Salivary Tissue Research Articles

Ganaxolone Therapy After Preterm Birth Restores Cerebellar Oligodendrocyte Maturation and Myelination in Guinea Pigs.

The postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development. Guinea pig sows delivered at term (∼69 days gestation) or were induced to deliver preterm (∼62 days), with preterm pups receiving ganaxolone or vehicle until TEA. Postnatal assessments comprised salivary cortisol (corrected postnatal age [CPA] 0, 7, 38), behavioral analysis (CPA7, 38), and tissue collection (CPA0 and CPA40). Neurodevelopmental markers (MBP, Olig2, and NeuN) were assessed in the cerebellum by immunohistochemistry, whereas RT-PCR was utilized to investigate key inhibitory/excitatory pathways and oligodendrocyte lineage markers. Following preterm birth, there was evidence of a hyperactive phenotype, increased salivary cortisol concentrations, and impaired myelination and oligodendrocyte maturation at the protein level. mRNA expressions of key inhibitory/excitatory pathways and myelin stability were also altered following preterm birth. Importantly, we showed that neurosteroid replacement therapy returns cerebellar development and behavior toward a term-like phenotype. Therefore, ganaxolone may reduce the vulnerability of the cerebellum to postnatal challenges arising from preterm birth.

Subpopulation dynamics of T and B lymphocytes in Sjögren's syndrome: implications for disease activity and treatment.

Sjögren's syndrome (SS) is an autoimmune disorder primarily affecting the body's exocrine glands, particularly the salivary and lacrimal glands, which lead to severe symptoms of dry eyes and mouth. The pathogenesis of SS involves the production of autoantibodies by activated immune cells, and secretion of multiple cytokines, which collectively lead to tissue damage and functional impairment. In SS, the Immune interaction among T and B cells is particularly significant. Lymphocytic infiltration in the salivary glands is predominantly composed of CD4+ T cells, whose activation cause the death of glandular epithelial cells and subsequent tissue destruction. The excessive activity of T cells contributes significantly to the disease mechanism, with helper T cells (CD4+) differentiating into various subgroups including Th1/Th2, Th17, as well as Treg, each contributing to the pathological process through distinct cytokine secretion. In patients with SS, B cells are excessively activated, leading to substantial production of autoantibodies. These antibodies can attack self-tissues, especially the lacrimal and salivary glands, causing inflammation and tissue damage. Changes in B cell subpopulations in SS patients, such as increases in plasmablasts and plasma cells, correlate positively with serum autoantibody levels and disease progression. Therapies targeting T cells and B cells are extensively researched with the aim of alleviating symptoms and improving the quality of life for patients. Understanding how these cells promote disease development through various mechanisms, and further identifying novel T and B cell subgroups with functional characterization, will facilitate the development of more effective strategies to treat SS.

Salivary glands - a new site of Helicobacter pylori occurrence.

The role of Helicobacter pylori (Hp) in the pathological processes of the gastric mucosa is well understood. Decreasing trend in successful eradication of HP from the stomach was observed in last years. This lack of succes is mainly caused by increasing ATB resistance. Nevertheless other possible causes of this phenomenon are being explored. Thus, many studies have focused on the search for extragastric reservoirs as potential sources of persistence or reinfection after successful Hp eradication. The pathological potential of Hp at these localities has also been studied. Our study aimed to determine the presence of Hp inside the salivary glands ductal system through its detection from sialolites. Subsequently, we tried to prove the possible ability of Hp to penetrate the salivary gland parenchyma by detecting Hp from the tissue of salivary tumors. Concrements and salivary tumor tissue samples were collected using sialendoscopy or standard surgery, and Hp detection and genotyping were performed through PCR. Hp was detected in 68.3% of the sialopathy samples. VacA S1AM1 was the most common genotype. CagA-positive genotype represented only 34% of the total number of positive samples. Our findings of Hp positivity in concrements provide compelling evidence of Hp presence in the ductal system of salivary glands. Confirmation of Hp presence in tumor tissue suggests its potential ability to infiltrate the gland's parenchyma. Further research is needed to confirm Hp's ability to cause local infection, as well as the possible causal association between Hp presence in the studied region, sialolithiasis, and salivary gland tumors.

Altered characteristics of regulatory T cells in target tissues of Sjögren’s syndrome in murine models

Sjӧgren’s syndrome (SS), also known as Sjögren’s disease, is a chronic autoimmune condition predominantly affecting the salivary and lacrimal glands. The disease is driven by autoimmune responses involving the activation and actions of major innate- and adaptive immune cell subsets. However, the specific characteristics and roles of regulatory T cells (Tregs) in SS remain elusive. This study seeks to clarify the main phenotypic and functional attributes of Tregs in the salivary glands and their draining lymph nodes in murine models of SS. Our flow cytometric analysis revealed that Tregs in the salivary gland-draining lymph nodes of female non-obese diabetic (NOD) mice, a spontaneous model of SS, exhibited a greater proportion of activated Tregs and fewer resting Tregs compared to Balb/c mice. Furthermore, Tregs from the salivary gland-draining lymph nodes of female C57BL/6.NOD-Aec1Aec2 (B6.NOD-Aec) mice, a model for primary SS, demonstrated significantly lower IL-10 production but markedly higher IFNγ- and IL-17 production than their C57BL/6 counterparts. Additionally, treatment of C57BL/6 Tregs with IL-7, a cytokine critical for SS pathogenesis, resulted in diminished IL-10 production and enhanced IFNγ and IL-17 production in these cells. Notably, the alterations in B6.NOD-Aec Tregs also included an increased expression of the immune-inhibitory molecule CTLA-4 compared to the C57BL/6 Tregs. Intriguingly, in vitro co-cultures of Tregs with conventional CD4 T cells and other key immune populations from lymph nodes indicated that Tregs from salivary gland-draining lymph nodes of both B6.NOD-Aec and C57BL/6 strains exhibited comparable and limited immunosuppressive effects on the proliferation and function of conventional CD4 T cells. The ability of B6.NOD-Aec Tregs to directly inflict damages to salivary gland epithelial tissues and contribute to SS pathologies through IFNγ and IL-17 that they produce warrants further investigations. In addition, enhancing the relatively weak immunosuppressive capacities of these Tregs may also serve as a viable strategy to alleviate the SS phenotype in the mouse models and potentially in patients.

Salivary pepsin testing for laryngopharyngeal reflux: will it change our management?

This review focus on the clinical value of salivary and laryngopharyngeal tissue pepsin measurement in the diagnosis and treatment of laryngopharyngeal reflux (LPR). A growing body of research suggests that salivary pepsin detection provides a noninvasive method for the identifying LPR occurrence. Pepsin detection testing is still variable, and an optimal method that balances utility with accuracy has not been agreed. Timing and number of test samples recommended also remains controversial, however literature indicates that increasing the number of tests over a day increases pepsin detection rate. It remains unclear whether detection of pepsin alone can be used to confirm LPR diagnosis. Pepsin positivity is correlated with improved response to proton pump inhibitor (PPI) therapy, and therefore may play a role in guiding therapeutic choices. Detection of pepsin in laryngeal tissue has the same clinical value as detection in saliva and requires further investigation to determine utility. As a noninvasive method for the diagnosis of LPR, the detection of salivary pepsin in the oropharynx shows potential clinical value, however the exact method of detection and diagnostic values are unclear. Salivary or tissue-based pepsin detection may be helpful in predicting therapeutic effects of PPI and providing personalized treatment options. The detection threshold of salivary pepsin may be different in different countries and regions. Timing and number of samples needed for detection is still controversial.

Intratumoral microbiome of adenoid cystic carcinomas and comparison with other head and neck cancers

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.

Comparative Genomics and the Salivary Transcriptome of the Redbanded Stink Bug Shed Light on Its High Damage Potential to Soybean.

The redbanded stink bug, Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae), is a significant soybean pest in the Americas, which inflicts more physical damage on soybean than other native stink bugs. Studies suggest that its heightened impact is attributed to the aggressive digestive properties of its saliva. Despite its agricultural importance, the factors driving its greater ability to degrade plant tissues have remained unexplored in a genomic evolutionary context. In this study, we hypothesized that lineage-specific gene family expansions have increased the copy number of digestive genes expressed in the salivary glands. To investigate this, we annotated a previously published genome assembly of the redbanded stink bug, performed a comparative genomic analysis on 11 hemipteran species, and reconstructed patterns of gene duplication, gain, and loss in the redbanded stink bug. We also performed RNA-seq on the redbanded stink bug's salivary tissues, along with the rest of the body without salivary glands. We identified hundreds of differentially expressed salivary genes, including a subset lost in other stink bug lineages, but retained and expressed in the redbanded stink bug's salivary glands. These genes were significantly enriched with protein families involved in proteolysis, potentially explaining the redbanded stink bug's heightened damage to soybeans. Contrary to our hypothesis, we found no support for an enrichment of duplicated digestive genes that are also differentially expressed in the salivary glands of the redbanded stink bug. Nonetheless, these results provide insight into the evolution of this important crop pest, establishing a link between its genomic history and its agriculturally important physiology.

Parotid glands have a dysregulated immune response following radiation therapy.

Head and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3- cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8- double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors.

Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor

PurposeSalivary gland tumors are histologically diverse. Ionocytes and tuft cells, rare epithelial cells found in normal salivary glands, might be associated with salivary tumors. Here, we explored the expression of FOXI1 and POU2F3, master regulators of ionocytes and tuft cells, respectively, for common salivary neoplasms using immunohistochemistry.MethodsWe analyzed normal salivary tissues and nine salivary gland tumors; Warthin tumors (WT), pleomorphic adenomas (PA), basal cell adenomas, and oncocytomas were benign, whereas mucoepidermoid, adenoid cystic, acinic cell, salivary duct carcinomas, and polymorphous adenocarcinomas were malignant.ResultsNormal salivary glands contained a few FOXI1- and POU2F3-positive cells in the ducts instead of the acini, consistent with ionocytes and tuft cells, respectively. Among the benign tumors, only WTs and PAs consistently expressed FOXI1 (10/10 and 9/10, respectively). The median H-score of WTs was significantly higher than that of PAs (17.5 vs. 4, P = 0.01). While WTs and PAs harbored POU2F3-positive cells (10/10 and 9/10, respectively), the median H-score was higher in WTs than in PAs (10.5 vs 4, respectively). Furthermore, WTs exhibited a unique staining pattern of FOXI1- and POU2F3-positive cells, which were present in luminal and abluminal locations, respectively. Whereas none of the malignant tumors expressed FOXI1, only adenoid cystic carcinoma consistently expressed POU2F3 (5/5), with a median H-score of 4.ConclusionThe expression patterns of the characteristic transcription factors found in ionocytes and tuft cells vary among salivary gland tumor types and are higher in WT, which might be relevant for understanding and diagnosing salivary gland neoplasms.

Differentiation of Salivary Gland and Salivary Gland Tumor Tissue via Raman Imaging Combined with Multivariate Data Analysis.

Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.

Salivary Organotypic Tissue Culture: An Ex-vivo 3D Model for Studying Radiation-Induced Injury of Human Salivary Glands.

An organotypic tissue culture model canmaintain the cellular and molecular interactions, as well as the extracellular components of a tissue ex vivo. Thus, this 3D modelbiologically mimics in vivo conditions betterthan commonly used 2D culture in vitro models. Here, we provide a detailed workflow for generating live 3Dorganotypic tissue slices from patient-derived freshly resected salivaryglandular tissues. We also cover the processing of these tissues for various downstream applications like live-dead viability/cytotoxicity assay, FFPE sectioning and immunostaining, and RNA and protein extraction with a focus on the salivary gland radiation injury model. These procedures can be applied extensively to various solid organs and used for disease modeling for cancer research, radiation biology, and regenerative medicine.

Integrative analysis of transcriptome and proteome in primary Sjögren syndrome

ObjectivePrimary Sjögren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immune-mediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. MethodTranscriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjögren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. ResultsAs a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. ConclusionHerein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

Novel Biodistribution of PSMA Radiotracer in the Uvula of Patients Undergoing PSMA PET/CT.

Prostate-specific membrane antigen (PSMA) PET/CT is an imaging technique that detects primary and metastatic prostate cancer and evaluates treatment effectiveness. The radioligands for PSMA PET/CT are known to have physiological off-target uptake in various tissues. These include the well-known off-target major and minor salivary glands. We report that, in addition to this location, radioligand uptake can be seen in the uvula, which we suggest is from salivary tissue in this location. PSMA uptake in the uvula is not reported in the literature and is a rare, but normal location for tracer biodistribution in some patients.

Submandibular Sialolithiasis in a 9-Years-Old Child: Case Report

Sialolithiasis rarely occurs in children; it is observed more commonly in adults. Various treatment modalities for sialolithiasis have been reported in literature; we report the case of 9 years old child, with no particular pathological history. For 4 years, he had a tumefaction of the left submandibular region, associated with painful blocking episodes of salivation and an increase in the size of the tumefaction (accentuated during meals). Clinical examination found a slight painless tumefaction of the left sub-mandibular region, with no pus or blood outflow, no endobuccal expression and no palpable calculi ultrasound examination shows a heterogeneous left submandibular gland, discreetly vascularized by Doppler, with multiple calculi. The patient was operated by cervical approach, a submandibularectomy was performed after detachment of the musculocutaneous flaps, preservation of the artery and the facial vein and the lingual nerve, and dissection of the submandibular canal. Anatomo-pathological study was performed and it showed macroscopically a yellowish enclosed calculus of 3mm of great axis. Microscopically, it shows a salivary glandular tissue with no signs of malignity, in this article, clinical findings, etiologies and different treatment approaches were reviewed.

Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction are the pathophysiological hallmarks of pSS. Macrophages are one of the most important cells involved in the induction and regulation of an inflammatory microenvironment. Although studies have reported that an abnormal tissue microenvironment alters the metabolic reprogramming and polarisation status of macrophages, the mechanisms driving macrophage infiltration and polarisation in pSS remain unclear. Immune cell subsets were characterised using the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from patients with pSS (n = 5) and healthy individuals (n = 5) in a public dataset. To evaluate macrophage infiltration and polarisation in target tissues, labial salivary gland biopsy tissues were subjected to histological staining and bulk RNA-seq (pSS samples, n = 24; non-pSS samples, n = 12). RNA-seq data were analysed for the construction of macrophage co-expression modules, enrichment of biological processes and deconvolution-based screening of immune cell types. Detailed mapping of PBMCs using scRNA-seq revealed five major immune cell subsets in pSS, namely, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs) and monocyte-macrophages. The monocyte-macrophage subset was large and had strong inflammatory gene signatures. This subset was found to play an important role in the generation of reactive oxygen species and communicate with other innate and adaptive immune cells. Histological staining revealed that the number of tissue-resident macrophages was high in damaged glandular tissues, with the cells persistently surrounding the tissues. Analysis of RNA-seq data using multiple algorithms demonstrated that the high abundance of pro-inflammatory M1 macrophages was accompanied by the high abundance of other infiltrating immune cells, senescence-associated secretory phenotype and evident metabolic reprogramming. Macrophages are among the most abundant innate immune cells in PBMCs and glandular tissues in patients with pSS. A bidirectional relationship exists between macrophage polarisation and the inflammatory microenvironment, which may serve as a therapeutic target for pSS.

Human Rotavirus Replicates in Salivary Glands and Primes Immune Responses in Facial and Intestinal Lymphoid Tissues of Gnotobiotic Pigs.

Human rotavirus (HRV) is a leading cause of viral gastroenteritis in children across the globe. The virus has long been established as a pathogen of the gastrointestinal tract, targeting small intestine epithelial cells and leading to diarrhea, nausea, and vomiting. Recently, this classical infection pathway was challenged by the findings that murine strains of rotavirus can infect the salivary glands of pups and dams and transmit via saliva from pups to dams during suckling. Here, we aimed to determine if HRV was also capable of infecting salivary glands and spreading in saliva using a gnotobiotic (Gn) pig model of HRV infection and disease. Gn pigs were orally inoculated with various strains of HRV, and virus shedding was monitored for several days post-inoculation. HRV was shed nasally and in feces in all inoculated pigs. Infectious HRV was detected in the saliva of four piglets. Structural and non-structural HRV proteins, as well as the HRV genome, were detected in the intestinal and facial tissues of inoculated pigs. The pigs developed high IgM antibody responses in serum and small intestinal contents at 10 days post-inoculation. Additionally, inoculated pigs had HRV-specific IgM antibody-secreting cells present in the ileum, tonsils, and facial lymphoid tissues. Taken together, these findings indicate that HRV can replicate in salivary tissues and prime immune responses in both intestinal and facial lymphoid tissues of Gn pigs.

Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands

Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Casein genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands, induced 10,000-fold during pregnancy and account for 50% of mRNAs during lactation, Prr27 and Fdcsp are salivary-specific and Odam has dual specificity. We probed the function of 12 candidate regulatory elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Csn1s2b, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitates activation of Csn2 during pregnancy. Our work identifies the regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.

A Case of Heterotopic Salivary Gland in the Neck Mimicking a Brachial Cleft Anomaly

Heterotopic salivary gland tissue (HSGT) consists of salivary tissue in places where it does not normally exist. Usually, HSGT presents as a draining sinus or nodule of the neck. The pathogenesis of HSGT of the neck remains uncertain. But HSGT in the neck is most widely thought to arise from defective closures and ectodermal hetroplasia of the precervical sinus of His. HSGT in the neck is rare and only a few cases have been reported in Korea. We recently experienced a case of HSGT in the neck presenting as a fistula of the anterior lower neck. We thought this as a 2nd brachial cleft anomaly; however, biopsy revealed HSGT. HSGT in the neck should be considered as one of the causes of a neck mass or fistula in children. Herein, we report this case of HSGT with a literature review.

Comparison of four convolutional neural networks for histopathological diagnosis of salivary gland carcinomas

Malignant salivary gland tumors represent aparticular diagnostic challenge due to the large number of histopathological entities, their rare occurrence, and the diverse clinical and histological presentations. The aim of this work is to investigate and compare convolutional neural networks (CNNs) as adiagnostic tool for histological diagnosis of salivary gland cancer. From salivary gland cancer preparations of 68patients, 118histological slides were digitized at high resolution. These virtual sections were then divided into small image sections, and the resultant 83,819images were sorted into four categories: background, connective tissue, non-neoplastic salivary gland tissue, and salivary gland cancer tissue. The latter category grouped the entities adenoid cystic carcinoma, adenocarcinoma (not otherwise specified), acinar cell carcinoma, basal cell carcinoma, mucoepidermoid carcinoma, and myoepithelial carcinoma. The categorized images were then processed in atraining, validation, and test run by the ImageNet pretrained CNN frameworks (Inception ResNetv2, Inceptionv3, ResNet152, Xception) in different pixel sizes. Accuracy values ranged from 18.8% to 84.7% across all network architectures and pixel sizes, with the Inceptionv3 network achieving the highest value at 500 × 500pixels. The recall values/sensitivity reached up to 85% for different pixel sizes (Inceptionv3 network at 1000 × 1000pixels). The minimum F1 score achieved was 0.07 for the InceptionResNetv2 and the Inceptionv3 at 100 × 100 pixels each, the maximum F1 score achieved was 0.72 for the Xception at 1000 × 1000pixels. Inceptionv3 was the network with the shortest training times, and was superior to all other networks at any pixel size. The current work was able to demonstrate the applicability of CNNs for histopathological analysis of salivary gland tumors for the first time and provide acomparison of the performance of different network architectures. The results indicate aclear potential benefit for future applications.

Phosphorylated signal transducer and activator of transcription proteins 1 in salivary glandular tissue: an important histological marker for diagnosis of primary Sjögren’s syndrome

ObjectivesThe pathological diagnostic criteria for primary Sjögren’s syndrome (SjS) have certain limitations. We first explored the key pathogenic pathways of SjS through a bioinformatics approach, and then evaluated the diagnostic...