Search Results (6,107)

Background: Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are rare hematopoietic disorders that exhibit overlapping pathological and molecular features of both MDS and MPN. This study aimed to investigate the mutational profiles and prognostic implications of MDS/MPN subtypes in Korean patients. Methods: We retrospectively reviewed 53 patients with MDS/MPN who underwent bone marrow examination and next-generation sequencing panel testing. Overall survival was analyzed with 3-year censoring. The cohort included chronic myelomonocytic leukemia (CMML; N = 30); MDS/MPN with neutrophilia (N = 6); MDS/MPN with SF3B1 mutation and thrombocytosis (N = 4); and MDS/MPN, not otherwise specified (MDS/MPN-NOS; N = 13). Results: The most frequently mutated gene was ASXL1 (52.8%), followed by TET2 (39.6%) and U2AF1 (18.9%), in total MDS/MPN. U2AF1 mutations were particularly frequent in myelodysplastic CMML (33.3%) and MDS/MPN-NOS (30.8%). In CMML, ASXL1 and TET2 mutations were associated with a trend toward better prognosis compared with wild-type (HR 0.21, p = 0.052; HR 0.25, p = 0.057, respectively), while U2AF1 mutations were associated with adverse prognosis in univariate analysis with borderline significance (HR 12.20, p = 0.050). Clinical/Molecular CMML-Specific Prognostic Scoring System and Mayo Molecular Model showed stepwise survival patterns across risk groups without statistical significance. In univariate analysis, transfusion dependency was associated with poor prognosis (HR 7.78, p = 0.013). Conclusions: This study provides the first single-institution analysis in Korean patients with MDS/MPN and identified U2AF1 mutations as a potentially significant prognostic factor, enhancing the molecular understanding of MDS/MPN. Full article

Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. Full article

Pulmonary neuroendocrine tumors (PULMONARY NETs) are heterogeneous tumors ranging from well-differentiated to highly aggressive neoplasms. The aim of this study is to prospectively test pre-operative circulating free DNA (cfDNA) in PULMONARY NET patients undergoing surgery and evaluate its relationship to clinicopathological features. From February to December 2024, 136 patients with suspected primary lung cancer underwent pre-operative blood sampling, of whom 21 were diagnosed with PULMONARY NETs. Total cell-free nucleic acid extraction was performed using the Genexus Purification System (Thermofisher). cfDNA was quantified using a fluorometric assay with the Qubit dsDNA HS Assay kit (Thermofisher) and a capillary electrophoresis-based assay (cell-free DNA ScreenTape kit) on the Tape Station 4200 systems (Agilent). A cfDNA quality assessment was also obtained (cfDNA sizing and % cfDNA). Most patients had Stage I (18/21.85.7%) typical carcinoids (16/21.76.2%). Nodal involvement was detected in one patient (0.5%). Six months after surgery, all patients were alive without recurrence. Larger tumors presented higher levels of cfDNA. The mean tumor size in patients with cfDNA > 40 ng was 266 mm (±16.7 mm), compared to 13.2 mm (±7.3 mm) for cfDNA < 40 ng (p-value = 0.018). Higher levels of cfDNA were observed in patients with pStages greater than IA (p-value = 0.007). Although limited by a small sample group and biases of a surgical series, we observed that larger/advanced PULMONARY NETs presented higher cfDNA levels pre-operatively. Full article

Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC. Full article

Background: Amino acid tracer positron emission tomography–magnetic resonance imaging (PET-MRI) was shown to be superior to MRI alone for evaluating central nervous system (CNS) tumours in adults. This study aimed to investigate the utility of amino acid PET-MRI in children with CNS tumours. Methods: We reviewed the amino acid PET-MRI findings of children with suspected or confirmed CNS neoplasms managed in a territory-wide referral centre in Hong Kong from 2022 to 2025. Maximal standardized uptake values (SUVmax) were captured, and tumour-to-background SUVmax ratios (TBRmax) were measured with reference to adjacent or contralateral normal brain structures. Comparisons were made among patients with clinical high-grade and low-grade/non-neoplastic lesions. Results: Thirty-seven patients were included, with 63 PET-MRIs performed. PET-MRI was performed as part of initial diagnostics in 41% of the cases, for response assessment in 48%, and evaluation of residual/relapsed disease in 11%. High-grade lesions had a significantly higher SUVmax and TBRmax compared to low-grade/non-malignant lesions (median SUVmax 3.7 vs. 1.6, p = 0.00006; median TBRmax 2.06 vs. 0.91, p = 0.00002). Optimal SUVmax and TBRmax cut-offs by ROC analysis were 2.38 and 1.62, respectively. Similar performance was reproduced by focusing on the subset of patients with suspected CNS germ cell tumours (CNS-GCT). The impact of amino acid PET availability is considerable, as clinical management was modified in 65% of patients. Conclusions: Our study demonstrates the performance and clinical utility of amino acid PET-MRI in the management of children with CNS pathologies. Amino acid PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for decision-making. Full article

Background: Primary spinal gliomas are rare in the pediatric population. Separately, FGFR1 genomic aberrations are also uncommon in spinal cord tumors. We report a case of a previously well adolescent who presented with progressive symptoms secondary to an intramedullary tumor with unique radiological and molecular characteristics. Case Presentation: A previously well 17-year-old male presented with worsening mid-back pain associated with lower limb long-tract signs. Magnetic resonance imaging (MRI) of his neuro-axis reported a long-segment intramedullary lesion with enhancing foci and a multi-septate syrinx containing hemorrhagic components from C4 to T12. The largest enhancement focus was centered at T7. Additional MRI sequences observed no intracranial involvement or vascular anomaly. He underwent an emergent laminoplasty and excision of the thoracic lesion. Intraoperative findings demonstrated a soft, grayish intramedullary tumor associated with extensive hematomyelia that had multiple septations. Active fenestration of the latter revealed blood products in various stages of resolution. Postoperatively, the patient recovered well, with neurological improvement. Final histology reported a circumscribed low-grade glial neoplasm. Further molecular interrogation via next-generation sequencing panels showed activating FGFR1 p.K656E and V561M missense alterations. The unique features of this case are presented and discussed in corroboration with a focused literature review. Conclusions: We highlight an interesting case of an intramedullary tumor with unusual radiological and pathological findings. Emphasis is on the importance of tissue sampling in corroboration with genomic investigations to guide clinical management. Full article

The accurate classification of pancreatic cystic lesions remains clinically challenging due to overlapping imaging features and variable malignant potential. Mucinous cystic neoplasms, in particular, require early identification given their premalignant nature. RNA profiling presents a promising alternative to current diagnostic limitations—a molecular lens sharpened by AI-driven pattern recognition. This study aimed to evaluate the diagnostic potential of RNA signatures for differentiating pancreatic cyst subtypes and to clarify their roles in their pathophysiology. The study included 31 patients with pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration. RNA was extracted from cyst fluid, tissue, and peripheral blood. Expression of 17 target genes was analyzed using qPCR. Gene expression patterns were compared across mucinous cystic neoplasms, serous cystic neoplasms, pseudocysts, adenocarcinoma, and chronic pancreatitis cohorts. Diagnostic accuracy was evaluated via ROC analysis. Mucinous cysts exhibited significant overexpression of MUC1, ITGA2, ELOVL6, and MUC5AC genes compared to serous cysts and pseudocysts. PKM gene expression correlated with increasing malignant potential. In blood plasma, only MUC1, MUC4, and PYGL were elevated in adenocarcinoma compared to mucinous neoplasms. We identified a distinct RNA signature that can distinguish mucinous cystic neoplasms from benign cystic lesions (serous cysts and pseudocysts), which could be useful for guiding patient management and improving clinical outcomes. Validation in broader cohorts is essential for clinical implementation. Full article

Background: Glioblastomas (GBMs) are the most aggressive and common neoplasms that affect glial cells, presenting rapid growth, invasion, and resistance to treatments. Studies have demonstrated the potentially inhibitory effect of flavonoids on glioblastoma cells’ stemness and viability. However, further research is needed to explore sensitivity and the mechanism of action in chemoresistant cells. Methods: In this study, we characterized the impact of apigenin treatment on the viability and differentiation of human GBM cells in vitro and its effects on tumorigenesis and regulation of the inflammatory response in vivo. Results: The flavonoid apigenin reduced the viability of U-251 cells, patient-derived cells TG-1 and OB-1 stem cells in a dose-dependent manner, associated with the induction of acidic vesicle organelles formation and apoptosis. Treatment with apigenin also inhibited migration and induced neural differentiation in the remaining viable cells, characterized by a decrease in the expression of the precursor marker nestin and an increase in the expression of astrocyte and neuron markers, GFAP and β-III tubulin, respectively. The xenotransplantation of apigenin-pretreated U251 cells into rat brains did not lead to tumor formation, unlike untreated cells. The surrounding area of transplanted untreated U251 cells exhibited reactive microglia and astrocytes, along with increased VEGF expression, which was absent in implant sites of apigenin-pretreated GBM cells. Moreover, in this implant area, we observed a significant decrease in the expression of mRNA for inflammatory factors IL-1β, TNF, and NOS2, and the downregulation of IL-10 and IL-4. Conclusions: These results demonstrate that apigenin inhibits the growth of tumoral cells, affecting the viability of tumor stem cells and impairing tumorigenicity, while altering the regulatory profile of immunomodulatory proteins. Therefore, this flavonoid can be considered for further studies to determine its use as an adjuvant to the treatment of human GBMs. Full article

Cutaneous leiomyosarcoma is a rare, malignant tumor that arises from smooth muscle cells, accounting for less than 3% of all cutaneous sarcomas. Our case report details a 63-year-old male patient who presented with a rapidly growing, painful nodule in the popliteal region. The patient underwent initial surgical excision in September 2021, followed by three subsequent resections until March 2022 due to local recurrence. Histopathological analysis of all specimens revealed a dermal neoplasm composed of spindle cells arranged in intersecting fascicles with storiform patterns. The immunohistochemistry profile showed strong positivity for the markers SMA and desmin, confirming the diagnosis. Despite early interventions, the deep surgical margins were positive, and further surgeries were required until tumor-free margins were achieved. This case emphasizes the morphological characteristics, clinical behavior, and therapeutic challenges in managing cutaneous leiomyosarcoma. A favorable prognosis is achieved with long-term follow-up and a multidisciplinary approach. Full article

Purpose: Renal angiomyolipomas (AMLs) are benign renal neoplasms that may lead to spontaneous hemorrhage. Transcatheter arterial embolization (TAE) is a nephron-sparing treatment option, yet data on predictors of hemorrhage and re-intervention remain limited. This study evaluates clinical and radiologic outcomes of TAE and identifies predictors of hemorrhage and repeat embolization. Materials and Methods: A retrospective review of 66 patients (69 AMLs) undergoing TAE between 2010 and 2024 was conducted. Clinical, radiological, and procedural variables were analyzed. Tumor size, vascularity, and aneurysmal features were assessed pre- and post-embolization. Logistic regression models identified predictors of hemorrhage and repeat TAE. Results: Pre-treatment tumor diameter was the only significant predictor of hemorrhage (p = 0.011), with a threshold of 6.8 cm yielding 84.6% sensitivity and 71.3% specificity. All hemorrhagic tumors measured ≥4 cm. Post-embolization tumor volume predicted repeat TAE (p = 0.001), with a 248 mL cutoff. TAE significantly reduced tumor diameter (−33.5%) and volume (−60%) (p < 0.001). Radiologic success was achieved in 97% of cases, with a durable success rate of 84%. Clinical success was 94%, and complications occurred in 7.2% of patients, including two major events. Conclusions: TAE is a safe and effective treatment for renal AMLs. Tumor diameter >6.8 cm is a strong predictor of hemorrhage, while larger post-embolization volumes predict the need for re-intervention. These findings challenge the conventional 4 cm treatment threshold and support more individualized management strategies incorporating tumor morphology and response to embolization. Full article

Background: Cardiotoxicity remains a concern across cancer therapies. To date, there is a lack of extensive studies evaluating the potential impact of radioligand therapy (RLT) on myocardial injury in patients with neuroendocrine tumors (NETs), particularly in subgroups with increased susceptibility to such injury. This study aimed to assess the potential cardiotoxic effects and myocardial dysfunction associated with RLT using both [¹⁷⁷Lu]Lu-DOTA-TATE and tandem therapy with [¹⁷⁷Lu]Lu-DOTA-TATE/[⁹⁰Y]Y-DOTA-TATE in patients with NETs, including specific high-risk subgroups such as patients with pre-existing heart failure, carcinoid heart disease or those previously treated with chemotherapy, by monitoring serum concentration of troponin I, CK-MB, and NT-proBNP before and after RLT. Methods: We conducted a retrospective observational analysis of 60 consecutive NET patients who underwent 228 RLT courses. A comprehensive cardiac assessment, including a detailed medical history, was performed. Additionally, serum troponin I, CKMB and NT-proBNP concentrations were measured prior to treatment and 48 h post-therapy. Fifty-two patients received [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy, while eight patients were treated with tandem therapy. Results: No increase in cardiotoxicity markers was observed in the overall study population following RLT administration (ΔTroponin −0.2 [−1.4–0.3]ng/L, p = 0.007; ∆CKMB 0.0 [−4.0–3.0]U/L, p = 0.90; ΔNT-proBNP 4.0 [−45.6–33.6]pg/mL) as well as in the subgroup receiving tandem therapy (ΔTroponin 0.7 [−1.7–013]ng/L, p = 0.68; ΔCKMB −0.5 [−10.7–3.0]U/L, p = 0.21; ΔNT-proBNP −21.6 [−44.1–16.7]pg/mL). Furthermore, none of the predefined patient subgroups exhibited signs of cardiotoxicity or evidence of myocardial dysfunction. Conclusions: RLT is a safe anticancer treatment option for patients with NETs in terms of cardiotoxicity and cardiac dysfunction, including those at higher risk of cardiovascular complications. Full article

Abnormalities were observed in the testes of common carp Cyprinus carpio collected from Willow Beach, Arizona, USA, a site on the lower Colorado River, downstream of Lake Mead and Hoover Dam. Testicular tissue collected from this site in 2003 exhibited numerous large, pigmented macrophage aggregates (MAs) and a novel, previously undescribed hypertrophy and proliferation of putative Sertoli cells. In testes samples collected in 2007, numerous testicular MA, testicular oocytes, and proliferations of Sertoli cells were observed. Three carp collected in 2007 also had raised nodules within the testes, and, microscopically, seminoma, spermatogenic seminoma, and mixed stromal cell–germ cell neoplasms were diagnosed. Several risk factors for these adverse effects were identified. Carp collected at this site in 2003 ranged in age from 35 to 54 years and had the oldest mean age of the thirteen sites sampled within the Colorado River basin. This site also has an unusual thermal regime when compared to other sites studied in Lake Mead and upstream sites, in that temperatures varied little over the seasons (amplitude around 1.5 °C) and barely reached 15 °C. Additionally, carp from this site had the highest total polychlorinated biphenyl (PCB) body burden. Hence, advanced age, low water temperature, and exposure to PCBs and other environmental contaminants may contribute to the observed abnormalities, highlighting the complex environmental factors initiating pre-neoplastic and neoplastic changes in wild carp. Full article

Phyllodes tumors are rare fibroepithelial neoplasms of the breast, and their malignant forms present significant diagnostic and therapeutic challenges. This review summarizes current knowledge across the benign-to-malignant spectrum, focusing on diagnostic approaches, histopathological classification, molecular alterations, and treatment strategies. While recent molecular studies have revealed recurrent genetic mutations, their clinical implications remain under investigation. Surgical excision remains the cornerstone of treatment, and systemic therapies are generally adapted from soft tissue sarcoma protocols. Future efforts should focus on improving diagnostic accuracy, identifying molecular targets for therapy, and fostering international collaboration to advance clinical research in this rare tumor type. Full article

Although methotrexate (MTX) is a magnificent cure for cancerous neoplasms and inflammatory disorders, its usage is bound due to associated hazards, especially nephrotoxicity. The present study investigated the possible therapeutic impact of alogliptin (ALO), prescribed for managing type 2 diabetes, on renal injury caused by MTX and explored the mechanisms that could illustrate this suggested protective effect. Four rat groups were involved: control, ALO (20 mg/kg/d, intragastrically (I.G.)) for ten days, MTX, and MTX + ALO groups. The latter two groups were given MTX (20 mg/kg, I.P.) on the 7th day, while the MTX + ALO group was administered ten days of 20 mg/kg of ALO. A significant impairment in renal function, catalase activity, reduced glutathione content, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expressions, coupled with an increase in kidney injury molecule-1 (KIM-1), malondialdehyde, tumor necrosis factor-alpha (TNF-α), and cleaved caspase-3 (c-caspase-3) expressions, was observed in MTX-intoxicated rats, evidenced by remarkable deterioration in renal construction. Conversely, ALO improved renal function and architecture. Moreover, ALO retrieved the oxidative balance, the attenuated Nrf2/HO-1 expression, and the elevated KIM-1, TNF-α, and c-caspase-3 expression. In conclusion, ALO might abrogate MTX-elicited kidney damage by rectifying the deviation in oxidative status, apoptotic and inflammatory pathways, paving the way for managing MTX-induced nephrotoxicity. Full article

Background and Clinical Significance: Adenoid cystic carcinoma (ACC) is a rare neoplasm of salivary glands, accounting for approximately 2–4% of all ACCs of head and neck malignancies. Adenoid cystic carcinoma (ACC) of the larynx is exceedingly rare, accounting for only 0.07–0.25% of all laryngeal tumors. Within the larynx, ACC may arise in various locations; however, the subglottic region is most commonly affected, representing approximately 64% of cases. ACC typically manifests as a slow-growing tumor with a pronounced tendency for perineural invasion and local recurrence. Current treatment strategies primarily involve surgical resection followed by adjuvant radiotherapy. Chemotherapy demonstrates limited efficacy and is generally reserved for advanced, recurrent, or metastatic disease. Given the rarity of this malignancy and the limited number of cases reported in the literature, we aim to contribute to the existing body of knowledge by presenting a clinical case of laryngeal ACC. Case Presentation: A 77-year-old male with a significant smoking history (more than 20 cigarettes per day for over 40 years) presented to our department in October 2023 with persistent dysphonia lasting several months. Endoscopic evaluation of the upper aerodigestive tract revealed an extensive neoplastic lesion involving the larynx. Contrast-enhanced computed tomography (CT) confirmed the presence and extent of the lesion. The patient subsequently underwent surgical resection and was referred for adjuvant postoperative radiotherapy. Unfortunately, the patient died of a myocardial infarction a few days before radiotherapy could be initiated. Conclusions: Due to the rarity of laryngeal adenoid cystic carcinoma, further studies are necessary to define optimal management strategies. Sharing clinical experiences and outcomes is essential, as there is currently no universally accepted treatment consensus for this uncommon malignancy. At the same time, our aim is to highlight the importance of histological subtype and perineural invasion which have to be considered as important prognostic factors when dealing with ACC. Full article