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Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of the minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics, particularly acinic cell carcinoma, prior to 2010. It was first recognized as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histologic and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed in the same way as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biologic agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy. Due to the limited number of reported cases, the spectrum of clinical behavior, best practices for management, and long-term treatment outcomes for secretory carcinoma remain unclear. A long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient, is reported. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management. [ABSTRACT FROM AUTHOR]

Simple Summary: Salivary gland tumors (SGTs) are rare and complex, making them difficult to diagnose and treat. This work focuses on the role of exosomes, extracellular vesicles secreted by almost all cell types, in the development and progression of SGT. Exosomes are crucial in cell-to-cell communication and play significant roles in tumor biology, including modulating the tumor environment, aiding metastasis, and affecting immune responses. A better understanding of exosome biology can lead to their use as biomarkers for diagnosis and prognosis, as well as targets for treatment, potentially transforming SGT management and improving patient outcomes. Exosome-based liquid biopsies could offer non-invasive, real-time diagnostics and enhance patient care through precision medicine. This review explores the advancements in salivary exosome analysis, highlighting its potential for non-invasive cancer detection and the development of innovative diagnostic techniques. Backgroud: Salivary gland tumors (SGTs) are rare and diverse neoplasms, presenting significant challenges in diagnosis and management due to their rarity and complexity. Exosomes, lipid bilayer vesicles secreted by almost all cell types and present in all body fluids, have emerged as crucial intercellular communication agents. They play multifaceted roles in tumor biology, including modulating the tumor microenvironment, promoting metastasis, and influencing immune responses. Results: This review focuses on the role of exosomes in SGT, hypothesizing that novel diagnostic and therapeutic approaches can be developed by exploring the mechanisms through which exosomes influence tumor occurrence and progression. By understanding these mechanisms, we can leverage exosomes as diagnostic and prognostic biomarkers, and target them for therapeutic interventions. The exploration of exosome-mediated pathways contributing to tumor progression and metastasis could lead to more effective treatments, transforming the management of SGT and improving patient outcomes. Ongoing research aims to elucidate the specific cargo and signaling pathways involved in exosome-mediated tumorigenesis and to develop standardized techniques for exosome-based liquid biopsies in clinical settings. Conclusions: Exosome-based liquid biopsies have shown promise as non-invasive, real-time systemic profiling tools for tumor diagnostics and prognosis, offering significant potential for enhancing patient care through precision and personalized medicine. Methods like fluorescence, electrochemical, colorimetric, and surface plasmon resonance (SPR) biosensors, combined with artificial intelligence, improve exosome analysis, providing rapid, precise, and clinically valid cancer diagnostics for difficult-to-diagnose cancers. [ABSTRACT FROM AUTHOR]

Objective: To explore the biological function and mechanisms of CEBPB and NAT10‐mediated N4‐acetylcytidine (ac4c) modification in salivary adenoid cystic carcinoma (SACC). Materials and Methods: CEBPB and NAT10 were knocked down in SACC–LM cells by siRNA transfection and overexpressed in SACC‐83 cells by plasmid transfection. Malignant phenotypes were evaluated using CCK‐8, Transwell migration and colony formation assays. Real‐time PCR, western blotting, ChIP and acRIP were used to investigate the molecular mechanisms involved. Results: We found that CEBPB was highly expressed in SACC tissues and correlated with lung metastasis and unfavourable prognosis. Gain‐ and loss‐of‐function experiments revealed that CEBPB promoted SACC malignant phenotypes. Mechanistically, CEBPB exerted its oncogenic effect by binding to the vimentin gene promoter region to enhance its expression. Moreover, NAT10‐mediated ac4c modification led to stabilization and overexpression of CEBPB in SACC cells. We also found that NAT10, the only known human enzyme responsible for ac4C modification, promoted SACC cell migration, proliferation and colony formation. Moreover, CEBPB overexpression restored the inhibitory effect of NAT10 knockdown on malignant phenotypes. Conclusions: Our study reveals the critical role of the newly identified NAT10/CEBPB/vimentin axis in SACC malignant progression, and the findings may be applied to improve treatment for SACC. [ABSTRACT FROM AUTHOR]

Objectives: To compare the clinicopathological, molecular, and immune features of conventional and high‐grade transformation (HGT) secretory carcinoma (SC) in salivary glands. Materials and Methods: The clinicopathological data of 88 cases including 74 conventional SCs and 14 SCs with HGT were reviewed. Targeted next‐generation sequencing was performed in 11 SCs with HGT and 7 conventional SCs. The level of PD‐L1 and CD8+ TILs was determined by immunohistochemistry. Results: Compared with the conventional group, the rates of nodal metastasis, local recurrence, distant metastasis and mortality were significantly higher in the HGT cohort. Mutations of ARID1A/B, KMT2A, HOXD13, NRG1 and ETV6 genes were identified in HGT SCs. A recurrent E307G mutation in GATA6 gene was also observed in two cases. Two deceased HGT patients with distant metastasis harboured NOTCH3 mutations. ETV6‐RET translocation was prone to occur in the HGT SCs. Additionally, PD‐L1 expression was low, and CD8+ TILs were sparse in most HGT cases. Conclusion: Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD‐L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology. [ABSTRACT FROM AUTHOR]

Objective: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. Methods: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. Results: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. Conclusion: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes. [ABSTRACT FROM AUTHOR]

Context.--Fine-needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions, despite challenges imposed by salivary gland tumor diversity, complexity, and cytomor-phologic overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). The MSRSGC consists of 6 diagnostic categories, which incorporate the morphologic heterogeneity and overlap among various nonneoplastic, benign, and malignant lesions of the salivary glands. In addition, each MSRSGC diagnostic category is associated with a risk of malignancy and management recommendations. Objective.--To review the current status of salivary gland FNA, core needle biopsies, ancillary studies, and the beneficial role of the MSRSGC in providing a framework for reporting salivary gland lesions and guiding clinical management. Data Sources.--Literature review and personal institutional experience. Conclusions.--The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histo-logic correlation, quality improvement, and research. Since its implementation, the MSRSGC has gained international acceptance as a tool to improve reporting standards and consistency in this complex diagnostic area, and it has been endorsed by the 2021 American Society of Clinical Oncology management guidelines for salivary gland cancer. The large amount of data from published studies using MSRSGC served as a basis for the recent update of the MSRSGC. [ABSTRACT FROM AUTHOR]

Background: Orofacial neoplasms in children and young adults may differ significantly from those observed in adults. Our aim was to describe the epidemiological characteristics of histologically diagnosed orofacial neoplasms among children and young adults in Nigeria. Methods: This was a multicenter cross-sectional study across geopolitical zones in Nigeria. Annual reports of clinical information and surgical biopsies submitted at the Oral Pathology Laboratory, clinic day registries, surgical day case registries and operative theatre registries were retrieved from January 2008 to March 2024. The relevant demographic data were obtained for each patient. The study subjects were categorized by age into children, adolescents and young adults. Tissue involvement was classified as soft tissue involvement, bony involvement or both soft tissue and bony involvement. The site and behaviour of the lesions were subdivided according to the ICD-10 codes. Statistical analysis was performed via the R programming language. Results: A total of 1889 cases were observed during the period under review, with a mean age of 15 years. Cases were more common in females (52%) and in young adults (47%). Most cases were benign neoplasms (85%), and bony affectation (54%) was slightly predominant. Odontogenic tumours (38%) and fibro-osseous lesions (20%) were the most common category of lesions observed, whereas salivary gland tumours (2.2%) and neoplasms of epithelial origin (2.5%) were the least common. Neoplasms in children involved mostly soft tissues, whereas those in adolescents and young adults had a preference for bone (p < 0.001). In all age groups, benign lesions were mostly observed in the mouth and pharynx. For malignant lesions, in children, the bones of the skull and face were mostly involved, whereas in adolescents, the mandible was the predominant site (p < 0.001). In children, mesenchymal neoplasms were the most prevalent category of lesions, whereas in both adolescents and young adults, odontogenic tumours were more common. The proportion of malignant neoplasms in males was significantly greater than that in females (p < 0.001). Conclusion: This study revealed that although most biopsied orofacial lesions were more often benign, the proportion of malignant neoplasms in this population was greater than that previously reported. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC) is a recently described neoplasm entity that presents only in the sinonasal tract. Histologically, it displays features of both a surface-derived carcinoma and a salivary gland carcinoma, and is associated with high-risk HPV, specifically HPV type 33. Whereas majority of the cases display high-grade histologic features, HMSC paradoxically behaves in a relatively indolent fashion. It is important and meaningful to distinguish HMSC from other histopathologic mimickers as the clinical features and management are distinctive. A 64-year-old woman presented having intermittent left-side epistaxis and progressive nasal obstruction. A well-defined, solitary, friable mass with an irregular surface that easily bled upon contact was found in the posterior part of the left nasal cavity. Endoscopic excision of the tumor which was originated from left nasal septum was done and the tumor was confirmed as HMSC. After surgery, definitive radiotherapy was performed in 28 fractions. HMSC is a histopathological type that has been rarely reported so that we report this case with literature review. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether synthetic MR imaging can distinguish between benign and malignant salivary gland lesions. Methods: The study population included 44 patients with 33 benign and 11 malignant salivary gland lesions. All MR imaging was obtained using a 3 Tesla system. The QRAPMASTER pulse sequence was used to acquire images with four TI values and two TE values, from which quantitative images of T1 and T2 relaxation times and proton density (PD) were generated. The Mann–Whitney U test was used to compare T1, T2, PD, and ADC values among the subtypes of salivary gland lesions. ROC analysis was used to evaluate diagnostic capability between malignant tumors (MTs) and either pleomorphic adenomas (PAs) or Warthin tumors (WTs). We further calculated diagnostic accuracy for distinguishing malignant from benign lesions when combining these parameters. Results: PAs demonstrated significantly higher T1, T2, PD, and ADC values than WTs (all p < 0.001). Compared to MTs, PAs had significantly higher T1, T2, and ADC values (all p < 0.001), whereas WTs had significantly lower T1, T2, and PD values (p < 0.001, p = 0.008, and p = 0.003, respectively). T2 and ADC were most effective in differentiating between MTs and PAs (AUC = 0.928 and 0.939, respectively), and T1 and PD values for differentiating between MTs and WTs (AUC = 0.915 and 0.833, respectively). Combining T1 with T2 or ADC achieved accuracy of 86.4% in distinguishing between malignant and benign tumors. Similarly, combining PD with T2 or ADC reached accuracy of 86.4% for differentiating between malignant and benign tumors. Conclusions: Utilizing a combination of synthetic MRI parameters may assist in differentiating malignant from benign salivary gland lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Adenoid cystic carcinoma is a rare but devastating disease. Currently, treatment options are very poor, and ACC does not respond well to conventional chemotherapy or radiation therapy and has a high rate of recurrence or metastasis. The molecular drivers that govern disease pathology are currently poorly understood. We conducted a molecular analysis of adenoid cystic carcinoma of the salivary and lacrimal glands in order to better understand these mechanisms and pave the way for the development of future therapeutics. Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Salivary gland neoplasms (SGNs) pose a challenge to both pathologists and clinicians. Despite research, the etiology of these neoplasms remains unclear. This study aimed to identify any potential association between the presence of hepatitis C virus (HCV) at the protein or gene level and epithelial salivary gland neoplasms. Methods: Formalin-fixed paraffin-embedded (FFPE) blocks of epithelial salivary gland neoplasms were retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University within the 5-year period from 2016 to 2020. Immunohistochemistry was used to assess HCV core antigen, while reverse transcription polymerase chain reaction was employed for the evaluation of HCV RNA. Results: A total of 44 specimens were collected, 28 of which were benign neoplasms and 16 were malignant neoplasms. There was a statistically significant difference in HCV positivity between the two groups (P-value = 0.036). Benign tumors showed a statistically significant lower percentage of positive cases than malignant tumors. The localization of staining was also evaluated, revealing various patterns of HCV core antigen expression, including diffuse cytoplasmic, patchy cytoplasmic, nuclear, and a combination of nuclear and cytoplasmic expression. There was no statistically significant difference between the expression patterns in benign and malignant tumors (P-value = 0.616). Given that Pleomorphic Adenoma and Mucoepidermoid Carcinoma were the predominant tumor types in this study, four cases were selected for RNA detection. HCV RNA was detected in all cases using RT-PCR. Conclusions: HCV core antigen is frequently detected in SGNs and is suggested to be a potential risk factor for the development of these neoplasms. Further studies are required to discover other biomarkers, their roles, and the pathways associated with HCV in SGNs. [ABSTRACT FROM AUTHOR]

Epithelial–myoepithelial carcinoma (EMC) is a rare tumor that occurs mainly in the major salivary glands. Cases occurring in the nasal cavity are rarely reported. The patient was a 48-year-old woman with a postoperative pathological diagnosis of EMC. The patient recovered well after surgery. We consulted and summarized all previous cases of nasal EMC. We also discuss the clinical presentation, treatment, and prognosis of EMC of the nasal cavity and paranasal sinuses. [ABSTRACT FROM AUTHOR]

Simple Summary: We present in this study novel data which demonstrates that the most common type of tumor of the salivary glands may be accurately diagnosed using a specific type of radiological imaging. This may be used to help discriminate this tumor or recurrent versions of it amid various types of benign and malignant tumors. Furthermore, this data suggest that new avenues of minimally invasive therapy may be viable for these tumors and potentially even malignant versions of these tumors and should be examined in further studies. Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. [ABSTRACT FROM AUTHOR]

The Canadian Association of Radiologists (CAR) Head and Neck Expert Panel consists of radiologists, a laryngologist and laryngeal surgeon, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 11 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 17 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 26 recommendation statements across the 11 scenarios. This guideline presents the methods of development and the referral recommendations for sinus disease, tinnitus, thyroid and parathyroid disease, neck mass of unknown origin, acute sialadenitis, chronic salivary conditions, and temporomandibular joint dysfunction. [ABSTRACT FROM AUTHOR]

Background: Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR‐26a, miR‐26b, and miR‐191), and three pro‐oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers. Methods: This cross‐sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase‐real‐time polymerase chain reaction. Results: All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR‐26a And miR‐191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH. Conclusion: The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR‐26a, miR‐191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers. [ABSTRACT FROM AUTHOR]

Adenoid Cystic Carcinoma (ACC) is an uncommon form of malignant neoplasm of the salivary gland. ACC is a rare epithelial, slow-growing yet aggressive neoplasm with a remarkable capacity for recurrence. It most commonly develops in the salivary glands or other regions of the head and neck. Hereby, authors present a case of a 72-year-old female who presented with a rapidly enlarging swelling in the right submandibular region, which had recurred three times. Histopathological examination reported it as ACC grade II. ACC is known for its ability to invade perineurally, its high frequency of local and distant recurrence and its poor long-term prognosis. In the present case, the treatment provided was complete surgical resection. The patient underwent wide surgical excision of the lesion with appropriate margins, as well as a completion neck dissection of level IA. The histopathological diagnosis is based on tissue examination findings that exhibit typical histologic features. The presence and percentage of solid architecture reflect clinical outcomes and should be reported in the pathology report. Current diagnostics mainly rely on histomorphology, along with immunohistochemistry and cytogenetics. Poor prognostic factors include large tumour size, solid growth pattern, positive surgical margins, nodal status, nuclear atypia, high mitotic activity, high-grade transformation, lymphovascular invasion and tumour necrosis. The patient was kept on regular follow-up and there was no recurrence or metastasis noted over two years. ACC remains extremely difficult to treat due to its high recurrence and metastasis rates. The authors are presenting a case of right submandibular gland ACC for its rarity, multiple recurrences, aggressive clinical behaviour and associated radiological and histopathological findings.

Objectives: The purpose of this review was to present the basic concepts of metabolomics methodology and the use of saliva for diagnostic, prognostic, and predictive strategies. Material and methods: This review followed the focus in: “saliva metabolomics” and “oral diseases”. The authors searched studies on PubMed database. The inclusion criteria were original studies and reviews that assessed metabolomics techniques. A descriptive analysis was performed considering the study design, approach system, clinical steps, and tools for the determination of profile or biomarkers metabolites, and the advantages and disadvantages. Results: Metabolomic analyses use a combination of analytical instrumentation and informatic tools to provide information on metabolite characteristics. In this review we described different technologies applied and the advantages and limitations of each technique. Furthermore, in the literature search, we retrieved 25 studies that investigated saliva metabolites in oral diseases: 8 studies used targeted analysis and 17 untargeted metabolomics approaches. Most studies included patients with periodontal diseases, oral squamous cell carcinoma, and Sjögren Syndrome. The most frequently reported metabolites were glycine, leucine, phenylalanine, dipeptides, linoleic acid, arachidonic acid, tyrosine, choline, taurine, lactate, valine, and proline. Conclusions: Metabolomics analysis has emerged as a powerful tool for tumor diagnosis and to enhance tumor classification, including salivary gland tumors (SGTs). It also holds promise for developing personalized treatment plans and defining more precise prognostic categories. Clinical relevance: Metabolomics is the most functional and comprehensive technique for monitoring and understanding gene functions and identifying the biochemical state of an organism in response to genetic and environmental changes. [ABSTRACT FROM AUTHOR]

Background: Salivary gland tumors (SGTs) globally account for

The article reviews the development and purpose of the Great Britain Multidisciplinary Head and Neck Cancer Guidelines, highlighting their role in standardizing care and improving outcomes through a multidisciplinary approach. It also discusses the nature of head and neck cancers, the impact of HPV on cancer incidence, and the organization of head and neck cancer services and patient management.

Simple Summary: Given the low incidence, heterogeneous behavior, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This is the first systematic review and meta-analysis to report the cumulative evidence on postoperative radiotherapy (PORT) for SGC of the head and neck. Based on 2962 patients with SGC from 26 studies, this study demonstrated the long-term survival and toxicities of PORT as a local treatment modality for SGC. Considering the suboptimal disease-free survival and distant metastasis-dominant recurrent patterns, however, an intensified treatment strategy is needed. Background: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. Results: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56–66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0–100%), 40% (0–77%), and 31% (0–75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89–94%), 89% (95% CI, 86–93%), and 84% (95% CI, 73–92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70–83%), 67% (95% CI, 60–74%), and 61% (95% CI, 55–67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79–88%), 75% (95% CI, 72–79%), and 68% (95% CI, 62–74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3–14%). Conclusion: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted. [ABSTRACT FROM AUTHOR]

Salivary glands tumors are uncommon neoplasms with variable incidence, heterogenous histologies and unpredictable biological behaviour. Most tumors are located in the parotid gland. Benign salivary tumors represent 54–79% of cases and pleomorphic adenoma is frequently diagnosed in this group. Salivary glands malignant tumors that are more commonly diagnosed are adenoid cystic carcinomas and mucoepidermoid carcinomas. Because of their diversity and overlapping features, these tumors require complex methods of evaluation. Diagnostic procedures include imaging techniques combined with clinical examination, fine needle aspiration and histopathological investigation of the excised specimens. This narrative review describes the advances in the diagnosis methods of these unusual tumors—from histomorphology to artificial intelligence algorithms. [ABSTRACT FROM AUTHOR]

Sublingual gland herniation into the submandibular space through a mylohyoid muscle defect is a common anatomical variation; however, salivary gland cancers that arise from a herniated sublingual gland have not been described yet. Here, we report three patients with salivary gland cancers originating from a herniated sublingual gland. All tumors were detected as palpable submandibular masses, located anterior to the submandibular gland, medial to the mandible, and lateral to the mylohyoid muscle, with contact with the sublingual gland through a mylohyoid muscle defect. Intraoperative findings confirmed that the masses were derived from herniated sublingual glands. Pathological examination showed one case of mucoepidermoid carcinoma and two cases of adenoid cystic carcinoma. Imaging findings of the tumor location, in addition to the continuity with the sublingual gland through the mylohyoid muscle defect, are crucial for accurately diagnosing the tumor origin, which is essential for determining the appropriate clinical management. [ABSTRACT FROM AUTHOR]

Objectives: To examine trends in incidence and mortality and evaluate overall survival (OS) of oral cancer in Singapore between 1968 and 2017. Methods: All diagnosed oral cancers by anatomical sites and population size were extracted from the Singapore Cancer Registry and the Department of Statistics Singapore. The trend of age‐standardized incidence rate (ASIR) and mortality rate (ASMR) (per 100 000 person‐years) of the lip, oral cavity and salivary gland cancers were evaluated by Prais‐Winsten regressions for each ethnicity and gender. Kaplan–Meier curves were performed to evaluate the OS by anatomical sites in each age group by ethnicity and sex. Results: Overall, 49, 3494 and 1066 people were diagnosed, and 28, 2310 and 476 died from lip, oral cavity and salivary gland cancers, respectively. The oral cavity cancer ASIR and ASMR reduced from 3.07 (1968–1972) to 2.01(2008–2012) and from 2.06 (1978–1982) to 1.21 (2013–2017) per 100 000 person‐years, respectively, with both highest in Indians throughout the whole period. Male:Female ratio ranged from 3.43 (1973–1977) to 1.75 (2013–2017) and from 3.41 (1978–1982) to 2.40 (2013–2017) for ASIR and ASMR, respectively. However, both salivary gland cancer ASIR and ASMR increased from 0.50 (1968–1972) to 0.80 (2008–2012) and from 0.18 (1968–1982) to 0.42 (1988–1992) per 100 000 person‐years, respectively, with both higher in males since 1993. Oral cavity cancer ASIR decreased for males aged ≥60, and Indian females ≥25, but increased among Chinese females aged ≥60. Oral cavity cancer ASMR decreased among Chinese aged 25–59, and among Malay males and Indian females. Salivary gland cancer ASIR increased among Chinese males aged ≥60 and Malay males aged 25–59; while ASMR increased among Chinese males aged ≥60. The median OS for oral cavity, lip and salivary gland cancers were 3.0, 9.3 and 18.1 years, respectively, with females surviving longer than males. Conclusions: Singapore has experienced a decline in the incidence and mortality of lip, oral cancer, an increase in in the incidence and mortality of salivary gland cancer, with an increase in the median overall survival rate. Monitoring the magnitude of oral cancer burden and the demographic, and temporal variations is necessary for tailoring health planning and setting priorities for future clinical care and research. [ABSTRACT FROM AUTHOR]

Background Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers. Patients and Methods Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1. Results At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs. Conclusion Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers. ClinicalTrials.gov numbers NCT02122913 and NCT02576431. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed‐1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient‐derived organoids (PDOs). TGFβ‐induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ‐induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC. [ABSTRACT FROM AUTHOR]

Background: Observational studies have found associations between smoking, alcohol, radiation, body mass index (BMI), periodontitis, and the hazard of benign salivary gland neoplasms (BSGNs). Nevertheless, the etiology of BSGNs remains unclear. This study aims to assess the causal association between these modifiable factors and the BSGNs. Methods: Genetic instruments associated with exposures at the genome‐wide significance level were selected from corresponding genome‐wide association studies. The summary statistics for BSGNs were obtained from the FinnGen consortium (2445 cases and 340,054 controls). The inverse variance‐weighted method was used as the primary analysis, and several sensitivity analyses were performed to test the reliability. Results: Genetically predicted higher lifetime smoking index (odds ratio [OR] = 2.10, p = 0.012) and BMI (OR = 1.58, p = 2.29 × 10−5) were associated with elevated risk of BSGNs, whereas other exposures do not. Sensitivity analyses showed consistency. The causal effect of the lifetime smoking index became more significant after adjusting for BMI (OR = 2.89, p = 0.005) and alcohol consumption (OR = 2.49, p = 0.002). A slight negative association emerged for alcohol consumption with adjustment for cigarettes per day (OR = 0.53, p = 0.034) but disappeared when adjusting for cigarettes per day and BMI. Conclusion: This study supports the independent causal role of lifetime smoking index and BMI in BSGNs risk. [ABSTRACT FROM AUTHOR]

Objective: Investigating T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3), Galectin 9 (Gal‐9), CD160 expression and tumor‐infiltrating lymphocytes (TILs) and correlation with clinicopathological characteristics of salivary adenoid cystic carcinoma (SACC). Methods: Sixty cases of SACC were detected by immunohistochemical staining to evaluate TIM‐3, Gal‐9, and CD160 expression and analyze the correlation between TIM‐3, Gal‐9, CD160 expression and clinicopathologic features by rank‐sum test. The association of TILs with TIM‐3, Gal‐9, and CD160 expression in SACC stromal was done by Chi‐square test. Results: TIM‐3 and CD160 overexpression were correlated with recurrence of SACC (p = 0.029, p = 0.007, respectively). High Gal‐9 expression was correlated with pathological classification (p = 0.018). The average percentage of TILs was 18.2% in SACC and most of TILs were more likely to occur in minor salivary glands (p = 0.038). Pairwise positive correlations were observed between the expression of TIM‐3, Gal‐9, and CD160 in tumor cells as well as in TILs, respectively. Conclusion: Low density of TILs was characteristic of the SACC microenvironment, with upregulation of TIM‐3, Gal‐9, and CD160 all occurring. However, TIM‐3, Gal‐9, and CD160 expression in the stromal dependent on the number of TILs represent potential therapeutic targets in SACC. [ABSTRACT FROM AUTHOR]

Background: Salivary gland tumors (SGTs) globally account for <2% of all tumors, with an annual incidence ranging from 0.4 to 13.5/100,000 persons. However, there is a notable dearth of information on SGTs in India, prompting this study to explore the histological spectrum in the Vindhya region. Aims and Objectives: The primary goal is to determine the epidemiological patterns of distinct SGTs in the Vidhya Region through a meticulous examination of histological characteristics. Comparative analysis with existing literature aims to enhance insights into these rare tumors. Materials and Methods: Ninety-one SGT biopsies from Shyam Shah Medical College underwent comprehensive scrutiny over a five-year period. Patient-specific data, including age, sex, and location, were collected. The histopathological examination involved formalin fixation, paraffin sections, and staining, with the occasional use of specialized stains for comprehensive categorization based on microscopic examination. Results: Out of 91 cases, 39.56% were malignant, and 60.44% were benign. The parotid gland exhibited the highest incidence, with pleomorphic adenoma (PA) as the most common benign tumor. Notably, in our study, adenoid cystic carcinoma surpassed mucoepidermoid carcinoma as the most frequent malignant tumor. Conclusion: This study provides valuable insights into the patterns of occurrence of SGTs in the Vindhya region, highlighting the significance of further research in this underexplored field. Notably, PA, mucoepidermoid carcinoma, and adenoid cystic carcinoma are prominently reported, with a notable male predominance. [ABSTRACT FROM AUTHOR]

Background: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors. Case Report: We report the diagnostic imaging, surgical treatment, and histopathological findings a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years. Conclusion: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Salivary gland tumors (SGTs) present a diagnostic challenge due to their diverse histological subtypes and variable clinical behavior. Methods: This research conducted a retrospective analysis of SGT cases diagnosed and managed at a tertiary care center between 2017 and 2022. Clinical and pathological data were retrieved from medical records and histopathology reports. Statistical analysis was performed to identify factors associated with recurrence and survival outcomes. Results: A total of 150 SGT cases were included, comprising 70% benign and 30% malignant tumors. Pleomorphic adenoma and adenoid cystic carcinoma were the most prevalent benign and malignant subtypes, respectively. Surgical resection was the primary treatment modality, with varying recurrence rates observed among different treatment groups. Conclusion: The current study provides insights into the histological variations and clinical outcomes of SGTs. Surgical resection remains the mainstay of treatment, with adjuvant therapy reserved for cases with adverse prognostic factors. Further research is needed to optimize therapeutic strategies and improve patient outcomes.

Background and Aims: Adenoid cystic carcinoma is a rare and slowly progressing cancer that frequently starts in minor salivary glands, often causing no symptoms. Therefore, advanced stage at initial presentation is frequently reported. Case Presentation: We provide a case study of a 33-year-old young woman with pT1 staging adenoid cystic tumour, emphasising the clinical presentation, treatment plan and patient prognosis. Comprehensive examination and imaging tests showed that the patient had a growing mass at the base of her mobile tongue. The diagnosis was supported by histopathological examination. Based on the tumour's small size and minimal invasion, pT1 was assigned as its staging. A comprehensive treatment strategy was used, and during surgery, the tumour was removed with precise margins that preserved both function and appearance. One-year follow-up showed no evidence of recurrence or ongoing problems. Conclusion: This case report emphasises the significance of early diagnosis, thorough treatment planning and attentive follow-up. It also highlights the infrequent presentation of disease. [ABSTRACT FROM AUTHOR]

Basal cell adenoma (BCA) is a rare benign salivary gland tumor accounting for only 1–2% of all salivary gland tumors. We report a case of a 50-year-old man presenting a BCA of the parotid gland. A pleomorphic adenoma was initially suspected based on radiological features and fine needle aspiration cytology findings (FNAC). [ABSTRACT FROM AUTHOR]

Introduction: The parotid gland is the most common site for salivary gland neoplasms. Cancers of the parotid gland occur rather often. Nearly eighty percent of parotid tumors are noncancerous neoplasms. Most benign parotid tumors (80%) are found in the superficial lobe. Cancer is more likely to develop in deep lobe neoplasms. This study has been done to study the various modes of presentation of parotid tumors and to compare the FNAC of parotid tumor with the biopsy post operations. Materials and methods: This is a prospective observational study conducted from 2021 January to 2023 January at Siddhartha Medical College, Vijayawada over 30 patients attending the surgical OPD. Patients who are immunocompromised, on chemotherapy, less than 15 years have been excluded from the study. Results: The age incidence of the patients in the study group ranged from 14-76 years. The malignant tumors occurred between the age group of 17-60 years. Most patients in this series were in the 4th decade of life (33.33%). The mean age was 37.6 years for benign tumors and 43 years for malignant tumors. Out of 30 patients, 5 patients presented with pain (16.67%) in swelling, out of which 4 were benign and 1 was malignant. Pain occurred in 20% of the patients with malignant tumors and 16% of the patients with benign tumors. Superficial parotidectomy was performed in 25 patients (83.33%), and conservative total parotidectomy in 5 patients (16.67%). Conclusion: Parotid tumors are mostly benign and they involve the superficial lobe whereas the malignant tumors arise from the deep lobe. Pain is the most common presenting symptom. Ultrasound can detect the tumors and FNAC aids in confirming the diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. Materials and Methods: This retrospective study enrolled 144 AdCC patients. RNA‐sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over‐expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate‐resistant acid phosphatase staining and resorption assays. Results: RNA‐sequencing analysis showed that genes down‐regulated in Notch‐mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1‐wild‐type AdCCs showed SPARC over‐expression, whereas 30 out of 34 (88.2%) Notch1‐mutant tumours showed low SPARC expression. SPARC over‐expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over‐expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. Conclusions: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target. [ABSTRACT FROM AUTHOR]

Objectives: To analyze and summarize the clinicopathological features, risk factors for cervical nodal metastasis, and prognostic factors of malignant sublingual gland tumors (MSLGT). Methods: Patients diagnosed with MSLGT were retrospectively reviewed from January 2005 to December 2017 at Shanghai Ninth Hospital. The clinicopathological features were summarized, and the correlations between clinicopathological parameters, cervical nodal metastasis, and local–regional recurrence were evaluated using the Chi‐square test. Kaplan–Meier method and Cox regression analysis were performed to assess the survival and independent prognostic factors. Results: Seventy‐nine patients were included, and the 5‐year overall survival and disease‐free survival rates was 85.7% and 71.7%, respectively. Gender and clinical tumor stage were risk factors for cervical nodal metastasis. Tumor size and pathological lymph node (LN) stage were independent prognostic factors for adenoid cystic carcinoma (ACC) of the sublingual gland; while age, pathological LN stage, and distant metastasis were prognostic factors for patients with non‐ACC of the sublingual gland. Patients with higher clinical stage were more likely to undergo tumor recurrence. Conclusions: Malignant sublingual gland tumors are rare, and neck dissection should be performed in male MSLGT patients with higher clinical stage. Among patients with both ACC and non‐ACC MSLGT patients, pN+ indicate a poor prognosis. [ABSTRACT FROM AUTHOR]

We report an unusual case of carcinoma ex pleomorphic adenoma (CXPA) in the submandibular gland. The mass had a unique calcification. Panoramic tomography revealed sponge-like calcification. The central portion displayed heterogeneous high signal intensity on T1-weighted image (T1WI) and T2-weighted image (T2WI), and heterogeneously moderate signal intensity on a short-TI inversion recovery (STIR) image. The ADC was low (0.78 × 10−3mm2/sec). After surgical excision, a pathological examination revealed that the mass contained CXPA as a minor component. Tumor cells with large hyperchromatic nuclei and eosinophilic or clear cytoplasm proliferated in irregular small tubule formations or cribriform or Roman-bridge structures in hyalinized or focally ossified stroma. The entire mass was calcified, particularly in the central region. Taken together, the reduced T1 relaxation times were related to the surface effects of diamagnetic particles, which were observed at calcium particle concentrations of up to 30%. We report a CXPA with unusual sponge-like calcification, which appeared unusually hyperintense on T1WI due to a surface effect. [ABSTRACT FROM AUTHOR]

Copyright of Polish Otorhinolaryngological Review / Polski Przegląd Otorynolaryngologiczny (Index Copernicus) is the property of Index Copernicus International and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Ewing's sarcoma is a rare malignant entity. Extraosseous Ewing's sarcoma (EES) of the head and neck region is a rare occurrence, and Ewing's sarcoma of the parotid gland is even rarer. To the best of our knowledge, we reported the first case of extraskeletal ES originating from the parotid gland in the Tunisian literature. Case report: We report a rare case of EES of the parotid gland in a 35-year-old female. She presented with left parotid tumefaction. Physical examination revealed solid and fixed mass associated with facial paralysis. Magnetic resonance imaging illustrated a left intra-parotid process occupying the entire gland measuring 42 mm infiltrating the masseter and pterygoid muscles. The patient had a total left parotidectomy with ipsilateral triangular lymph node dissection. The definitive pathological examination and the immunohistochemical staining confirmed a primary peripheral neuroectodermal tumor or PNET with the presence of a specific EWING/PNET-type translocation in 60% of the tumor cells. She had an adjuvant chemotherapy (four cycles of vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide) followed by external radiotherapy. Conclusion: A clinical and radiological follow-up by cervical MRI was done every 3 months and The 10-month follow-up showed no locoregional and distant recurrence. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinomas (ADCC) are distinctive salivary gland neoplasms with characteristic histomorphology. The diagnosis of dedifferentiation/high-grade transformation (HGT) indicates poor prognosis and is most often made on histopathology. We present a case of ADCC arising from a minor salivary gland tumor exhibiting HGT, reaching up to the submandibular gland and having lymph node metastases, suspected on fine-needle aspiration cytology. The index case highlights the awareness of the entity of the HGT of salivary gland tumors and raises suspicion for cytological diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Salivary duct carcinomas (SDC) can present with distinct immunologic profiles similar to breast cancer, such as androgen receptor (AR) and HER-2/Neu-positivity, raising the hypothesis that these tumors may respond to hormonal signaling. No consensus exists on how to best manage this entity. The data evaluating the use of targeted therapies, such as androgen deprivation therapy and HER-2 receptor inhibitors, in the front-line setting when treating curatively is limited. We studied patients with AR+ SDC, demonstrating high rates of control and survival using an aggressive approach to treatment. Immunoprofiles were highly variable, highlighting the potential for future treatment individualization. We hope that this may allow for personalization of treatment in the future, using molecular profiling to determine whether the addition of biological agents in the definitive setting against specific targets, such as AR and HER-2/Neu, will further improve outcomes for these patients. Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan–Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8–6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of immunotherapies in salivary gland cancer (SGC) remains controversial. To optimize immunotherapy, understanding the tumor microenvironment (TME) of SGC is necessary. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma exhibit immune-hot TME. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies have shown promising clinical efficacy of ICIs indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies. This review discusses the current understanding and future directions of immunotherapies for SGCs. Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0–33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Facial nerve palsy is a potential complication of parotidectomy for benign salivary gland tumours, necessitating a comprehensive understanding of its incidence and associated risk factors for improved patient counselling and preoperative planning. This single-centre retrospective study aimed to assess the rate of facial nerve palsy following benign parotidectomy at a University Teaching Hospital. Over a 3-year period, 160 patients undergoing parotid surgery for benign tumours were included. Data, encompassing sex, age, operation technique, tumour pathology, facial nerve function, and follow-up duration, were collected from medical records. Exclusion criteria comprised patients with prior parotid gland surgery or preoperative facial nerve palsy. The study revealed a 3.75% incidence of facial nerve palsy with no total paralysis post-parotidectomy for benign disease. Pleomorphic adenoma (50.6%) and Warthin's tumour (44.4%) were the predominant tumour types. No significant differences were noted between groups with and without postoperative facial palsy based on obtained covariates. Our findings endorse partial superficial parotidectomy and extracapsular dissection as low-risk treatments for benign parotid tumours. However, prospective studies are warranted to elucidate recovery rates and long-term consequences of facial nerve palsy, contributing to refined surgical approaches and patient care in parotid surgery. [ABSTRACT FROM AUTHOR]

Objectives: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). Subjects and Methods: SGC patients with (sec‐SGC) and without (one‐SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec‐SGC and one‐SGC patients. Subgroup analyses for sec‐SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec‐SGC patients with different prognostic risks. Results: 9098 SGC patients were enrolled. Overall, sec‐SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one‐SGC patients. In subgroup analysis, only sec‐SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec‐SGC patients into high‐, intermediate‐ and low‐risk groups with different prognosis. Conclusions: Sec‐SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec‐SGC patients with different risks. [ABSTRACT FROM AUTHOR]

The article focuses on analyzing exclusive proteins associated with malignant phenotype acquisition in pleomorphic adenoma (PA), highlighting their structural and functional roles. Topics include the identification of exclusive proteins in PA, residual PA, and carcinoma ex pleomorphic adenoma (CXPA), their biological processes, and their potential implications in the pathogenesis of PA and CXPA.

Introduction: The study analyses the occurrence and treatment outcomes of tumors of the major salivary glands in our patients. Material and methods: Between 2019 and March 2023, a total of 182 salivary gland surgeries were conducted at our clinic. Of these, 111 were on females aged 18 to 76 years, and 71 on males aged 18 to 82 years. Diagnosis comprised a medical history, otolaryngological physical examination, ultrasonography (USG), fine-needle aspiration (FNA) biopsy of tumor, laboratory tests (CBC, CRP), and contrastenhanced computed tomography (CECT) or magnetic resonance imaging (MRI). Results: Predominantly (176 patients), benign tumors and neoplasms were found in the parotid salivary gland. Histopathology most commonly revealed pleomorphic adenoma (PA, 74 cases) and Warthin's tumor (WT, 70 cases). Other benign tumors and neoplasms made up only 18% of cases. Malignant neoplasms were only identified in the parotid salivary gland in 3.3% of cases; these were diagnosed as epithelial-myoepithelial carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, and ductal carcinoma. Conclusions: In our dataset, most patients with tumors of the major salivary glands were operated on at ages above 60 years. A low incidence of malignant tumors and a high incidence of WT of the large salivary glands were observed. The main postoperative complication was facial nerve paresis in 7.6% of cases. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we will analyze the main mutations predominant in the various histotypes of salivary gland carcinomas, we will discover whether they behave as driver mutations, and finally we will make hypotheses relating to the best targeted therapy to be used in salivary gland carcinomas, apart from polychemotherapy. Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most cases, which can also play an important role in oligometastatic disease. Where surgery cannot be used, systemic therapy comes into play. Systemic therapy for many years has been represented by polychemotherapy, but recently, with the affirmation of translational research, it can also count on targeted therapy, at least in some subtypes of SGCs. Interestingly, in some SGC histotypes, predominant mutations have been identified, which in some cases behave as "driver mutations", namely mutations capable of governing the carcinogenesis process. Targeting these driver mutations may be an effective therapeutic strategy. Nonetheless, it is not always possible to have drugs suitable for targeting driver mutations—and targeting driver mutations is not always accompanied by a clinical benefit. In this review, we will analyze the main mutations predominant in the various histotypes of SGCs. [ABSTRACT FROM AUTHOR]