Giant Parapharyngeal Space Pleomorphic Adenoma of the Deep Lobe of Parotid Presenting as Obstructive Sleep Apnoea: A Case Report & Review of the Diagnostic and Therapeutic Approaches

Introduction

Salivary gland tumours constitute about less than 4 % of all head and neck tumours. Pleomorphic adenoma, also called benign mixed tumour, is the most common tumour of the salivary glands. About 80–90 % of these tumours occur in the major salivary gland mainly parotid gland and 10 % of them occur in the minor salivary glands.

Aims and Methods

Aim of this case report is to discuss the unique case of giant parotid pleomorphic adenomas arising in the deep lobe involving the parapharyngeal space and difficulty in respiration at sleep during nights repoted at this institute. The patient was undergoing treatment for obstructive sleep apnea syndrome when she reported at this institute for disturbed sleep. Diagnosis was based on computed tomography scan and magnetic resonance imaging and cytology by means of fine needle aspiration biopsy.

Conclusion

An exhaustive pre-operative diagnostic algorithm is mandatory before approaching such lesions involving parapharyngeal space. Fine needle aspiration biopsy is, in our opinion, mandatory to avoid histological surprises. The surgical approach varies according to the location of the tumour and should provide excellent visibility with wide surgical exposure to secure local neurovascular structures.     

Development of peroxidase-mediated antibacterial activity in embryonic salivary glands of the mouse.

Thiocyanate peroxidase (TPO) activity of the submandibular gland of mice began to appear on the 17th day in utero and increased with time. This enzyme activity was lacking in the sublingual gland. Cultured glands of embryonic mice in a Rose chamber revealed proliferation and differentiation in both submandibular and sublingual glands. After 3 days cultivation, peroxidase was detected in the cells of the terminal tubules of the submandibular gland, but not in the sublingual. TPO activity measured by ¹⁴CO₂ production from [¹⁴C]-thiocyanate by cultured composite submandibular and sublingual glands became evident on the 4th day of cultivation. The results suggest that the peroxidase activity involved in the TPO system is of salivary gland origin.     

Interobserver and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography

Background Data regarding the inter- and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography are missing in the current literature. This study assessed the inter- and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography (CBCT).Material and Methods In 107 patients, 130 salivary glands (65 parotid and 65 submandibular) with clinical signs of obstruction were assessed by four independent observers; 2 residents OMFS and 2 experienced OMFS. The observers analyzed the CBCT images and determined the absence or presence of one or more salivary stones in the affected gland. This procedure was repeated after three months.Results Interobserver agreements showed kappa values of 0.84 for the parotid gland, and 0.93 for the submandibular gland. Intraobserver agreements for the whole group reported kappa values between 0.83 - 0.95. There was no significant difference between residents and experienced OMFS.Conclusions Due to the good inter- and intraobserver agreement, CBCT appears to be a reproducible imaging modality for detecting salivary stones in patients with signs and symptoms of obstructed parotid and submandibular glands. Key words:Salivary gland calculi, cone-beam computed tomography, observer variation.     

Characteristics of neurokinin A-induced salivary fluid secretion in perfused rat submandibular gland

Tachykinins such as neurokinin A (NKA) and substance P have been demonstrated to induce salivary fluid secretion in vivo. However, characteristics of salivary fluid secretion induced by tachykinins in salivary glands have not been well elucidated. In this study, the effects of the tachykinin NKA on salivary fluid secretion were investigated in isolated, perfused rat submandibular gland. NKA provoked salivary fluid secretion, which consisted of transient and sustained phases, in a dose-dependent manner. In fura-2-loaded dispersed cells of the rat submandibular gland, the doses of NKA in which induced salivary fluid secretion caused an increase in intracellular Ca²⁺ concentration. When Ca²⁺ was removed from the perfusate to examine the effect of Ca²⁺ mobilization on NKA-induced fluid secretion, only the transient salivary fluid secretion occurred. When the gland was perfused with the Ca²⁺-free perfusate containing the intracellular Ca²⁺ chelator BAPTA-AM, NKA failed to induce salivary fluid secretion. NKA also induced an increase in oxygen consumption, but which was reduced by the removal of Ca²⁺ from perfusate. Salivary fluid is secreted via transcellular and paracellular pathways in acinar cells of salivary glands. To examine the contribution of paracellular pathway to NKA-induced salivary fluid secretion, the glands were perfused with a perfusate containing Lucifer yellow (LY), a cellular impermeable substance, and then were stimulated with NKA, which provoked secretion of LY in the saliva. These results suggest that the NKA-induced salivary fluid secretion is Ca²⁺-dependent and that the paracellular pathway contributes to the secretion.     

Saliva secretion in engrafted mouse bioengineered salivary glands using taste stimulation

PurposeThe aim of this study was to compare saliva flow and protein composition induced using five basic taste stimulations between natural and bioengineered salivary glands.Materials and methodsWe developed a mouse saliva secretion model using taste stimulation and analyzed the saliva secretion from natural and bioengineered salivary glands using an assay. The protein components and alpha-amylase in the natural and bioengineered saliva were analyzed by gel electrophoresis and Western blotting.ResultsThe salivary flow responses induced by sour (citric acid) and bitter (quinine-HCl) stimuli were significantly high in the natural and bioengineered salivary glands. Although the protein concentrations in the natural and bioengineered saliva induced using five basic taste stimulations were similar, the protein composition and the amylase concentration in the natural saliva after taste stimulation had different profiles. Sympathetic and non-sympathetic nerves were observed around the acini and ducts in the natural and bioengineered salivary glands. However, the frequency of neuropeptide Y-positive sympathetic nerves in the bioengineered gland was relatively high compared to that in the natural gland.ConclusionsThese results suggest that the signal balance between the sympathetic and parasympathetic components of the efferent nerves in an engrafted bioengineered salivary gland may differ from that in a natural salivary gland.     

Changes of salivary functions in experimental periodontitis model rats

ObjectiveThis study was designed to investigate the mechanism of salivary dysfunction in an experimental periodontitis rat model and to examine the improvements in salivary secretion following treatment of the experimental periodontitis.MethodsIn the experimental periodontitis rat model, which included a unilateral ligature for 4 weeks around the second upper molar, several salivary functions were investigated. Changes in the salivary function were evaluated 4 weeks after removal of the ligature in some rats.ResultsThe periodontitis model showed significant reductions in the weight of the bilateral major salivary glands and pilocarpine-induced salivary secretion. The model also showed an increase in the number of apoptotic cells in bilateral salivary glands. According to Ca²⁺ imaging and Western blotting, there were no differences in the muscarine-induced intracellular Ca²⁺ mobilization in acinar cells or in the M3 receptor and AQP5 expression levels in the salivary glands between the sham and the periodontitis model. Following removal of the ligature, differences in the weights of salivary glands and pilocarpine-induced salivary secretion between the sham and the periodontitis model animals were not found.ConclusionThese results suggest that experimental periodontitis leads to hyposalivation and that relief from it improves salivary function. It is likely that lower levels of salivary secretion are caused by the decrease of functional acinar cells in salivary glands in the experimental periodontitis model, and the bilateral gland effects in the unilateral periodontitis model are caused by systemic rather than by local effects.     

Salivary gland tumours: 25 years of experience from a single institution in Croatia

IntroductionThe aim of this study was to determine the types, frequency, distribution, and demographic characteristics of salivary gland tumours in a large representative sample.Patients and methodsWe retrospectively analysed the medical records of 779 patients with tumours of the salivary glands surgically treated from 1985 to 2009 at a single institution.ResultsThere were 500 benign and 279 malignant tumours. The average age of patients with benign tumours was 50 years and of malignant salivary gland tumours 56 years. No differences in age and incidence of tumours existed between males and females. The majority of the tumours occurred in the parotid gland (509), followed by the minor salivary glands (212), the submandibular gland (51) and lastly, the sublingual gland (7). Minor salivary gland tumours occurred most frequently on the palate, the pleomorphic adenoma being the most frequent benign tumour type and the adenoid cystic carcinoma being the commonest malignant tumour. Tumours of the sublingual gland were rare, but all were malignant. Malignant tumours were more common in the minor salivary glands and the submandibular gland.ConclusionThis large study of salivary gland tumours in Croatia could improve our understanding of the significant differences in the global distribution of salivary gland tumours which have been reported.     

Correlation of apparent diffusion coefficient with histopathological parameters of salivary gland cancer

The aim of this study was to correlate the apparent diffusion coefficient (ADC) with histopathological parameters of salivary gland cancer. A retrospective analysis of 44 patients with salivary gland cancer who underwent diffusion-weighted magnetic resonance imaging of salivary glands was performed. The ADC of salivary gland cancer was correlated with pathological tumour type and grade, stage (T stage and N stage), and morphological (perineural spread and location) prognostic parameters. There was a significant difference in ADC values between low–intermediate- and high-grade tumours (P = 0.024), lower T stages (T1, T2) versus higher T stages (T3, T4) (P = 0.001), lower N stages (N0, N1) versus higher N stages (N2, N3) (P = 0.001), and the presence versus absence of perineural spread (P = 0.001). The cut-off ADC values to predict higher-grade, higher T stage, nodal spread, and perineural spread were 0.94, 0.92, 0.94, and 0.98 × 10⁻³ mm²/s, with area under the curve of 0.847, 0.858, 0.900, and 0.798 and accuracy of 75.0%, 75.0%, 75.0%, and 77.3%, respectively. The ADC value is a non-invasive imaging parameter that correlates with histopathological parameters of salivary gland cancer.     

Advances in imaging of obstructed salivary glands can improve diagnostic outcomes

Introduction

Obstruction of the major salivary glands is a relatively common condition defined as the blockage of the salivary outflow in the glandular ductal system. It can however mimic more aggressive pathology.

Methods

The most common cause of salivary obstruction is sialolithiasis, followed by ductal strictures. Salivary obstruction is clinically characterized by a food-related painful swelling of the affected gland, known as ‘mealtime syndrome’.

Results

When obstruction is clinically suspected, the role of imaging consists of confirming the obstruction, identifying its cause, evaluating the position and extent of the obstruction and evaluating for associated complications. However, if imaging shows up signs of a tumour or other pathology which can mimic an obstructed gland clinically instead, the radiologist can alert the clinician accordingly to change the course and plan of treatment. Several imaging techniques are available for investigating the obstructed salivary glands.

Conclusions

This review looks at the causes of obstruction and the use, diagnostic performance and practicality of the various imaging modalities. Importantly, an imaging approach algorithm for the evaluation of the obstructed salivary gland is also proposed.     

Immunohistochemical analysis of P53 and bcl-2 in benign and malignant salivary glands tumors

J Oral Pathol Med (2010) 39 : 48–55 Background: Salivary glands tumors are relatively uncommon neoplasm with widely variable histopathologic and biologic characteristics. Alteration in some proto‐oncogenes and tumor suppressor genes may lead to the development and progression of these tumors. Aims: The purpose of this study was to analyze the immunohistochemical expression of P₅₃ and bcl‐2 in some salivary gland tumors in relation to tumor size, histologic grade, and extent of invasion. Setting and design: The sample consisted of 22 formalin‐fixed paraffin embedded blocks of benign and malignant salivary glands tumors. Material and method: P₅₃ and bcl‐2 immunoreactivity was semi‐quantitatively evaluated in at least 1000 cells examined under the microscope at 40× magnification and recorded as percentage of P₅₃ or bcl‐2 positive tumor cells over the total number of cells examined in the same area. Percentage scores were subsequently categorized using the 5% cut‐off point for positive staining. Results and conclusion: Pleomorphic adenoma (PA) showed negative expression of P₅₃ and bcl‐2 in 70% of cases, whereas all malignant salivary glands tumors were positive for P₅₃ and bcl‐2. P₅₃ positive/bcl‐2 positive immunostaining reaction was week in small size PA and was totally absent in larger lesions. However, all malignant tumors expressed P₅₃, with the highest record in low‐grade adenocarcinoma (76%) and the lowest score was observed in both low‐grade carcinoma in PA and adenocystic carcinoma. bcl‐2 immunostaining was also assessed, the highest recorded score was in high‐grade adeno cystic carcinoma (90%) and the lowest in both low‐grade carcinoma ex‐PA and low‐grade cystic mucoepidermoid carcinoma (3%). P₅₃/bcl‐2 immunostaining reactivity could be helpful in demonstrating salivary glands tumor behavior in terms of progression and extent of invasion.     

Underlying protective mechanism of α1-adrenoceptor activation against irradiation-induced damage in rat submandibular gland

Objectives

Damage to salivary gland after radiotherapy for head and neck malignant tumours can lead to irreversible oral complaints, which severely impair quality of life. The protective effect of α₁-adrenoceptor activation on the salivary glands after irradiation has previously been demonstrated. However, the exact mechanism remains unclear. In this study, we investigated the underlying cytoprotective mechanism of α₁-adrenoceptor activation in rat submandibular glands after irradiation.

Study design

Rats were locally irradiated using a linear accelerator in the head and neck region with a dose of 20 Gy. After irradiation, phenylephrine (5 mg/kg) was injected intraperitoneally for 7 successive days and the submandibular glands were then collected. The antiapoptotic effect of phenylephrine on the gland was examined by TUNEL, the proliferative cellular nuclei antigen (PCNA) was determined by immunohistochemistry, and the activation of c-Jun N-terminal kinase (JNK) was detected by Western blot.

Results

The irradiation only group showed severe atrophy, increased apoptosis, enhanced cell proliferation, and the phosphorylation of JNK was markedly increased by 26.89% (P < 0.05), compared to the control. The phenylephrine-treated group, however, showed remarkably alleviated atrophy, decreased apoptosis, and further increased cell proliferation, and the phosphorylation of JNK was markedly decreased by 36.00% (P < 0.05), compared to the irradiation only group.

Conclusions

The data showed that the underlying protective mechanism of α₁-adrenoceptor activation in irradiated gland might be related to improved cell proliferation, inhibited cell apoptosis, and depressed activation of JNK. It could be helpful in protecting salivary glands against irradiation damage.     

Removal of parotid, submandibular, and sublingual glands

Surgical removal of the major salivary glands is a common task for the oral and maxillofacial surgeon. The major salivary glands have complex anatomic relationships with the surrounding neurovascular structures, and a thorough understanding of the surgical anatomy is essential for any surgeon involved in the management of salivary gland disease. This article reviews the indications, surgical anatomy, diagnostic evaluation, and surgical techniques for removal of the major salivary glands.     

Radiological imaging features of the salivary glands in xerostomia induced by an immune checkpoint inhibitor

The clinical features of xerostomia induced by immune checkpoint inhibitors (ICI) are similar to those of Sjögren’s syndrome (SS), whereas the immunohistological and serological features are known to differ from those of SS. However, the radiologic imaging features of salivary glands are not yet well known. We report a case of a 56-year-old male patient diagnosed with ICI-induced xerostomia. The patient underwent various imaging examinations to investigate the condition of the salivary glands, which indicated the following: (1) less specific findings on contrast-enhanced computed tomography, (2) mixed with intermediate and low signal intensity on both T₁-weighted and fat-suppressed T₂-weighted magnetic resonance imaging and poor “salt and pepper” appearance on magnetic resonance sialography, and (3) multiple ovoid hypoechoic areas with hyperechoic bands without acute sialadenitis on ultrasound. These radiologic imaging findings suggested remarkable lymphocyte infiltration, which could be a characteristic of ICI-induced xerostomia.

     

Carbachol-induced in vitro secretion of certain human submandibular proteins investigated by mass-spectrometry

Objective

To investigate protein content of saliva produced in vitro by samples of human submandibular gland following stimulation with the muscarinic agent carbachol.

Design

Tissue samples, obtained at surgery from seven patients and showing normal morphological appearance, were tested for 30 min: in absence of carbachol and atropine; in presence of carbachol (10 μM); in presence of carbachol (10 μM) and atropine (20 μM); or in presence of just atropine (20 μM). Medium was analysed by high-performance liquid chromatography-mass-spectrometry. Neither before nor during surgery were the patients exposed to drug treatments that were likely to influence the in vitro secretion.

Results

Proline-rich proteins (PRP)-1 and -3, peptide PC and PB, statherin, cystatins SN, S1 and S2 were invariably found in control gland tissue medium. Mean concentrations of these proteins/peptides in the medium were non-proportionally elevated following carbachol exposure to the gland tissues. Difference between basal release and carbachol-induced secretion achieved statistical significance as to all the proteins/peptides under study but for statherin. Atropine alone or atropine plus carbachol caused no significant changes compared to the basal release of proteins/peptides.

Conclusions

In vitro studies on salivary glands make it possible to study protein secretion from individual glands and thus, to reveal the contribution of the various types of gland to protein/peptide content of whole saliva. The disproportional responses to carbachol may imply that the proteins/peptides are not confined to the same cells or to the same intracellular locations and are therefore not secreted as packages at parasympathetic cholinergic activity.     

Bilateral parotid glands aplasia: a case report and literature review

Objectives

Bilateral parotid gland aplasia is a rare congenital anomaly that almost consistently leads to xerostomia and caries. It is often associated with other congenital craniofacial abnormalities. The objective was to describe a case with asymptomatic bilateral parotid gland aplasia and to review previously reported cases.

Methods

Panoramic radiograph, computed tomography and magnetic resonance imaging were obtained and an in-depth assessment of patient’s dental status and sequence analysis of FGF10, FGFR2 and FGFR3 genes were performed. Previous reports of bilateral parotid gland aplasia were assessed.

Results

In a 64-year-old woman with extensive basal cell carcinoma of nasal skin an incidental bilateral parotid gland aplasia was noted during radiotherapy treatment planning. Dental status revealed surprisingly numerous (n?=?15) teeth without active caries lesions. No other craniofacial abnormalities were identified. To rule out most probable syndromes associated with parotid gland aplasia, sequence analysis of FGF10, FGFR2 and FGFR3 genes was performed showing no pathogenic variants. With a literature review, we identified 148 cases of salivary gland aplasia in which median age at diagnosis was 21 years and one third were asymptomatic. In only 10 of these cases, the patients presented with bilateral aplasia of parotid glands without other craniofacial abnormalities.

Conclusions

Absence of salivary glands can have a debilitating effect on oral health and is often accompanied by other craniofacial abnormalities. However, relatively frequent asymptomatic course suggests that this rare malformation is probably underdiagnosed. Therefore, we propose systematic reporting of salivary gland aplasia to assess its true prevalence in general population.

     

The biphasic effect of extracellular glucose concentration on carbachol‐induced fluid secretion from mouse submandibular glands

Cholinergic agonists evoke elevations of the cytoplasmic free‐calcium concentration ([Ca²⁺]_i) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh‐induced fluid secretion. The CCh‐induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium–glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1‐mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl^? secretion in real‐time. High extracellular glucose levels may suppress the CCh‐induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca²⁺]_i signals.     

In vitro metabolism of testosterone-4-14C by canine salivary glands

Testosterone-4-¹⁴C (2430 pmol, 0.48 μM) was incubated aerobically in 67 mM phosphate buffer pH 7.4 with homogenates and minces of salivary glands from male dogs. Extracted radiosteroids were resolved by thin-layer chromatography on silica gel, removed and quantitated. Substantially higher NAD⁺-dependent 17 β-hydroxy-C¹⁹-steroid oxidoreductase activity was found in submaxillary gland homogenates than in similar parotid-gland preparations. Preliminary evidence is presented that the enzyme activity per unit wet weight of the minced submaxillary gland is decreased in the 2-week male castrate, in the absence of any recognizable histologic changes in the gland. Testosterone metabolism by canine salivary glands is thus oxidative, contrasting with the reductive 17 β-hydroxysteroid pathway characteristic of androgen-dependent organs such as the prostate, and is more extensive than in this accessory sex tissue. Our findings suggest that the canine salivary glands are not target organs for circulating male hormone.     

In vitro production of sulphated mucosubstances by the labial and palatine glands of the monkey Macaca irus

Radioactively labelled (Na₂³⁵SO₄ and ³H-lysine) secretory products of the minor mucous glands were obtained by in vitro cultivation of glandular tissue. Isoelectric fractionation of the culture media on polytetrafluoroethylene-coated columns indicated that sulphated mucosubstances with virus-haemagglutination inhibition activity focused at pH < 3. Glucuronic acid was not detected in these fractions. A component of pI 4.7, incorporated lysine but not sulphate. In the neutral and alkaline part of the gradient no incorporation of radioactivity was found. The electrofocusing pattern of the secretory products of the labial and palatine glands was less complex than those previously reported from the major salivary glands. It may be concluded that the minor mucous glands, together with the major sublingual gland, are a main source of sulphated mucosubstances in mixed saliva.