Chronic sclerosing sialadenitis of the submandibular and parotid glands: a report of a case and review of the literature

Chronic sclerosing sialadenitis (also known as Küttner tumor) is a chronic inflammatory condition of the salivary glands, first described by Küttner in 1896. Clinically, the disease cannot be distinguished from a true neoplasm. The submandibular gland is affected more commonly than any other salivary gland. This report is of a case of widespread swelling of the salivary glands in which histologic features of chronic sclerosing sialadenitis were seen in the submandibular and parotid glands. The etiology, pathogenesis, and differential diagnosis of this disease and the clinical outcome of this case are discussed and presented.     

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands

Objective:  The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands.
Methods:  Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA.
Results:  CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent.
Conclusion:  The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.     

The enigmatic mechanism of irradiation-induced damage to the major salivary glands

Irradiation is a central treatment modality administered for head and neck malignancies. Its major and most devastating side-effect is an induced damage to the major salivary glands. This article aims at suggesting a comprehensive explanation for the underlying mechanism of this damage, which has been considered as enigmatic throughout the 90 years since it was first described in 1911. The mechanism suggested is based on the considerable literature concerning this enigma in rat salivary glands. According to this proposed mechanism, the irradiation results in a sublethal DNA damage, which manifests and becomes lethal at a delayed phase. Thus, when the acinar progenitor cells are going through a reproductive phase when parenchymal replenishment is required, they die. The injurious agents, which result in this delayed reproductive cell death, appear to be highly redox-active transition metal ions, such as iron and copper. These metal ions, which seem to be associated with secretion granules, are not necessarily contained within the granules as previously suggested, but rather are probably located at sites more proximal to the DNA.     

Adenoid cystic carcinoma of the palate in a 9-year-old boy

Malignant tumors of salivary glands in children are extremely rare. A case of an adenoid cystic carcinoma affecting the palate in a 9-year-old child is described. This tumor has not previously been reported as affecting the minor salivary glands among patients in this age group.     

唾液腺:新型冠状病毒的“蓄水池”和“受累者”

新型冠状病毒引发的肺炎(简称新冠肺炎,coronavirus disease 2019,COVID-19)已在全球蔓延并快速进展,对人类的健康、经济活动和生活方式造成了巨大影响。口腔诊疗操作依赖牙科涡轮机,产生大量气溶胶,使口腔医护人员暴露于高风险环境中。唾液腺是唾液的来源,其是否感染新型冠状病毒和口腔诊疗风险密切相关。本文搜集国内外已发表的相关文献,总结新冠病毒对唾液腺感染及其在唾液腺内的复制过程和对唾液腺功能影响等方面的最新信息,旨在为口腔医护人员在疫情暴发及常态化防控期间的防护提供帮助。     

Autonomic control of salivary secretion

The view is generally held that the secretory elements of the major salivary glands are supplied with parasympathetic (cholinergic) nerve fibres, while the extent of the sympathetic (adrenergic) innervation varies considerably not only between different species but also between the glands of the same species. Parasympathetic stimulation evokes a copious flow of saliva. In contrast, sympathetic stimulation produces either a small flow, which is rich in protein, or no flow at all. In recent years it has become evident that secretion of saliva may not be elicited only by cholinergic or adrenergic agonists but also by peptides, injected into the bloodstream, and further, that the salivary secretion in response to stimulation of the parasympathetic innervation is not always completely abolished by the muscarinic receptor blocker atropine (and adrenoceptor antagonists). The present communication focuses on this "atropine-resistant" parasympathetic influence on the salivary glands and on a possible role for neuropeptides in mediating "atropine-resistant" parasympathetic responses in the glands. Immediate effects as well as long-term trophic effects are considered.     

Genetic regulation of salivary proteins in rodents

The presence of a protein in the cell is the result of a complex pathway that is known by the term gene expression. In this article we review the existing literature on the structure and expression of representative salivary gland genes and their regulated expression during development and upon extracellular stimulation. The expression of one of the "nuclear" protooncogenes, c-fos, in rat parotid glands is also discussed. Finally, we present some suggestions for future studies that will help to understand the mechanisms leading to gene regulation in rat salivary glands.     

P-glycoprotein expression in human major and minor salivary glands

Sodium pump and carbonic anhydrase activity have been described in the salivary glands. However, it remains to be elucidated whether these energy sources are used for secretion, excretion or both. In addition, the differences in the function of excretion and the role of the excretory duct cells are currently unknown in salivary glands. Expression of P-glycoprotein (P-gp), which is an ATPase-binding efflux pump, was tested in normal major and minor salivary glands from humans. P-gp was distributed on the basolateral membrane of serous acinar cells in the major salivary glands and the minor salivary glands. In particular, it was found to be present on the basolateral membrane and cytoplasm of acinar demilunar cells in the anterior lingual gland. Intense expression was identified in the basolateral membrane of the striated duct cells of the major salivary glands. P-gp was distinctly positive in the basolateral and/or luminal membranes of the initial part and in the luminal membrane of the terminal part of the excretory duct cells of the major salivary glands, whereas it was positive in the luminal membranes of both the initial part and the terminal part of the excretory duct cells of the minor salivary glands. These disparate distributions between the major and the minor salivary glands suggest different physiological excretions in the striated duct. P-gp may be physiologically involved in an important part of the transporter system, not only in the acinar serous cells and the striated duct cells, but also in the excretory duct cells in the salivary glands.     

Immobilization stress induces BDNF in rat submandibular glands

Brain-derived neurotrophic factor (BDNF) promotes survival and differentiation of the cells of the central and peripheral nervous systems. BDNF has been identified in non-neural tissue, including the heart, lung, platelets, lymphocytes, and lacrimal glands. Immobilization stress modifies BDNF mRNA expression in some organs. The present study examines the effect of immobilization stress on BDNF, and its receptor TrkB, in male rat submandibular glands. Increased BDNF mRNA and protein expression were observed in duct cells as a result of immobilization stress, as demonstrated by real-time PCR, Western blot, immunohistochemistry, and analysis by microdissection. TrkB mRNA was not detected in salivary gland tissue, or oral or esophageal mucosa, by RT-PCR. Rat submandibular gland was thus identified as an organ which expresses BDNF. Furthermore, the results of this study suggest that increased salivary BDNF expression occurs following immobilization stress.     

Expression of epithelial and nervous-system-related antigens on pleomorphic adenoma of the salivary glands--an analysis of 20 cases

The expression of cytokeratin (40-52 kD), carcinoembryonic antigen (CEA), vimentin, neuron-specific enolase (NSE), S-100 protein, glial fibrillary acidic protein (GFAP) were investigated in 20 cases of pleomorphic adenoma of the salivary glands and 10 cases of normal salivary glands, in order to analyze and correlate the antigens' expressions with the probably histogenetic mechanisms of the various histopathological differentiations in pleomorphic adenoma of the salivary glands and their probably original cells in normal salivary glands. Immunohistochemistry has provided some evidence for the relationship of the tumor cells to normal salivary glands: In the normal glands, the acinic cells exhibited cytokeratin, CEA and focal, predominantly nuclear S-100 protein staining. In both normal glands and pleomorphic adenomas, the duct-lining cells were immunoreactive for cytokeratin, CEA and had both cytoplasmic and nuclear S-100 positivity; The myoepithelial cells of the normal glands as well as the periduct cells, epithelial nests/cords, squamous metaplasia and the stellate/spindle/cartilaginous cells in the myxomatous-chondroid areas of the pleomorphic adenoma contain immunoreactive vimentin, NSE, S-100 proteins and GFAP, and lesser amounts cytokeratin (40-52 kD)/CEA. The varicosities of the terminal axon may lie directly on the basal membrane, or penetrate the basal membrane and lie in direct contact with the effector cells (duct-acinar-myoepithelial cells) of the salivary glands. The peripheral neurons and axons of the autonomic nervous system were identified by vimentin, NSE, S-100 proteins and GFAP. The combination of epithelial cytokeratin and nervous system-related vimentin, NSE, S-100 and GFAP immunostaining in myoepithelium of the normal glands and in all component elements (particularly the periduct cells) of pleomorphic adenoma reflects pleomorphic adenoma of the salivary glands is an epithelial tumor, the probably original cells or the probably histogenetic mechanisms of the various histopathological differentiations is correlated not only with "duct-acinar-myoepithelial cells" but also with the neuroectoderm in the normal salivary glands."     

Vasoactive intestinal peptide interacts with alpha-adrenergic-, cholinergic-, and substance-P-mediated responses in rat parotid and submandibular glands

Secretory dose-response curves were obtained with both acetylcholine and phenylephrine treatment in rat parotid and submandibular glands. Vasoactive intestinal peptide (VIP), which produced relatively low volumes of protein-rich saliva in rat salivary glands, also enhanced acetylcholine-, phenylephrine-, and substance-P-mediated fluid and protein secretion when administered in combination with these agents. The specific mechanisms involved in the synergistic actions of VIP with substances such as acetylcholine, phenylephrine, and substance P, which are primarily linked to the production of fluid secretion in rat salivary glands, have yet to be determined.     

Vascular endothelial growth factor in minor salivary glands: effect of ageing

Morphological and physiological age changes are described in human salivary glands. Vascular endothelial growth factor (VEGF) is neoangiogenic growth factor found in normal salivary glands. Considering the neoangiogenic properties of VEGF and its important function in inflammation, repair and, probably, in oral mucosa homeostasis, the purpose of the present study was to evaluate the effect of ageing on the immunolocalization of VEGF in minor salivary glands. Paraffin-embedded tissue blocks containing normal labial salivary glands were retrieved and classified according to the patients' age in two groups (< 20 and > 40-year-old). The biotin-streptavidin-peroxidase system was used to detect the VEGF antigen. The results demonstrated that the mean level of VEGF immunoreaction in the young group was not statistically different from the old group when compared by the Mann-Whitney U-test (P = 0.54). This may indicate that although salivary flow reduction may develop in old patients, some properties of the salivary glands may not be affected.     

Rad50在放射后大鼠涎腺中的表达

目的:检测Rad50在放射后大鼠涎腺组织中的表达水平。方法:选用60只Wistar大白鼠,随机分成6组,每组10只。分为对照组(未照射)、3 Gy组、6 Gy组、9 Gy组、12 Gy组、15 Gy组。放射组大白鼠用60Co一次性照射后2 h内处死,立即取出其腮腺、下颌下腺组织备用。用电镜观察放射后各组涎腺组织超微结构的变化,用反转录聚合酶链反应(RT-PCR)检测Rad50基因表达水平的变化,用免疫组织化学法观察其蛋白表达水平的变化。结果:各放射组涎腺组织中Rad50的表达均高于对照组(P<0.05),但不同放射剂量的各放射组之间Rad50的表达无明显差异(P>0.05)。透射电镜下可见大鼠腮腺、下颌下腺细胞超微结构随着放射剂量的增加,发生较明显改变。结论:放射可引起涎腺组织Rad50表达水平增高,但其表达水平并未随放射剂量的增加而增高,提示Rad50在涎腺放射损伤修复中的表达水平有限,这可能是涎腺放射敏感性机制之一。     

The physiology of salivary secretion

Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands – the submandibular, parotid and sublingual glands – along with secretions from many minor submucosal salivary glands. Salivary gland secretion is a nerve‐mediated reflex and the volume of saliva secreted is dependent on the intensity and type of taste and on chemosensory, masticatory or tactile stimulation. Long periods of low (resting or unstimulated) flow are broken by short periods of high flow, which is stimulated by taste and mastication. The nerve‐mediated salivary reflex is modulated by nerve signals from other centers in the central nervous system, which is most obvious as hyposalivation at times of anxiety. An example of other neurohormonal influences on the salivary reflex is the circadian rhythm, which affects salivary flow and ionic composition. Cholinergic parasympathetic and adrenergic sympathetic autonomic nerves evoke salivary secretion, signaling through muscarinic M3 and adrenoceptors on salivary acinar cells and leading to secretion of fluid and salivary proteins. Saliva gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells as it flows to the mouth. The major proteins present in saliva are secreted by salivary glands, creating viscoelasticity and enabling the coating of oral surfaces with saliva. Salivary films are essential for maintaining oral health and regulating the oral microbiome. Saliva in the mouth contains a range of validated and potential disease biomarkers derived from epithelial cells, neutrophils, the microbiome, gingival crevicular fluid and serum. For example, cortisol levels are used in the assessment of stress, matrix metalloproteinases‐8 and ‐9 appear to be promising markers of caries and periodontal disease, and a panel of mRNA and proteins has been proposed as a marker of oral squamous cell carcinoma. Understanding the mechanisms by which components enter saliva is an important aspect of validating their use as biomarkers of health and disease.     

Salivary gland endoscopy: A new technique for diagnosis and treatment of sialolithiasis

To describe the use of endoscopy as a technique for diagnosing and treating sialolithiasis. Sialolithiasis is a common pathology of the major salivary glands, yet its accurate detection and treatment is still intriguing. Eight cases of sialolithiasis were treated with our new technique which combines endoscopy and treatment. Two illustrative patients treated by this technique are described in detail. Endoscopy, has gained popularity in most surgical fields. We found that the available standard equipment used for TMJ arthroscopy can be used for exploration and extraction of calculi from the salivary ductal system.     

Secretion from minor salivary glands following ablation of the major salivary glands in rats

Since minor salivary glands are tiny and dispersed, ductal cannulation cannot be used when studying their function. The present study was devised to develop a method of measuring minor salivary gland function by excision of the major glands. Female rats (230–280 g) were anaesthetized with sodium pentobarbital. Ablation of the submandibular, sublingual and parotid glands was performed through a sagittal neck incision. Sham-operated rats served as controls. Groups of sialadenectomized animals were investigated immediately and after 1 week, 2 weeks and 3 months. To study secretory function, the mouth was rinsed with 250 μl water in every 5 min and protein and amylase concentrations were measured. After an initial 50 min of basal secretion pilocarpine (1 mg/kg, i.p.) was given. Bilateral ablation of both submandibular, sublingual and parotid glands led to a moderate loss of body weight and a considerable increase in water intake. No other obvious abnormality was observed for periods up to 90 days following surgery. We deduce that the minor glands secrete approximately 14% of protein and 1% of amylase in whole saliva. Secretion is maintained even after 90 days following removal of the major glands. Surgical removal of the major salivary glands allows the secretory function of the minor glands in rats to be studied in vivo.     

Radiation-induced salivary dysfunction: clinical course and significance

Salivary gland dysfunction commonly occurs as a result of radiation therapy for cancers of the head and neck region. The effect of radiation on salivary glands is immediate and predictable. Histologic and sialochemical studies indicate both the acini and ducts are affected. The extent of salivary dysfunction is primarily determined by the radiation field and dose. Radiation-induced salivary dysfunction is permanent and leads to a host of clinical sequelae, both oral and systemic.     

Epidermal growth factor concentration in hyperplastic and hypertrophic submandibular salivary glands of mice.

Submandibular salivary glands of mice contain high concentrations of epidermal growth factor (EGF). The EGF content of mouse submandibular salivary glands undergoing hyperplastic and hypertrophic changes was measured and compared to that in the glands of control mice. Salivary gland hyperplasia was induced by giving mice a single injection of isoprenaline and hypertrophy was produced either by repeated, daily injections of isoprenaline, repeated amputation of a lower incisor tooth or by removing the right submandibular salivary gland and thus producing a compensatory hypertrophy of the left submandibular gland. The EGF content of the hyperplastic submandibular salivary glands was not different from that of the control glands. While the EGF content of the hypertrophied glands resulting from either repeated isoprenaline injections or partial sialoadenectomy did not differ from that of the control glands, the concentration of EGF was significantly lower. This reduced concentration is probably a reflection of acinar hypertrophy with a resultant smaller proportionate contribution of the granular tubules to the mass of the gland. Incisor-amputation-induced hypertrophy did not result in a reduced concentration of EGF in the submandibular salivary glands, but the reason for the different response is unknown.The findings provide no evidence for the involvement of EGF in the induced changes of submandibular salivary gland hyperplasia or hypertrophy resulting from either isoprenaline treatment or partial sialoadenectomy. The reason for the higher concentration of EGF in hypertrophied submandibular salivary glands resulting from incisor amputation compared to that measured in hypertrophied glands resulting from the other stimuli used remains unresolved.     

Adenoid cystic carcinoma of the tongue: case report and literature review

Adenoid cystic carcinoma is a common malignant neoplasm originated from salivary glands. The clinical and pathological findings typical of this tumor include slow growth, perineural invasion, and potential local recurrence. It accounts for nearly 2% to 4% of head and neck area tumors. In minor salivary glands it usually affects the palate. We described herein the case of a patient who presented a posterior tongue lesion, which was treated with surgery and radiotherapy as additional treatment. We also carried out a brief literature review on the subject.     

Age-related changes in IGF-1 expression in submandibular glands of senescence-accelerated mice

Saliva is known to play important roles in such functions as swallowing, mastication, speech, and taste. Furthermore, salivary glands synthesize and secrete a number of growth factors involved in cell/tissue homeostasis. It has been demonstrated that IGF-1, which is structurally analogous to insulin, has been shown to be expressed in mouse submandibular glands, and that IGF-1 stimulates DNA synthesis, amino acid uptake, protein synthesis, and glucose transport in various cells. Diminished function of the salivary glands is thought to lead to increased dental caries and periodontal diseases, which are commonly associated with aging. However, very little is known regarding the effects of age on IGF-1 expression in submandibular glands. The senescence-accelerated mouse (SAM), an experimental murine model of accelerated aging, has been extensively used to examine the mechanisms responsible for aging. In the present study, IGF-1 production and mRNA levels in the submandibular glands of SAM-P1 mice were examined. IGF-1 levels were determined by radioimmunoassay and IGF-1 mRNA levels by semi-quantitative RT-PCR. We found that IGF-1 protein levels in homogenates and IGF-1 mRNA levels decreased with age in SAMP1 mice. These findings suggest that IGF-1 synthesis in submandibular glands decreases with aging, and this may result in lower levels of cellular proliferation, regeneration and wound healing in aged oral tissues.