Search Results (1,216)

Malignant melanoma demonstrates strikingly varied clinical presentations, on account of which it is often challenging to diagnose. We describe herein a rare case of amelanotic malignant melanoma (AMM) in the buccinator muscle presenting as a solitary mass. A middle-aged woman presented with a non-pigmented swelling under the right buccal mucosa. Magnetic resonance imaging (MRI) revealed a well-circumscribed lesion without local invasion. A needle biopsy did not establish the diagnosis and was instead interpreted as suggestive of a salivary gland tumor, reinforcing an initial impression of myoepithelioma. Histopathological analysis of an excised specimen revealed poorly defined, pleomorphic tumor cells and a scattering of melanin-containing cells. The diagnosis of AMM was established by integrating these histopathological features with the clinico-radiological findings and the immunohistochemical results, which were positive for HMB-45, S-100, and SOX10 and negative for cytokeratin. Whole-body positron-emission tomography-computed tomography found no primary lesion. Because tumor nests suggesting possible residual disease were observed near the resection margin, a wider, secondary excision including the affected portion of the buccal mucosa and overlying skin was performed together with neck dissection. Histopathological examination of the re-resection specimen showed no residual tumor, indicating that no malignant cells were identified in the adjacent oral mucosa or facial skin. The patient has remained disease-free for three years. Full article

Background: Salivary gland dysfunction is a central manifestation of Sjögren’s syndrome, but the relationship between quantitative salivary impairment and salivary microcrystallization remains insufficiently defined. This study aimed to assess unstimulated and stimulated whole salivary flow and salivary pH in patients with primary and secondary Sjögren’s syndrome and to explore salivary microcrystallization indices as complementary descriptive markers of salivary physicochemical patterns. Materials and Methods: This cross-sectional observational study included 126 patients diagnosed with primary or secondary Sjögren’s syndrome. Unstimulated whole salivary flow, stimulated whole salivary flow, and salivary pH were assessed under standardized conditions. Salivary dysfunction severity was classified according to predefined functional salivary parameters. Salivary microcrystallization was evaluated microscopically on dried saliva samples and expressed using the IMK-RFR and IMK-RFS indices. Differences between disease subtypes and associations between salivary parameters, microcrystallization indices, and dysfunction severity were analyzed. Results: The mean unstimulated salivary flow rate was 0.272 ± 0.246 mL/min, while the mean stimulated salivary flow rate was 1.04 ± 0.50 mL/min. In unadjusted analyses, patients with primary Sjögren’s syndrome showed lower unstimulated and stimulated salivary flow rates than patients with secondary Sjögren’s syndrome. Both salivary flow parameters were inversely associated with salivary dysfunction severity. In an exploratory internal consistency ROC analysis, unstimulated salivary flow showed good internal agreement with grade ≥ 3 salivary dysfunction, while stimulated salivary flow showed very high internal agreement. Salivary pH showed limited internal consistency with dysfunction severity. Firth penalized logistic regression indicated that stimulated whole salivary flow remained associated with grade ≥ 3 salivary dysfunction after adjustment for unstimulated salivary flow. IMK values described salivary microcrystallization patterns within the Sjögren’s syndrome cohort; however, they were not robustly correlated with salivary flow, pH, or dysfunction severity. Conclusions: Salivary flow assessment remains a simple, non-invasive, and clinically relevant method for evaluating glandular dysfunction in Sjögren’s syndrome. In this cohort, primary Sjögren’s syndrome was associated with lower salivary flow rates, but these unadjusted findings should be interpreted as descriptive. Salivary microcrystallization provided exploratory information on qualitative salivary patterns, but its clinical value remains limited and requires methodological standardization and validation in larger prospective studies. Full article

Background/Objectives: Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by a wide range of clinical manifestations, often leading to delayed diagnosis. This study aimed to evaluate and compare the clinical and laboratory characteristics of patients with primary and secondary SjD and those with sicca symptoms without SjD. Methods: This comparative cross-sectional study included 84 participants enrolled between 2019 and 2024: 27 patients with primary Sjögren’s disease (pSjD), 4 with secondary Sjögren’s disease (sSjD), and 53 with sicca symptoms without SjD (non-SjD/NSjD). Primary SjD was diagnosed according to the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Results: Compared with NSjD patients, those with pSjD and sSjD had significantly lower unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) flow rates (p < 0.001), a higher prevalence of antinuclear antibodies (ANA) (twice as frequent) (p = 0.005), and higher frequencies of anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La, and rheumatoid factor (RF) positivity (p = 0.002, p = 0.003, p = 0.005, and p = 0.019, respectively). In addition, SjD patients had higher EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scores (p = 0.026) and more frequently demonstrated a focus score (FS) ≥ 1 on minor labial salivary gland (MLSG) biopsy (p < 0.001). Serum vitamin D levels were lower in pSjD patients than in NSjD patients; however, the difference was not statistically significant (57.8 ± 20.4 vs. 70.6 ± 18.3; p = 0.259). Conclusions: Patients with pSjD exhibited distinct clinical and laboratory characteristics compared with those with sicca symptoms without SjD. Sialometry, anti-SSA antibodies, and MLSG biopsy were identified as the most important diagnostic tools for differentiating SjD from NSjD. Full article

Introduction: The ecto-endodermal boundary in the human oral cavity remains debated. Rather than a distinct line, this transition forms a complex interface, especially in the developing mouth and pharynx. This ambiguity is clinically relevant, as, for example, HPV-induced tumors often arise where ecto- and endoderm meet. The boundary is generally placed at the posterior third of the tongue and behind the uvula, though its developmental basis remains unclear. This review summarizes the literature on the embryological development of the mouth and pharynx to trace origins and interactions of ectodermal and endodermal derivatives and identify potential tumor initiation regions. Methods: PubMed articles on oral structures were reviewed to approximate the ecto-endodermal border. Results: Teeth originate from ectoderm. The origin of salivary glands and papillae depends on their location. No study reports were found for the tonsils, incisive papilla, tubarial glands, and faucial pillars. Conclusions: A clear educational image of the origin of the structures of the human mouth is made to help identify regions of risk for oral cancer. Full article

Background/Objectives: This paper synthesizes and evaluates the potential origins of ectopic salivary gland pathologies in the human nasopharynx. By combining historical reports with an original comparative analysis, this study aims to clarify the precise anatomical and functional status of the proposed tubarial salivary-type glands. Methods: A literature search through December 2025 across major electronic databases identified 84 relevant publications on nasopharyngeal glandular pathologies. The methodological quality in the histomorphological literature was evaluated using the AQUA tool. Concurrently, histological samples were harvested from the inner Eustachian tube opening/torus tubarius region of human, canine, and rodent cadavers and analyzed using histomorphological and immunohistochemical protocols. Results: Most of the literature addressing histologically indicated nasopharyngeal glandular pathology described these findings as controversial, largely overlooking salivary gland origins. The AQUA appraisal identified significant vulnerabilities, showing a high risk of bias in the Study Design domain and yielding moderate inter-rater agreement (κ = 0.435). The empirical morphological study revealed mixed glands with strong mucous predominance in the torus tubarius region of humans and dogs, whereas rodents displayed exclusive PAS positivity within a trabecular stroma. Human samples uniquely demonstrated distinct compartmentalization, duct- and capsule-like formations, and negative α-amylase immunoreactivity. Conclusions: Our pilot empirical evidence, combined with the literature data, suggests a possible pathogenetic link between specific nasopharyngeal neoplasms and the baseline glandular structures of the human torus tubarius. Exhibiting traits of both major and minor salivary systems, the tubarial glands may represent an intermediate structural entity. Furthermore, the animal models utilized do not provide a completely reliable translational framework, highlighting the need for standardized research using fresh human biopsies. Full article

Background/Objectives: Preoperative characterization of salivary gland tumors remains challenging because conventional MRI and diffusion-weighted imaging may show overlapping features, particularly between Warthin tumors and malignant lesions. This study evaluated the diagnostic value of quantitative permeability MRI based on dynamic contrast-enhanced pharmacokinetic analysis for differentiating salivary gland tumors. Methods: This retrospective single-center study included 51 patients with 59 histologically confirmed salivary gland lesions examined between January 2022 and November 2024. MRI included diffusion-weighted imaging and dynamic contrast-enhanced MRI (DCE-MRI). Quantitative pharmacokinetic analysis based on the Extended Tofts model provided Ktrans, Kep, Ve, and Vp. Interobserver reproducibility was assessed using the intraclass correlation coefficient, and diagnostic performance was evaluated by receiver operating characteristic analysis. Results: Of 59 lesions, 44 were benign, and 15 were malignant. Warthin tumors showed significantly higher Kep values than malignant lesions (median, 998 vs. 480 × 10⁻³/min; p = 0.002) and lower Ve values (median, 121 vs. 245 × 10⁻³; p = 0.004). ADC values partially overlapped between Warthin tumors and malignant lesions. Interobserver agreement was good, with ICC values ranging from 0.78 to 0.86. Kep showed the highest diagnostic performance in this cohort, with an AUC of 0.96. A Kep threshold of 723 × 10⁻³/min yielded 92.3% sensitivity and 93.3% specificity. Conclusions: Quantitative DCE-MRI, particularly Kep, may provide additional information for differentiating Warthin tumors from malignant salivary gland lesions within a multiparametric MRI assessment. The threshold identified in this cohort is exploratory and requires external validation before routine clinical use. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and dysfunction of the exocrine glands, with manifestations extending beyond glandular sicca symptoms to multiple extraglandular systems. Although the pathogenesis of SjD remains incompletely understood, growing evidence indicates that a complex cytokine network involving both innate and adaptive immune pathways plays a central role in disease development. This narrative review summarizes recent updates on cytokine signaling in SjD across three clinically relevant domains. In glandular inflammation, activation of salivary gland epithelial cells through Toll-like receptor pathways triggers type I interferon (IFN) signaling via plasmacytoid dendritic cells, while IFN-γ, Th17-related cytokines (IL-6, IL-17, IL-22), BAFF/APRIL, and chemokines (CXCL10, CXCL12, CXCL13) collectively sustain local inflammation and ectopic lymphoid organization. The BAFF/APRIL axis, a systemic type I IFN signature, and IL-21–follicular helper T cell–B cell interactions primarily drive systemic immune activation, which together underlie autoantibody production, hypergammaglobulinemia, and a lymphoma-prone phenotype. In contrast, constitutional symptoms such as fatigue, pain, and dryness frequently dissociate from classical inflammatory activity and are better explained by neuroimmune–metabolic mechanisms, including the IFN-γ–IDO–kynurenine pathway and symptom-associated proteomic signatures. Collectively, these findings underscore the heterogeneous nature of SjD, in which glandular inflammation, systemic immune activation, and constitutional symptoms are driven by distinct yet partially overlapping cytokine pathways. Recognizing this heterogeneity has direct implications for cytokine-targeted therapy, suggesting that future trials should stratify patients by disease phenotype (IFN-high, B cell-dominant, and symptom-dominant) rather than treating SjD as a uniform population. Full article

Assessing mosquito vector competence for emerging arboviruses, including the underlying determinants of infection, is a foundational line of investigation towards understanding arbovirus transmission dynamics and vector–virus interactions. We developed a novel quantitative immune gene array that measures the relative expression of 22 immune genes with functional representation across five major immune pathways using quantitative reverse-transcriptase polymerase chain reaction. Homologous primers were developed for Culex tarsalis, Cx. quinquefasciatus, and Ae. aegypti mosquitoes. As an initial pilot test for this array, Cx. tarsalis and Ae. aegypti mosquitoes were orally challenged with Rift Valley fever virus (RVFV) MP12 strain. Midguts, legs/wings, and salivary glands were harvested at 3 and 7 days post-challenge. Differential gene expression was measured against Rpl32 as a housekeeping gene. This assay was sensitive enough to generate results for single mosquito midgut and salivary gland tissues, providing an initial snapshot of the types of gene expression patterns that can be observed for two mosquito species infected with MP12. This new tool will be broadly applicable for assessing mosquito immune profiles for arbovirus infection across major immune genes in five key pathways, as well as generating comparable results across mosquito and arbovirus systems. Full article

Feline chronic gingivostomatitis (FCGS) is a chronic inflammatory disease of the oral mucosa. Mesenchymal stem cell (MSC) treatments have been investigated as a potential treatment for this condition; however, the biodistribution profile of MSCs remains poorly understood. The goal of this study was to assess the relative pharmacokinetics of MSCs by comparing their biodistribution in healthy cats to that in cats suffering from FCGS. Two studies were performed to evaluate the biodistribution of radiolabelled equine peripheral blood-derived mesenchymal stem cells (ePB-MSCs) following intravenous and subcutaneous administration in healthy cats (n = 3) and in cats with FCGS (n = 4). Total body scintigraphic scans were obtained using a gamma camera. Free ^99mTechnetium accumulation was primarily observed in the heart, lungs, stomach, bladder, thyroid, and salivary glands. Following intravenous administration of radiolabelled ePB-MSCs, increased radiopharmaceutical uptake (IRU) was mainly detected in the lungs, liver, kidneys, and bladder. After subcutaneous administration, IRU was predominantly observed at the injection site. In cats affected by FCGS, a higher radiotracer signal was observed in the rostral oral region following intravenous administration, with a mean 3.4-fold increase compared with healthy cats. The biodistribution pattern of radiolabelled ePB-MSCs differed from that of free ^99mTechnetium. These findings provide preliminary information regarding the biodistribution of radiolabelled ePB-MSCs in cats. Full article

Background/Objectives: Menopause is a complex physiological transition characterized by progressive estrogen deficiency and systemic biological changes that can affect multiple organs and tissues, including the oral cavity. Growing evidence suggests that hormonal fluctuations during the menopausal transition may influence periodontal health, salivary function, oral sensory perception, and overall oral health-related quality of life. Objective: This narrative review aims to provide a comprehensive overview of the biological mechanisms and clinical manifestations associated with the relationship between menopause and oral health, with particular attention to periodontal outcomes, salivary changes, oral discomfort, dental status, and the potential role of hormone replacement therapy (HRT). Methods: This narrative review was based on a structured literature search conducted in PubMed/MEDLINE and Scopus to identify studies published between January 2005 and May 2026. Predefined eligibility criteria were applied to identify relevant human studies. The retrieved evidence was synthesized narratively according to major oral health domains and menopausal phenotypes. Results: Fifty studies met the inclusion criteria. Overall, menopause was associated with poorer periodontal parameters, including increased probing depth, clinical attachment loss, and periodontal inflammation. Reduced salivary flow, dry mouth, altered salivary composition, burning symptoms, and taste disturbances were frequently reported in peri- and postmenopausal women. A higher prevalence of caries and tooth loss was also reported, although the contribution of age and other confounding factors varied across studies. New evidence suggests that estrogen deficiency may influence oral health through interconnected pathways involving immune regulation, bone metabolism, salivary gland function, and host–microbiome interactions. Evidence regarding the effects of HRT has been mixed, although several studies have reported improvements in salivary function and periodontal outcomes among treated women. Conclusions: Menopause appears to act as an important systemic modifier of oral health through multifactorial biological mechanisms. Menopause-associated oral manifestations go beyond local tissue changes and reflect broader interactions between hormonal status, inflammation, bone metabolism, and microbial ecology. Increased awareness among dental and medical professionals and a multidisciplinary approach could improve the prevention, diagnosis, and management of oral diseases in postmenopausal women. Further, well-designed longitudinal studies are needed to clarify causal relationships and identify effective therapeutic strategies. Full article

Background/Objectives: Metastasizing pleomorphic adenoma (MPA) is a rare salivary gland tumor characterized by benign pleomorphic adenoma morphology despite regional or distant metastatic behavior. Because most evidence derives from case reports and small series, this systematic review and pooled case-report analysis aimed to summarize published patient-level data and to explore clinicopathologic features, metastatic distribution, treatment, and survival without inferring causal treatment effects. Methods: PubMed, Scopus, Google Scholar, and reference lists were searched for English-language reports published up to 1 August 2025. Eligible reports described primary pleomorphic adenoma and metastatic disease reported as MPA with benign morphology; carcinoma ex pleomorphic adenoma and other malignant pleomorphic adenoma variants were excluded. The primary pooled analysis was restricted to 122 published case-report patients. Institutional cases are presented separately as illustrative cases and were not included in the primary pooled statistical analyses. Unknown, not reported, NA, and unclear values were treated as missing, and denominators are reported. Because only 16 deaths were available, survival analyses were exploratory and no multivariable Cox model was fitted. No formal risk-of-bias or certainty-of-evidence assessment was performed. Results: In the 122 published patients, sex was available for 121 patients and 71/121 (58.7%) were female. Primary tumors most frequently arose in the parotid gland (92/122, 75.4%), followed by the submandibular gland (15/122, 12.3%) and palate/soft palate (10/122, 8.2%). The median interval between primary pleomorphic adenoma and MPA was 12 years (IQR 7–21; range 0–69; n = 118). Metastatic site was reported in 120 patients and was non-mutually exclusive: bone/skeleton and lymph nodes/neck were each reported in 42/120 patients (35.0%), followed by lung/pulmonary metastases in 31/120 (25.8%). Treatment information was available for 98/122 patients. MPA-directed surgery was performed in 86/98 patients with available treatment information (87.75%). The non-surgical cohort received radiotherapy, chemotherapy, palliative treatment, treatment refusal, observation, or other non-surgical strategies. A total of 72 patients had complete covariate data for the reported Cox analyses, including 16 deaths. Estimated 1- and 5-year overall survival were 89.97% and 66.2%, respectively. Surgery was associated with improved overall survival in exploratory Kaplan–Meier comparison (log-rank p = 0.008) and univariable Cox analysis (HR 0.119, 95% CI 0.018–0.810, p = 0.030), but this association should not be interpreted as causal. Conclusions: MPA remains difficult to predict and the available evidence is limited by case-report design, missing data, publication bias, and heterogeneous follow-up. Surgical management may be considered in selected patients when technically feasible and clinically appropriate, but the observed survival association is exploratory and may be influenced by selection bias and disease characteristics. Multicenter registries, standardized reporting, centralized pathology review, molecular characterization, and longer follow-up are needed. Full article

Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Objective: This scoping review mapped current evidence on diagnostic challenges, differential diagnostic criteria, management strategies, and surveillance considerations for LESA. Eligibility criteria: Sources were selected using the Population–Concept–Context framework and included the literature addressing salivary gland lymphoepithelial lesions, LESA, Sjögren’s disease-associated salivary gland involvement, or related lymphoid-rich salivary gland disorders published from 2010 onward. Sources of evidence and charting methods: Google Scholar was searched, records were screened in sequential stages, and relevant data were charted narratively across clinical, serological, imaging, histopathological, immunophenotypic, molecular, therapeutic, and follow-up domains. Results: Thirty-seven sources were included. The evidence indicates that LESA is usually characterized by chronic lymphoplasmacytic inflammation, acinar atrophy, lymphoepithelial lesions, and preserved lobular architecture; however, these findings may overlap with early or established MALT lymphoma. Immunohistochemistry, assessment of light-chain restriction, clonality testing, serological markers, and imaging are useful adjuncts, but no single test is independently definitive. Conservative management and symptomatic care are appropriate for stable disease, whereas corticosteroids, immunomodulatory therapy, sialendoscopy, surgery, radiotherapy, or systemic lymphoma therapy may be considered according to clinical context. Conclusions: LESA requires integrated clinicopathological interpretation and multidisciplinary follow-up. Key evidence gaps include the absence of standardized LESA-specific diagnostic criteria, limited validation of molecular and flow cytometric approaches in salivary gland specimens, and lack of consensus surveillance protocols. Full article

Background/Objectives: Lutetium (¹⁷⁷Lu) TLX591 (¹⁷⁷Lu-TLX591) is a radio antibody–drug conjugate (rADC) that utilizes a novel monoclonal antibody-based approach for treatment of patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). ProstACT SELECT (NCT04786847) was a multicenter, single-arm, open-label Phase 1 trial evaluating patient selection for ¹⁷⁷Lu-TLX591 therapy using ⁶⁸Ga-PSMA-11 PSMA positron emission tomography (PET) in a heterogenous sample of patients with mCRPC. Primary and key secondary objectives were to evaluate safety and tolerability, biodistribution, and organ radiation dosimetry of ¹⁷⁷Lu-TLX591 in combination with the best standard of care (SOC) for patients with PSMA-expressing mCRPC who progressed despite prior treatment with an androgen receptor pathway inhibitor. Methods: Thirty patients received ¹⁷⁷Lu-TLX591 intravenously in combination with investigator-determined SOC. Cohort 1 (n = 5) received an imaging dose of ¹⁷⁷Lu-TLX591 (1 GBq [27 mCi]), followed 14 days later by one therapeutic dose (2.8 GBq [76 mCi]). Cohort 2 received two therapeutic doses of ¹⁷⁷Lu-TLX591, 14 days apart. Baseline ⁶⁸Ga-PSMA-11 PET was performed to confirm eligibility and was qualitatively compared with serial ¹⁷⁷Lu-TLX591 single-photon emission computed tomography (SPECT)/CT, which was performed at five timepoints following the first ¹⁷⁷Lu-TLX591 administration and also used to evaluate organ radiation dosimetry. Safety assessments included monitoring for treatment-emergent adverse events and collection of laboratory samples at specified timepoints used for biomarker analyses. Results: Tumor targeting observed on ¹⁷⁷Lu-TLX591 SPECT/CT imaging was qualitatively consistent with uptake observed on ⁶⁸Ga-PSMA-11 PET imaging. No new safety signals were observed. Radiation exposure was within safety limits, with the highest absorbed dose to liver (clearance organ; 2.44 ± 0.56 Gy/GBq) and with lower exposure to salivary glands (0.07 ± 0.03 Gy/GBq) and kidneys (0.64 ± 0.17 Gy/GBq). Activity was retained in tumor lesions through to the final protocol-specified imaging timepoint (312 h) following administration. Conclusions: In this Phase 1, single-arm study, ⁶⁸Ga-PSMA-11 PET supported patient selection for ¹⁷⁷Lu-TLX591 therapy. In a heterogenous population representative of a real-world setting, ¹⁷⁷Lu-TLX591 therapy in combination with SOC demonstrated a manageable and predictable safety profile, durable retention, and low salivary gland radiation exposure. Further evaluation in larger, randomized studies is warranted. Full article

Background/Objectives: Salivary gland tumors account for 2.0–6.5% of all head and neck neoplasms, approximately 70% of which are located in the parotid gland. Preoperative determination of tumor histology is a crucial step in the diagnostic and therapeutic pathway because it guides the choice of surgical technique, affecting the achievement of adequate resection margins and preservation of the facial nerve. Fine-needle aspiration (FNA) cytology is the most commonly used cytologic method. However the complex and heterogenous histologic architecture of salivary gland tumors is associated with a significant proportion of false results. Dynamic contrast-enhanced magnetic resonance imaging (DCE–MRI) is a valuable complementary diagnostic tool that enables noninvasive analysis based on perfusion assessment and tissue characterization. The aim of this study is to evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the diagnosis of salivary gland tumors and to compare its diagnostic performance with fine-needle aspiration (FNA). Methods: We present a study of 25 patients who underwent DCE-MRI, FNA and postoperative histopathologic examination. Results: Among the 25 patients included, DCE-MRI results were concordant with the postoperative histopathologic diagnosis in 76% of cases, whereas only 36% of positive FNA results correlated with the histopathologic diagnosis. Conclusions: DCE-MRI demonstrates greater correlation with postoperative histopathologic diagnosis compared with FNA. Advantages of DCE-MRI include its noninvasive nature and the ability to image the entire region of interest. Key benefits of FNA are its wide availability and low cost. Selecting the most appropriate preoperative diagnostic modality can positively influence subsequent diagnostic and therapeutic management. Full article

Background/Objectives: Hypoxia-inducible factor 1-alpha (HIF-1α) is a transcription factor that escapes proteasomal degradation under hypoxic conditions, translocates to the nucleus, and activates genes involved in anaerobic glycolysis (e.g., GLUT1 and LDH-A) and vascular endothelial growth factor (VEGF) expression. Through its role in tumor progression, angiogenesis, and metabolic reprogramming, elevated HIF-1α levels have been reported in various malignancies; however, its serum concentration in malignant salivary gland neoplasms remains unexplored. This study aimed to assess serum HIF-1α levels in patients with salivary gland malignancies. Methods: Serum samples were collected from 30 patients diagnosed with malignant salivary gland neoplasms. HIF-1α concentration was determined using an enzyme-linked immunosorbent assay (ELISA). Results: The mean serum HIF-1α concentration was 89.20 ± 44.56 pg/mL. Exploratory analyses demonstrated higher HIF-1α levels in stage III tumors compared with stage II tumors and in high-grade tumors compared with lower-grade lesions. Conclusions: This is the first study to quantify serum HIF-1α levels in patients with malignant salivary gland neoplasms. The findings suggest that while HIF-1α may have potential as a biomarker, its potential as a biomarker of tumor aggressiveness or of malignant salivary gland neoplasms is limited due to high interindividual variability. Further studies with larger cohorts and standardized methodologies are necessary to establish reference values and clarify the clinical significance of HIF-1α in salivary gland malignancies. Full article