Search Results (2,726)

Endometrial cancer is increasingly diagnosed in patients who have not yet completed childbearing. For carefully selected patients with grade 1 endometrioid endometrial carcinoma confined to the endometrium, fertility-sparing treatment (FST) can preserve reproductive potential but requires rigorous histologic surveillance. In eligible patients, oral progestins and/or the levonorgestrel-releasing intrauterine system (LNG-IUS) remain the mainstay of fertility-sparing treatment, with hysteroscopic lesion resection incorporated in selected cases. Obesity, polycystic ovary syndrome, abnormalities in glucose metabolism, molecular subtype, and primary or acquired progestin resistance collectively contribute to heterogeneity in treatment response and the risk of recurrence. This narrative review critically integrates current guidelines, randomized controlled trials, prospective studies, retrospective cohorts, and early exploratory evidence to evaluate the biological rationale, clinical positioning, efficacy, safety, and maturity of evidence for progestin-based therapy, metabolic interventions, combined endocrine approaches, molecularly guided strategies, and exploratory immunotherapeutic approaches. We further propose an integrated clinical pathway encompassing candidate selection, molecular assessment, response evaluation, transition to pregnancy, retreatment after recurrence, and timely conversion to definitive surgery. Importantly, this review distinguishes guideline-supported approaches from adjunctive, investigational, and exploratory strategies. Major evidence gaps include inconsistent definitions of treatment response, limited prospective molecularly stratified data, uncertain reproductive safety of emerging systemic therapies, and insufficient long-term data on pregnancy outcomes and offspring. Full article

Background/Objectives: Cervical cancer recurrence after definitive treatment remains a major clinical challenge, and early detection may improve patient outcomes. This study evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) for detecting recurrent cervical cancer according to clinical context. Methods: We retrospectively reviewed 1727 post-treatment PET/CT examinations obtained from 659 patients who achieved a complete response after definitive treatment between 2005 and 2024. After excluding 15 examinations that detected second primary malignancies, the recurrence-specific analysis included 1712 examinations from 654 patients. PET/CT findings were classified as true positive, true negative, false positive, or false negative based on histopathology or serial imaging follow-up. Generalized estimating equations were used to account for within-patient clustering. Subgroup analyses were performed according to histology, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage, interval from treatment completion to PET/CT, and clinical context. Results: Of the 1712 examinations, 136 (7.9%) were true positive, 1525 (89.1%) were true negative, 43 (2.5%) were false positive, and 8 (0.5%) were false negative. Overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 94.4%, 97.3%, 76.0%, 99.5%, and 97.0%, respectively. Diagnostic performance was similar across histologic subtypes and FIGO stages. In routine follow-up settings without clinical suspicion of recurrence, PET/CT showed a high NPV (100.0%), whereas examinations performed for clinically suspected recurrence showed a high PPV (96.5%). Conclusions: These findings suggest that the diagnostic interpretation and clinical utility of post-treatment PET/CT may vary according to the clinical setting. Full article

Background: Head and neck cutaneous squamous cell carcinoma (HNcSCC) presents intersecting oncologic, functional, and reconstructive challenges. Although numerous clinicopathologic factors have been associated with recurrence, metastasis, and survival, their relationship with reconstructive complexity and patient-centered outcomes remains insufficiently studied. This review aimed to examine how established oncologic risk factors might inform reconstructive planning while distinguishing measured reconstructive evidence from hypothesis-generating clinical inferences. Methods: A structured PubMed/MEDLINE search conducted through 15 July 2026 was used to identify the literature addressing clinicopathologic prognostic factors in HNcSCC. Twenty-nine prognostic publications were retained for structured charting. Additional reconstructive, functional, aesthetic, and patient-reported outcome sources were identified through reference-list screening and were used solely for narrative contextualization. Because no dedicated multi-database systematic search of reconstructive outcomes was performed, the article is presented as a structured narrative review and hypothesis-generating research framework rather than a systematic review of reconstructive evidence. Results: The prognostic literature reported associations between adverse oncologic outcomes and factors including tumor size and depth, perineural invasion, lymphovascular invasion, poor differentiation, immunosuppression, recurrent disease, positive margins, nodal involvement, and extranodal extension. However, most of these studies did not measure post-excision defect characteristics, reconstructive technique, wound complications, functional recovery, scar quality, aesthetic outcomes, or patient-reported outcomes. Direct reconstructive evidence was limited and predominantly derived from site-specific, mixed-histology, technical, or methodological publications. Consequently, clinicopathologic factors should be regarded as potential upstream variables for future investigation rather than validated predictors of reconstructive outcomes. Conclusions: Current evidence supports oncologic risk stratification more strongly than prediction of reconstructive difficulty or patient-centered outcomes in HNcSCC. Prospective studies should jointly measure patient, tumor, treatment-field, defect, reconstructive, functional, aesthetic, and patient-reported variables. The proposed framework is intended to guide such research and is not a validated clinical prediction model. Full article

Artificial intelligence (AI) is increasingly being integrated into medical practice, offering promising tools to improve diagnostic accuracy and clinical efficiency. In the field of breast pathology, AI applications, particularly those based on deep learning (DL) and machine learning (ML), are emerging as decision-support tools in both diagnostic and prognostic workflows. This review provides a comprehensive overview of current AI-based approaches, with a focus on their clinical utility in tumor detection, histological classification, biomarker assessment, and prediction of treatment response. In addition to summarizing available AI platforms, the review critically examines their level of clinical validation, regulatory status, and integration into routine practice. Key challenges are also discussed. Overall, AI is expected to play an increasingly important role in supporting pathologists and advancing precision medicine in breast cancer management. Full article

Epithelioid sarcoma (EPS) is an ultra-rare malignant mesenchymal neoplasm of uncertain differentiation that comprises two distinct clinicopathological subtypes: classic and proximal. Classic EPS most commonly occurs in the distal upper extremity of adolescents and young adults, whereas proximal-type EPS most often affects the truncal regions of young to middle-aged adults. Both classic and proximal-type EPSs exhibit aggressive clinical behavior, including a higher risk of local recurrence and regional lymph node or distant metastasis. Histologically, classic EPS is characterized by irregular nodules composed of epithelioid and spindled cells, while proximal-type EPS consists of multinodular distributions and sheets of large polygonal cells. EPS has a distinctive immunoprofile with characteristic expression of cytokeratins and epithelial membrane antigen. Loss of nuclear expression of SMARCB1 protein occurs in the vast majority of cases. Moreover, SMARCB1 homozygous deletions have also been observed in both subtypes. Surgery is the mainstay treatment approach for localized EPS. Systemic treatment options for metastatic or unresectable locally advanced disease are very limited. The withdrawal of tazemetostat has created a significant gap in available treatment options. In this review, we provide an overview of the current knowledge on the clinical and radiological features, histopathology, immunohistochemistry, pathogenesis, and management of EPS. Full article

Background: The growing awareness of breast cancer’s molecular diversity has not changed the technical foundations of surgery itself, but it has profoundly reshaped how surgeons think about surgery. Rather than molecular biology prescribing specific surgery, it is the surgeon’s interpretation of biological behavior—tumor subtype, genomic risk, treatment responsiveness—that influences surgical timing, extent, and feasibility. This is particularly important in the developing world, where mastectomy continues to be the default surgery, not always because it is required, but because biological nuance is underutilized in surgical planning. This review integrates existing evidence, guidelines, and real-world clinical experience to show how a surgeon who understands tumor biology can meaningfully expand safe breast conservation, de-escalate axillary surgery, and align operative choices with systemic therapy. In essence, molecular biology becomes a lens through which surgeons can practice more personalized, precise, and less invasive surgery, without compromising oncologic safety. Recent findings: We present evidence-based algorithms focusing on Luminal A, Luminal B, HER2-positive, and triple-negative subtypes, while discussing the nuances of multifocal and multicentric disease, metaplastic histologies, and discordant lesion management. The review addresses axillary management in the molecular era, specifying the appropriateness of sentinel lymph node biopsy, targeted axillary dissection, or completion axillary dissection, and how subtype-specific nodal responses to neoadjuvant therapy can guide de-escalation strategies. Through clinical vignettes, we exemplify how molecular integration into surgical planning can modify clinical courses, enabling oncoplastic conservation in downstaged tumors and justifying definitive resection in chemo-resistant cases. We examine the implications of germline and somatic genetic testing on surgical decision-making, particularly in relation to BRCA1/2 and PALB2 mutation carriers, alongside ethical and practical counseling considerations. Additionally, we review emerging biomarkers—such as circulating tumor DNA and immune and radiomic signatures—and propose research priorities for their incorporation into surgical trials. Conclusions: Effective implementation necessitates enhanced surgeon education, standardized assays, and multidisciplinary coordination to promote equitable access, consistent utilization of biology-driven algorithms, and rigorous quality oversight. This review furnishes breast surgeons with a pragmatic framework for translating molecular knowledge into multidisciplinary, patient-centered care pathways that optimize oncological safety, aesthetic outcomes, and overall quality of life. Full article

Ischemic heart disease is currently diagnosed mainly through cardiac computed tomography (CT) angiography and functional testing, both of which detect only advanced arterial macrocalcification, at a stage when treatment can merely slow disease progression rather than reverse it. Yet, macrocalcification represents the end product of a much earlier molecular process, which is microcalcification. This process is driven by smooth muscle cell and macrophage apoptosis, matrix vesicle release, and osteogenic phenotypic transitions within the arterial intima, occurring years to decades before mineral deposits become visible on CT. [¹⁸F]Sodium fluoride (NaF) positron emission tomography (PET) exploits fluoride binding at accessible hydroxyapatite surfaces to detect increased tracer uptake associated with active mineral deposition, including mineralization occurring at a microscopic scale below the direct spatial resolution of clinical PET. Studies demonstrate that anti-atherosclerotic interventions, including statins, and tissue-nonspecific alkaline phosphatase inhibition can suppress NaF uptake even when CT-based calcium scores remain unchanged or continue to rise, a dissociation now also observed in human trials of statins and PCSK9 inhibitors. This review traces the cellular and histological basis of arterial calcification, outlines the principles and limitations of NaF-PET imaging, and evaluates its emerging role—supported by artificial intelligence-based quantification—as a tool for monitoring targeted anti-atherosclerotic treatment. Full article

Main pancreatic duct (MPD) dilatation may occur in both main-duct intraductal papillary mucinous neoplasm (MD-IPMN) and chronic pancreatitis (CP). In selected patients, MRI/MRCP, endoscopic ultrasonography (EUS), and contrast-enhanced EUS may remain inconclusive. Peroral pancreatoscopy (POPS) permits direct ductal inspection and targeted biopsy, but the available evidence is heterogeneous and does not establish diagnostic accuracy or clinical utility in the specific differential diagnosis of MD-IPMN versus CP. We performed a narrative review of POPS for suspected pancreatic duct neoplasia and report a retrospective, descriptive, single-center series of five highly selected patients evaluated between January 2023 and November 2024. The case series is presented only to illustrate a multidisciplinary diagnostic pathway; no estimates of accuracy, sensitivity, specificity, or clinical benefit were calculated. All five patients had MPD dilatation > 10 mm, imaging findings compatible with definite or possible chronic pancreatitis, and persistent concern for MD-IPMN after MRI/MRCP, EUS, and contrast-enhanced EUS. POPS-guided biopsies showed low-grade dysplasia in one patient and high-grade dysplasia in two patients. These three patients underwent surgery, and examination of the resection specimens confirmed the same dysplasia categories identified by POPS-guided biopsy. In the remaining two patients, POPS showed regular-appearing ductal epithelium with focal hyperemia, and targeted biopsies revealed nonspecific inflammatory changes. These patients were managed conservatively without surgery. As definitive surgical histopathology was not available, their final diagnostic status remained unconfirmed. Both patients underwent ongoing planned annual surveillance with MRI or EUS and serum CA 19-9 measurement to identify any morphological or biochemical changes. At the most recent follow-up, approximately 192 days (IQR, 116.5–205.5 days) after POPS, no significant changes had been observed. This small, selected series illustrates how POPS may contribute additional visual and histological information when conventional evaluation is discordant. It cannot demonstrate that POPS prevents missed lesions, excludes IPMN, reduces unnecessary surgery, or improves outcomes. Prospective multicenter studies with predefined referral criteria, blinded interpretation, complete reference standards, and long-term follow-up are needed. Full article

The Breast Cancer (BRCA) genes play an important role in repairing double-strand deoxyribonucleic acid (DNA) breaks. Mutations in these genes are associated with the development of malignancies, most notably breast and ovarian cancer. Carriers of these mutations are often faced with issues that have serious implications for their reproductive choices, including the occurrence and treatment of breast or ovarian cancer, recommendations for preventive mastectomy and salpingo-oophorectomy, and the risk of transmitting the BRCA gene mutation to an offspring. These issues often lead to the search for methods of fertility preservation or assisted reproduction. This review aims to highlight and explain all the ways in which BRCA gene mutations affect fertility in women. Specifically, the effect of BRCA carriage is assessed at the molecular, histological, clinical, and laboratory levels. Next, fertility preservation methods in carriers are analyzed and evaluated in terms of their safety and effectiveness. In addition, the effect of systemic therapies for breast cancer on ovarian reserves is explained. Finally, the possibility of preimplantation diagnosis of BRCA gene carriage is also examined. 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: Onychomycosis is a common fungal nail infection that may contribute to foot morbidity in adults with type 2 diabetes mellitus (T2DM), particularly when neuropathy, peripheral vascular disease, nail dystrophy, local trauma, tinea pedis, or poor glycaemic control coexist. This systematic review and meta-analysis aimed to estimate the prevalence of onychomycosis in adults with T2DM and to explore sources of between-study heterogeneity. Methods: MED-LINE/PubMed, Scopus, Web of Science, LILACS, and EMBASE were searched from 1 January 2000 to 31 January 2026. Observational studies reporting onychomycosis prevalence in adults with T2DM were included. Pooled prevalence was estimated using a random-effects model, and subgroup, sensitivity, and exploratory meta-regression analyses were performed according to diagnostic method, sampling type, geographic region, publication year, and mean age. Results: Eighteen studies, including 6764 participants, were included. The random-effects pooled prevalence was 31.4% (95% CI: 21.7–42.0%), with extreme heterogeneity (I² = 98.8%). Prevalence ranged from 3.8% to 71.7% across studies. Laboratory- or histology-confirmed studies showed a lower pooled prevalence than clinically diagnosed studies, suggesting that clinical diagnosis alone may overestimate onychomycosis prevalence. Exploratory meta-regression indicated that diagnostic method was the main methodological factor associated with prevalence differences, whereas publication year, sampling type, and mean age did not explain heterogeneity. Conclusions: Onychomycosis is frequent among adults with T2DM, but prevalence estimates vary substantially across studies. The pooled estimate should be interpreted cautiously because of extreme heterogeneity and differences in diagnostic definitions. Future studies should use standardised clinical and mycological or histological diagnostic criteria and report diabetes-related risk factors to improve comparability. Full article

Background/Objectives: High-grade pulmonary neuroendocrine carcinoma (HGNEC-L), including SCLC and LCNEC, is aggressive and usually treated according to SCLC paradigms. The clinical relevance of de novo actionable genomic alterations (AGA) remains incompletely defined. Methods: We performed a retrospective multicenter analysis of advanced HGNEC-L with de novo AGA, assessing rwORR, rwDCR, rwPFS, and OS. Findings were contextualized by a structured literature review and exploratory pooled reconstructed-IPD Cox analysis, with targeted therapy modeled as a source-stratified time-dependent covariate. Results: Ten patients from four tertiary centers were included. Most were women (90.0%) and never-smokers (70.0%); histology was LCNEC in 60.0% and SCLC/mixed SCLC in 40.0%. AGA included EGFR mutations (n = 6), EML4-ALK fusions (n = 2), KIF5B-RET fusion (n = 1), and KRAS p.G12C (n = 1). Targeted-containing regimens achieved rwORR 77.8%, rwDCR 88.9%, and median rwPFS 9.0 months (95% CI, 2.0–18.7), as opposed to 3.7 months for ICI-containing regimens and 2.6 months for chemotherapy alone. Median OS for the entire cohort was 17.2 months (95% CI, 4.8–36.3); overall survival did not differ significantly between patients with and without targeted-containing exposure (19.0 vs. 17.2 months; log-rank p = 0.50). In pooled reconstructed-IPD time-dependent Cox analysis (72 patients, 39 deaths), targeted therapy showed a favorable but non-significant OS association (HR, 0.89; 95% CI, 0.31–2.56; p = 0.831), maintained directionally in the age/sex-adjusted subset (HR, 0.54; 95% CI, 0.16–1.77; p = 0.306). Conclusions: De novo AGA-positive HGNEC-L represents a clinically relevant subgroup with potential sensitivity to genotype-matched targeted therapy, supporting comprehensive molecular profiling and early targeted therapy consideration. Full article

Diffusion-weighted imaging (DWI) has evolved from a niche research sequence into an increasingly valuable adjunct to conventional magnetic resonance imaging (MRI) in musculoskeletal (MSK) radiology. By providing qualitative and quantitative information on tissue microstructure through assessment of water diffusion and apparent diffusion coefficient (ADC) mapping, DWI offers functional insights beyond conventional morphological imaging. We aim to present the current evidence for DWI in MSK imaging organised around established applications and emerging applications, with particular emphasis on composition-related interpretive pitfalls relevant to differentiating tumours and other pathologies, and to review the technique’s evolving role in routine practice. This narrative review synthesises the current literature on the clinical utility of DWI in MSK imaging. It is structured in four parts: foundations and the tissue composition signal framework, including the basis of qualitative and quantitative assessment; established applications; emerging applications; and assessment of tissue composition-related interpretive as well as technical pitfalls, including those arising due to myxoid matrix, chondroid matrix, blood degradation products, organising thrombus, crystalline or mineralised material, keratinaceous debris, purulent content, cellular haematopoietic marrow, by using original cases from the authors’ institution, which have been confirmed either histologically or surgically. Applications are stratified by strength of evidence. Established applications of DWI include soft tissue abscess detection, differentiation of malignant from benign soft tissue tumours, differentiation of malignant from benign vertebral compression fractures, and myeloma staging and response assessment, as well as treatment response in soft tissue and bone sarcomas. Whole-body MRI with DWI for staging and response assessment in multiple myeloma is guideline-endorsed and supported by prospective multicentre data. Soft tissue abscess detection, soft tissue and bone tumour characterisation, and characterisation of vertebral compression fractures are supported by consistent evidence from multiple independent cohorts, although no universally transferable ADC threshold exists. The emerging applications, which are promising adjuncts supported by small, single-centre or heterogeneous studies with thresholds that have not been externally validated, include ADC ghost sign in osteomyelitis (high specificity but sensitivity of only 20%), peripheral nerve sheath tumour characterisation and surveillance in NF1 patients, peripheral neuropathy and plexopathy, predisposing conditions such as Li Fraumeni syndrome in paediatric cancers, inflammatory myopathy, and postsurgical assessment of residual disease, as well as opportunistic detection of venous thrombosis. Radiomics and machine learning approaches remain experimental. Recent technical advances, including reduced field-of-view imaging, multi-shot acquisition and improved fat suppression, have mitigated but not eliminated historical limitations of susceptibility artefacts and limited spatial resolution. DWI has become an important functional imaging technique that complements conventional MRI across a broad range of musculoskeletal disorders. Understanding the relationship between tissue composition and the diffusion signal is central to both interpreting DWI correctly and avoiding its characteristic pitfalls. DWI is best regarded not as a stand-alone technique but as one component of a multiparametric assessment, in which its functional information is integrated with conventional morphological imaging. Ongoing technical improvement and expanding clinical evidence are expected to further support its integration into routine MSK imaging and its development as a quantitative biomarker for diagnosis, prognostication, and treatment monitoring. Full article

The expansion of neoadjuvant immune checkpoint blockade, chemoimmunotherapy, and targeted therapies in oncogene-driven tumors is reshaping the management of resectable non-small cell lung cancer (NSCLC). Major pathologic response (MPR) and pathologic complete response (pCR), defined respectively as 10% or less residual viable tumor (RVT) within the primary tumor bed and the complete absence of viable tumor in both the resected primary tumor and sampled regional lymph nodes, have become widely adopted early efficacy endpoints. Both are consistently associated with favorable survival outcomes at the patient level, although their validity as trial-level surrogates for long-term outcomes remains incompletely established. Accurate pathologic response assessment requires rigorous standardization of gross specimen handling, tumor bed sampling, and microscopic quantification of viable tumor, necrosis, and stroma. International recommendations have improved methodological harmonization, and reproducibility studies have demonstrated good interobserver agreement when standardized protocols are applied. Increasing evidence also indicates that RVT behaves as a continuous prognostic variable and that integration of primary-tumor and nodal response may improve postoperative risk stratification. Beyond quantification of RVT alone, additional histologic characteristics of the residual tumor, together with stromal and immune therapy-related features, may provide complementary prognostic information. Digital pathology and artificial intelligence may support more reproducible quantitative assessment, whereas circulating tumor DNA-based molecular residual disease evaluation may capture systemic risk not represented by the resection specimen. These emerging approaches remain investigational and require prospective validation. This review critically examines the methodological standardization, biological interpretation, and prognostic validation of pathologic response in resectable NSCLC, and discusses future strategies integrating histopathologic, digital, and molecular variables into post-neoadjuvant risk assessment. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, and its progressive inflammatory phenotype, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by hepatocellular injury, inflammation, and fibrosis. These processes are closely linked to altered metabolite networks, including lipotoxic lipids, oxidized lipid mediators, bile acids, amino acids, acylcarnitines, redox-related metabolites, gut-derived metabolites, and extracellular matrix remodeling products. The recent introduction of resmetirom and semaglutide for MASH with moderate-to-advanced fibrosis provides two complementary models for interpreting these networks. Resmetirom, a liver-directed thyroid hormone receptor-β agonist, primarily enhances intrahepatic lipid handling, mitochondrial fatty acid metabolism, cholesterol turnover, and lipoprotein remodeling. Through this “inside-out” mechanism, resmetirom may reduce hepatocyte lipotoxic stress and secondarily attenuate inflammatory and fibrogenic signaling. Semaglutide, a glucagon-like peptide-1 receptor agonist, mainly acts through systemic metabolic unloading by reducing energy intake, body weight, insulin resistance, and adipose–liver substrate flux. Through this “outside-in” mechanism, semaglutide may improve the hepatic metabolite environment indirectly. However, histological improvement does not by itself establish causal metabolite mediators, and many specific metabolite-level mechanisms remain incompletely defined in human MASH. This review summarizes metabolite networks linked to inflammation and fibrosis in MASLD/MASH, compares the metabolic implications of resmetirom and semaglutide, and discusses how therapeutic metabolomics may support biomarker discovery, patient stratification, and precision pharmacotherapy. Full article