Search Results (501)

Background and Clinical significance: Cowden syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in the PTEN tumor suppressor gene. It is characterized by multiple hamartomas and an increased lifetime risk of malignancies affecting the breast, thyroid, endometrium, and gastrointestinal (GI) tract. Pediatric presentations may include macrocephaly, scrotal tongue, and intellectual disability. Gastrointestinal involvement is frequent, with juvenile-like hamartomatous polyps occurring in at least half of patients and distributed throughout the GI tract, posing a risk for malignant transformation. Early diagnosis and surveillance are crucial for improving patient outcomes. Case Presentation: We report a case of a 10-year-old Caucasian female with Cowden syndrome, with a history of a malignant germ cell tumor of the ovary consisting of a yolk sac tumor and low-grade immature teratoma diagnosed at age six, and thyroidectomy at age nine. The patient has mild intellectual disability. Routine radiological surveillance revealed a right colon intraluminal mass, prompting referral for pediatric gastroenterology evaluation. Endoscopy identified multiple polyps throughout the colon, stomach, and small intestine. Polypectomy of larger lesions was performed, and histopathology confirmed juvenile-like hamartomatous polyps without dysplasia or malignancy. This case highlights the necessity of comprehensive gastrointestinal evaluation in pediatric Cowden syndrome patients. Endoscopic surveillance is essential for early detection and management of polyps. Conclusions: Given the multisystem involvement and elevated cancer risk associated with PTEN mutations, a multidisciplinary approach that includes genetic counseling, dermatologic evaluation, and ongoing oncologic monitoring is recommended. Increased awareness of gastrointestinal manifestations enables timely intervention and may reduce morbidity and mortality in this high-risk population. Full article

BST2 has emerged as a multifunctional molecule that bridges antiviral defense, membrane architecture, and tumor immunity. Originally characterized as an interferon-inducible restriction factor that tethers virions to the plasma membrane, BST2 is now recognized as an oncogenic driver and immunoregulatory hub in diverse malignancies. In cancer, BST2 expression is frequently upregulated through promoter hypomethylation and transcriptional activation. Functionally, BST2 promotes proliferation, epithelial–mesenchymal transition, anoikis resistance, and chemoresistance, whereas its loss sensitizes tumor cells to proteotoxic and metabolic stresses. Beyond tumor cells, BST2 modulates the tumor microenvironment by promoting M2 macrophage infiltration, dendritic cell exhaustion, and natural killer (NK)-cell resistance, thereby contributing to immune evasion. Elevated BST2 expression correlates with poor prognosis in glioblastoma, breast, nasopharyngeal, and pancreatic cancers, and it serves as a circulating biomarker within small extracellular vesicles. In conclusion, BST2 is a dual-function molecule that integrates oncogenic signaling and immune regulation, making it an attractive diagnostic and therapeutic target for hematological and solid tumors. Full article

Background: Prostate cancer (PCa) is a prevalent malignancy with a rising incidence. Advanced PCa, often resistant to therapy, remains a major clinical challenge, underscoring the need to identify novel molecular drivers. Methods: Utilizing transcriptomic data from the TCGA and GEO databases, we identified APOBEC3C (A3C) as a key candidate through WGCNA, differential expression analysis, and LASSO regression. Its clinical relevance was assessed via Kaplan–Meier survival analysis. Then, we validated A3C expression patterns using immunohistochemistry and Western blot in normal and malignant prostate cell lines. The functional effects of A3C on proliferation, migration, and invasion and mechanisms of such were evaluated through in vitro gain- and loss-of-function assays (CCK-8, Ki67 staining, wound healing, Transwell, Western blot, etc.). Results:A3C was significantly downregulated in PCa, and this low expression strongly correlated with adverse clinicopathological features, including advanced T stage, higher Gleason scores, and worse survival. Bioinformatically, high A3C expression was associated with an activated anti-tumor immune microenvironment, characterized by enhanced CD8+ T cell infiltration, reduced M2 macrophage abundance, and upregulation of the immune checkpoint CD40. In vitro, A3C overexpression effectively suppressed PCa cell proliferation, migration, and invasion, while its knockdown promoted these malignant phenotypes. Mechanistically, A3C enhances the expression of the STING1 and its downstream related molecules Caspase-1, IL-18, and IL-1β; upregulates DNA damage-protective genes (GSTP1 and GPX3); and enhances the expression of cell cycle regulator GAS1. Conclusions: This study establishes A3C as a suppressor in PCa, which impedes tumor progression by regulating key molecules involved in cellular inflammation, cell cycle arrest, and DNA damage response. Full article

Over the past several decades, rapid advances in molecular genomics have transformed our understanding of thyroid malignancies and are increasingly integrated into international clinical guidelines. Mutational profiles and epigenetic events are now recognized not only as diagnostic and prognostic tools but also as predictors of therapeutic response. Papillary, follicular, oncocytic, medullary, and anaplastic thyroid carcinomas harbor distinct early driver mutations, such as BRAFV600E, RAS, and fusion events (RET, NTRK, and ALK), that cooperate with secondary alterations (TERT promoter, TP53, PIK3CA, and CDKN2A/B loss) to drive dedifferentiation, metastasis, and therapeutic resistance. Insights from The Cancer Genome Atlas (TCGA) and transcriptomic scoring systems (e.g., BRAF–RAS score) now link genotype to tumor morphology, metastatic tropism, and radioactive iodine refractoriness. These molecular insights have been incorporated into updated risk stratification frameworks, preoperative surgical planning, and treatment algorithms, informing the selection of kinase inhibitors, redifferentiation strategies, and enrollment in genotype-directed clinical trials for radioiodine-refractory disease. This review synthesizes recent evidence connecting genomic alterations to clinical behavior and highlights their translation into evolving approaches for thyroid cancer management. Full article

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic–catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability. Full article

Background/Objectives: Unstable intertrochanteric femur fractures (IFFs) in geriatric patients are associated with high rates of morbidity and mortality due to poor bone quality, multiple comorbidities, and limited functional capacity. This study aimed to compare the clinical outcomes of cementless bipolar hemiarthroplasty (BHA) performed via a transtrochanteric approach and proximal femoral nailing (PFN) in elderly patients with unstable IFFs. Methods: This retrospective comparative study included 131 patients aged ≥70 years who underwent surgery for AO/OTA 31-A2 and 31-A3 unstable fractures between January 2021 and July 2025 were retrospectively reviewed. 64 patients received cementless BHA and 67 underwent PFN. Eligible patients were ambulatory prior to fracture (independently or with a cane/walker); patients with pathological fractures/malignancy, alternative procedures (cemented or posterolateral BHA, total hip arthroplasty, tumor prosthesis, or other osteosynthesis methods), incomplete records, or <6 months of follow-up were excluded. Demographics, perioperative variables, mechanical complications, revision requirement, time to mobilization, and 1- and 6-month mortality rates were analyzed. Primary outcomes were mortality and perioperative clinical parameters. Results: The two groups were comparable in age, sex, ASA scores, and fracture patterns. Intraoperative blood loss and transfusion requirements were significantly higher in the BHA group (both p < 0.001). Mobilization was observed earlier in patients treated with BHA (1 [1,2] vs. 3 [2,3] days; p < 0.001). Mechanical complications were more frequently observed after PFN, which was associated with a higher revision requirement (17.9% vs. 4.7%; p = 0.018). Operative time, hospital stay, and 1- and 6-month mortality rates showed no significant differences between the groups. Conclusions: In geriatric patients with unstable IFFs, cementless BHA performed via a transtrochanteric approach may be considered a viable surgical option with appropriate patient selection, taking into account its association with earlier mobilization and the observed mechanical complication profile. PFN offers advantages of reduced blood loss and lower transfusion needs. Surgical decision-making should be individualized based on fracture morphology, bone quality, and the patient’s overall medical condition. Given the heterogeneity of unstable fractures within the AO/OTA classification and the retrospective nature of the present study, larger, multicenter prospective investigations incorporating functional outcomes are warranted to further clarify optimal treatment strategies. Full article

Background/Objectives: Astrocytoma IDH-mutant CNS WHO grade 4 is a malignant tumor of the central nervous system characterized by tumor necrosis, microvascular proliferation, and/or homozygous CDKN2A/B deletion. This study aims to investigate the prognostic role of the consequences of hypoxic events leading to necrosis and microvascular density, observing their associations with clinical-imaging parameters and morphogenetics. Methods: We performed a retrospective analysis over a 10-year period. Clinical and imaging data were collected from observation sheets and electronic databases. Six immunohistochemical markers and FISH testing were used to evaluate the prognosis and neoformation of blood vessels. Based on the whole slide image, the necrotic percentage was assessed, and the microvascular density was quantified. All data were statistically analyzed. Results: We identified 44 cases, with a mean age of 57.86 years. From a clinical perspective, advanced age, arterial hypertension, diabetes mellitus, and acute onset of clinical manifestations represent negative prognostic factors. In imaging, the increased rate of resectability is a protective factor, while the presence of residual volume and an increased residual volume have a negative impact on survival. The consequences of hypoxic events (tumor necrosis and microvascular density) are negative risk factors for survival. Added to these are p53 overexpression, loss of PTEN, deletion, and amplification of the CDKN2A gene. Conclusions: We observed that necrosis and increased microvascular density resulting from microvascular proliferation are both defining features of the tumor and impact patient prognosis and survival. In addition, they induce or are associated with other essential changes (p53, PTEN, CDKN2A) that promote tumor aggressiveness. Full article

Background and Objectives: Robot-assisted procedures represent a significant advancement in minimally invasive liver resection techniques. Nonetheless, the introduction of a novel surgical technique in a new environment necessitates meticulous planning and a gradual, stepwise approach. This study describes the adoption of a robotic surgical platform for liver resection at a high-volume tertiary care center. Materials and Methods: We retrospectively analyzed data that had been prospectively collected from fifty robot-assisted liver resections. Descriptive statistics, including frequencies, percentages, means/medians, and standard deviations, were employed for description and summary. Results: The median operative duration was 166 min (range: 85–400 min), with an average intraoperative blood loss of 200 mL (range: 50–1000 milliliters). Intraoperative or postoperative blood transfusion was required in 8% of patients. Conversion to open resection was necessary in one patient (2%). The mean duration of hospitalization was 5 days (range: 3–20 days), with a 30-day readmission rate of 6% and no mortality within 90 days. Postoperative complications classified as Clavien-Dindo grade 3 or higher were observed in five patients (10%). The mean tumor size varied according to pathology: 58.5 mm (range: 30–120 mm) in the hepatocellular carcinoma group; 27.4 mm (range: 10–32 mm) in the secondary malignancy group; and 42.6 mm (range: 24–60 mm) in the intrahepatic cholangiocarcinoma group. The median number of lymph nodes harvested during lymphadenectomy (IHHCA/GBCA) was 5.4, ranging from 1 to 11. The R0 resection rate for malignant tumors was 88.2% (of 30/34). Conclusions: This study validates the safe integration of robot-assisted surgery into liver disease treatment, supported by our initial experience. Despite its technical advantages, robotic-assisted liver surgery remains complex and demanding. Structured robotic training within established programs, meticulous patient selection, and a stepwise implementation approach are critical during the early phases to optimize the outcomes. Full article

Background/Objectives: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, creating an urgent need for novel biomarkers to improve risk stratification. The prognostic significance of the transmembrane glycoprotein CD44 and its isoforms (CD44s, v5, v6) in CCA remains controversial. This preliminary study aimed to investigate whether the combined loss of these isoforms could serve as a distinct prognostic indicator. Methods: We evaluated the expression of CD44s, CD44v5, and CD44v6 via immunohistochemistry on a retrospective cohort of 61 paraffin-embedded CCA patient tissue blocks from Ramathibodi Hospital, Bangkok, Thailand. Expression levels were correlated with clinicopathological parameters. Survival analyses, including Kaplan–Meier and Cox proportional hazards models, were used to determine the prognostic value of individual isoforms and the complete absence of all three. Results: Expression of CD44s, CD44v5, and CD44v6 was found in 52.5%, 47.5%, and 82.0% of tumors, respectively. In univariate and multivariate analyses, the expression of any single isoform was not a significant predictor of overall survival. However, a subgroup of 8 patients (13.1%) was identified whose tumors were negative for all three isoforms, a phenotype we termed “CD44s-v5-v6 Null”. This status was significantly associated with advanced TNM stages (p = 0.022). Patients with these Null tumors also showed a clinically relevant, though not statistically significant, trend towards poorer survival (median 7.0 vs. 12.0 months, p = 0.336). Conclusions: Individual CD44 isoforms did not serve as reliable independent prognostic markers in this cohort. Instead, the complete loss of the CD44 expression program characterizes a potential “CD44s-v5-v6 Null” phenotype associated with advanced-stage disease. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, typically diagnosed at an advanced stage. The identification of prodromal symptoms could support earlier detection. Among these, depression is frequently reported, raising the question of whether it may represent not only a reactive response but also a paraneoplastic manifestation. Methods: We conducted a narrative review of clinical, epidemiological and biological literature published between 1988 and 2025. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to pancreatic cancer, depression, prodromal symptoms, cytokines, and the kynurenine pathway. Eligible studies included clinical cohorts, population-based analyses, biological investigations, and case reports exploring the temporal or mechanistic link between depression and PDAC. Results: A substantial proportion of patients (10–20%) exhibit depressive symptoms in the months preceding the clinical diagnosis of pancreatic cancer. In several cases, depression occurs independent of weight loss and new-onset diabetes. Biological evidence highlights the involvement of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), NF-κB signaling, and activation of the tryptophan–kynurenine pathway (IDO), suggesting a link between tumor-related processes and mood alterations. These mechanistic findings are actually hypothesis-generating, deriving mainly from small clinical cohorts and preclinical models. Clinically, depression is associated with reduced adherence to treatment, poorer quality of life, and shorter survival. However, no specific depressive phenotype has been identified. Conclusions: Depression may represent a potential prodromal symptom of pancreatic cancer, reflecting systemic biological processes as well as psychological reactions. Its utility as a standalone marker remains limited; future studies should integrate psychiatric, clinical and biological biomarker assessments to enhance early clinical diagnosis. Full article

Background: Cannabinoids (CBs) are FDA-approved for mitigating chemotherapy-induced side effects such as pain, nausea, and loss of appetite. Beyond palliative care, CBs exhibit anti-tumor properties in various cancers, including non-Hodgkin’s lymphoma (NHL). Previously, we demonstrated the cytotoxic effect of endogenous and exogenous cannabinoids on human and canine B- and T-cell-type NHL cell lines. The purpose of this study was to establish the cytotoxic effect of cannabinoids in combination with the components of CHOP and lomustine. This traditional NHL chemotherapy regimen comprises cyclophosphamide, doxorubicin, vincristine, and prednisolone. Methods: In this study, we studied three cannabinoids, one from each of the three major categories of cannabinoids (endocannabinoid AEA, phytocannabinoid CBD, and synthetic cannabinoid WIN-55 212 22). Each cannabinoid was selected based on potency, as determined in our previous experiments. For the combination, we used five NHL chemotherapy drugs. We analyzed the cytotoxicity of each drug alone and in combinations using canine malignant B-type NHL cell line 1771 and a colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) cell proliferation assay and combination index (CI) based on the Chou–Talalay method. Results: Our results demonstrate that the cytotoxic effects of all traditional NHL chemotherapy drugs are synergistically enhanced (interaction with CI < 1) by each of the three cannabinoids at sub-IC₅₀ concentrations. Conclusions: This work provides a proof of concept for using cannabinoids and traditional NHL drugs in combination to reduce the dose, and thereby potentially reducing the toxicity, of chemotherapeutic drugs and increasing the survival benefit in lymphoma clinical translation studies, offering a significant advancement in cancer treatment. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

Objectives: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by rapid proliferation, early metastasis, and limited therapeutic response. Metabolic reprogramming is increasingly recognized as a key feature of small cell lung cancer progression, yet the contribution of specific metabolic enzymes remains incompletely understood. This study aimed to investigate the role of asparagine synthetase in small cell lung cancer tumorigenicity and disease progression. Methods: Integrative analyses were performed using public transcriptomic datasets, proteomic profiling, and functional assays in vitro and in vivo. Asparagine synthetase expression levels were evaluated in normal lung, non-small cell lung cancer, and small cell lung cancer tissues using public microarray datasets. Loss of function studies were conducted using shRNA mediated knockdown in murine and human small cell lung cancer cell models. Tumor growth and survival were assessed using xenograft mouse models. Results: Asparagine synthetase expression was significantly elevated in small cell lung cancer compared with normal lung and non-small cell lung cancer tissues. Genetic depletion of asparagine synthetase impaired cellular proliferation and colony forming capacity in vitro. In vivo, asparagine synthetase knockdown suppressed tumor growth and was associated with prolonged survival in xenograft mouse models. Conclusions: These findings demonstrate that asparagine synthetase contributes to tumor growth and metabolic adaptability in small cell lung cancer. The results support a functional role for asparagine synthetase in malignant progression and suggest that targeting asparagine metabolism may represent a potential therapeutic approach in aggressive small cell lung cancer. Full article

The MTAP (methylthioadenosine phosphorylase) gene, located on chromosome 9p21, plays a crucial role in the methionine salvage pathway and is frequently co-deleted with CDKN2A in various malignancies. Loss of MTAP expression leads to the accumulation of methylthioadenosine (MTA), which selectively inhibits protein arginine methyltransferase 5 (PRMT5) and creates a unique metabolic vulnerability in MTAP-deficient tumors. These alterations have emerged as promising therapeutic targets in precision oncology. Recent advances highlight the potential of exploiting MTAP loss through synthetic lethality approaches using PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibitors. Preclinical and early clinical data indicate that targeting these pathways can selectively impair tumor growth while sparing MTAP-proficient cells. Moreover, MTAP deletion has been associated with specific molecular and immunologic profiles that may influence treatment response and tumor microenvironment characteristics. This review summarizes current knowledge on the biological functions of MTAP, the mechanisms linking its loss to oncogenesis, and the evolving landscape of therapeutic strategies targeting MTAP-deficient cancers. Understanding these molecular dependencies offers novel opportunities for the development of precision-based therapies across diverse tumor types. Full article

Neurofibromatosis type 1 (NF1) predisposes to a spectrum of peripheral nerve sheath tumors, ranging from benign plexiform neurofibromas (PN) to atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP) and malignant peripheral nerve sheath tumors (MPNST). Tumorigenesis follows a multistep molecular cascade initiated by biallelic NF1 inactivation, followed by CDKN2A loss and disruption of the Polycomb Repressive Complex 2 (PRC2). These events guide chromatin remodeling, widespread epigenetic dysregulation, and activation of oncogenic pathways such as RAS/MAPK and PI3K/AKT. Here, we integrate genomic, transcriptomic, and epigenomic studies to delineate the molecular trajectories underlying tumor progression and to define promising biomarkers for the early detection of malignant transformation. Emerging liquid biopsy approaches, based on circulating tumor DNA (ctDNA) analyses, reveal distinctive copy number variations (CNVs) and methylation patterns that mirror tissue-derived profiles, enabling the detection of malignant transformation. Together, these findings support a model in which cumulative genetic and epigenetic alterations drive the PN–ANNUBP–MPNST continuum. They also underscore the value of multi-omics and liquid biopsy-based strategies to improve early diagnosis, patient risk stratification, and personalized management of NF1-associated tumors, thereby advancing precision medicine in this complex disease spectrum. Full article