Search Results (1,910)

Contrast-enhanced spectral mammography (CESM) provides low-energy images acquired in standard craniocaudal (CC) and mediolateral oblique (MLO) views, and clinical interpretation relies on integrating both views. This study proposes a dual-view classification framework that combines deep CNN feature extraction with transformer-based fusion for breast-side classification using low-energy (DM) images from CESM acquisitions (Normal vs. Tumorous; benign and malignant merged). The evaluation was conducted using 5-fold stratified group cross-validation with patient-level grouping to prevent leakage across folds. The final configuration (Model E) integrates dual-backbone feature extraction, transformer fusion, MC-dropout inference for uncertainty estimation, and post hoc logistic calibration. Across the five held-out test folds, Model E achieved a mean accuracy of 96.88% ± 2.39% and a mean F1-score of 97.68% ± 1.66%. The mean ROC-AUC and PR-AUC were 0.9915 ± 0.0098 and 0.9968 ± 0.0029, respectively. Probability quality was supported by a mean Brier score of 0.0236 ± 0.0145 and a mean expected calibration error (ECE) of 0.0334 ± 0.0171. An ablation study (Models A–E) was also reported to quantify the incremental contribution of dual-view input, transformer fusion, and uncertainty calibration. Within the limits of this retrospective single-center setting, these results suggest that dual-view transformer fusion can provide strong discrimination while also producing calibrated probabilities and uncertainty outputs that are relevant for decision support. Full article

Residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remain a complex diagnostic and therapeutic challenge. Although NAC has significantly improved pathologic complete response (pCR) rates and transformed surgical approaches, the persistence or evolution of microcalcifications may not accurately reflect residual disease. This discrepancy complicates radiologic interpretation, impacts surgical decision-making, and may lead to overtreatment or unnecessary mastectomies. This review synthesizes current evidence on the radiologic–pathologic correlation of post-NAC microcalcifications, their prognostic value, and their relevance to guiding surgical management in contemporary precision oncology. A narrative review of the literature was performed, focusing on imaging evolution after NAC, pathologic correlations, predictive and prognostic implications, and the role of microcalcifications in defining optimal surgical strategies, ranging from breast-conserving surgery to mastectomy. Emerging contributions from digital breast tomosynthesis, contrast-enhanced mammography (CEM), Magnetic Resonance (MR) and radiomics are also examined. Studies consistently demonstrate that residual microcalcifications are often poor predictors of viable tumor tissue after NAC. Up to half of cases with persistent calcifications may reflect minimal or absent residual invasive cancer, whereas calcifications may also persist in areas of treatment-induced necrosis or fibrosis. Reliance on calcifications alone may therefore lead to unnecessary extensive resections. Conversely, specific morphologic patterns, especially fine pleomorphic or branching calcifications, are more strongly associated with residual malignancy. Advanced imaging and radiomics show promise in improving predictive accuracy. Residual microcalcifications after NAC should not be interpreted as a direct surrogate of residual disease. A multimodal assessment integrating imaging evolution, tumor biology, and treatment response is essential to optimize surgical planning and avoid overtreatment. Precision surgery in the NAC era increasingly requires individualized decision-making supported by advanced imaging and robust radiologic–pathologic correlation. Full article

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL. Full article

Objective: This study aimed to evaluate serum and salivary podoplanin (PDPN) levels in patients with oral cancer (OC) and oral leukoplakia (OL) and to investigate their potential role as diagnostic biomarkers in distinguishing between these conditions. Materials and Method: Ninety participants were enrolled: 30 healthy controls, 30 patients with OL, and 30 patients with histopathologically confirmed OC. All cases were recruited from the Department of Otorhinolaryngology, Cerrahpaşa Medical Faculty and Istanbul Atlas University Hospital. Demographic characteristics, comorbidities, and biochemical parameters were recorded. Serum and salivary PDPN levels were measured using the ELISA method. Results: Serum PDPN levels were significantly higher in the OC group (3.25 ± 0.80 ng/mL) compared with both OL (1.85 ± 0.56 ng/mL) and controls (0.98 ± 0.42 ng/mL) (p < 0.001). Salivary PDPN levels showed a similar pattern, being highest in OC (2.65 ± 0.75 ng/mL), followed by leukoplakia (1.40 ± 0.45 ng/mL), and controls (0.72 ± 0.30 ng/mL) (p < 0.001). Importantly, both serum and salivary PDPN concentrations increased progressively with increasing epithelial dysplasia severity among patients with OL (one-way ANOVA, p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy for OC: AUC = 0.976 for serum PDPN (cut-off: 2.0 ng/mL; sensitivity 93.3%, specificity 100%) and AUC = 0.987 for salivary PDPN (cut-off 1.24 ng/mL; sensitivity 93.3%, specificity 95%). Conclusions: Serum and salivary PDPN levels were significantly elevated in patients with OC and demonstrated excellent diagnostic performance in distinguishing malignant lesions from OL and healthy controls. The observed stepwise increase in PDPN levels with dysplasia severity further supports its role in malignant transformation. Notably, salivary PDPN represents a non-invasive, practical, and reproducible biomarker that may aid in early detection and risk stratification of high-risk oral premalignant lesions. PDPN assessment could therefore complement clinical and histopathological evaluation, although larger prospective studies are warranted to validate its diagnostic and prognostic utility. Full article

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

Epithelial, endothelial, and many connective tissue cells are normally attached to the extracellular matrix (ECM). These cells rely on the ECM for structural support, signaling, and regulation of their behavior. When these cells lose this attachment or are in an inappropriate location, these cells soon die by a mechanism called anoikis (homelessness). Anoikis is a programmed cell death of an apoptotic nature; however, it can, in certain cases, be overcome, and detached cells can survive in the absence of the correct signals from the ECM. This is the case of malignant cells, where anoikis resistance is a prerequisite for invasion and metastasis. Without anoikis resistance (anchorage-independency), tumors would be unable to abandon their normal sites and would invade neighboring tissues and metastasize at distant locations. Anoikis is the natural barrier against cancer progression. Therefore, overcoming anoikis is a major step in cellular transformation. Cancer cells have developed many successful strategies to bypass anoikis. The main mechanism, albeit not the only one, involves hyper-activating survival pathways and over-expressing anti-apoptotic molecules. There is a strong and intertwining association between epithelial–mesenchymal transition and anoikis resistance that is discussed in depth. A better understanding of these anoikis resistance mechanisms has led to the research and development of pharmaceuticals that can counteract them. Full article

Background: Lung cancer screening using low-dose computed tomography (LDCT) demands not only early pulmonary nodule detection but also accurate estimation of malignancy risk. This remains challenging due to subtle nodule appearances, the large number of CT slices per scan, and variability in radiological interpretation. The objective of this study is to develop a unified computer-aided detection and diagnosis framework that improves both nodule localization and malignancy assessment while maintaining clinical reliability. Methods: We propose Seg-CADe-CADx, a dual-stage deep learning framework that integrates segmentation-guided detection and malignancy classification. In the first stage, a segmentation-guided detector with a lightweight 2.5D refinement head is employed to enhance nodule localization accuracy, particularly for small nodules with diameters of 6 mm or less. In the second stage, a hybrid 3D DenseNet–Swin Transformer classifier is used for malignancy prediction, incorporating probability calibration to improve the reliability of risk estimates. Results: The proposed framework was evaluated on established public benchmarks. On the LUNA16 dataset, the system achieved a competitive performance metric (CPM) of 0.944 for nodule detection. On the LIDC-IDRI dataset, the malignancy classification module achieved a ROC-AUC of 0.988, a PR-AUC of 0.947, and a specificity of 97.8% at 95% sensitivity. Calibration analysis further demonstrated strong agreement between predicted probabilities and true malignancy likelihoods, with an expected calibration error of 0.209 and a Brier score of 0.083. Conclusions: The results demonstrate that hybrid segmentation-guided CNN–Transformer architectures can effectively improve both diagnostic accuracy and clinical reliability in lung cancer screening. By combining precise nodule localization with calibrated malignancy risk estimation, the proposed framework offers a promising tool for supporting radiologists in LDCT-based lung cancer assessment. Full article

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are elevated in metastatic cases, whereas let-7 family members and miR-326 are upregulated in aggressive disease, highlighting their prognostic value. Moreover, dynamic changes in reported miRNAs during therapy provide real-time insights into treatment response. In androgen-deprivation therapy (ADT), oncogenic miRNAs, such as miR-21 and miR-125b, increase upon resistance, whereas a decline in tumor-suppressive miRNAs, such as miR-23b/-27b, flags the transition to castration-resistant PCa (CRPC). Similarly, baseline levels of miRNAs (e.g., miR-200b/c, miR-20a) can predict chemotherapy outcomes. Integrating multi-miRNA panels has demonstrated superior accuracy for risk stratification and monitoring, paving the way for personalized treatment. Although promising, clinical implementation of miRNA-based assays requires further validation, standardization of protocols, and large-scale prospective studies. Harnessing circulating miRNAs could usher in a new era of precision oncology for PCa, improving early diagnosis, prognostication, and real-time therapeutic guidance. Full article

Background/Objectives: Small-cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid proliferation, early metastasis, and near-universal relapse after initial therapy. While chemo-immunotherapy modestly improves first-line outcomes, survival after progression remains poor and highlights the urgent need for biomarker-directed strategies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on SCLC antibody studies. All authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Recent advances in antibody–drug conjugates (ADCs) and T-cell engagers (TCEs) have transformed therapeutic development by targeting antigens selectively expressed on SCLC cells, enabling more precise and potentially durable tumor control. DLL3 has emerged as the most clinically relevant target to date, with the bispecific TCE tarlatamab demonstrating meaningful and durable response, manageable cytokine-release toxicity, and ultimately achieving accelerated FDA approval for previously treated extensive-stage SCLC. Concurrently, DLL3-directed ADCs have shown variable efficacy, underscoring the importance of payload selection, linker chemistry, and antigen density. Beyond DLL3, next-generation ADCs targeting TROP2, B7-H3, and SEZ6 have reported encouraging early-phase activity, including response rates exceeding those of existing second-line cytotoxic options, though myelosuppression, interstitial lung disease, and hepatic toxicity remain key considerations. Conclusions: Collectively, these emerging immunotherapies illustrate a shift toward antigen-specific targeting in a disease historically defined by limited therapeutic innovation. Continued optimization of antigen selection, payload and linker engineering, and biomarker-driven trial design will be critical for translating early promise into durable clinical benefit and reshaping the treatment landscape for SCLC. Full article

Central nervous system (CNS) tumors consist of a diverse set of malignancies that remain clinically challenging due to their biological complexity, high morbidity, and limited responsiveness to current therapies. A growing body of genomic evidence has revealed that dysregulation of the mitogen-activated protein kinase (MAPK) signaling pathway is a recurrent and unifying characteristic across many pediatric and adult CNS tumor entities. Alterations affecting upstream receptor tyrosine kinases (RTKs), RAS GTPases, RAF kinases, and other associated regulators contribute to MAPK signaling pathway hyperactivation, shaping tumor behavior, therapy response and resistance. These aberrations ranging from hotspot mutations such as BRAF V600E and oncogenic fusions like BRAF–KIAA1549 are particularly enriched in gliomas and glioneuronal tumors, highlighting MAPK signaling as a key oncogenic driver. The expanding availability of molecularly targeted compounds, including selective inhibitors of RAF, MEK and ERK, has begun to transform treatment approaches for specific molecular subtypes. However, the clinical benefit of MAPK-directed therapies is frequently limited by restricted blood–brain barrier (BBB) penetration, intratumoral heterogeneity, parallel pathway reactivation, and an immunosuppressive tumor microenvironment (TME). In this review, we synthesize current knowledge on MAPK pathway alterations in CNS tumors and evaluate the therapeutic landscape of MAPK inhibition, with emphasis on approved agents, emerging compounds, combination strategies, and novel drug-delivery technologies. We also discuss mechanisms that undermine treatment efficacy and highlight future directions aimed at integrating MAPK-targeted therapy into precision-based management of brain tumors. Full article

Cervical cancer, primarily caused by high-risk Human Papilloma Virus (HPV), remains a global health concern. Prognostic biomarkers reflecting systemic inflammation and immune response—the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—have recently attracted interest for their potential predictive value in cervical cancer. We conducted a retrospective observational study including 344 patients who underwent loop electrosurgical excision of cervical intraepithelial neoplasia at Semmelweis University, Budapest, Hungary, between 2021 and 2024. Demographic, cytologic, histologic, and laboratory data were collected, and SII and SIRI were calculated. Statistical analyses, including Receiver Operating Characteristic (ROC) analyses, were performed. Higher SII and SIRI values were significantly associated with higher-grade lesions and invasive carcinoma. ROC analyses indicated good discriminatory performance, with negative predictive values of 96–100%, suggesting potential utility in ruling out malignant transformation. SII and SIRI are simple, cost-effective, and minimally invasive biomarkers that correlate with lesion severity in cervical disease. Their high negative predictive value supports a potential role as complementary rule-out tools in diagnostic evaluation. Further prospective studies are needed to validate these findings and to define clinically meaningful cut-off values for routine use. 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

Background/Objectives: Oral potentially malignant disorders (OPMDs), including oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), have varying risks of progression to oral squamous cell carcinoma (OSCC). Biomarkers such as aldehyde dehydrogenase 1 (ALDH1) and mammary serine protease inhibitor (Maspin) have shown potential for diagnostic and prognostic use in oral cancer. The present study aimed to evaluate the immunoexpression of aldehyde dehydrogenase 1, a cancer stem cell marker associated with aggressiveness, and the mammary serine protease inhibitor, a potential tumor suppressor, in OPMD and OSCC tissues. Methods: A retrospective analysis was performed on 145 biopsy specimens collected from January 2015 to January 2023, including normal epithelium, OPMDs (OLK, OLP, AC), and OSCC. ALDH1 and Maspin expression levels were evaluated using immunohistochemistry, considering both the percentage of positive cells and staining intensity. Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS, version 29.0; IBM Corp., Chicago, IL, USA). Results: Normal oral epithelium showed no expression of ALDH1, whereas 40.6% of OPMDs and 44.4% of OSCC samples exhibited high cytoplasmic ALDH1 expression. Nuclear ALDH1 expression was elevated in 29.7% of OPMDs and 38.9% of OSCCs (p < 0.001). Nuclear Maspin expression was high in 95.2% of normal tissues, in 67.2% of OPMDs and in 55.6% of OSCCs (p < 0.001). Maspin showed strong nuclear and cytoplasmic expression in normal tissue, but its expression decreased in OPMDs and OSCCs, with statistically significant reductions in both compartments (p < 0.001). Conclusions: The results indicate that ALDH1 upregulation and Maspin downregulation are hallmark events in oral carcinogenesis. Their combined evaluation provides a powerful tool for assessing dysplastic severity and malignant transformation risk in OPMDs. Future studies on larger cohorts are needed to confirm the prognostic utility of this dual-marker model. Full article