either the pure endometrioid or pure serous carcinomas. Conclusions: Mixed and mixed-feature carcinomas share origins with pure endometrial serous and endometrioid carcinoma subtypes but exhibit distinct molecular alterations. These findings highlight the importance of molecular subtyping for diagnosis and treatment planning. Future research could focus on larger cohorts and targeted sequencing to better understand the pathogenesis of mixed and mixed-feature carcinomas in order to refine therapeutic strategies. Full article

Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience BCG failure, creating a critical decision point between additional bladder-sparing therapy (BST) and early radical cystectomy (RC). Recent clinical data from the CISTO study suggest that, in appropriately selected patients, RC may be associated with higher 12-month recurrence-free survival while maintaining comparable cancer-specific survival and physical functioning. In this narrative review, we synthesize contemporary evidence on NMIBC genomic and transcriptomic subtypes, immune contexture, and clinicopathologic features associated with BCG response and progression risk, with emphasis on clinically oriented classification systems such as BCG Response Subtypes (BRS1–3) and UROMOL21. We highlight how tumor-intrinsic biology (e.g., EMT-associated programs), immune phenotypes (inflamed vs. immune-cold microenvironments), and genomic alterations may help refine risk stratification beyond traditional clinicopathologic models. To facilitate clinical integration, we propose a conceptual decisional framework that combines molecular subtype assignment, immune profiling, key pathologic risk factors, and patient considerations to generate probabilistic risk tiers that support selection among early RC, BST, and clinical trial strategies. Standardized multicenter cohorts and prospective evaluation are needed to validate integrated models and define their clinical utility for the precision timing of cystectomy in BCG-unresponsive NMIBC. Full article

Background: Accurate detection of cervical lymph node metastases is a critical determinant of prognosis and treatment planning in head and neck squamous cell carcinoma (HNSCC). Although ultrasound-guided fine-needle aspiration biopsy (USgFNAB) is widely used as a minimally invasive diagnostic tool, its sensitivity for detecting occult metastases remains limited. Current preoperative staging modalities are further constrained by operator dependency and suboptimal specificity in early-stage disease. Integration of molecular diagnostics, particularly the analysis of long non-coding RNAs (lncRNAs), represents a promising strategy to enhance diagnostic accuracy. Objective: This review synthesizes the current evidence on lncRNA expression profiles in HNSCC, with an emphasis on their association with lymph node metastasis and potential application in FNAB-derived material for pre-treatment staging. Methods: A structured literature search was conducted, focusing on studies evaluating lncRNA expression profiles in HNSCC and their relevance to lymph node metastasis, with a particular focus on the feasibility of analysis of USgFNAB samples. Results: Multiple lncRNAs, including HOTAIR, MALAT1, UCA1, TUG1, AFAP1-AS1, H19, MEG3, and ADAMTS9-AS2, have been implicated in metastatic progression through their involvement in diverse mechanisms such as epithelial-to-mesenchymal transition, chromatin remodeling, angiogenesis, and pre-metastatic niche formation. Elevated expression of several of these transcripts correlates with adverse clinicopathological features, including advanced tumor stage, extranodal extension, and reduced survival. However, no studies have profiled lncRNA expression in matched primary tumors and metastatic lymph nodes, and transcriptomic analysis of FNAB samples remains largely unexplored in HNSCC. Conclusions: lncRNAs represent promising molecular biomarkers for enhancing the sensitivity and specificity of USgFNAB in detecting occult cervical metastases. Future research should prioritize paired tumor–node lncRNA profiling, validation of FNAB-based molecular assays, and integration of multi-omics data for predictive modeling. Overall, integrating lncRNA analysis into ultrasound-guided fine-needle aspiration biopsy may enhance the detection of occult nodal metastases in head and neck squamous cell carcinoma and support more accurate nodal staging in clinically node-negative patients. Full article

This study describes the clinicopathological features of seven canine cases showing a diffuse cobblestone-like gastric mucosal pattern on endoscopy. Cases were retrospectively retrieved from endoscopic databases (2017–2025). Clinical data, treatment history, endoscopic findings, and histology were reviewed. Endoscopically, all dogs exhibited thickened, irregular, and poorly distensible gastric folds. Histopathologic examination showed mild-to-moderate foveolar hyperplasia, variable cystic dilation of the fundic glands, mild chronic lymphoplasmacytic inflammation, and interstitial fibrosis. Parietal-cell population was variably increased and predominant (hyperplasia). Because these features can overlap widely among reactive and hyperplastic gastropathies, interpretation required correlation with clinical and endoscopic findings in addition to histopathology. All dogs had a history of prolonged omeprazole administration, and most showed clinical improvement after dose reduction or treatment withdrawal. Follow-up endoscopy in two dogs documented divergent outcomes, with marked improvement in one dog and only minimal changes in the other. These findings suggest that this cobblestone-like pattern represents a benign, reactive, and potentially regressive gastropathy, possibly associated with chronic acid suppression. Recognition of this appearance may assist clinicians in differentiating reactive gastropathy from proliferative or neoplastic conditions and supports prudent use of long-term proton pump inhibitors in dogs with chronic gastrointestinal disease. Full article

Background/Objectives: Cribriform architecture is an adverse histopathologic feature in prostate cancer and has been associated with poor oncologic outcomes. Emerging evidence suggests that cribriform-positive tumors may behave as a biologically non-localized disease, raising the possibility of early occult dissemination. Lymphovascular invasion (LVI) is a key pathological marker of metastatic potential, but its relationship with cribriform architecture has not been evaluated. We examined the association between cribriform morphology and LVI to provide biological context for the aggressive clinical course of cribriform-positive prostate cancer. Methods: We performed a retrospective analysis of patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. Cribriform architecture was determined by a centralized pathology review, and LVI status was obtained from original pathology reports. Unadjusted associations were evaluated using contingency tables. Multivariable logistic regression was used to assess whether cribriform architecture was independently associated with LVI after adjustments for Gleason score, tumor stage, and nodal status. Results: Among 338 patients, 28 (8.3%) had LVI and 123 (36.4%) had cribriform architecture. LVI was more common in cribriform-positive than cribriform-negative tumors (17.9% vs. 2.8%; p < 0.001), corresponding to a crude odds ratio (OR) of 7.6 (95% CI, 3.0–19.3). Cribriform architecture remained independently associated with LVI after adjustment (adjusted OR, 5.20; 95% CI, 2.12–1.40; p < 0.001). Conclusions: Cribriform architecture is strongly and independently associated with LVI, supporting a biological link between cribriform morphology and early metastatic dissemination. These findings support the design of prospective, biomarker-driven studies to evaluate treatment intensification strategies in this high-risk subgroup. Full article

Background: The tumor microenvironment (TME), composed of diverse immune and stromal cells, plays a key role in cancer progression. Among its components, tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR) have emerged as important modulators of tumor behavior. While each has been extensively studied, their interrelationship and association with tumor grade and clinicopathological parameters remain unclear. Aim: This hypothesis-generating study aimed to explore the relationship between the presence of TANs, various types of DR, the grade of tumor malignancy, and other fundamental clinicopathological characteristics commonly studied in daily clinical practice. Materials and Methods: The study included a cohort of 65 cancer patients (N = 65). The average number of TANs was recorded. In hematoxylin and eosin (H&E)-stained sections, “hot spots” representing areas with the highest neutrophil density were first identified. The tumor-associated polymorphonuclear neutrophils were then counted in ten consecutive high-power fields (HPFs). In the same specimens, the DR was assessed and classified according to stromal texture. Results: TANs did not follow a normal distribution across any clinicopathological category (p < 0.05). Significant differences in TAN levels were observed among DR types (Kruskal–Wallis H = 9.890, p = 0.007), with higher counts in myxoid compared to mature stroma (Mean Rank = 41.58 vs. 24.80, p = 0.006). TAN levels also varied significantly with tumor grade (H = 22.384, p < 0.001), increasing from Grade 1 to Grade 3 (p < 0.013–0.001). Higher TAN counts were associated with cellular erythroblastic oncogene B2 (c-erbB2) positivity (H = 6.547, p = 0.038), perineural invasion (Mann–Whitney U = 179.5, p < 0.001), and ER/PR negativity (p = 0.016 and p = 0.044, respectively). No significant association was found with necrosis (p = 0.083). A near-significant relationship was identified between DR type and tumor differentiation grade (χ² = 9.448, p = 0.051), with mature stroma most common in Grade 1 tumors, keloid-like stroma in Grade 2, and myxoid stroma in Grade 3. Conclusions: High TAN levels were linked to aggressive tumor features and specific DR patterns. The association of myxoid stroma with elevated TAN infiltration may reflect a highly aggressive TME. These preliminary results warrant validation in larger, prospective studies. Full article

Background and Objectives: This study aimed to describe the clinical characteristics and survival outcomes of three representative complex karyotype soft tissue sarcoma (STS) subtypes—undifferentiated sarcoma (US, primarily undifferentiated pleomorphic sarcoma (UPS)), myxofibrosarcoma (MFS), and leiomyosarcoma of soft tissue (LMS-ST)—using data from a single-institution cohort. Materials and Methods: A retrospective review of 124 patients treated at a single tertiary referral center between 2002 and 2024 was conducted. Clinicopathologic characteristics and survival outcomes were analyzed. Kaplan–Meier methods were used to estimate overall survival (OS). Cox proportional hazards regression models were applied to identify independent prognostic factors for survival, incorporating variables such as age, sex, tumor stage, and treatment modality. Results: The cohort comprised 36 cases of US, 64 of MFS, and 24 of LMS-ST. OS and survival after cohort enrollment (S-NCC) were evaluated both by subtype and across the entire cohort to assess potential differences across tumor subgroups. In both univariable and multivariable analyses, US subtypes showed poorer survival than MFS and LMS-ST. FNCLCC grade 3 emerged as a significant adverse prognostic factor for survival across all three subtypes. For FNCLCC grade 3 patients, the presence of benign prostatic hyperplasia (BPH) was significantly associated with an increased risk of death. Conclusions: Among the three subtypes, US demonstrated the most aggressive clinical course, MFS was notable for frequent local recurrence but relatively favorable survival, and LMS-ST showed intermediate outcomes. These findings highlight the clinical heterogeneity of complex karyotype STS and provide a foundation for future studies integrating molecular and multi-omics data to refine risk stratification and therapeutic strategies. Full article

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Long-term immunomodulatory therapies, including corticosteroids, used in the management of rheumatoid arthritis are associated with a higher risk of infections. Leishmaniasis is a neglected protozoal infection that may arise in these patients. Cutaneous presentation is the most common and is characterized by a wide spectrum of clinical manifestations and courses, depending on the interplay between species involved and the host’s immune response. Here, we report the rare and intriguing case of a patient with long-standing rheumatoid arthritis, chronically treated with systemic prednisone, whose rheumatoid nodules were colonized by Leishmania major. In this context, therapeutic strategies must be tailored to species and patient factors. This report expands the differential diagnosis of rheumatoid nodule, highlighting the importance of considering opportunistic infections in exuberant presentations, particularly in immunosuppressed patients coming from or travelling in endemic regions. Intracellular pathogens may exploit the localized immunological niche represented by the rheumatoid nodule of an immunocompromised host to survive and replicate undisturbed. It also underscores the value of the clinico-pathological correlation and the importance of integrating molecular analyses to identify unexpected microorganisms that can be hidden by concomitant disease, avoiding misdiagnosis, ensuring timely treatment, and improving patients outcomes. Full article

Background: Early local recurrence (ELR) in musculoskeletal sarcoma is associated with poor oncologic outcomes, yet the relative impact of tumor biology versus system-level factors remains insufficiently understood. This multicenter real-world study within the Swiss Sarcoma Network evaluated whether the initial care pathway influences the risk and timing of ELR. Methods: Patients with histologically confirmed sarcoma and documented local recurrence were classified according to initial management within a Comprehensive Care Pathway (CCP) or a Fragmented Care Pathway (FCP). ELR was defined as recurrence within 12 months after index surgery. Associations were analyzed using restricted Cox proportional hazards models and Firth-penalized logistic regression, adjusting for key clinicopathologic factors. Follow-up was calculated from index surgery to death or administrative censoring (median 88.2 months; interquartile range, 54.9–141.6). Results: Among 158 patients with local recurrence, 96 (60.8%) were treated within CCP, and 62 (39.2%) entered through FCP. ELR occurred in 53 patients (33.5%) and was more frequent in the FCP cohort. Fragmented care was independently associated with ELR in both time-to-event analysis (hazard ratio 2.00, 95% CI 1.14–3.51) and penalized logistic regression (odds ratio 2.83, 95% CI 1.09–6.94). Unplanned (“whoops”) procedures and incomplete resection margins were substantially more common in FCP and independently predicted ELR. Tumor grade also contributed to risk, but the magnitude of the pathway effect was comparable. ELR was associated with higher rates of synchronous metastases and inferior survival compared with late local recurrence. Adjuvant therapy did not independently reduce ELR risk after adjustment for surgical quality. Conclusions: These findings indicate that ELR in musculoskeletal sarcoma is strongly influenced by modifiable system-level factors. Early referral, multidisciplinary evaluation, and expert margin-oriented surgery are critical to reducing early recurrence and improving patient outcomes. Full article

Introduction: Mounting evidence indicates that the p53 Pro72Arg single-nucleotide polymorphisms (SNPs) may play a role in modulating hepatocarcinogenesis in the setting of chronic HBV infection. However, there is currently a lack of studies focusing on this genetic variant in Indonesia, a country characterized by its diverse genetic landscape comprising over 1300 distinct ethnic groups. We aimed to investigate the association between the p53 Pro72Arg polymorphism and the risk of hepatocellular carcinoma (HCC) among Indonesian patients with chronic HBV infection. Methods: A total of 140 patients with chronic hepatitis B (CHB) were recruited, including 79 with HCC and 61 without HCC serving as controls. We used direct sequencing of DNA extracted from peripheral blood to analyze the SNPs of p53 codon 72. Results: The distribution of p53 Pro72Arg genotypes among Indonesian CHB patients was 12.9% for proline homozygotes (Pro/Pro), 31.4% for arginine homozygotes (Arg/Arg), and 55.7% for proline/arginine heterozygotes (Pro/Arg). Despite the lack of association between the SNPs and HCC risk in the overall population, both the Pro/Arg and Arg/Arg genotypes demonstrate an increased susceptibility to HCC compared to Pro/Pro genotypes exclusively in the Madurese ethnic group. Additionally, we discovered that in those with decompensated cirrhosis, the heterozygote Pro/Arg was more likely to develop HCC than the homozygous Pro/Pro. No significant association was found between the SNPs of p53 Pro72Arg and the clinicopathological characteristics of HCC. Conclusions: The p53 Pro72Arg polymorphism might contribute to hepatocarcinogenesis in Indonesian chronic hepatitis B patients, particularly Madurese and those with liver decompensation. Full article

The World Health Organization (WHO) and International Consensus Classification (ICC) systems have classified EBV-positive NK/T-cell neoplasms in adults and EBV-positive T/NK-cell lymphoid lymphoproliferative disorders (LPD) in children. Recent molecular profiling techniques have revealed the pathogenesis of these disorders, showing interactions among EBV-encoded proteins, host immune responses, and genetic alterations. Extranodal NK/T-cell lymphoma (ENKTL) shows molecular diversity, with various subtypes (TSIM, MB, and HEA) identified through a multiomics approach. Aggressive NK-cell leukemia (ANKL) has mutations in JAK/STAT, epigenetic regulators, and TP53 pathways. EBV-positive nodal T- and NK-cell lymphoma (ENTNKL) is a new entity, distinguished by primary nodal presentation and a unique molecular profile. Severe mosquito bite allergy (SMBA), hydroa vacciniforme lymphoproliferative disorder (HVLPD), and systemic chronic active EBV disease (CAEBV) are rare childhood EBV-driven LPDs defined by clinico-pathologic criteria, with largely unexplored genomic landscapes. Studies of CAEBV samples have found ENKTL-like driver mutations, including DDX3X and KMT2D, in EBV-infected NK/T cells, while KMT2D and chromatin modifier mutations were common in HVLPD. Comprehensive molecular sequencing of SMBA and Systemic EBV-positive T-cell lymphoma of childhood remains lacking. These findings suggest all EBV⁺ NK/T-cell LPDs exist on a biological continuum of viral oncogenesis. The integration of clinical, pathological, and molecular information aims to create a more accurate classification system, enabling better risk evaluation and tailored treatment strategies for patients with these complex disorders. Full article

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been widely used as the first-line treatment for PCa. However, most PCa will progress to castration-resistant PCa (CRPC) that resists ADT 1 to 3 years after the treatment. Steroidogenesis from cholesterol is one of the mechanisms leading to ADT resistance. In PCa cells, low-density lipoprotein (LDL) mediated uptake is the major venue to acquire cholesterol. However, the mechanism of regulating this process is not fully understood. Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase (RTK) that is ectopically expressed in PCa cells and promotes PCa progression by activating downstream signaling pathways. To comprehensively determine the roles of FGFR1 in PCa, we generated FGFR1-null DU145 cells and compared the transcriptomes of FGFR1-null and wild-type cells. We found that ablation of FGFR1 reduced the expression of genes promoting LDL uptake and de novo synthesis of cholesterol, thereby reducing the overall cholesterol pool in PCa cells. Detailed mechanistic studies further revealed that FGFR1 boosted the activation of sterol regulatory element-binding protein 2 (SREBP2) through ERK-dependent phosphorylation and cleavage, which, in turn, increased the expression of low-density lipoprotein receptor (LDLR) and enzymes involved in de novo cholesterol synthesis. Furthermore, in silico analyses demonstrated that high expression of FGFR1 was associated with high LDLR expression and clinicopathological features in PCa. Collectively, our data unveiled a previously unrecognized therapeutic avenue for CRPC by targeting FGFR1-driven cholesterol uptake and de novo synthesis. Full article

Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of four autophagy pathway components (BECLIN, p62/, LC3b, ATG3) in pathogenetic mechanisms of thymic epithelial tumors (TETs) with possible prognostic importance. Methods: Immunohistochemistry was used to evaluate the cytoplasmic expression of BECLIN, p62, LC3b, and ATG3 in tumor cells of 99 TETs, and possible correlations with clinicopathological parameters were examined. Results: Higher BECLIN and p62 expression was associated with male gender (p = 0.027 and p = 0.014, respectively). B3 thymomas and thymic carcinomas (TCs) displayed higher p62 expression (p = 0.019), while LC3b expression was marginally higher in non-B3/TC TETs (p = 0.098). A positive correlation between higher BECLIN expression and advanced Masaoka–Koga stage was also observed (p = 0.009). ATG3 was not associated with any of the investigated clinicopathological parameters (p > 0.05). There was also no significant correlation between any of the four examined molecules and overall survival or relapse. Conclusions: Our findings indicate autophagy activation in B3/TC and advanced Masaoka–Koga stage cases. Further studies are needed to explore the role of these autophagy related proteins as potential biomarkers and therapeutic targets in TETs. Full article

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea’s National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced CC patients from South Korea’s cancer registry (2012–2019), alongside claims and death records (2012–2021). Among these 2792 patients diagnosed after bevacizumab’s NHI inclusion (August 2015), survival outcomes were compared between those receiving bevacizumab with platinum-based chemotherapy (n = 1787, 64.0%) versus chemotherapy alone (n = 1005, 36.0%). Overall survival (OS) was assessed using Cox proportional hazard regression with inverse probability of treatment weighting. Results: Following NHI coverage of bevacizumab, median OS increased from 1.5 to 2.5 years, and the 5-year OS rate increased from 25.6% to 41.4% (weighted hazard ratio [wHR], 0.63; 95% confidence interval [CI], 0.60–0.67). Among patients receiving bevacizumab, median OS was 2.6 years compared to 2.2 years for those not receiving bevacizumab, with 5-year OS rates of 42.0% and 40.2%, respectively (wHR, 0.84; 95% CI, 0.78–0.90). Subgroup analyses revealed that bevacizumab was associated with significantly better OS in patients with prior concurrent chemoradiation therapy (CCRT) history (wHR, 0.67; 95% CI, 0.61–0.75), regardless of histologic subtype (squamous cell carcinoma [SCC]: wHR, 0.69 [95% CI, 0.61–0.78] vs. non-SCC: wHR, 0.66 [95% CI, 0.55–0.79]). Conclusions: The national investment in the implementation of bevacizumab was associated with favorable survival outcomes in advanced CC patients. Particularly, bevacizumab showed pronounced survival benefit for patients with prior CCRT history, regardless of histologic subtype. Full article

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the aggressiveness of rare variants of PTC by analyzing clinicopathological characteristics (CPCs) and survival outcomes. Methods: We analyzed 80 patients with rare PTC variants treated between 2009 and 2019 who were compared with cPTC and matched with a control group for age and tumor size. The variants were categorized into high-risk (HRV: tall cell, diffuse sclerosing, columnar cell, and hobnail variants), intermediate-risk (IRV: solid variant (SV)), and low-risk (LRV: oncocytic (OV) and Warthin-like (WLV)) variants. Different CPCs (capsule and blood vessel invasion, lymphonodal metastases, microscopic and macroscopic extrathyroid extension, multifocal and bilateral presentation) and survival outcomes—overall (OS), disease-specific (DSS), and disease-free survival (DFS) were compared. Results: HRVs exhibited significantly more aggressive CPCs and worse OS, DSS, and DFS compared to cPTC (p < 0.001). IRVs showed no significant difference in CPCs or survival outcomes compared to cPTC. LRVs showed excellent survival but were associated with several unfavorable CPCs. Multivariate analysis identified classification in HRVs as the only independent predictor of recurrence (p = 0.014). Conclusions: Tumors in the HRV group should retain their status as aggressive PTC variants due to unfavorable behavior and poorer prognosis. SVs, despite earlier assumptions, do not exhibit aggressive characteristics. Although the OV and WLV have similar survival to cPTC, their potential for adverse CPCs requires caution. Full article