Parotid Tissue Research Articles

Tempol mitigates inflammation, oxidative stress, and histopathological alterations of cadmium-induced parotid gland injury in rats

Cadmium (Cd) is a potent environmental pollutant that causes functional and structural damage to the salivary glands. Tempol (TEM) has powerful antioxidant activity that can potentially preserve organ function. Aims: This study was designed to investigate the protective effects of TEM on Cd-induced toxicity in rat parotid salivary glands. Materials and methods: Twenty-four adult Wistar male rats were randomly assigned to four equal groups: control, TEM (27.5 g/100 ml), Cd (0.6 g/100 ml), and TEM plus Cd (at the same doses). All treatments were dissolved in distilled water and administered subcutaneously four times a week for four weeks. Parotid gland tissues were isolated and subjected to molecular and histo-biochemical assessments. Key findings: TEM exerted a prophylactic effect against Cd-induced toxicity in the parotid glands by controlling inflammation through the downregulation of toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/ interleukin-1 beta mRNA expression, upregulation of aquaporin-5 mRNA expression, improvement of the oxidant/antioxidant status in the parotid gland, mitigation of endoplasmic reticulum stress, and repair of the associated histological and ultrastructural abnormalities. Significance: TEM protects against Cd-induced toxicity in the parotid glands of rats, attributable at least in part to its anti-inflammatory and antioxidant properties, as well as its ability to inhibit ER stress and facilitate glandular repair. However, the protective effects of TEM did not reach the levels observed in the control group. TEM could be a promising clinical candidate for protecting the salivary glands, particularly in high-risk groups such as workers exposed to Cd and cigarette smokers.

The single-strand DNA-binding protein SSB1 is involved in the expression of salivary gland radiation injury repair.

Single-strand DNA-binding protein 1 (SSB1) plays a crucial role in the cellular response to DNA damage. This study aimed to explore the expression and regulation of SSB1 in normal rat salivary gland tissues and tissues following radiation, with a specific emphasis on its involvement in the repair of salivary gland injury. A total of 45 adult SD rats were randomly assigned to one control group or eight experimental groups. In the control group, five rats were euthanized without irradiation, and their parotid gland tissues were collected for analysis. The experimental groups received a dose of 6Gy of radiation targeting the head and neck region; subsequently, five rats from each group were euthanized hly to collect parotid gland tissue samples, resulting in a total of eight experimental groups. The expression levels of SSB1, γ-H2AX, and PARP1 in the parotid gland tissues were assessed via immunohistochemistry, while changes in SSB1 gene expression were quantified via RT-qPCR. No significant morphological differences were observed between the two groups following HE staining. In the immunohistochemistry (IHC) analysis, notable tissue-specific variation in SSB1 expression was identified, with higher levels detected in the ducts than in the acini and connective tissue. The expression of SSB1 gene initially increased post-radiation before subsequently decreasing, ultimately returning to baseline levels, as corroborated by the RT-qPCR results. In contrast, γ-H2AX and PARP1 exhibited minimal expression in the control group; however, their expression peaked at 1h in the experimental group before gradually declining to levels comparable to those of the control group. Radiation induces time-dependent upregulation of SSB1 expression in rat salivary glands, indicating that SSB1 may play a role in radiation-induced repair processes.

First experience using a plate for fixing histological specimens of parotid salivary gland tumors

Relevance. Accurately assessing all resection margins during the removal of parotid salivary gland tumors is crucial due to the risk of recurrence and the potential for benign processes to become malignant over time. Macroscopic specimens obtained during these surgeries are sent to the pathology laboratory in containers filled with fixative solution. During fixation, the soft tissue fragments, typically round in shape, can alter their configuration because of the tissue's heterogeneity. This can create challenges for the pathologist in properly orienting the surgical specimen, which in turn complicates the precise evaluation of the resection margins.Materials and methods. To address this issue, the "Plate for fixing histological specimens of parotid salivary gland tumors" (patented) was developed. Twenty cases of its clinical use were analyzed: the surgical material (parotid gland tissue containing a tumor) was sent to the pathology department, fixed on this plate to preserve its original anatomical orientation. A macroscopic and histological evaluation of the neoplasms was then carried out, with special attention given to the accurate identification of all resection margins. In all 20 clinical cases, the use of this invention improved the convenience for the pathologist in handling the excised tissue block by standardizing the method and clearly identifying the resection margins.Conclusion. The application of this invention enhances the accuracy of marking and evaluating the resection margins in parotid gland tumors.

Does Radiofrequency Radiation From Mobile Phones Affect the Formation of Parotid Gland Malignancy? An Experimental Study.

Objectives: The use of mobile phone is increasing around the world. Although it is beneficial in terms of communication, the electromagnetic radiations emitted by mobile phones may cause undesirable biological effects on the human body. In practical use, the tissue with which mobile phones come into most and are closest is the parotid gland. This study investigated the effects of the 1800 MHz electromagnetic field created by a generator on the parotid gland in rats. Methods: A total of 21 Sprague-Dawley Albino rats were included in the study. The rats were randomly divided into three equal groups. To simulate a mobile phone in conversation mode, the first study group was exposed to an 1800-MHz electromagnetic field for 6 hours a day for 30 days, and the second study group was exposed to an 1800-MHz electromagnetic field for 12 hours a day for 30 days. After 30 days, rats were sacrificed, and histopathological and immunohistochemical methods were used to evaluate the effects on the parotid gland. The total antioxidant level and the total oxidant level were measured biochemically in homogenized parotid tissue. Results: Histopathological results showed an increase in degeneration in rats exposed to electromagnetic fields for 6 and 12 hours a day, and immunohistochemical analysis showed an increase in the apoptotic index in both study groups (P = .001, P < .001). Intranuclear inclusions was observed during histopathological examination performed by electron microscopy. Conclusions: This study observed that the 1800 MHz electromagnetic field caused undesirable adverse histopathological and biochemical effects on the parotid gland of rats. Histopathological and biochemical findings were detected with increasing contact and exposure time. This study will lead to other studies on this topic and contribute to the literature by completing other studies.

Effects of Glucose Intolerance on Physiological Accumulation in Salivary Glands and Palatine Tonsils During 18F-Fluorodeoxyglucose Positron Emission Tomography.

We evaluated the effects of chronic hyperglycemia on physiological accumulation in salivary glands and tonsils during18F-fluorodeoxyglucose positron emission tomography (FDG-PET/CT). 12,738 patients underwent whole-body FDG-PET/CT in our institute during the study period. Of these, the case group comprised 777 patients with a blood glucose (BG) level >140 mg/dL; the control group comprised an equal number of randomly selected age- and sex-matched individuals with a BG level <110 mg/dL. Within the case group, the diabetic subgroup was defined as individuals with a BG level >200 mg/dL. Visual assessment and accumulation intensity among tissues were compared between the case and control groups, including (1) the mean difference in maximum standardized uptake value (SUVmax), (2) the difference in the proportion of patients with visible tissues on maximum intensity projection images, and (3) differences between the diabetic subgroup and the control group. Parotid, submandibular, sublingual, and tonsillar tissues all showed significantly lower SUVmax in the case group than in the control group. The proportions of individuals with visible uptake in the parotid and tonsillar tissues and in the sublingual gland were significantly smaller in the case group than in the control group. Tonsillar uptake was observed in more than 90% of individuals in the control group but in two-thirds of patients in the diabetic subgroup. Accumulation in the parotid and submandibular glands was visible in approximately 80% of individuals in the control groupbut only half of patients in the diabetic subgroup. Physiological accumulation in salivary glands and tonsils is significantly reduced among individuals with hyperglycemia or diabetes.

Endometriosis and Sjögren's syndrome: Bidirectional associations in population-based 15-year retrospective cohorts.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder affecting salivary and lacrimal glands, while endometriosis involves uterine-like tissue growth outside the uterus, causing pelvic pain and infertility. Investigating their intricate relationship using real-world data is crucial due to limited research on their connection. This population-based cohort study included patients with endometriosis and controls without endometriosis. Propensity score matching was used to balance baseline differences in demographic and clinic characteristics between the two groups. Cox proportional hazards model were used to estimate the effect of endometriosis on the risk of new-onset pSS over time. A symmetrical cohort study, including patients with pSS and propensity score-matched controls without pSS, was conducted to investigate the effect of pSS on the risk of endometriosis over time. To elaborate on the mechanisms linking endometriosis and pSS, Ingenuity Pathway Analysis was performed to identify activated pathways in eutopic endometrium from patients with endometriosis and parotid tissues from patients with pSS. A total of 15 947 patients with endometriosis and 15 947 propensity score-matched controls without endometriosis were included. Patients with endometriosis presented a significantly greater risk of pSS compared to non-endometriosis controls (adjusted hazard ratio, aHR = 1.57, 95% CI = 1.29-1.91, p < 0.001). In the symmetrical cohort study, which included 4906 pSS patients and 4,906 propensity score-matched controls without pSS, patients with pSS were found to be at a significantly higher risk of endometriosis compared to non-pSS controls (aHR = 1.51, 95% CI = 1.12-2.04, p = 0.012). Ingenuity Pathway Analysis showed that the underlying cellular mechanisms involved autoimmune-related pathways, including activation of dendritic cell maturation, and chronic inflammatory pathways,including the fibrosis signaling pathway. These findings support a bidirectional association between endometriosis and pSS, which may be driven by dendritic cell maturation and fibrosis signaling pathways.

Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress.

Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).

First report on parotid tissue choristomas within and adjacent to TMJ ligaments

PurposeTo report the first examples of ectopic salivary glands of TMJ ligaments & capsules. Methods and MaterialsNine subjects with chronic TMJ disorders were found incidentally to have ectopic salivary glands (choristomas) within or near damaged TMJ ligaments and capsules. Clinicopathologic characteristics of 12 TMJs are summarized. ResultsThe 9 subjects were ages 22-64 years (average = 43.0); 6 were female. Microscopic examination revealed major, almost complete ligament replacement by dense, avascular fibrous scar tissue in all but 1 sample. Chronic inflammatory cells were present in the stroma of 3 samples. A total of 33 lobular, independent salivary structures of variable sizes where embedded in or near ligaments and/or capsules. Half were multiple in the same joint; 13 were bilaterally located in the joints of a single subject, with 8 small glandular lobules in one TMJ. All glands consisted of histologically normal serous acini except 1 which showed a focal lobule of mucus acini and another comprised only of mucus acini. Serial sections showed no connection to parotid glands. Some choristomas showed the aging phenomena of fatty infiltrates (n = 7) and oncocytosis (n = 7). Additionally, 3 of the 12 TMJ samples contained preauricular lymph nodes, with 3 nodes in 1 joint and bilateral involvement in 1 subject. Of the 5 identified nodes, all but one was hyperplastic, with nonspecific inflammatory histiocytosis. ConclusionsWe report, for the first time, independent salivary gland choristomas (n = 33) within the soft tissues of the TMJ (n = 12), with one joint containing 8 such choristomas. All consisted of normal serous tissue except one, a mucus gland. Additionally, a fourth of TMJ surgical samples contained hyperplastic preauricular lymph nodes.

Multispectral optoacoustic tomography of benign parotid tumors in vivo: a prospective observational pilot study

Parotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p < 0.05). The mean MSOT parameters were all significantly higher (all p < 0.05) in the WT compared to healthy parotid gland except for HbT and sO2. Comparing both tumors directly, the mean values of MSOT parameters were not different between PA and WT (all p > 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p < 0.05). This preliminary MSOT parotid tumor imaging study showed clear differences for PA or WT compared to healthy parotid tissue. Some MSOT characteristics of PA and WT were different but needed to be explored in larger studies.

Lymphoma presenting as preauricular tumor in unilateral parotid gland agenesis: a case report and review of literature

BackgroundParotid gland agenesis is a rare, congenital, usually asymptomatic disorder. Until now, only 24 cases with unilateral, incidentally found, parotid gland agenesis have been described. Here, we present the first reported case of an ipsilateral preauricular neoplasm in a patient with unilateral parotid gland agenesis. During surgery, the position of the greater auricular- and facial nerves was documented. Furthermore, we performed the first sialendoscopy for this rare disorder to assess the number of duct branches, which might be indicative of the abundance of parotid tissue. Moreover, we looked for sialendoscopic characteristic features that could aid in identifying these patients in the ambulatory setting.Case presentationA 50-year-old Greek man presented with a painless, slowly enlarging mass in the right parotid space. Magnetic resonance imaging revealed a complete absence of the right parotid gland without accessory parotid tissue. The right parotid gland was replaced by fatty tissue and the radiologist suggested a benign parotid tumor. Fine needle aspiration was indicative of a reactive lymph node. Sialendoscopy revealed only two branches within the right parotid duct. Surgical resection was performed through a conventional lateral parotidectomy. This revealed typical anatomic position of the greater auricular- and facial nerves despite the parotid tissue agenesis. Histopathology revealed a small lymphocytic lymphoma.ConclusionsSurgeons should feel confident to resect tumors of the parotid space in patients with parotid gland agenesis. Reduced branching observed during sialendoscopy might indicate parotid gland agenesis. Physicians should be even more cautious than usual with the watch and wait strategy in patients with tumors of parotid gland agenesis, since the probability of a tumor being a benign salivary gland tumor might be lower than usual.

The possible protective role of vitamin C on rat parotid gland exposed to mobile phone radiation

The widespread use of cell phones recently has raised interest in studying the safety of exposure to their electromagnetic waves. This study aimed to evaluate the possible protective role of vitamin C (Vit. C) against the pathological effects produced by the relatively long duration of third-generation mobile phone radiation exposure in the parotid gland of male white albino rats. Also, to detect the expected recovery after 4 weeks of withdrawal by immunohistochemical, histopathological, and biomolecular studies. Forty male adult white albino rats were used in this study, equally divided into 4 groups of 10 rats in each group: Group I served as the sham control group; Group II was exposed to radiation by phone generator (2100 MHz) for 3 hours/day for 5 days/week for 6 weeks; and Group III was exposed to phone radiation similar to Group II and supplemented with Vit. C at a dose of 40 mg/kg for 5 days per week for 6 weeks. Group IV (withdrawal) was exposed to radiation as Group II, then left without intervention for 4 weeks. Histological and immunohistochemical, and the biochemical evaluation of oxidative stress within parotid tissue (malonaldehyde (MDA), superoxide dismutase (SOD), salivary total protein, and amylase activity). qRT-PCR for TGF, MMP2, NFKB, and TNF gene expression was performed in this study. Histological examination of the parotid gland in group II showed many histological changes, such as degenerative changes in the duct system, epithelial lining of the acini, interstitial space which. different collagen fibers and polysaccharides, blood capillaries, and nuclei. Also, alpha smooth muscle actin (α-SMA) and Ki-67 were aggravated. The statistical analysis showed that treating rats with vitamin C improved the parotid glands’ ability to secrete amylase activity and total protein. It also fixed the antioxidant. Inflammatory cytokines TNF, NFKB, and fibrotic marker TGF and MMP2 gene expression were significantly upregulated in the exposed group, which was restored nearly to the control group after Vit C supplementation. Long-term exposure to mobile radiation affected. the. secretory function and the histological structure of the parotid tissues. Vitamin C supplementation ameliorated these pathological effects.

Management of Mandibular Condylar Sagittal Fracture Accompanied by Lateral Condylar Crest Defect.

The sagittal fracture of the mandibular condyle can be fixed with absorbable long screws. Absorbable long screws are generally inserted from the lateral crest of the condyle and are as close as possible to the medial pole of the condyle to obtain sufficient retention force. However, in clinical practice, patients with locally comminuted condylar fractures and partial defects in the lateral crest are often encountered. We validated the use of absorbable plates and long screws to fix mandibular condylar fractures with lateral crest defects, and postoperative follow-up showed good results. The preoperative design indicated that if conventional long screws were used, more soft tissue need to be pulled downward to achieve the appropriate drilling angle. If an absorbable plate was used, the degree of downward pulling of soft tissue was smaller, which can better protect the parotid gland tissue and facial nerve. The surgery was performed according to the preoperative design, using an absorbable plate scheme. Postoperative CT confirmed a stable anatomical reduction of condyle. Four-month follow-up showed that the patient's facial shape, occlusion, and mouth opening were all good. Follow-up CT showed good fracture healing. It is feasible to use absorbable plates and long absorbable screws to fix mandibular condylar sagittal fracture accompanied by lateral condylar crest defect.

Radiation-induced Xerostomia is Related to Stem Cell Dose-dependent Reduction of Saliva Production

Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (Dmean,SCR) is the strongest dosimetric predictor for the risk of patient-reported daytime xerostomia. This study aimed to test whether the relationship between patient-reported xerostomia and Dmean,SCR is explained by a dose-dependent reduction of saliva production. In 570 head and neck cancer patients treated with definitive radiation therapy (RT), flow from the parotid (FLOWPAR) and submandibular/sublingual glands (FLOWSMSL) and patient-reported daytime (XERDAY) and nighttime xerostomia (XERNIGHT) were prospectively measured before, and at 6 and 12 months after RT. Using linear mixed effect models, the relations of mean dose to the parotid glands (Dmean,par), Dmean,SCR, non-SCR parotid gland tissue (Dmean,non-SCR), submandibular glands (Dmean,sub) and oral cavity (Dmean,oral) with salivary flow and xerostomia were analyzed while correcting for known confounders. Dmean,SCR proved to be responsible for the effect of Dmean,par on FLOWPAR (p≤0.03), while Dmean,non-SCR did not affect FLOWPAR (p≥0.11). To illustrate, increasing Dmean,SCR by 10 Gy at fixed Dmean,non-SCR, reduced FLOWPAR by 0.02 (25%) after RT. However, if the opposite happened, no change in FLOWPAR was observed (0.00 ml/min [4%]). As expected, Dmean,sub was significantly associated with FLOWSMSL (p<0.001). For example, increasing Dmean,sub by 10 Gy, reduced FLOWSMSL with 0.07 ml/min (26%) after RT. Xerostomia scores were also affected by dose to the salivary glands. Dmean,SCR and Dmean,oral were associated with higher XERDAY scores (p≤0.05), while Dmean,sub increased XERNIGHT scores (p=0.01). For example, an increase of 10 Gy in Dmean,SCR raised XERDAY scores with 2.13 (5%) points after RT, while an additional 10 Gy in Dmean,subs increased XERNIGHT scores with 2.20 points (6%) after RT. Salivary flow was not only associated with radiation dose, but also with xerostomia scores in line with the salivary glands' functions, i.e., FLOWPAR only influenced XERDAY (p<0.001, 10.92 points lower XERDAY per 1 ml/min saliva), while FLOWSMSL affected XERDAY and XERNIGHT (p≤0.004, 6.69 and 5.74 points lower XERDAY and XERNIGHT, respectively, per 1 ml/min saliva). Therefore, the observed relations between dose and xerostomia were corrected for salivary flow. As hypothesized, Dmean,SCR only increased XERDAY scores via reducing FLOWPAR; whereas the effects of Dmean,oral on XERDAY and of Dmean,sub on XERNIGHT were independent of salivary flow. Higher SCR region dose reduced parotid gland saliva production, subsequently resulting in higher daytime xerostomia scores. Consequently, this study supports the clinical implementation of stem cell sparing RT to preserve salivary flow with the aim of reducing the risk of xerostomia.

Alternative surgical restoration of aesthetic defect during superficial parotidectomy – Case report

Tumors in the parotid gland, which is the largest salivary gland, could appear as a swelling in the cheek area or in the area in front of and below the earlobe. The majority are benign tumors. In all cases, removal of the tumor by parotidectomy is the main option. In the majority of these operations, postoperatively a defect remains in the lateral region of the face after the removal of the tumor. Many solutions have been proposed internationally to treatment this aesthetic defect. In this study, a proposal is presented to use part of the remaining parotid tissue, to restore the defect that appears after the removal of the tumor and the preparation of the facial nerve.

Parotid Lipomas: Case Series and Literature Review – A Case Report

Background: Lipomas are the most frequent neoplasm of mesenchymal origin in the head-and-neck region. Around 15% of lipomas are found in the head-and-neck region. The usual site where lipomas can be found in the head-and-neck region is in the posterior triangle of the neck but they can also be found in the anterior neck, infratemporal fossa, submandibular space, larynx, pharynx, and parotid gland. The incidence of parotid lipoma ranges from 0.6% to 4.4% of all parotid neoplasms. There are two histological variants, focal lipoma and diffuse infiltrating variant. We describe two cases of rare focal lipoma of the parotid gland, therefore, must be reported. As rare as it may appear, existing relevant literature suggest management to includes definitive radiological investigations such as magnetic resonance imaging (MRI) and complete removal of lipoma with or without a cuff of parotid tissue. Case Report: Two cases were identified with a parotid lipoma on final histology. Case 1 is a 57-year-old male with a history of painless left parotid swelling for 2 years, reported to be 5 cm × 4 cm size on ultrasound, therefore, underwent superficial parotidectomy. Case 2 is a 67-year-old male who presented with right parotid swelling for 15 years, reported on ultrasound to be 5 cm × 5 cm, and underwent excision of intraparotid tumor. He later went on to develop breast carcinoma. The facial nerve was intact of both patients. Conclusion: Parotid lipomas are rare entities that should be a differential for clinically soft parotid swellings. Management includes definitive radiological investigations such as MRI and complete removal of lipoma with or without a cuff of parotid tissue instead of regular ultrasound followed by fine-needle aspiration cytology. Although our cases were managed on the same regular outlines, but reporting these cases would suffice the potential role of MRI and computed tomography scan for parotid swelling as per existing literature.

Abstract 3911: A FGFR-p53 developmental signaling axis drives progression of salivary cancer

Abstract Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland (SG) malignancy. Treatments for high grade (HG) MEC are lacking due to a limited understanding of its diverse histological and clinical features. Consequently, patients with non-resectable HG MEC are often treated with adjuvant radiotherapy and suffer from increased rates of recurrence and metastasis with poor 5-year survival rates (30-50%) as compared to low grade (LG) MEC (76-95%). We previously demonstrated a role for IGF-1 signaling, an important mediator for SG development and branching morphogenesis, in MEC pathogenesis (Musicant et al, 2021). Here, we analyzed transcriptome profiles shared between fetal and adult normal parotid (PAR) tissues with MEC tumors to investigate programs involved in MEC progression. Using this information, we developed the first genetically engineered mouse model (GEMM) of advanced HG MEC via targeted oncogene expression in SG ductal cells. MEC samples from 21 PAR tumors (8 LG/13 HG), 8 age-matched normal, and 3 fetal PAR glands aged between 22-24 weeks of gestation (Saitou et al, 2020) were retrospectively collected from UCSF or UNC Surgical Pathology. RNAseq was performed on FFPE samples using Illumina HiSeq. Differential gene expression, gene set enrichment analyses (GSEA), and alternative splicing analyses were compared between fetal/normal/MEC according to tumor grade and CRTC1 (CREB-regulated transcription coactivator 1)/MAML2 (Mastermind-like 2) (C1/M2) status. Based on these analyses, we developed a GEMM combining C1/M2 expression with TP53 loss. GEMM tumors were subjected to RNAseq and reviewed by two independent pathologists for diagnostic confirmation of HG MEC.GSEA revealed significant overlap between MEC tumors and fetal SG for genes governing proliferation and developmental pathways associated with branching morphogenesis. Interestingly, upregulation of the negatively regulated p53 target FOXM1 along with a mutant-p53 gene signature (Troester et al, 2006) revealed that p53 dysregulation in HG tumors phenocopies that seen in fetal SG. Cre-inducible expression of C1/M2 alone was insufficient to induce MEC-like lesions when targeted to distinct salivary cell types (ductal Krt14-CreER, acinar Mist1-CreER, serous demilune Dcpp1-CreER). However, p53 alteration (Tp53KO) with ductal C1/M2 expression drove MEC formation with histological and molecular features of human HG-MEC. Notably, transcriptome profiles implicate an FGFR-p53 developmental signaling axis in MEC progression. Our autochthonous GEMM recapitulates advanced HG-MEC in vivo providing the field with a powerful platform for identifying pathways for developing targeted therapies. Taken together, the integrated bioinformatics and mouse modeling of this study provide a critical step toward elucidating salivary MEC progression and suggest a role for FGFR targeted therapies in the treatment of non-resectable HG MEC. Citation Format: Julia M. Billington, Adele M. Musicant, Jessica L. Cote, Jennifer Modliszewski, Yi-Hsuan Tsai, Luane J. Landuau, John Powers, Renee Betancourt, Radhika Sekhri, Ricardo J. Padilla, Juan C. Hernandez-Prera, David N. Hayes, Trevor G. Hackman, Omer Gokcumen, Sarah M. Knox, Jimena Guidice, Antonio L. Amelio. A FGFR-p53 developmental signaling axis drives progression of salivary cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3911.

A Rare Synchronous Existence of Warthin’s Tumour and Oral Cancer

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide while Warthin’s tumor (WT) is a common type of benign salivary gland neoplasm mostly seen in the parotid gland but rarely involves extra parotid tissues. Extra parotid WT is itself a rare entity and its synchronous occurrence with OSCC is an unusual phenomenon. It is vital to accurately identify the pathology as confusion may arise due to its rare occurrence and an intriguing presentation of resembling metastasis in lymph nodes. In the present review, a systematic literature search was performed and case reports and series in which synchronous existence of WT and OSCC were included. Total 13 papers have been included with 17 cases of synchronous WT and OSCC. Quality assessment for cases was done based on the CARE guidelines. The given results describe the histological features and site of WT in individuals who also had OSCC. Most of the studies described the histological findings of WT, which were seen involving the lymph nodes. More than 50% of the included cases had a history of tobacco chewing or smoking. The cases that have reported for follow up showed no evidence of any recurrence. WT with OSCC synchronous occurrence at a different site from the primary tumor can mimic a metastatic lesion from a primary lesion. It is a diagnostic challenge and could alter the management of these patients if not identified accurately. Awareness about this synchronous occurrence can avoid the overtreatment in such cases. Majority of the WTs described were seen in cervical lymph nodes.&#x0D; Keywords: Oral cancer; Warthin tumor; Benign Neoplasm; Mixed salivary gland tumor; Synchronous neoplasm; metastasis; Second malignancy; Prognosis.

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.

Transcriptome analysis of salivary glands of rabies-virus-infected mice.

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.

Venous vascular malformation of the parotid gland

AbstractVenous vascular malformations of the parotid gland are very rare vascular tumors, especially among adults. This case report discusses the presentation and challenges of diagnosing a venous vascular malformation of the parotid gland in a patient with previous oncologic history. Our patient is a 45‐year‐old female with a history of breast cancer, meningioma, and secreting pituitary adenoma who presented with a malformation on magnetic resonance imaging, incidentally demonstrating a T2 intense mass in the superficial lobe of the right parotid gland. She was otherwise asymptomatic. Ultrasound‐guided fine needle aspiration was nondiagnostic. She underwent a right inferior superficial parotidectomy. Histologic section analysis demonstrated a well‐delineated vascular tumor made of large vascular spaces with thin walls surrounded by a parotid tissue consistent with a venous vascular malformation of the parotid gland. Venous vascular malformations are exceedingly rare, especially among adults. Ultrasound‐guided fine needle aspiration can be of limited value. Parotidectomy may be electively considered for diagnostic and therapeutic purposes.