Search Results (252)

Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article

Background/Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Metastatic spread occurs in up to 80% of high-grade tumors; however, the mechanisms underlying this process are largely unknown. Large-scale microRNA (miRNA) expression profiling studies of human cancers have demonstrated that dysregulation of miRNA is frequently associated with many cancer types. This study aimed to investigate the miRNA profiles of metastatic and non-metastatic MECs. Methods: Using real-time RT-PCR (qPCR), we analyzed the expression of 377 miRNAs in four non-metastatic MECs, three MECs with lymph node metastasis, three MECs with distant metastasis, and two non-neoplastic human salivary glands. To identify differentially expressed miRNAs, bioinformatics analysis was performed using hierarchical clustering analysis. Results: The miRNA profile discriminated between non-neoplastic and tumor samples and between metastatic and non-metastatic tumors. Twelve miRNAs were differentially expressed between non-neoplastic and non-metastatic MECs. MEC analysis of non-neoplastic and lymph node metastases demonstrated that 10 miRNAs were differentially expressed. In non-neoplastic versus distant metastatic MECs, three miRNAs were differentially expressed: one downregulated and two upregulated. By comparing non-metastatic MECs with lymph node metastatic MECs, we identified 17 upregulated miRNAs. Considering non-metastatic MECs versus distant metastatic MECs, two miRNAs were upregulated. One miRNA was differentially expressed between lymph node metastatic and distant metastatic MECs. Conclusions: Our findings indicated that miRNA profiles may serve as valuable biomarkers for distinguishing the metastatic potential of salivary MECs, warranting further investigation to validate their utility in clinical practice. Full article

Background/Objectives: Pleomorphic adenomas (PAs) are the most common salivary gland tumors, with a known risk of recurrence, especially after inadequate surgical excision. Understanding how surgical approach influences recurrence remains essential to optimize management. This study aimed to synthesize recurrence rates of PAs based on different surgical techniques and to illustrate the implications of surgical strategy through a representative case of multifocal deep lobe recurrence. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. Three electronic databases (PubMed, Cochrane, and Google Scholar) were searched for studies published in the last ten years, reporting recurrence rates of PAs by surgical approach. Data were extracted on recurrence, complications, and tumor characteristics. Additionally, a complex clinical case of recurrent deep lobe PA (DLPA) was presented to contextualize the findings. Results: Fifteen studies were included, comprising a total of 2095 patients. Recurrence rates were 3.27% after extracapsular dissection (ED), 0.73% after partial superficial parotidectomy (PSP), and 2.41% after superficial parotidectomy (SP). Recurrent PA (RPA) is often multifocal and associated with increased risks of facial nerve palsy and positive surgical margins. The presented case involved five surgical procedures, with ultimate total parotidectomy and facial nerve preservation despite infiltrative recurrence in the prestyloid space. Conclusions: Techniques such as ED and PSP have demonstrated their efficacy and safety compared to more invasive approaches, although their application should be carefully evaluated based on tumor size and location. RPA remains a challenging entity to treat. Avoiding outdated techniques and ensuring evidence-based decision making may improve long-term outcomes in PA management. Full article

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article

Salivary gland cancers (SGCs) pose a therapeutic challenge due to their aggressive nature and limited treatment options. Ion transporters, particularly the sodium/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I⁻) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-κB or TNF-α and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress’s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application. Full article

Background and clinical significance: Polymorphous adenocarcinoma of the oral cavity is predominantly located in the palate. It is characterized by a slow rate of growth and thus may be misdiagnosed as a benign tumor. Its histology is intricate with other salivary malignancies, thus necessitating specific immunohistochemical stains. Our case report illustrates an adenocarcinoma localized in the palate of a 61-year-old female patient. Case presentation: The patient came to the postgraduate clinic of Oral Medicine and Pathology, Department of Oral Medicine and Pathology, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece and provided written informed consent for the subsequent examination. The patient complained about the presence of a mass on the palate, which was otherwise asymptomatic, without being able to pinpoint when the tumor initially emerged. The lesion was biopsied and the histology suggested the immunophenotype p63+/p40- which constitutes an important diagnostic clue for polymorphous adenocarcinoma. The patient was referred to the Department of Oral and Maxillofacial Surgery. Conclusions: The standard therapeutic approach primarily involves surgical excision. The goal is to achieve optimal patient outcome while minimizing unnecessary morbidity. As surgical techniques and understanding of the disease continue to advance, it is crucial for healthcare providers to stay informed and integrate these developments into practice to improve treatment outcomes for patients. Full article

Notch-mediated signaling pathways represent a system that is conserved from an evolutionary point of view, demonstrating a key role in determining cell fate in development; in fact, Notch operates at multiple levels during tissue and organ organization, intervening in the key processes of organogenesis. As a consequence of this, a dysregulation of the Notch-mediated pathways leads to the onset of various pathological conditions such as autoimmune diseases or tumors. The activation of Notch-mediated molecular pathways has also been demonstrated in the development of salivary glands (SGs) and in associated pathologies. Although the numerous advances made in recent years have clarified various aspects of the activation of transductional cascades involving Notch in SGs development and diseases, there are still many aspects that require experimental investigation. In this review, we report, for therapeutic purposes, what is present in the literature relating to the mechanisms regulating the development of Notch-mediated SGs and the most recent discoveries relating to SGs pathologies that derive from alterations of the Notch-mediated pathways. Full article

Background/Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the minor salivary glands, often affecting the hard palate. Preoperative diagnosis and surgical planning are challenging due to anatomical complexity and limitations in sampling, generally obtained by fine-needle aspiration (FNA). This study retrospectively evaluated the diagnostic and therapeutic performance of a high-definition ultrasound (HDUS)-guided fine-needle aspiration cytology/biopsy (FNAC/FNAB) protocol in diagnosing intraoral MEC, based on the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with the relative clinical outcomes. Methods: A cohort of 64 patients with histologically confirmed MEC of the minor salivary glands, treated between 2000 and 2022, was retrospectively analyzed. All patients underwent HDUS-guided FNAC/FNAB, imaging (CT, MRI, and panoramic X-ray), and subsequent surgical treatment. The cytological specimens were classified using the MSRSGC. Surgical margins, histopathological findings, lymph node status, and follow-up outcomes were recorded. Results: Of 64 MECs, 42 cases were finally diagnosed as low-grade (LG)/intermediate grade (IG) and 22 as high-grade (HG) carcinomas, using a two-tier histological classification system. HDUS accurately delineated the lesion size, infiltration depth, and bone proximity, with excellent correlation with surgical specimens (difference ≤ 0.6 mm). MSRSGC classification distributed the cases across all categories, with 28 classified as malignant (category VI). Repeat FNAC improved the diagnostic yield in non-diagnostic and atypical cases. FNAB confirmed the cytological findings in all cases, with immunohistochemistry investigation with Ki-67 supporting tumor grading. Surgical margins were clear in all resections. Lymph node metastases were identified in all patients who underwent neck dissection (n = 18), all with HG-MEC. No recurrences occurred among the LG/IG-MEC patients during a median 2-year follow-up. Conclusions: The combined use of HDUS and FNAC/FNAB, interpreted through the MSRSGC framework, offers a highly accurate, minimally invasive approach for preoperative diagnosis and surgical planning in intraoral MEC. HDUS-guided cytology significantly improves diagnostic reliability, particularly in LG/IG and cystic variants, facilitating tailored surgical management. Also, the clinical outcomes may support the possibility of using a simplified grading classification for two histopathological types. Full article

Background/Objectives: Salivary gland tumors (SGTs) are a rare and histologically heterogeneous group of neoplasms that are challenging to diagnose due to phenotypic heterogeneity and overlapping histomorphological markers. Accurate diagnosis is required for clinical management, particularly in unusual subtypes. The objective of this study was to ascertain whether attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, in combination with enzymatic deglycosylation, would be useful in SGT classification by detecting glycosylation-related metabolic variations. Methods: 155 tissue sections, consisting of 80 SGTs and 75 controls, were analyzed. ATR-FTIR spectroscopy was used to record the mid-infrared (MIR) spectra (4000–400 cm⁻¹) of enzymatically untreated and deglycosylated samples. Spectral data were preprocessed and analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Enzymatic deglycosylation focused on sialic acid and fucose residues with α2-3,6,8 neuraminidase, α1-2,4,6 fucosidase O, and α1-3,4 fucosidase. Results: Tumor and control samples were discriminated with an OPLS-DA model, achieving an accuracy of 81.9% (78.7% for controls and 85.0% for tumors), especially in the glycosylation-relevant spectral range (850–1250 cm⁻¹). Classification between benign and malignant tumors was more challenging, with an accuracy of 70.0% (72.5% for benign and 67.5% for malignant cases). Enzymatic deglycosylation resulted in detectable changes in the MIR spectra, confirming the contribution of glycosylation to tumor-specific signatures. Benign vs. malignant tumor discrimination was still poor and was not much enhanced in the sense of incorporating glycosylation-specific regions. Conclusions: ATR-FTIR spectroscopy coupled with enzymatic deglycosylation can distinguish tumor and control tissues based on glycan-associated spectral differences. Application of the technique to benign/malignant SGT discrimination is hampered by spectral overlap and tumor heterogeneity. Further research will be necessary to explore other clustering algorithms and larger and more homogeneous datasets for improved diagnostic accuracy. Full article

Background: The management of salivary gland tumors (SGTs) during pregnancy is a subject that has received scant attention in the medical literature. While treatment recommendations for cancer therapy in pregnancy have been delineated, those for benign tumors remain unspecified. The present inquiry focuses on the number of women of reproductive age with SGTs and the optimal diagnostic and treatment strategies for tumors occurring during pregnancy. Materials and Methods: This was a retrospective multicenter cohort study based on data from the Polish Salivary Network Database, collected between 2018 and 2022. From a total of 2653 patients with salivary gland tumors (SGTs), we identified 1313 women, including 300 of reproductive age (16–42 years). Among them, six cases of SGTs diagnosed during pregnancy were included for detailed analysis. Ethical approval was obtained for this study. Results: Among the 300 women of reproductive age, 285 had benign SGTs and 15 had malignant SGTs. Six tumors were diagnosed during pregnancy: four benign (pleomorphic adenomas) and two malignant (salivary duct carcinoma and mucoepidermoid carcinoma). All benign tumors were monitored during pregnancy and surgically treated postpartum. One malignant tumor was resected postpartum, while the second showed a rapid progression in late pregnancy and required early intervention. Individual case details highlighted the diagnostic and therapeutic complexity in this population. Conclusions: A standard diagnostic protocol, incorporating ultrasounds and a fine-needle aspiration biopsy, is recommended during pregnancy. For cases in which the clinical and imaging characteristics suggest a benign origin, surveillance is proposed. Conversely, surgical resection is recommended for malignant SGTs, irrespective of the gestational stage. The potential for the malignant transformation of benign tumors during pregnancy in young women underscores the necessity for surgical intervention prior to planned conception. Full article

Klotho, an anti-aging protein, has been extensively studied in systemic conditions such as chronic kidney disease and cardiovascular disorders. In recent years, its pivotal protective role and clinical significance in various oral and maxillofacial diseases have been increasingly demonstrated. It has been demonstrated that Klotho regulates oxidative stress, apoptosis, inflammation, and fibrosis via multiple molecular signaling pathways, including Nrf2, NF-κB, PI3K/Akt/FoxO1, insulin/IGF-1, FGF/FGFR, and Wnt/β-catenin. Consequently, these regulatory effects have been observed in conditions such as periodontitis, oral squamous cell carcinoma, malignant salivary gland tumors, oral submucous fibrosis, etc. Moreover, the decreased expression or dysfunctional activity of Klotho is frequently associated with the onset and progression of these diseases. This study provides a comprehensive review of the underlying mechanisms and recent advances in Klotho research within the realm of oral and maxillofacial diseases, offering novel perspectives for future basic and clinical investigations. Full article

Background: Malignant tumors of minor salivary glands (MGSTs) are rare and exhibit significant heterogeneity in terms of etiology, histology and prognosis. Methods: This retrospective analysis of 48 resected MGSTs employed Receiver Operating Characteristic (ROC) curves and logistic regression models to evaluate the association between the systemic inflammatory response index (SIRI), the systemic immuno-inflammation index (SII), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) with overall survival (OS). Although these biomarkers showed some correlation with OS, none were statistically significant when considered individually. Results: Significant correlation was observed between the SIRI, SII, and NLR with overall survival (OS). Among these, SIRI was the most reliable predictor, with an area under the curve (AUC) of 0.713, 80% sensitivity, and 70% specificity. Conclusions: While these inflammatory biomarkers correlate with the prognosis and risk stratification of MGSTs, there is currently no clinical utility in decision making due to the lack of standardization and their limited application in clinical practice. Full article

Salivary gland carcinomas (SGCs) represent a rare and heterogeneous group of malignancies accounting for 3–6% of all head and neck cancers. While surgical resection and radiotherapy remain the standard for locoregional control, systemic treatment is indicated for recurrent or metastatic disease. Advances in molecular profiling have identified actionable targets such as NTRK gene fusions, HER2, immune checkpoint regulators, androgen receptors, and RET receptors. These have facilitated the development of targeted therapies, including TRK inhibitors, HER2-directed agents, and androgen receptor modulators, as well as emerging combinations of immunotherapy and chemotherapy. Despite these advancements, challenges such as resistance mechanisms and limited therapeutic efficacy persist. Overall response rates remain relatively low across most systemic therapies, reflecting a persistent unmet clinical need. This review discusses the current landscape of treatment options and explores promising clinical trials and future directions to enhance outcomes for patients with SGCs. Full article

Background: Primary and secondary salivary gland malignancies differ significantly in treatment and prognosis. However, conventional ultrasonography often struggles to differentiate between these malignancies due to overlapping imaging features. We aimed to develop and evaluate noninvasive diagnostic models based on traditional ultrasound features, radiomics, and deep learning—independently or in combination—for distinguishing between primary and secondary salivary gland malignancies. Methods: This retrospective study included a total of 140 patients, comprising 68 with primary and 72 with secondary salivary gland malignancies, all pathologically confirmed, from four medical centers. Ultrasound features of salivary gland tumors were analyzed, and a radiomics model was established. Transfer learning with multiple pre-trained models was used to create deep learning (DL) models from which features were extracted and combined with radiomics features to construct a radiomics-deep learning (RadiomicsDL) model. A combined model was further developed by integrating ultrasound features. Least absolute shrinkage and selection operator (LASSO) regression and various machine learning algorithms were employed for feature selection and modeling. The optimal model was determined based on the area under the receiver operating characteristic curve (AUC), and interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: The RadiomicsDL model, which combines radiomics and deep learning features using the Multi-Layer Perceptron (MLP), demonstrated the best performance on the test set with an AUC of 0.807. This surpassed the performances of the ultrasound (US), radiomics, DL, and combined models, which achieved AUCs of 0.421, 0.636, 0.763, and 0.711, respectively. SHAP analysis revealed that the radiomic feature Wavelet_LHH_glcm_SumEntropy contributed most significantly to the mode. Conclusions: The RadiomicsDL model based on ultrasound images provides an efficient and non-invasive method to differentiate between primary and secondary salivary gland malignancies. Full article

Nectins constitute a family of Ca(2+)-independent immunoglobulin-like adhesion molecules. They are involved in cell proliferation, morphogenesis, growth, development, and immune modulation. Due to their broad involvement in physiological processes, extensive research is being conducted on the expression of individual nectins in a variety of cancers and their potential in diagnosis, prognosis, and treatment. The overexpression of nectin-1 may be a poor prognostic factor in gastrointestinal cancers (intestine and pancreas). Similarly, the overexpression of nectin-2 is a worse prognostic factor (greater tumor advancement and shorter patient survival) in cancers such as gallbladder, esophagus, and breast cancer. Changes in nectin-3 expression also affect the advancement of, e.g., colorectal cancer. Additionally, a significant factor here seems to be the change in the localization of nectin-3 expression within cellular structures. The most extensively studied nectin-4 also shows prognostic potential in many cancers. Most often, its high expression correlates with poor prognosis (e.g., gastric cancer), but it may also be a positive prognostic factor, e.g., in salivary gland cancer. Therapy based on nectin-4 is already known and used in the case of urothelial cancers. The expression of nectin-like protein 5 (necl-5) also shows prognostic and therapeutic potential in pancreatic and lung cancers, as well as in multiple myeloma. Full article