Apoptotic cell death during regressive changes in salivary glands: a morphological perspective.

BACKGROUND: Apoptosis was initially identified through transmission electron microscopy. Subsequent advances in morphological techniques for apoptosis detection have revealed its involvement in multiple pathological conditions in various tissues. This review summarizes previous experimental studies on apoptotic cell death during regressive changes in the salivary glands, with a focus on morphological observations. HIGHLIGHT: Obstructive sialadenitis is histologically characterized by acinar cell loss and increased number of duct cells. Although acinar cells were previously believed to dedifferentiate into duct cells, there is evidence that they are eliminated by apoptosis. Animals fed a soft diet exhibited parotid gland atrophy, in which acinar cells decreased in size and disappeared because of apoptosis. Age-related changes in the salivary glands involved a reduced number of acinar cell through apoptosis. Additionally, apoptotic acinar cell death occurs in other pathological conditions, including the regression of hypertrophic and irradiated salivary glands. CONCLUSION: Apoptosis often eliminates acinar cells during atrophic alterations in the salivary glands. Unlike necrosis, apoptosis is an active form of cell death, thereby helping prevent the complete destruction of the salivary glands. However, the contribution of apoptosis to regressive changes in the salivary glands remains unclear and warrants further investigation.

Nepali oral microbiomes reflect a gradient of lifestyles from traditional to industrialized.

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. RESULTS: Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the USA within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain sources. CONCLUSION: Our findings demonstrate that by studying populations within Nepal, we can isolate an important role of lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes. Video Abstract.

Myeloid-derived growth factor promotes M2 macrophage polarization and attenuates Sjögren's syndrome via suppression of the CX3CL1/CX3CR1 axis.

Introduction: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary glands. The re-establishment of salivary glands (SGs) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, its potential to restore SGs function during pSS has not yet been investigated. Methods: Nonobese diabetic (NOD)/LtJ mice (pSS model) were intravenously administered with adeno-associated viruses carrying MYDGF at 11 weeks of age. Salivary flow rates were determined before and after treatment. Mice were killed 5 weeks after MYDGF treatment, and submandibular glands were collected for analyses of histological disease scores, inflammatory cell infiltration, PCR determination of genes, and Western blotting of functional proteins. Furthermore, mRNA sequencing and bioinformatics were used to predict the mechanism underlying the therapeutic effect of MYDGF. Results: Treatment of NOD/LtJ mice with MYDGF alleviated pSS, as indicated by increased salivary flow rate, reduced lymphocyte infiltration, attenuated glandular inflammation, and enhanced AQP5 and NKCC1 expression. The gene expression levels of cytokines and chemokines, including Ccl12, Ccl3, Il1r1, Ccr2, Cx3cr1, Il7, Mmp2, Mmp14, Il1b, and Il7, significantly decreased after treatment with MYDGF, as determined by RNA sequencing. Meanwhile, MYDGF inhibits infiltration of macrophages (Mϕ) in SGs, induces polarization of M2ϕ, and suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C motif receptor 1 (CX3CR1) axis. Conclusions: Our findings showed that MYDGF could revitalize the SGs function of pSS, inhibit infiltration of Mϕ, and promote M2ϕ polarization via suppression of the CX3CL1/CX3CR1 axis, which has implications for potential therapy for pSS.

Mucocele of the Lower Lip and Its Surgical Management.

We report a case of mucocele of the lower lip in a 17-year-old female patient. She complained of a painless swelling on her lower lip for the last one month. The patient also gave a history of lip-biting. Upon clinical inspection, a soft, round, dome-shaped bluish lesion with a pearly appearance was identified on the right lower labial mucosa. On palpation, the lesion was mobile and non-adherent to the underlying tissues. An excisional biopsy was performed under local anesthesia, and the excised sample was sent for histopathological evaluation. Histopathology revealed mucus pooling, surrounded by compressed connective tissue stroma and areas of chronic inflammation indicative of a mucocele. The post-excisional review was done after 10 days, and the patient's healing was satisfactory. The patient had no signs of recurrence after two years of follow-up.

Classification of salivary gland biopsies in Sjögren's syndrome by a convolutional neural network using an auto-machine learning platform.

BACKGROUND: The histopathological analysis of minor salivary gland biopsies, particularly through the quantification of the Focus Score (FS), is pivotal in the diagnostic workflow for Sjögren's Syndrome (SS). AI-based image recognition using deep learning models has demonstrated potential in enhancing diagnostic accuracy and efficiency in preclinical research. OBJECTIVES: The primary aim of this investigation was to utilize an auto-machine learning (autoML) platform for the automated segmentation and quantification of FS on histopathological slides, aiming to augment diagnostic precision and speed in SS. METHODS: A cohort comprising 86 patients with sicca syndrome (37 diagnosed with SS based on the 2016 ACR/EULAR Classification Criteria and 49 non-SS) was selected for an in-depth histological examination. A repository of 172 slides (two per patient) was assembled, encompassing 74 slides meeting the classificatory thresholds for SS (FS ≥ 1, indicative of lymphocytic infiltration) and 98 slides showcasing normal salivary gland histology. The autoML platform utilized (Giotto, L2F, Lausanne Switzerland) employed a Convolutional Neural Network (CNN) architecture (ResNet-152) for the training and validation phases, using a dataset of 172 slides. RESULTS: The developed model exhibited a reliability score of 0.88, proficiently distinguishing SS cases, with a sensitivity of 89.47% (95% CI: 66.86% to 98.70%) and a specificity of 88.24% (95% CI: 63.56% to 98.54%). The model found histological slides of suboptimal quality (e.g., those compromised during fixation or staining processes) to be the most challenging for accurate classification. CONCLUSION: AutoML platforms offer a rapid and flexible approach to developing machine learning models, even with smaller datasets, as demonstrated in this study for SS. These platforms hold significant potential for enhancing diagnostic precision and efficiency in both clinical and research settings. Multicentric studies with larger patient cohorts are essential for thorough evaluation and validation of this innovative diagnostic approach.

Malignant Salivary Gland Neoplasm of the Tongue Base with EWSR1::BEND2 Fusion: An Unusual Case with Literature Review.

PURPOSE: Salivary gland malignancies may have overlapping architectural patterns, tumor morphology, and immunohistochemical phenotypes, presenting challenges in precise classification. Molecular phenotyping has become quite useful for providing an additional diagnostic modality, and potential drug targets. Here we reported a young female patient with salivary gland tumor of the tongue base harboring genetic alterations by next generation sequencing (NGS). METHODS: The morphological, immunohistochemical and molecular features of this case were described, and related literature was reviewed. RESULTS: The tumor showed an epithelial myoepithelial architecture arranged in cords and tubules interwoven with a chondromyxoid stroma, along with perineural invasion and adjacent striated muscle infiltration. Myoepithelial cells were positive for CK5/6, partially positive for P63 and CK7, and sporadically positive for S100. Immunoprofiling revealed a low density of infiltrating lymphocytes and macrophages and the absence of programmed death ligand 1 (PD-L1). Notably, RNA-based NGS showed EWSR1::BEND2 gene fusion in this tumor, and EWSR1 break-apart was confirmed by fluorescence in situ hybridization. This led to a final diagnosis of a minor salivary gland malignancy with EWSR1::BEND2 fusion. Only two other cases of salivary gland tumors with EWSR1::BEND2 fusion had been previously reported, which were also detected via RNA-based NGS. CONCLUSION: This study emphasized that EWSR1::BEND2 fusion may drive the carcinogenesis in salivary glands neoplasia. In clinic RNA-based NGS could be essential for precise genotyping of EWSR1 fusion in this rare disease.

Clinical Features and Prognosis of Primary Epithelial-Myoepithelial Carcinoma of Salivary Gland: A Surveillance, Epidemiology, and End Results Database-Based Study.

OBJECTIVE: The clinical characteristics and prognosis of primary epithelial-myoepithelial carcinoma of salivary gland (EMC-SG) have not been defined well due to its rarity. The purpose of this study is to assess the proportion of EMC-SG among salivary gland cancers, describe the clinicopathological features and prognosis of this disease, further analyze the factors associated with EMC-SG survival, and establish individual survival-predicting models. METHODS: Data on patients diagnosed with salivary gland malignancy between 2000 and 2020 were collected from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were employed to estimate survival of EMC-SG patients. Univariable and multivariable Cox proportional hazards models were developed to determine the EMC-SG survival-associated factors. Furthermore, EMC-SG nomograms were constructed. RESULTS: A total of 15 212 patients with salivary gland malignancy were identified. Of these, 310 cases were diagnosed with EMC-SG, representing a prevalence of 2.03% (95%CI 1.82%-2.28%). The overall survival (OS) rates for all 310 EMC-SG patients at 2-year, 5-year, and 10-year were 92.43%, 84.85%, and 73.39%, respectively. Age, primary site, and T stage were independent prognostic factors for OS, while pathological grade and the use of surgery were independent prognostic factors for cancer-specific survival (CSS). The concordance index (C-index) for the OS- and CSS-specific nomograms was 0.72 (95%CI 0.64-0.80) and 0.77 (95%CI 0.67-0.87), respectively. The calibration curve and receiver operating characteristic analysis demonstrated that the predicted values aligned well with the actual observations. Decision curve analysis indicated the superiority of the nomograms over the traditional Tumor Node Metastasis staging system. CONCLUSIONS: This study represents the largest cohort of EMC-SG patients used to investigate the characteristics and prognosis of this disease. EMC-SG patients often have a less aggressive course and favorable prognosis. The established nomograms provide a useful tool for clinicians to predict patient outcomes, and can assist in customizing the counseling approach for this rare disease.

Mechanical characterization and structural analysis of elastodontic appliances under intraoral and artificial aging conditions.

BACKGROUND: This study focused on the aging mechanism and degradation of mechanical and structural features of elastodontic appliances (EA) under artificial and intraoral aging to achieve oral myofunctional therapy with particular removable silicone elastomer devices. MATERIALS AND METHODS: EAs artificially aged in saliva with different pH values were investigated through cyclic compression testing along with characterization techniques (Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy), and characterization analysis was also performed on clinically retrieved EAs. RESULTS: Artificial aging was found to have minimal effect on the structural properties of EAs, and intraorally aged samples showed perceptible micro-morphology. The Mullins index and peak stress decreased (P<0.01), while the compression set increased with prolonged aging time. Samples in alkaline saliva showed the largest Mullins effect (P<0.05). CONCLUSIONS: The aging mechanism of the elastomer was found to be the crosslinking of main chains and scission of side chains. The presence of OH- enhanced the rupture degree of side bonds. The decline in viscoelastic properties was shown to be more severe with longer service durations. CLINICAL RELEVANCE: Research on how the salivary environment and pH affect the aging characteristics of EAs is vital for guiding clinical applications and future modifications to extend their clinical lifetime.

Application of Strain Elastography in Dentistry: A Systematic Review.

Strain elastography, a non-invasive imaging technique complements traditional diagnostic methods by offering quantitative and qualitative information about soft and hard tissues within the oral cavity. The article aimed to provide an overview of the currently available data on the use of strain elastography in dentistry. To support the review of strain elastography applications in dentistry, a wide range of articles was searched using both online and offline databases. Inclusion and exclusion criteria were defined according to the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) approach. The results show that 12 of the 107 papers found to be eligible for inclusion in a qualitative examination of the use of strain elastography in dentistry satisfied the PICOS criteria. Elastography is a promising tool for diagnosing various dental diseased conditions, but sufficient evidence is not available. More studies on a larger population should be performed to determine its accuracy in diagnosis.

Natural history of salivary gland secretory carcinoma: A REFCOR study.

BACKGROUND AND OBJECTIVES: Salivary gland Secretory Carcinoma (SC), characterized by Skalova in 2010 is a rare tumor studied within the REFCOR (French Network of experts on Rare Head and Neck Cancers). We conducted a prospective multicentric cohort study of 108 SC cases in the REFCOR database up to July 2021, analyzing diagnostic, therapeutic, and survival data. METHODS: Data was collected prospectively from diagnosis to the last update. Each patient had two histological readings including one by a REFCORpath pathologist, and all cases underwent molecular testing to confirm diagnosis. Statistical analyses were performed using R software. RESULTS: MRI was not contributive to malignancy diagnosis. After 2 histological readings, 79 % of patients were diagnosed, with 21 % requiring molecular testing to confirm diagnosis. Surgical treatment typically involved tumor excision and lymph node dissection. The tumor exhibited low lymph node involvement, with 95 % of patients being cN0, and no nodal metastases post-dissection. Five-year overall survival and recurrence-free survival were 91.4 % {95 % CI (0.84-1)} and 89 % {95 % CI (0.81; 0.98)} respectively, indicating a favorable prognosis. CONCLUSIONS: SC is a rare and newly recognized tumor, with generally favorable outcomes. Our cohort, among the largest to date, provides valuable insights. Future research should refine treatment guidelines.

Clinicopathological analysis of hybrid carcinomas of the salivary glands: A systematic review.

Hybrid carcinomas (HC) are the association of two or more malignant neoplasms arising within the same topographical area. The present study is a systematic review of HC of the salivary glands. This study aimed to assess HC clinicopathological features and molecular profile. Observational studies, case series, and case reports were included. PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched until June 2024. A total of 18 articles including 34 patients were included. HC of the salivary glands is presented as a painless mass affecting mainly the parotid gland of adults with a preference for male patients. Histologically, adenoid cystic carcinoma and epithelial-myoepithelial carcinoma were the most prevalent association, being surgical excision with radiotherapy the most common treatment. It's seen that the most aggressive component might guide the patient's treatment and prognosis. Further molecular studies are necessary to determine if HC are distinct entities or biologically identical to the individual neoplasms. In conclusion, this systematic review may contribute to a better understanding of this rare lesion, their biological behavior, treatments employed, and the outcome of these patients.

Sentinel lymph node biopsy in cT1-2N0 minor salivary gland cancer in oral cavity.

OBJECTIVE: To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity. METHODS: A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model. RESULTS: A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64-0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation. CONCLUSION: In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth.

Salivary Duct Carcinoma Metastasis in the Pleural Fluid.

Salivary duct carcinoma (SDC) is a relatively rare, highly aggressive tumor with a poor prognosis that can be challenging to distinguish on cytology specimens. Awareness of the cytomorphologic and immunocytochemical findings is essential in arriving at a definitive diagnosis. This case report describes the primary diagnosis of a metastatic SDC on effusion fluid cytology.

A Recognition System for Diagnosing Salivary Gland Neoplasms Based on Vision Transformer.

Salivary gland neoplasms (SGNs) represent a group of human neoplasms characterized by a remarkable cyto-morphological diversity, which frequently poses diagnostic challenges. Accurate histological categorization of salivary tumors is crucial to make precise diagnoses and guide decisions regarding patient management. Within the scope of this study, a computer-aided diagnosis model utilizing Vision Transformer, a cutting-edge deep-learning model in computer vision, has been developed to accurately classify the most prevalent subtypes of SGNs. These subtypes include pleomorphic adenoma, myoepithelioma, Warthin's tumor, basal cell adenoma, oncocytic adenoma, cystadenoma, mucoepidermoid carcinoma and salivary adenoid cystic carcinoma. The dataset comprised 3046 whole slide images (WSIs) of histologically confirmed salivary gland tumors, encompassing nine distinct tissue categories. SGN-ViT exhibited impressive performance in classifying the eight salivary gland tumors, achieving an accuracy of 0.9966, an AUC value of 0.9899, precision of 0.9848, recall of 0.9848, and an F1-score of 0.9848. When compared to benchmark models, SGN-ViT surpassed them in terms of diagnostic performance. In a subset of 100 WSIs, SGN-ViT demonstrated comparable diagnostic performance to that of the chief pathologist while significantly reducing the diagnosis time, indicating that SGN-ViT held the potential to serve as a valuable computer-aided diagnostic tool for salivary tumors, enhancing the diagnostic accuracy of junior pathologists.

Identification of salivary proteins in the rice leaf folder Cnaphalocrocis medinalis by transcriptome and LC-MS/MS analyses.

Salivary proteins in the oral secretion (OS) of chewing insects play a crucial role in insect-plant interactions during feeding. The rice leaf folder Cnaphalocrocis medinalis, a notorious pest in global rice production, triggers defense responses during feeding, but little is known about its salivary proteins. In this study, we confirmed that C. medinalis releases OS during feeding. By employing transcriptomic analysis and liquid chromatography-tandem mass spectroscopy (LC-MS/MS), we examined the salivary proteins from labial salivary glands and OS from C. medinalis. A total of 14,397 genes were expressed at the RNA level and 229 salivary proteins were identified. Comparative analysis with other 25 arthropod species revealed that 43 proteins were unique to C. medinalis. Expression pattern analysis revealed that most of the selected genes were highly expressed in the gut and the larval stages (4th-5th instar). These findings provide a comprehensive resource for future functional studies of salivary proteins, offering new insights into the molecular mechanisms by which C. medinalis modulates plant defenses and potential applications in pest management.

Mandibular salivary gland plasma cell tumor in a dog.

An 8-year-old, intact male, Jack Russell Terrier dog was admitted with a 10-day history of an enlargement in the right submandibular area. Clinical examination revealed a subcutaneous, solid, firmly attached and painless mass (3 × 2 cm) located in the area of the right mandibular salivary gland, in an otherwise seemingly healthy dog. Fine-needle-aspiration cytology suggested a round cell neoplasia, most consistent with a plasma cell tumor. Histopathologic and immunohistochemical (MUM1) examination, following surgical excision of the mass, confirmed the diagnosis of a plasma cell tumor embedded in the right mandibular salivary gland. Clinical staging reasonably excluded a disseminated plasma cell tumor. The dog remains healthy and in complete remission 23 months following surgical excision of the mass. Albeit rare, extramedullary plasma cell tumors can affect the salivary glands of dogs.

Do not Judge a book by its Cover: A Secretory Carcinoma Arising from a Salivary Gland Heterotopia in Laterocervical lymph-node.

Heterotopia, the occurrence of specific tissues in ectopic sites during embryogenesis, includes the presence of salivary gland tissue in unusual locations. Salivary gland neoplasms arising from heterotopic sites are rare. Secretory Carcinoma (SC) is a rare salivary gland carcinoma characterized by ETV6-NTRK3 fusion gene, very rarely described in salivary gland heterotopia. Here a case of SC originating from salivary gland heterotopia in a neck lymph node is reported, together with a literature review.A 66-year-old male presented with a left neck mass. Imaging and fine needle aspiration cytology indicated a preliminary diagnosis of a benign/low-grade malignancy neoplasm.Following surgery (superficial parotidectomy and mass excision), histological examination revealed SC within an intranodal salivary heterotopia, confirmed by molecular analysis.Heterotopic salivary gland tissue (HSGT) is rare, and its association with neoplasms is even rarer. Tumours arising on HSGT, share histological similarities with those affecting orthotopic salivary glands. This unique case expands the understanding of SC occurrences on HSGT.

Imaging of the Major Salivary Glands in Rheumatic Disease.

Salivary gland involvement is a common feature of rheumatologic disease. The authors review the anatomy of the major salivary glands and the uses of imaging modalities such as ultrasound, MRI, computed tomography, sialography, and scintigraphy in evaluating the major salivary glands in rheumatologic disease.