Pancreatic ductal adenocarcinoma (PDAC) is molecularly characterized by near-universal KRAS mutations and recurrent alterations in TP53, CDKN2A, and SMAD4. Gene fusions are exceptionally rare and have not been established as canonical drivers of PDAC. We report a case of metastatic PDAC harboring an EIF3E::RSPO2 gene fusion in the absence of detectable KRAS or other common driver mutations. A 48-year-old female was diagnosed with stage IV PDAC via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Comprehensive molecular profiling using the Oncomine Precision Assay GX5 revealed no pathogenic single-nucleotide variants, indels, or copy number variations. However, an EIF3E::RSPO2 fusion, predicted to be a gain-of-function alteration, was identified as the sole genomic alteration. Immunohistochemistry showed retained mismatch repair protein expression and preserved SMAD4. Although RSPO2 fusions have been described in preclinical colorectal cancer models and are well-established activators of the Wnt signaling pathway in this setting, their clinical occurrence in PDAC remains poorly documented. This finding indicates a KRAS wild-type tumor with a potential KRAS-independent oncogenic mechanism that may involve aberrant Wnt/β-catenin signaling and raises the possibility of a rare, biologically distinct PDAC subset. Comprehensive genomic profiling in advanced PDAC may uncover actionable non-canonical drivers with therapeutic implications.

Colon cancer remains a leading cause of cancer-related deaths, and drug repurposing offers a promising strategy to identify new therapies. Hydroquinidine (HQ), a class I antiarrhythmic agent, has recently been suggested to possess anticancer properties; however, its preclinical safety and efficacy in colorectal cancer are not well defined. The safety of HQ was evaluated in Wistar rats following OECD guidelines. Rats received daily intraperitoneal doses (2.5-25 mg/kg) for 90 days, with hematological, biochemical, and histopathological assessments performed. HQ was well tolerated up to 12.5 mg/kg, whereas 25 mg/kg caused signs of hepatotoxicity without lethality. A 1,2-dimethylhydrazine-induced colorectal cancer model was then used to assess HQ at safe doses (6.25 and 12.5 mg/kg) compared with cisplatin. Tissue histopathology and selected molecular markers associated with inflammation, apoptosis, epithelial-mesenchymal transition, and PI3K/AKT/mTOR pathway activity were analyzed. In the DMH-induced colon cancer model, HQ improved colonic tissue architecture and was associated with lower histopathological scores compared with untreated tumor controls. HQ also modulated tumor-associated markers by reducing IL-6 immunoreactivity, increasing caspase-3 expression, enhancing E-cadherin immunoreactivity, and decreasing vimentin expression. Moreover, HQ was associated with reduced immunoreactivity of mTOR pathway-related markers, suggesting attenuation of pathway activation in this experimental context. Overall, HQ showed an acceptable safety profile at the selected doses and exerted favorable histopathological and molecular modulatory effects, supporting further investigation as a potential repurposing candidate.

Cardiovascular disease and cancer remain the leading causes of death worldwide. Although numerous cancer therapies have improved survival rates, they also increase the risk of cardiomyopathy, heart failure, and arrhythmias. These cardiovascular complications can limit treatment options and adversely affect the long-term quality of life of cancer survivors. Ca_V1.3, an L-type calcium channel encoded by CACNA1D, emerges as a central molecular mediator linking cardiovascular disease and cancer. It regulates calcium entry into cardiomyocytes and contributes to sinoatrial pacemaking and atrioventricular conduction. It also contributes to proliferation, migration, and therapy resistance in several cancers. Chemotherapy-induced oxidative stress, inflammatory signaling, hypoxia, and transcriptional changes can modulate the expression, gating, splicing, and trafficking of Ca_V1.3 channels. All these changes destabilize diastolic depolarization and impair conduction, thereby promoting arrhythmias in cancer patients. This review focuses on Ca_V1.3 biology in cardio-oncology, along with the mechanisms of chemotherapy-induced cardiotoxicity. It outlines the role of Ca_V1.3 as a key mediator linking cancer therapies to subsequent nodal dysfunction and increased arrhythmia susceptibility. It also expands on how patient-specific induced pluripotent stem cell-derived cardiomyocytes can model Ca_V1.3 dysregulation as well as support the development of targeted therapies. We propose that Ca_V1.3 represents a mechanistic bridge linking cancer therapy, calcium signaling, and cardiac electrophysiology, and that elucidating its pathophysiology may guide the design of targeted strategies in cardio-oncology.

Background: Thymic epithelial tumors (TETs) are the most common primary neoplasms of the anterior mediastinum and present a dual classification challenge, namely anatomical staging according to the Masaoka-Koga system and histological risk stratification according to the World Health Organization (WHO) classification. Both tasks rely on expert pathological assessment and may be affected by interobserver variability. This study applied supervised machine learning (ML) to quantitative immunohistochemical (IHC) H-score profiles to predict Masaoka-Koga stage and WHO risk group in TETs. Methods: Logistic regression (LR) and XGBoost were applied to 19 biomarkers, including cellular localization, across two parallel analyses. Masaoka-Koga stage prediction was performed in 81 patients, including 59 early-stage and 22 advanced-stage cases, using the Synthetic Minority Oversampling Technique (SMOTE) across 100 train/test splits. WHO risk group prediction was performed in 89 patients, including 45 low-risk and 44 high-risk tumors, without oversampling. A cross-endpoint analysis applied the optimal Masaoka-Koga model to the WHO endpoint. Results: LR consistently outperformed XGBoost. The optimal Masaoka-Koga model combined Eph receptor A6 (EphA6) membranous, Yes-associated protein (YAP) nuclear, and histone deacetylase 4 (HDAC4) cytoplasmic H-scores, achieving an area under the curve (AUC) of 0.756. The optimal WHO model combined transcriptional coactivator with PDZ-binding motif (TAZ) cytoplasmic, EphA6 membranous, and YAP nuclear H-scores, achieving an AUC of 0.936. The Masaoka-Koga triad predicted WHO risk group with an AUC of 0.901. No tetrad improved trivariate performance. Conclusions: IHC H-score profiling combined with supervised ML identifies biologically interpretable candidate signatures for TET classification, although prospective external validation is required before clinical application.

Background/Objectives: Although ultrasound-guided fine-needle aspiration biopsy with suction (FNA-S) is preferred for evaluating thyroid nodules, the capillary technique (FNA-C) is also used. However, the diagnostic performance of both techniques remains unclear. Our objective was to compare the diagnostic performance of FNA-S versus FNA-C for thyroid nodules. Methods: This retrospective, observational, exploratory, single-center pilot evaluation study was conducted at a tertiary hospital from January 2023 to June 2024. A total of 157 ultrasound-guided FNA biopsies were prospectively analyzed, comprising 71 FNA-S and 86 FNA-C procedures. Clinical, ultrasound, and cytological parameters were evaluated to compare the rates of non-diagnostic samples (Bethesda I) and the necessity for repeat punctures. Bivariate analyses and multivariate logistic regression were conducted. Results: Both techniques exhibited comparable rates of non-diagnostic samples (28.17% for FNA-S and 27.91% for FNA-C; p = 0.220) and repetition rates (38.03% for FNA-S and 43.02% for FNA-C; p = 0.637). The only factors significantly associated with sample adequacy, regardless of techniques employed, were the location and composition of the nodule. Conclusions: Ultrasound-guided FNA-S and FNA-C yield similar diagnostic performance for biopsy of thyroid nodules. The choice may depend on operator preference and nodule characteristics.

Methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) has emerged as a valuable diagnostic, prognostic, and therapeutic biomarker in modern oncologic pathology, primarily serving as a surrogate for CDKN2A/B homozygous deletion due to their close genomic proximity at chromosome 9p21. This review aims to systematically evaluate the clinical utility, diagnostic accuracy, and technical limitations of MTAP IHC across a diverse spectrum of human malignancies, while contextualizing its role within current molecular testing algorithms. We first examine the established diagnostic and grading performance of MTAP loss in central nervous system neoplasms and thoracic tumors, particularly malignant pleural mesothelioma, followed by an analysis of its emerging prognostic value in gastrointestinal, cutaneous, and genitourinary malignancies. Furthermore, we discuss the therapeutic implications of MTAP deficiency, focusing on the biological consequences of methylthioadenosine accumulation and the resulting synthetic vulnerabilities in the PRMT5/MAT2A pathway. By synthesizing diagnostic precision, prognostic relevance, and translational therapeutic insights, this review provides a comprehensive framework for integrating MTAP IHC into routine surgical pathology workflows and personalized oncology.

Background: Peripheral nerve sheath tumors of the oral cavity are rare and encompass both benign and malignant entities. Differentiating between these lesions remains challenging due to overlapping clinical and histopathological characteristics. Case presentation: We present two cases illustrating the biological spectrum of peripheral nerve sheath tumors in the oral cavity. The first case involves a 76-year-old male with a recurrent lower lip lesion initially diagnosed as benign, which progressed to a high-grade malignant peripheral nerve sheath tumor (MPNST). The second case describes a 20-year-old male presenting with a nodular lesion of the tongue, initially suspected to be reactive following trauma, but histologically confirmed as a benign schwannoma. Both patients underwent surgical treatment with favorable immediate postoperative outcomes. Conclusions: These cases highlight the diagnostic complexity and heterogeneous behavior of peripheral nerve sheath tumors. Histopathological and immunohistochemical evaluations are essential for definitive diagnosis. Clinicians should maintain a high index of suspicion and consider possible association with NF1 or schwannomatosis, particularly in recurrent or atypical lesions.

Inflammatory fibroid polyp (IFP) or Vanek's tumor is a rare benign submucosal lesion of the gastrointestinal tract that may radiologically mimic mesenchymal gastric tumors, particularly gastrointestinal stromal tumors. We present the case of a 65-year-old patient with a contrast-enhancing gastric submucosal mass detected on computed tomography, initially interpreted as a suspected mesenchymal neoplasm. CT imaging demonstrated a well-defined enhancing lesion arising from the gastric wall without evidence of metastatic disease. Surgical resection was performed because imaging findings were considered highly suggestive of GIST. Gross intraoperative appearance and pathological examination, however, established the final diagnosis of gastric inflammatory fibroid polyp (Vanek's tumor). Histopathological analysis demonstrated characteristic spindle-cell proliferation with inflammatory eosinophil-rich infiltrates, while immunohistochemistry excluded GIST. This case highlights the diagnostic challenge in differentiating IFP from other gastric submucosal neoplasms based solely on imaging findings and emphasizes the importance of histopathological confirmation for definitive diagnosis.

Objectives: This study evaluates the protocol-level image quality and quantitative diffusion metrics of a clinically implemented deep-learning-reconstructed readout-segmented echo-planar imaging protocol with water-excitation spectral fat saturation (DL-rs-EPI with WEXfs) compared with conventional rs-EPI using spectral attenuated inversion recovery (SPAIR) at 3 T. Methods: Overall, 80 patients underwent breast magnetic resonance imaging (MRI) with both conventional rs-EPI with SPAIR and DL-rs-EPI with WEXfs protocols (b-values: 0, 800, and 1200 s/mm²). ROI-based relative image-quality metrics, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and lesion contrast, were assessed at b = 800 and b = 1200 s/mm²; apparent diffusion coefficient (ADC) values were calculated using multi-b-value data. Fat suppression, background diffusion signal, lesion conspicuity, and artifact severity were qualitatively evaluated. A temperature-controlled diffusion phantom (CaliberMRI) was scanned; ADC values were compared with reference values at 24 °C. Results: DL-rs-EPI with WEXfs demonstrated higher ROI-based relative SNR estimates (b800: 5.79 vs. 5.28; b1200: 5.41 vs. 4.94; p < 0.001) and CNR estimates (b800: 3.35 vs. 3.12, p = 0.024; b1200: 3.67 vs. 3.37, p = 0.001), with unchanged lesion contrast. Tumor ADC values were comparable between protocols, whereas normal fibroglandular tissue ADC values were slightly higher, and ADC contrast increased with DL-rs-EPI with WEXfs. Phantom ADC values from both protocols closely matched reference values at 24 °C, without significant differences. DL-rs-EPI with WEXfs demonstrated more homogeneous fat suppression and reduced background diffusion signal, with comparable lesion conspicuity and artifact severity. Conclusions: The combined DL-rs-EPI with WEXfs protocol demonstrated improved qualitative and relative quantitative image quality while preserving tumor ADC measurements. As a protocol-level evaluation, these composite improvements support its clinical feasibility for high-quality breast DWI without implying the isolated effect of DL reconstruction alone.

Background: Precise intraoperative localisation of small colorectal tumours during laparoscopic surgery remains challenging due to absent tactile feedback and subserosal tumour location. Current standard methods, particularly India ink tattooing, demonstrate 15-30% failure rates for lesions less than 10 mm, leading to prolonged operative times, incomplete resections, and re-operations. Multiple emerging technologies promise improved localisation, yet comparative evidence remains fragmented. Objective: To map and characterise the current landscape of intraoperative marking and identification technologies for small colorectal tumour localisation during laparoscopic surgery, with emphasis on radiofrequency-based methods and alternative approaches, and to identify evidence gaps guiding future research. Methods: Following PRISMA-ScR guidelines, we systematically searched PubMed, Web of Science, and Scopus databases from January 2000 through December 2025 for studies evaluating tumour localisation technologies in colorectal cancer surgery, including primary tumour localisation during laparoscopic colectomy and localisation of colorectal liver metastases during hepatic surgery, or transferable anatomical applications with documented translational potential to colorectal surgery. Two independent reviewers screened all records, with discrepancies resolved through discussion and a third senior reviewer consulted for unresolved disagreements; data were extracted on technical performance, safety, feasibility, cost-effectiveness, usability, innovation potential, and evidence quality. Results: We included 89 studies comprising 18 colorectal-specific articles and 71 transferable/GI-adjacent studies. Detection success rates ranged from 71% to 100% across modalities. Near-infrared fluorescence with indocyanine green demonstrated the strongest clinical evidence with 75-100% detection across eight colorectal studies encompassing 2134 procedures and seamless workflow integration. Radiofrequency identification systems achieved 91.9-99% detection in feasibility studies with promising tissue penetration of 15-35 mm but limited colorectal validation. Electromagnetic navigation excelled in rigid organs with 85-98% success but showed degraded performance in mobile bowel at 71-75%. Critical evidence gaps included absent head-to-head comparative trials, non-standardised outcome metrics limiting cross-study comparability, and limited long-term safety data with only 14 studies providing follow-up exceeding six months. Conclusions: ICG fluorescence represents the most clinically mature technology identified, representing a priority candidate for colorectal-specific validation in challenging localisation scenarios. RFID systems demonstrate promising characteristics justifying prioritised research investment through adequately powered comparative trials. Future research must emphasise consortium-based comparative effectiveness studies, standardised outcome metrics, and integration with robotic and AI-assisted surgical platforms to accelerate clinical translation.