Search Results (1,014)

Background/Objectives: Accurate diagnosis of thyroid cancer is critical but challenging due to overlapping ultrasound (US) features of benign and malignant nodules. This study aimed to evaluate the diagnostic performance of non-invasive and minimally invasive US techniques, including B-mode US, shear wave elastography (SWE), color Doppler, superb microvascular imaging (SMI), and TI-RADS, in patients with suspected thyroid lesions and to assess their reliability and cost effectiveness compared with fine needle aspiration (FNA) biopsy. Methods: A prospective, single-center study (October 2023–February 2025) enrolled 300 patients with suspected thyroid cancer at a Spanish tertiary hospital. Of these, 296 patients with confirmed diagnoses underwent B-mode US, SWE, Doppler, SMI, and TI-RADS scoring, followed by US-guided FNA and Bethesda System cytopathology. Lasso-penalized logistic regression and a bootstrap analysis (1000 replicates) were used to develop diagnostic models. A utility function was used to balance diagnostic reliability and cost. Results: Thyroid cancer was diagnosed in 25 patients (8.3%). Elastography combined with SMI achieved the highest diagnostic performance (Youden index: 0.69; NPV: 97.4%; PPV: 69.1%), outperforming Doppler-only models. Intranodular vascularization was a significant risk factor, while peripheral vascularization was protective. The utility function showed that, when prioritizing cost, elastography plus SMI was cost effective (α < 0.716) compared with FNA. Conclusions: Elastography plus SMI offers a reliable, cost-effective diagnostic rule for thyroid cancer. The utility function aids clinicians in balancing reliability and cost. SMI and generalizability need to be validated in higher prevalence settings. Full article

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan^®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article

Endometrial cancer is one of the most prevalent gynecologic malignancies in developed countries, with its incidence steadily increasing each year. Early diagnosis is crucial for a favorable prognosis; however, certain patients experience recurrence and distant metastasis after surgery, similar to advanced cancer patients, with limited treatment options. Therefore, effective strategies for early screening, diagnosis, predicting local recurrence, and guiding rapid treatment interventions are essential for improving survival rates and prognosis. Liquid biopsy, a method known for being non-invasive, safe, and effective, has attracted widespread attention for cancer diagnosis and treatment. Although its clinical application in endometrial cancer is less established than in other cancers, research on biomarkers using liquid biopsy in endometrial cancer patients is currently in progress. This review examines the latest advancements in non-invasive biomarkers identified through liquid biopsy and provides a comprehensive overview of their clinical applications in endometrial cancer. Additionally, it discusses the challenges and future prospects of liquid biopsy, offering valuable insights into the diagnosis and personalized treatment of endometrial cancer. Full article

Mammary Paget disease (MPD) is a rare cutaneous malignancy associated with underlying ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC). Clinically, it appears as eczematous changes in the nipple and areola complex (NAC), which may include itching, redness, crusting, and ulceration; these symptoms can sometimes mimic benign dermatologic conditions such as nipple eczema, making early diagnosis challenging. A 56-year-old woman presented with persistent erythema and scaling of the left nipple, which did not respond to conventional dermatologic treatments: a high degree of suspicion prompted further investigation. Reflectance confocal microscopy (RCM) revealed atypical, enlarged epidermal cells with irregular boundaries, while line-field confocal–optical coherence tomography (LC-OCT) demonstrated thickening of the epidermis, hypo-reflective vacuous spaces and abnormally large round cells (Paget cells). These non-invasive imaging findings were consistent with an aggressive case of Paget disease despite the absence of clear mammographic evidence of underlying carcinoma: in fact, several biopsies were needed, and at the end, massive surgery was necessary. Non-invasive imaging techniques, such as dermoscopy, RCM, and LC-OCT, offer a valuable diagnostic tool in detecting Paget disease, especially in early stages and atypical forms. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype. Full article

Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility. Full article

Soft tissue tumors (STTs) are a heterogeneous group of mesenchymal neoplasms requiring accurate differentiation for optimal patient management. While histopathology remains the gold standard, imaging plays a crucial role in non-invasive assessment. Multiparametric ultrasound (mpUS) has emerged as a promising, cost-effective alternative to MRI, integrating B-mode, color and power Doppler, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) to provide comprehensive morphological, vascular, and biomechanical insights. Each modality offers distinct yet complementary diagnostic value, enhancing accuracy and potentially reducing unnecessary biopsies. This narrative review aims to serve as a practical guide, providing a readily accessible reference for mpUS parameters useful in the differential diagnosis of soft tissue tumors. Full article

Background: prostate fusion biopsies are key in the diagnosis of prostate cancer (PCa); however, the fusion imaging system is not always user-friendly or reliable. The aim of this study was to assess the feasibility, accuracy, and effectiveness of transperineal fusion biopsies performed with a novel fusion imaging device equipped with AI-driven auto-contouring. Methods: data from 148 patients who underwent MRI-targeted and systematic prostate fusion biopsy with UroFusion (Esaote) were prospectively collected. All biopsies were performed in-office, under local anaesthesia. Results: cancer detection rate was 64% overall and 56% for clinically significant PCa (csPCa, ISUP ≥ 2). PCa was detected in 35%, 65% and 84% of lesions scored as PI-RADS 3, 4 and 5, respectively. Outfield positive systematic cores were found in the contralateral lobe in one third of cases. Median device-time to obtain fusion imaging was 5 min and median biopsy duration was 15 min. Median difference in volume estimation between ultrasound and MRI auto-contouring was only 1 cc. Detection rate did not differ between experienced and novice, supervised users. Conclusions: in this initial prospective experience, fusion biopsies performed with UroFusion AI-driven auto-contouring system appeared time-efficient, accurate, well tolerated, and user-friendly, with comparable outcomes between experienced and novice users. Systematic biopsies remain highly recommended given the non-negligible rates of positive outfield cores. Full article

Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility. Full article

H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori. Full article

Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Background: The gold standard for diagnosing primary central nervous system lymphoma (PCNSL) is brain biopsy, an invasive procedure with significant risks. The role of cerebrospinal fluid (CSF) examination, limited to cytology and flow cytometry in current practice, is acknowledged as a less invasive diagnostic method. We aimed to summarize available data concerning the efficacy and actual use of current standard CSF diagnostics in the diagnosis of PCNSL. Methods: A systematic review and meta-analysis of 144 studies (n = 9493 patients) was conducted, assessing detection rates of cytology and flow cytometry and the proportion of diagnoses based on CSF analysis. The QUADAS-2 tool was used to evaluate study quality and bias. Results: Meta-analysis showed an 18% pooled detection rate for positive CSF results, with 17% for cytology and 20% for flow cytometry. Only 8% of diagnoses were made using CSF analysis. Most studies had a high risk of bias. Conclusions: Despite its established role in guidelines, CSF analysis remains underutilized for diagnosing PCNSL, with room to improve its clinical impact. Novel techniques, such as chemokines and circulating tumor DNA (cfDNA) analysis, hold promise to unlock the untapped potential of CSF diagnostics, offering significant advancements in non-invasive PCNSL diagnosis. Full article