Search Results (3,795)

Background/Objectives: Contralateral prophylactic mastectomy (CPM) is increasingly performed despite negative preoperative imaging. We evaluated the prevalence and MRI detectability of occult pathology in the contralateral breast. Methods: In this single-center retrospective cohort, 82 patients with unilateral invasive breast cancer underwent simultaneous CPM after preoperative contralateral MRI. Occult findings were classified as occult malignancy, atypical/high-risk lesions, or other lesions of uncertain malignant potential (B3 lesions); the primary outcome was clinically significant occult pathology (malignancy or an atypical/high-risk lesion). Proportions are reported with exact 95% confidence intervals and associations with exact odds ratios and Benjamini–Hochberg correction. Results: Occult malignancy occurred in 1/82 (1.2%; a single DCIS), clinically significant occult pathology in 14/82 (17.1%) and any occult pathology in 21/82 (25.6%). Among 59 patients with a negative MRI (BI-RADS 1–2), clinically significant occult pathology occurred in 18.6% and atypical/high-risk lesions in 16.9% (whole cohort, 15.9%). The single occult malignancy arose in an MRI-negative breast. No factor remained significant after correction for multiple comparisons. Conclusions: After preoperative MRI, occult malignancy is rare, whereas atypical and high-risk lesions frequently remain occult; a negative contralateral MRI excluded neither. These findings support individualized, shared decision-making rather than the yield of occult pathology as the basis for CPM. Full article

Machine learning and statistical classification methods are widely applied to microbiome data for diagnostic, prognostic, and phenotypic insights. However, the complex, multivariate nature of microbiome communities makes it difficult to assess the relative performance of these methods. Most comparisons rely on a small number of published datasets, without considering their underlying ecological properties or how these properties may, in turn, influence classification performance. We introduced a coenocline-based simulation framework to generate synthetic microbiome datasets that incorporate realistic ecological variation arising from species’ responses to host-associated gradients such as disease severity. To evaluate the ecological fidelity of these simulations, we compared synthetic datasets to five widely used real-world microbiome datasets: Cirrhosis, Colorectal Cancer (CRC), Type 2 Diabetes (Chinese and Women cohorts), and the Human Microbiome Project (HMP). Comparisons across α-diversity (species richness), β-diversity (species composition and turnover), and abundance distributions demonstrated that coenocline simulations closely recapitulate the key ecological structures of empirical data. Synthetic datasets exhibited similar richness and abundance patterns to disease-associated microbiomes, with realistic distributions of few dominant and many rare taxa. Moreover, community composition analyses (Bray–Curtis index) revealed that the simulated datasets captured natural levels of compositional dissimilarity among samples, spanning the same variability range observed in real data. When compared against 100 independently simulated datasets, the coenocline model consistently reproduced empirical ranges of species diversity, relative abundance, and between-group compositional differences (ANOSIM-R values), confirming the model’s robustness and reproducibility. This coenocline-based simulation framework provides a novel, flexible, and ecologically grounded approach for generating synthetic microbiome data with controlled complexity. By reproducing realistic ecological gradients and community structures, the framework supplies the controlled test beds needed for systematic future benchmarking of machine learning and statistical classification methods across diverse and biologically meaningful scenarios. In doing so, it will help bridge the gap between ecological realism and computational modeling, thereby supporting more reliable and generalizable inference from microbiome data. Full article

Background: Worldwide, around 400,000 children are diagnosed with cancer every year. Understanding survivors’ social and stigma-related experiences may help address their needs and improve their outcomes. Objectives: To explore the social and stigma-related experiences, coping strategies, and support needs of pediatric cancer survivors in Newfoundland and Labrador, a province of Canada. Methods: This is a qualitative, cross-sectional study focusing on retrospective participant experiences. Eligibility criteria included being diagnosed with cancer before the age of 18 and being diagnosed or treated in the province. Extensive recruitment activities were employed. Data collection occurred through semi-structured virtual interviews and completion of a sociodemographic survey. Participant interviews were transcribed verbatim, and themes were identified iteratively through inductive thematic analysis. Descriptive statistics were used to define the participants’ sociodemographic characteristics. Results: Seven participants were recruited. Thematic analysis identified five major themes: (i) isolation and being treated differently; (ii) support received, coping mechanisms, and support needs; (iii) resilience and interest to give back; (iv) workplace and disability related experiences; and (v) additional impacts of cancer. Our results showed that participants received substantial social support in various ways but inadequate professional mental health support. School was a significant setting for cancer-related stigmatization. Discrimination in the workplace was rare and was disability-related rather than cancer-related. Conclusions: Our results show that there are significant issues to address, such as stigma and isolation experienced by pediatric cancer survivors as well as the need to improve the psychosocial support programs offered to them. Our results also show that the participants had distinct lived experiences compared to adult-onset cancer populations. Overall, the findings presented are expected to inform further studies and healthcare-education policies to help address these issues and improve the experiences of pediatric cancer survivors. Full article

Background/Objectives: Liver metastasis develops in approximately 50% of patients with colorectal cancer. Invasion of the biliary tract from colorectal liver metastasis (CRLM) is rarely reported. Preoperative diagnosis remains elusive, prohibiting optimal surgical management. The objective of this systematic review was to summarize the clinical, radiological, pathological, and treatment characteristics of ibCRLM and describe the reported outcomes. Methods: A systematic literature search of the Medline, Embase, Web of Science, CENTRAL, and CINAHL databases was undertaken for studies reporting clinical outcomes of patients with ibCRLM, up to May 2026. An individual patient data analysis approach was utilized. Results: Thirty-eight case reports and 10 case-series, incorporating 228 patients with biliary involvement from CRLM, were identified. Mean age was 62.4 ± 10.9 years, with a male-to-female ratio of 3.2:1. The majority of metastatic lesions were metachronous in 71.1% and solitary in 59.1% of patients. Surgical treatment was implemented in 89.2% of patients. Major hepatectomy was the most common procedure, being performed in 46.2% of patients, followed by minor hepatectomy in 38.7% and pancreatoduodenectomy in 4.3%. After a median follow-up of 52.5 months (range 2–164 months), the survival rate was 60.5%. Non-survivors were found to have significantly more synchronous CRLM (50% versus 0, p = 0.008), while a single patient did not receive any curative-intent treatment and died 20 days following CRLM presentation. Conclusions: IbCRLM is a distinct clinicopathological presentation of CRLM with characteristic radiological and pathological features. The available evidence suggests that selected patients may achieve favorable long-term outcomes following complete surgical resection, although these findings should be interpreted with caution given the limitations of the available literature. Full article

Background/Objectives: Circulating tumor-associated cells (CTACs) are rare among peripheral blood nucleated cells (PBNCs), creating a challenge for image-based multi-cancer detection. We evaluated a predefined CTAC-detection pipeline incorporating Attention U-Net segmentation, post-processing, cytological feature extraction, and Random Forest classification. Methods: Model suitability was explored in asymptomatic individuals and patients with advanced solid tumors. Clinical performance was assessed in a case–control cohort of therapy-naive stage I/II cancers, benign conditions, and asymptomatic individuals, followed by four prospective cohort evaluations performed within the same laboratory and imaging workflow: recurrent cancer with low radiological tumor burden, peri-operative solid tumors, suspected cancer, and asymptomatic screening. PBNCs were stained with EpCAM/Hoechst 33342 and imaged. Pathologists’ review established ground truth annotations. Results: The model had 90.68% sensitivity and 99.53% specificity in the exploratory study. In the case–control cohort, sensitivity was 88.65% in therapy-naive stage I/II cancers, while specificity was 78.95% in benign conditions and >99.9% in asymptomatic individuals. In the prospective cohorts, CTAC detection sensitivity was 91.96% in pretreated low tumor burden cases; CTACs were detected in 100% of pre-surgery specimens and 29.41% of post-surgery specimens; and in suspected cancer cases, the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were 96.34% and 32.35%, respectively. In the asymptomatic screening cohort, 44/7183 participants were CTAC-positive; 16 had confirmed Stage I/II cancer, 10 had no radiologically detectable disease at the available assessment, and 18 remained unresolved. The conservative lower-bound PPV was 36.36%, and the NPV was 99.97%; estimates remain provisional pending complete follow-up. Conclusions: The integrated Attention U-Net/feature-based classification pipeline demonstrated consistent CTAC detection across the evaluated cohorts and supports its potential clinical utility for cancer detection. Full article

Background: Pleomorphic rhabdomyosarcoma (RMS) is a rare, adult-predominant high-grade sarcoma that usually arises in the deep soft tissues of the extremities. Primary oral pleomorphic RMS is exceptionally rare, and detailed CT and MRI characteristics of oral pleomorphic RMS remain sparsely documented. Case Presentation: A 66-year-old woman presented with a two-month history of lower anterior tooth pain and progressive mandibular swelling, initially misdiagnosed and treated as a dental infection. CT and MRI revealed a 3.8-cm heterogeneously enhancing mass centered in the mandibular gingiva, with aggressive cortical destruction, diffusion restriction, and anterior floor-of-mouth extension; oral cavity cancer (squamous cell carcinoma) was initially favored on imaging. The patient underwent wide excision with segmental mandibulectomy and fibular osteocutaneous free-flap reconstruction. Histopathologic examination confirmed a high-grade pleomorphic RMS with immunoreactivity for desmin and MyoD1. The patient received adjuvant chemotherapy and radiotherapy, with no recurrence at 8-month follow-up. Conclusions: Pleomorphic RMS of mandibular gingiva may be mistaken clinically for odontogenic infection and radiologically for squamous cell carcinoma. Although imaging findings are nonspecific, CT and MRI are essential for defining mandibular and floor-of-mouth involvement and planning resection; definitive diagnosis requires histopathologic and immunohistochemical confirmation. Full article

Background/Objectives: Total en bloc spondylectomy (TES) remains one of the most invasive and selectively used procedures in spine oncology. Its role has become more selective in the modern era of stereotactic body radiotherapy, separation surgery, targeted systemic therapy, immunotherapy, and multidisciplinary cancer care. This study evaluated long-term survival, imaging-defined systemic disease burden, operative morbidity, patient-reported outcomes, and frailty-related variables after TES in a rare single-center cohort, with the goal of identifying selection-relevant survival and treatment-burden signals rather than developing a validated decision algorithm. Methods: We performed a retrospective single-center cohort study of consecutive adults who underwent TES for spinal tumors between 2011 and 2022. Of the 36 screened patients, 30 had sufficient clinical and survival data for analysis; patients without reliable survival or last-contact data were not included. Contrast-enhanced CT and PET-CT were reviewed for extraspinal metastases, lymphadenopathy, pleural effusion, and soft-tissue extension. Survival was analyzed using Kaplan–Meier methods, log-rank testing, and exploratory univariate Cox regression. Patient-reported outcomes included the Oswestry Disability Index (ODI) and SF-36 when available; frailty was summarized with the modified frailty index-5 (mFI-5) when component data were present. Results: The cohort included 13 men and 17 women with a mean age of 54.8 ± 15.2 years. At final follow-up, 18 patients had died, and 12 were alive. Five-year overall survival was approximately 76% in the full cohort. Extraspinal metastases were present in 72.2% of deceased patients compared with 8.3% of survivors and showed the clearest exploratory association with increased mortality (HR 3.46, 95% CI 1.23–9.78; p = 0.019). Metastatic disease demonstrated inferior survival compared with primary bone or soft-tissue tumors. Perioperative blood loss and transfusion burden were substantial but were not associated with survival in univariate analysis. ODI and SF-36 data were available only in small subsets and were therefore interpreted as descriptive signals of treatment burden. Conclusions: TES remains relevant in modern spine oncology, but only as an increasingly selective intervention. In this rare cohort, systemic disease burden, particularly extraspinal metastases, was the clearest selection-relevant survival signal, while blood loss, transfusion requirements, complications, and limited patient-reported outcomes illustrated substantial treatment burden. These findings do not establish a validated selection algorithm but support a contemporary decision threshold that integrates tumor biology, systemic disease status, anticipated margins, physiologic reserve, operative morbidity, and patient goals. Full article

The identification of a pathogenic variant (PV) in one of the mismatch repair (MMR) genes confirms the diagnosis of Lynch syndrome (LS). Hence, the correct classification of MMR gene variants is of utmost importance for appropriate counselling, surveillance, and treatment of LS patients and their families. In 7/200 unrelated Tyrolean-suspected LS patients, we identified the rare variant MLH1:c.836T>G. Clinical and tumor data strongly indicate that this founder variant is associated with an increased risk for early-onset LS-associated tumors. We also demonstrate that the variant leads to aberrant mRNA splicing. However, the splice effect’s leakiness together with the small effect of the amino acid change p.(Val297Gly) encoded by the residual full-length transcripts in a functional assay preclude its formal classification as (likely) PV according to internationally accepted variant interpretation guidelines. The family histories of the carriers suggest that the obstacles to classify the variant as (likely) PV may be related with a reduced penetrance. Nonetheless, and despite the formal classification of MLH1:c.836T>G as a variant of uncertain significance, we show that carriers should undergo cancer surveillance and predictive testing should be offered to relatives. This variant illustrates the need for an improved classification framework for appropriate categorization of lower-penetrance alleles. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

Background/Objectives: Despite recommendations to exercise, many individuals living with and beyond cancer do not achieve or sustain recommended physical activity levels because access to structured exercise support remains limited. We evaluated the real-world delivery of a scalable, community-based exercise model designed to address this gap. Methods: We conducted a hybrid effectiveness–implementation study of a 12-week supervised exercise intervention delivered in community settings across Alberta, Canada (in person or virtual). The primary outcome was the proportion of participants meeting physical activity guidelines at one year. Secondary outcomes included physical fitness and patient-reported outcomes. Results: Among 2570 participants, completion (90.6%) and attendance (77.1%) were high. At one year, the proportion meeting physical activity guidelines increased from 24.1% to 38.9% (p < 0.001), exceeding the prespecified target. At 12 weeks, participants demonstrated clinically meaningful gains in physical fitness, including sit-to-stand performance (+2.8 repetitions; 95% CI, 2.6, 3.9) and six-minute walk distance (+39.9 m; 95% CI, 36.9, 42.8), along with improvements in patient-reported outcomes. Improvements in fatigue and quality of life were smaller among participants receiving chemotherapy. Adverse events were rare (0.5%), with all serious events occurring among participants receiving active cancer treatment. Conclusions: This study demonstrates that structured supervision and behavioural support can be delivered through scalable, community-based models integrated with cancer care and may help patients achieve and sustain recommended physical activity levels. These findings support the translation of established exercise evidence into real-world models of care while highlighting the need for additional strategies to support long-term behaviour change. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies. Full article

Research Background: Breast cancer is a malignant tumor that threatens women’s health. Among breast cancer patients, about 4.2% to 17% may suffer from multiple primary malignant neoplasms. Cases of patients suffering from both breast cancer and multiple myeloma are relatively rare in clinical practice. This paper reports one case of a patient who developed multiple myeloma during the treatment of breast cancer. Clinical Data: The patient was a 56-year-old female, admitted to hospital due to “fever for 4 days, one year after the treatment of left breast cancer”. The patient was diagnosed with left breast cancer (ypT1N1M0, HER2-overexpressing subtype) approximately one year prior to presentation. Following diagnosis, the patient was treated sequentially with TcbHP and THP chemotherapy regimens, and subsequently received local radiotherapy. The patient developed fever four days prior to admission. Further laboratory examinations revealed pancytopenia, positive IgA-λ-type monoclonal immunoglobulin by immunofixation electrophoresis, and myeloma cells accounting for 11% in bone marrow smears. Bone marrow immunophenotyping indicated abnormal plasma cells, and pathological results of bone marrow biopsy were consistent with multiple myeloma. The final diagnosis was breast cancer complicated with multiple myeloma. After confirmed diagnosis, the patient was transferred to another hospital for targeted treatment of multiple myeloma and has been receiving continuous treatment there up to the time of follow-up. Conclusions: For patients with breast cancer, if they develop bone pain, anemia, hypercalcemia or renal dysfunction that cannot be explained by tumor metastasis or conventional complications after surgery or during follow-up, clinicians should be alert to the possibility of second primary tumors. Full article

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC. Full article

Individuals with Laron syndrome, a rare condition characterized by congenital insulin-like growth factor 1 (IGF-1) deficiency, display a remarkably low incidence of cancer, suggesting the existence of protective mechanisms linking reduced IGF-1 signaling to decreased cancer susceptibility. Consistent with this observation, IGF-1 is a recognized promoter of prostate cancer (PCa) progression, although the underlying mechanisms remain incompletely understood. Methylglyoxal (MG)-derived glycative stress, reflected by the accumulation of MG-derived hydroimidazolone 1 (MG-H1), has been implicated in PCa progression but has never been investigated in Laron syndrome. We found that liver tissues from Laron mice exhibited lower MG-H1 levels, suggesting reduced MG-derived glycative stress associated with low IGF-1 signaling. These findings prompted us to investigate whether MG-derived glycative stress contributes to IGF-1-driven PCa progression. Compared with the less aggressive LNCaP cells, PC3 cells displayed higher basal IGF-1 and MG-H1 levels, consistent with a potential association between IGF-1 and MG-derived glycative stress in PCa progression. Moreover, IGF-1 stimulation of LNCaP cells increased MG-H1 accumulation, proliferation, colony formation, invasiveness, and gene expression of matrix metalloproteinase (MMP)-1, MMP-7, MMP-9, receptor for advanced glycation end-products (RAGE), and Osteopontin (OPN), all of which were markedly attenuated by the MG scavenger aminoguanidine (AG). Collectively, these findings support a potential contribution of MG-derived glycative stress to IGF-1-driven PCa progression. Full article