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Chronic sclerosing sialadenitis is commonly regarded as a manifestation of IgG4-related disease. We previously found that a high IgG4 expression or IgG4-related disease could accompany nonspecific sialadenitis, whereas chronic sclerosing sialadenitis was not directly associated with IgG4-related disease. Our previous findings lead us to hypothesize that these inflammatory conditions of the submandibular gland signify a continuous progression of disease rather than different disease entities. We, therefore, aimed to determine the presence of IgG4-positivity and genuine IgG4-related disease in a cohort of 165 submandibular gland specimens from patients who underwent surgery due to chronic nonspecific sialadenitis or sialolithiasis. To do so, we re-evaluated histopathological features and divided samples into three groups: (A) nonspecific sialadenitis without known sialolithiasis, (B) sialadenitis with sialolithiasis, and (C) sialolithiasis without sialadenitis. We performed immunohistochemical staining for IgG4, IgG, and CD31, and assessed the Boston consensus statement criteria for IgG4-related disease in IgG4-positive samples. We also reviewed patient records and supplemented follow-up data with a questionnaire among patients with IgG4-positive samples. IgG4-positive plasma cells (range 1-344) were found in 131 samples. Among these, 19 samples were classified as IgG4-positive (>= 70 IgG4-positive plasma cells/high-power field). Two IgG4-positive samples were histologically highly suggestive of IgG4-related disease, but only one had a clinically confirmed diagnosis of IgG4-related disease. Our results indicate that patients with sialadenitis and sialolithiasis often present with IgG4-positive lymphoplasmacytic infiltrates, but exceedingly rarely present with genuine IgG4-related disease. In sialolithiasis without sialadenitis, IgG4-positive plasma cells are often absent or appear in small numbers. These results support our hypothesis of a continuum of disease, and indicate that progressive inflammation of the submandibular gland leads to the development of more specific pathological features over time.

A 77-year-old Lithuanian man presented to our institution with recurrent episodes of periorbital cellulitis, submandibular swelling and sialadenitis. Investigations revealed a positive QuantiFERON, raised inflammatory markers and normal autoimmune screen. Cross-sectional imaging showed no signs of occult malignancy, and work-up for mycobacterial infection including imaging and bronchoalveolar lavage did not show active tuberculosis. During hospitalisation, the patient developed fevers of unknown origin, which were investigated with a positron emission tomography (PET) scan and a bone marrow aspiration, without evidence of occult infection or malignancy. Serum IgG4 level was three times the upper limit of normal. The patient responded well to oral steroids but relapsed after completing a slow taper. Serum IgG4 level was three times the upper limit of normal. He had an American College of Rheumatology/European League Against Rheumatism score of 20, in conjunction with involvement of orbital and salivary tissue. Therefore, IgG4-related disease was considered the most likely diagnosis, despite prominent fevers, which are among the exclusion criteria for this diagnosis. After a multidisciplinary review including rheumatology and ophthalmology, the patient was commenced on maintenance methotrexate with remission of symptoms.

Tuft cells are bottle-shaped, microvilli-projecting chemosensory cells located in the lining of a variety of epithelial tissues and, following their identification approximately 60 years ago, have been linked to immune system function in a variety of epithelia. Until recently, Tuft cells had not been convincingly demonstrated to be present in salivary glands with their detection by transmission electron microscopy only shown in a handful of earlier studies using rat salivary glands, and no follow-up work has been conducted to verify their presence in salivary glands of other species. Here, we demonstrate that Tuft cells are present in the submandibular glands of various species (i.e., mouse, pig and human) using transmission electron microscopy and confocal immunofluorescent analysis for the POU class 2 homeobox 3 (POU2F3), which is considered to be a master regulator of Tuft cell identity.

IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ.

To identify the clinical significance of sparing submandibular glands (SMG) for the amelioration of acute xerostomia using diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT).The prospective study enrolled 42 participants treated with HT. All patients underwent five times of DKI scans before HT (pre-HT), in the middle of the HT course (mid-HT), immediately after HT (post-HT), and 1 months (1m-HT), 3 months post-HT(3m-HT). Mean diffusion (MD) and mean kurtosis (MK) of SMG, parotid glands (PG) and sublingual glands (SLG), saliva flow rate measures under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire scores (XQ) were recorded. Comparisons between the SMG-spared and -unspared groups were analyzed using two-factor repeated-measures ANOVA for the group as the inter-subject factor and the time as the intra-subject factor.When sparing SMG, the dose of spared-SMG and ipsilateral SLG was lower compared to that of unspared glands (p 0.001). MD of spared-SMG and ipsilateral SLG in SMG-spared group were lower than that of SMG-unspared group (the simple effect for the group, p-value at mid-HT, post-HT, 1m- and 3m-HT was 0.014, 0.011, 0.000 and 0.000, respectively), MK of spared-SMG was higher conversely (the main effect for the group, p 0.001), while uSFR and sSFR were significantly lower in SMG-unspared group (the main effect for the group, p = 0.002, and p = 0.045, respectively). No significant differences were detected in MK of SLG, MD/MK of PG, and XQ between the two groups (the main effect for the group, p values were 0.9, 0.37, 0.15, 0.86, respectively). There were significant differences in the effect of the time for all MD/MK of the salivary glands and for uSFR, sSFR, and XQ between the SMG-spared and -unspared groups (p values were all0.001).Sparing SMG is of great clinical significance in alleviating acute xerostomia for NPC patients treated by helical tomotherapy as evaluated by diffusion kurtosis imaging and saliva flow rate.

Different therapeutic methods for chronic drooling in pediatric patients with neurological problems have been described in the scientific literature. However, there is no consensus on the ideal strategy of treatment. The aim of this study was to compare botulinum toxin injection therapy and surgical modalities to control drooling in pediatric patients with neurological disorders. A systematic literature research was conducted on nine electronic databases, which were published until April 2020. Six articles were included in this systematic review. The total sample consisted of 209 patients, 67.4% (n = 141) with cerebral palsy. All studies used injections of botulinum toxin type A with the application to the submandibular and/or parotid salivary glands. The surgical treatments performed were duct ligation in parotid and/or submandibular salivary glands, duct relocation in submandibular salivary glands and glandular excision of the submandibular and sublingual salivary glands. There were complications in only 16.1% (n = 27) of the sample: 11 cases due botulinum toxin application and 16 due to surgery. The drooling control was assessed by objective measures, and subjective measures.Although surgical procedures presented higher risk of adverse effects than the botulinum toxin type A, in all studies and measurements performed, they presented larger and longer-lasting positive effect on drooling than the botulinum toxin type A injection. We suggest performing bilateral submandibular duct relocation with bilateral sublingual gland excision or isolated bilateral submandibular duct ligation, which are the surgical techniques with the largest sample in this review. Nevertheless, further studies are necessary to compare samples with botulinum toxin type A and surgical treatment.

Hypoglossal nerve schwannomas originating extracranially and mimicking a submandibular salivary gland tumour are extremely rare. A 55-year-old woman presented with a painless, gradually increasing swelling in the right submandibular region for the past 1 year. Fine-needle aspiration cytology and contrast-enhanced CT of the swelling showed features of submandibular gland malignant lesion. Intraoperatively, the right submandibular gland with a hypoglossal nerve swelling was noticed. Right submandibular gland along with the hypoglossal swelling were excised with adequate margins. However, the postoperative histopathology was reported as hypoglossal nerve schwannoma and a normal salivary gland. Accurate preoperative diagnosis of hypoglossal schwannomas may be challenging. A high level of suspicion must be sought for in cases with unusual clinical presentations and imaging characteristics. Herein, we report a rare presentation of submandibular hypoglossal schwannoma along with its clinical features and its management.

Adenoid cystic carcinoma of the submandibular gland is a relatively rare malignancy of the oral and maxillofacial region. It is an insidious disease characterized by regional spread, perineural invasion, and potential distant metastases. Because of the aggressive nature of this lesion, it is often impossible to completely excise the tumor, necessitating combination therapy of surgery and radiation. The consequences of surgical ablation coupled with radiation treatment can result in complex considerations in the dental care of these patients. This case report outlines a patient who has recovered from multiple surgeries and radiation therapy, requiring mandibular dental implant reconstruction for a return to normal comfort and function.

The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS).Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer.A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P.01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P.05). The normal SMG concentration index (37.5% vs 96.67%, P.001) and secretion index (35% vs 96.67%, P.001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group.SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients.

As the largest salivary gland in oral cavity, the parotid gland plays an important role in initial digesting and lubricating food. The abnormal secretory function of the parotid gland can lead to dental caries and oral mucosal inflammation. In recent years, single-cell RNA sequencing (scRNA-seq) has been used to explore the heterogeneity and diversity of cells in various organs and tissues. However, the transcription profile of the human parotid gland at single-cell resolution has not been reported yet. In this study, we constructed the cell atlas of human parotid gland using the 10× Genomics platform. Characteristic gene analysis identified the biological functions of serous acinar cell populations in secreting digestive enzymes and antibacterial proteins. We revealed the specificity and similarity of the parotid gland compared to other digestive glands through comparative analyses of other published scRNA-seq data sets. We also identified the cell-specific expression of hub genes for Sjögren syndrome in the human parotid gland by integrating the results of genome-wide association studies and bulk RNA-seq, which highlighted the importance of immune cell dysfunction in parotid Sjögren syndrome pathogenesis.

Objective This study aimed to compare the performance of 3 deep learning models, including a model constructed with the transfer learning method, in detecting submandibular gland sialoliths on panoramic radiographs. Study Design We used data from 2 institutions (A and B) to create the models for use in institution B. In total, 224 panoramic radiographs with sialoliths were used. Model 1 was created using data from institution A only, model 2 was created using combined data from institutions A and B, and model 3 was created using the transfer learning method by having model 1 transferred and trained in various learning epochs using data from institution B. These models were tested and compared in their detection performance using testing data sets from institution B. Results Model 2 and model 3 with 300 epochs performed equally well and yielded the highest detection rates (recall: sensitivity of 85%, precision: positive predictive value of 100%, and F measure of 91.9%) for sialoliths on panoramic radiographs. Conclusion The results of this study suggest that use of the transfer learning method with an appropriate number of epochs may be an alternative to sharing patient personal data among institutions.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition of unknown etiology. Although the salivary glands are currently considered among the most commonly affected among them, oral and maxillofacial surgeons are generally not familiar with the condition. Enlargement of the major salivary glands may be the first identifiable sign of IgG4-RD. A salivary gland biopsy along with IgG4 serum level assessment may help differentiate IgG4-related sialadenitis (IgG4-RS) from malignancies, infectious diseases, and obstructive conditions. Greater knowledge and higher levels of awareness of IgG4-RS may contribute to the expansion of differential diagnostic and treatment approaches. This case report describes a patient with bilateral submandibular salivary gland swelling who was diagnosed as having IgG4-RS on the basis of the histopathologic findings of a submandibular salivary gland biopsy and subsequent IgG4 levels.

Objective Schwannoma is a slowly growing benign neurogenic tumor that develops from the cells of the nerve sheath. The occurrence of schwannoma in the submandibular space is very rare. Materials and Methods From January 2010 to March 2021, we reviewed all patients who had been operated on in the otolaryngology department over 11 years and found 61 patients diagnosed with schwannomas at the final biopsy after surgery. In these patients, only 3 submandibular schwannomas were identified, and their clinical characteristics were analyzed. Results Three schwannomas (4.9%) developed in the submandibular space. The main symptoms were neck swelling followed by neck discomfort. All submandibular schwannomas were removed surgically with a transcervical approach under general anesthesia. Two patients, who were diagnosed preoperative submandibular tumors, were considered to have developed schwannomas from the lingual nerve, and 1 patient was considered to have developed a schwannoma from the hypoglossal nerve. There were no major surgical complications, including postoperative nerve damage. Conclusions Submandibular schwannomas are extremely rare, but they should be included in the differential diagnosis of submandibular tumors.

Submandibular gland excision (SMGE) is suitable for the management of drooling in patients with non-progressive neurodisabilities. We aimed to investigate the long-term effects of SMGE.Patients who had SMGE between 2007 and 2018 were included. Main outcomes were a Visual Analogue Scale (VAS), Drooling Severity (DS), and Drooling Frequency (DF) collected at baseline, 8 weeks, 32 weeks and with a median of 313 weeks after SMGE (long-term). Secondary outcomes were satisfaction with the procedure, Drooling Quotient (DQ) and adverse events (AEs).We included thirty-five patients in the long-term analysis with a mean age of 14.5 years. A baseline VAS score of 80.4 was found, which improved on the long-term (mean difference -21.8, t(26) = 4.636, p 0.0005)). DS and DF decreased significantly at the long-term compared to baseline (Z = -4.361, p 0.0001 for DS, Z = -3.065, p = 0.002 for DF). Twenty-three out of 35 (66%) patients would recommend the procedure to peers.This study indicates a long-term stable effect on drooling after SMGE in patients with anterior drooling. Recurrence of drooling occurs due to unknown reasons, nevertheless most caregivers and/or patients are still satisfied and would recommend the procedure to others.

In this case series with retrospective review we compared the outcomes of patients with sialorrhoea who had a submandibular excision (SE) alone and those who had submandibular excision with parotid duct ligation (SE + PL) between 2012 and 2018. Primary endpoints of complication rates and caregivers' perceptions of success were collected. A total of 41 submandibular excisions were performed for sialorrhoea (26 patients underwent SE, while 15 underwent SE + PL). Significant differences in the groups existed at baseline with patients in the SE plus PL group being more likely to have a tracheostomy (p = 0.015), to use sublingual atropine (p = 0.038) and respiratory medications (albuterol p = 0.0075, gentamicin p = 0.018), to have more pneumonias six months prior to the procedure (p < 0.001), and more hospitalisations six months prior to the procedure (p = 0.046). More postoperative surgical site complications were associated with ligation (p = 0.012). There was no difference in systemic infection (p = 0.25), and no difference in caregivers' perceptions of success in reducing sialorrhoea (18/24 SE compared with 10/14 SE + PL, p = 1.00). There were more surgical site complications in those undergoing SE plus PL than in those who had SE alone. Given this data, parotid duct ligation may not yield additional benefit when combined with submandibular excision.

Background IgG4-related disease (IgG4-RD) includes a group of immune-mediated diseases histologically characterized by lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children. Here we report the case of IgG4-related sialadenitis in a six-year-old patient previously diagnosed as juvenile recurrent parotitis. Case presentation A six-year-old patient was referred to our Centre for left parotid swelling of 4 × 3 cm, that was tender, soft in consistency, with overlying red and warm skin. His general condition was good but he was subfebrile; general examination revealed mild enlargement of left cervical lymph nodes. In the last 2 years he had had five episodes of parotitis, diagnosed by another pediatric Center as juvenile recurrent parotitis. On ultrasound examination the left parotid gland appeared enlarged, inhomogeneous, with a colliquative intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests showed an increase of white blood cells and anti-VCA IgM and IgG positivity, with anti-EBNA e anti-EA I negativity. The patient was initially treated with oral antibiotics, but after 10 days the parotid became fluctuating, requiring surgical biopsy and drainage. Postoperative course was regular, with complete remission under oral antibiotic and steroid therapy. Microbiological tests, including cultures for aerobic and anaerobic bacteria, mycobacteria and Bartonella, were negative. Surprisingly, histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltrate with polyclonal plasma cells mostly expressing IgG4 immunoglobulins. Thus, the diagnosis of IgG4 related chronic sialadenitis in recurrent parotitis and recent EBV infection was made. Conclusions IgG4-related sialadenitis is very unusual in children. Histology plays a key role in diagnosis, considering that up to 30% of patients have normal serum IgG4 levels, as shown in our case. The lack of previous histological data makes it impossible to attribute our patient’s previous episodes of parotitis to IgG4-RD, though it is a very consistent possibility.

The COVID-19 mainly affects the respiratory system; however, a variety of atypical manifestations of this disease have been also reported. Herein, we report a case of a man in his late 50s with severe COVID-19 presenting with parotitis and sublingual gland sialadenitis. Six days after admission, swelling in the bilateral preauricular and lower jaw areas developed. CT demonstrated parotid and sublingual gland enlargement with surrounding fat stranding, indicating sialadenitis. This case suggests that, in the present COVID-19 pandemic, COVID-19 should be included in the differential diagnosis of sialadenitis and prompt isolation should be considered to reduce the spread of infection.

Background Secretory carcinoma of salivary glands (SCSGs) are generally low-grade salivary gland carcinomas, and are characterized by morphological resemblance to mammary analogue secretory carcinoma and ETV6–NTRK3 gene fusion. Several reports on histopathological features of SCSG have recently been published; however, little is known about the clinical characteristics of this new tumor, including its outcomes. The research is to investigate the clinicopathological characteristics of secretory carcinoma of major salivary glands and to analyze outcomes of these carcinomas as a reference for standardizing their diagnosis and treatment. Methods The cohort of this retrospective study comprised 23 patients treated for histopathologically-confirmed SCSG between January 2010 and December 2020. Their clinical characteristics and outcomes were retrieved from patient files. Results The 23 patients comprised 13 male and 10 female patients (male:female ratio 1.3:1). They were aged 10–69 years (median 45 years) and the average duration of disease was 2.44 years (0.25–20 years). Twenty-one patients (91.3%) had SCSGs in the parotid gland and two (8.7%) in the submandibular gland. All 23 patients had single nodules with diameters of 0.8–4.8 cm (average 2.6 cm). Five patients had lymph node metastases and two had distant metastases. All tumors were pathologically diagnosed as SCSGs. Immunohistochemical staining was strongly positive for S-100, mammaglobin, CK7, and Gata3, and negative for Dog1, P63 and calponin. Ki-67 positivity ranged from 1–50%. Fluorescence in situ hybridization data were available for 15 patients, in all of whom ETV6 gene rearrangement was confirmed. All patients had undergone oncological resections. Four had radioactive particles implanted postoperatively, one received chemotherapy, and seven underwent chemoradiotherapy. Six patients had regional recurrences, two distant metastases, and one had died at the time of last follow-up. Conclusions SCSGs are typically indolent with a low rate of locoregional recurrence and excellent survival. Their prognosis is correlated with clinical stage, pathological grade, and surgical procedures performed.

Conventional surgery for submandibular gland tumour is total excision of the gland affected by the tumour. Gland-preserving surgery is commonly used for benign tumours arising in the parotid gland but not in the submandibular gland. This study evaluated long-term oncological and functional outcomes after gland-preserving surgery in patients with pleomorphic adenoma of the submandibular gland via the submental approach. This longitudinal study included 105 consecutive patients with submandibular gland pleomorphic adenoma who underwent the gland-preserving surgery combined with the en-bloc resection of tumours via the submental approach. Salivary scintigraphy was performed 6 months after surgery, and ultrasonography was regularly followed. Intraoperative findings, postoperative complications, cosmetic and salivary functions, and tumour recurrence were assessed in these patients. Median tumour size and submental incision length were 2.0 and 3.3 cm, respectively. Median operation time and amount of blood loss were 25 min and 18.5 mL, respectively. None had marginal or lingual nerve paralysis and most patients were satisfied with incision scar and facial contour. The salivary function of the affected gland was equal to that of the unaffected gland. One patient (0.9%) had single nodular recurrence 54 months after surgery and others had no recurrence for follow-up of median 96 months. Pleomorphic adenoma of the submandibular gland can be safely removed by the gland-preserving surgery via the submental approach which has operation time, cosmetic and functional benefits with compromising oncological outcomes.

Objective To report initial experience in using a pneumatic lithotripter to treat salivary stones. Study Design Level IV retrospective study. Setting University hospital and tertiary referral center. Methods A pneumatic lithotripter was used to treat salivary stones after these were diagnosed. Probes with diameters of 0.7 mm were used. Total fragmentation was intended in all stones. Stone fragments were removed using several instruments in serial sialendoscopies to achieve complete stone clearance. Results A total of 62 patients with 77 stones were treated. Forty-three submandibular stones were treated in 34 patients, and 34 parotid stones were treated in 28 patients. An operating pressure of 2.5 bar and a single frequency mode were used. Complete fragmentation was achieved in all but one of the treated stones in both glands (98.7%). Among the patients, 90.32% became stone free and 100% symptom free. Multiple stones were treated in 24.19% of the patients, and multimodal therapy was also carried out in 24.19%. All of the glands were preserved. Conclusions The pneumatic lithotripter proved to be effective in the treatment of sialolithiasis. Stone size, location, and the gland involved were important clinical factors. The device was sufficient to achieve success without any increased risk for complications in the patients or damage to the sialendoscopes.

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.

A previously healthy 30-year-old man presented to the emergency department with a 3-day history of worsening right-sided swelling of floor of mouth with odynophagia. According to him, this was his first episode. There was no prior trauma, fever, toothache, foreign body ingestion or dental extraction. No associated neck swelling, shortness of breath or constitutional symptoms were found. On examination, patient was not septic looking, floor of mouth was raised on right side, erythematous with non-discharging punctum (figure 1). Bimanual palpation revealed hard …

The present study compares the plasma and salivary Metrnl levels of patients newly diagnosed with type-2 diabetes who were treated with metformin for three months with those of a healthy volunteer group and immunohistochemically analyzes Metrnl in salivary glands.30 healthy volunteers and 30 newly diagnosed type-2 diabetes patients were included in the study. The newly diagnosed diabetes patients were treated with metformin for three months, and the plasma and salivary metformin levels of both groups were measured at baseline and after the three months of metformin treatment in the patient group. Plasma HbA1c, low-density lipoprotein (LDL-C) and Triglyceride (TG) values of all groups were also measured at baseline following three months of metformin treatment. Biopsies were taken from the parotid and submandibular glands and immunohistochemical staining was performed to show Metrnl immunoreactivity.Plasma Metrnl, HbA1c, LDL-C and TG levels were higher in the newly diagnosed diabetes group than in the other group, and salivary Metrnl levels were higher than in the control group after three months of metrformin treatment. An examination of the immunohistochemical staining of salivary gland biopsies under light microscope revealed Metrnl immunoreactivity in the intralobular and interlobular ducts of the parotid gland, while Metrnl immunoreactivity was observed in the acinar cells in the intralobular striated duct and interlobular ducts in the submandibular gland.Plasma Metrnl, HbA1c, LDL-C and TG levels were higher in the newly diagnosed diabetes group than in the other group. Metrnl immunoreactivity was detected in the parotid and submandibular glands. The relationship between Metrnl and DM should be investigated in larger groups.

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

A 67-year-old woman complained of continuous low back pain for 4 months. She was referred for a 99mTc-MIBI parathyroid scintigraphy with neck SPECT/CT imaging. The planar images showed no abnormal uptake. However, on the SPECT/CT scan, a soft tissue nodule with high uptake was noted adjacent to the left submandibular gland, mimicking normal submandibular gland uptake. Pathological examination from surgical specimen showed that it was an ectopic parathyroid adenoma.

Resveratrol (Res), found abundant in many medicinal plants, exerts multiple biological functions in the body, including anti-inflammatory, antioxidant, and anti-aging properties. Xerostomia is a major symptom of salivary gland dysfunction in menopausal women, which significantly compromises the quality of life. Here, we investigated the effect of Res on estrogen deficiency-induced salivary gland dysfunction in rats. We found that Res administration could reduce body weight and water consumption, and increase salivary fluid secretion and blood flow of the submandibular gland. Furthermore, Res therapy alleviated histological lesions, increased AQP5 expression, and inhibited cell apoptosis in submandibular gland tissue. Meanwhile, the action of antioxidants was restored and the levels of inflammatory cytokines were attenuated by Res supplementation. Collectively, Res effectively improved estrogen deficiency-induced hyposalivation, which may provide a novel, safe, and practical approach to protect the salivary glands of estrogen-deficient females against xerostomia.

Background A sialendoscopy-assisted combined approach is well established in the surgery of sialolithiasis. In cases of proximal salivary stones, transcutaneous sialendoscopy-assisted extractions with parotid and submandibular gland preservation is the primary intention of treatment. We recently added computer tomography (CT) navigation to improve the results of this challenging surgery equally in both localizations. Patients and methods Al l the patients who submitted to sialendoscopy and sialendoscopy-assisted procedures at the tertiary institution between January 2012 and October 2020 were included in the present study. From November 2019, CT navigation was added in cases with sialolithiasis and a presumably poor sialendoscopic visibility. We evaluated the parameters of the disease, diagnostic procedures, sialendoscopic findings and outcomes, with or without optical surgical navigation. Results We performed 178 successful salivary stone removals in 372 patients, of which 118 were combined sialendos-copy-assisted approaches, including 16 transcutaneous proximal, 10 submandibular and 6 parotid stone operations. Surgical navigation was used in six patients, four times for submandibular and twice for parotid sialolithiasis. These were all non-palpable, sialendoscopically invisible or partially visible stones, and we managed to preserve five of the six salivary glands. Conclusions The addition of CT navigation to sialendoscopy-assisted procedures for non-palpable, sialendoscopically invisible and fixed stones is a significant advantage in managing sialolithiasis. By consistently performing sialendoscopy and related preservation procedures, we significantly reduced the need for sialoadenectomies in patients with obstructive salivary gland disease.

The aims of this pilot investigation were to calculate the levels of sensitivity and specificity of salivary glands ultrasonography (SGUS) in diagnosing Sjögren syndrome (SS) and to assess the ultrasonographic findings of parotid and submandibular glands.Patients diagnosed with SS or dry mouth and healthy controls were enrolled. Bilateral parotid and submandibular glands were assessed for (1) parenchymal inhomogeneity (PIH), (2) median size of the glands, (3) visibility of glandular posterior borders, and (4) size of sialolith, if present.This study included 34 female patients, of whom 12 had SS (35.3%), 12 had dry mouth (35.3%), and 10 were healthy controls (29.4%). Patients with SS showed higher PIH scores in all glands with the median differences being statistically higher in the right and left parotids and left submandibular glands (P.001, P = .012, and P.001, respectively). SGUS, with a PIH cutoff ≥2, showed a sensitivity of 100% and a specificity of 81.6% for detecting SS. The majority of SS had invisible glandular posterior borders (P.001). Median size of the glands and size of the sialolith did not show any statistically significant differences between groups.SGUS is a noninvasive imaging modality with good sensitivity and specificity that might be valuable as a diagnostic aid for SS.

Although there have been several reports of the diagnostic accuracy of frozen section biopsy (FSB) for parotid gland tumors, few studies have focused on its diagnostic accuracy for submandibular gland tumors.This study aimed to investigate the necessity of FSB with regard to its diagnostic accuracy for submandibular gland tumors (SGTs).About 42 SGT patients underwent both fine-needle aspiration cytology (FNAC) and FSB between 2005 and 2020. The results of FNAC and FSB were analyzed and compared with the final histological diagnoses.The respective sensitivity and specificity in detecting malignant tumors in 38 cases, excluding the four indeterminate FNAC cases, they were 0 and 97% for FNAC, and 100 and 97% for FSB. Considering the four indeterminate FNAC cases to be malignant, the respective sensitivity and specificity in detecting malignant tumors in the 42 cases were 50 and 92% for FNAC, and 100 and 95% for FSB.FSB may be useful for malignancy detection as a final histological diagnosis in cases that are diagnosed as benign or indeterminate by FNAC in SGTs.

The present case study reports contrast-enhanced magnetic resonance findings in three patients with histopathologically proven IgG4-related chronic sclerosing sialadenitis of the submandibular gland. All three patients presented with painless swelling of the submandibular region. The contrast-enhanced T1-weighted images showed reticular enhancement of the swollen submandibular gland. Radiological–pathological correlation revealed that the characteristic reticular enhancement corresponded to fibrosis and to inflammatory cell infiltration in the interlobular septa and in the periductal region of the submandibular gland.

Introduction This study examined whether time-activity curves (TAC) can be used to differentiate between patients with and without Sjogren's syndrome using SPECT/CT. Methods Thirteen xerostomia patients (5 with Sjogren's syndrome and 8 without Sjogren's syndrome) underwent SPECT/CT. Salivary gland secretion data were digitally observed, producing separate time-activity curves (TAC) for the submandibular glands and parotid glands using SPECT/CT. The salivary gland secretion fraction was defined as A (before stimulation test [counts/frame]) divided by B (after stimulation test [counts/frame]). The A/B ratios of patients with Sjogren's syndrome and those without Sjogren's syndrome were compared using the Mann-Whitney U test for nonparametric data. Results The A/B ratio of parotid glands with Sjogren's syndrome (1.3 ± 0.2) was significantly lower than for those without Sjogren's syndrome (2.7 ± 0.7). The A/B ratio of submandibular glands with Sjogren's syndrome (1.3 ± 0.4) is significantly lower than for those without Sjogren's syndrome (1.8 ± 0.6). Conclusion The TAC for the submandibular glands and parotid glands using SPECT/CT may be useful for the objective and quantitative diagnosis of Sjogren's syndrome.

INTRODUCTION Children who require submandibular gland excision for ptyalism often have multiple associated comorbidities, including neurodevelopmental disorders and respiratory risk factors. The purpose of this study is to utilize a large multicenter database to elucidate the perioperative profile of submandibular gland excision in children, with particular focus on children who require submandibular gland excision for ptyalism. METHODS The American College of Surgeons National Surgical Quality Improvement Program Pediatric dataset was queried for submandibular gland excision performed from 2012 through 2018. Indications were subclassified based on International Classification of Disease (ICD)-9 and ICD-10 codes. Complications, readmissions, and reoperations were analyzed with appropriate statistics. RESULTS During the study interval, 304 pediatric patients underwent submandibular gland excision, which was mostly performed for ptyalism (56.9%), followed by inflammatory conditions (20.7%). Patients requiring submandibular gland excision for ptyalism were significantly younger (P

Objective The purpose of this study was to quantitatively assess normal submandibular glands and submandibular sialadenitis (SS) using computed tomography (CT) texture analysis as part of radiomics quantitative analysis. Study Design In total, 31 patients with unilateral SS who underwent head and neck magnetic resonance imaging (MRI) and CT and were retrospectively reviewed. Submandibular glands with abnormal signals (STIR: high, T2-weighted image: high, T1-weighted image: low) on MRI were identified as SS. The radiomics features of the contralateral normal submandibular glands and SS were analyzed using an open-access software, MaZda Version 3.3. Sixteen radiomics features were selected with Fisher and probability of error and average correlation coefficient methods in MaZda from 279 original parameters calculated for each of the normal and SS glands. The results were statistically analyzed with the Wilcoxon rank sum test. Results One gray-level co-occurrence matrix feature and 9 gray-level run length matrix features displayed significant differences between normal submandibular glands and glands with SS (P Conclusions CT texture analysis was able to quantitatively distinguish between normal and diseased submandibular glands. It therefore may have the potential to detect SS.

Mucoepidermoid carcinoma (MEC) is generally characterized by an admixture of mucous, epidermoid and intermediate type cells. Numerous variants morphologies are described and defined by stromal and/or cytoplasmic tinctorial characteristics. We now report 11 cases of MEC with serous acinar differentiation, reflecting a distal intercalated duct/acinar phenotype, which we designate as mucoacinar carcinomas. Seven patients were female while 4 were male with a mean age of 55 years (range: 21 to 72 y). Ten cases were from the parotid while 1 was from the submandibular gland. Mean size of the tumors was 1.8 cm (range: 0.7 to 4.5 cm). Three cases were low grade, 7 were intermediate grade, and 1 was high grade. Low to intermediate grade cases demonstrated prominent clear to vacuolated cells with focal serous acinar differentiation. The high-grade case showed a distinctive scattering of acinar cells interspersed between epidermoid cells. Periodic acid Schiff after diastase (9/9), SOX-10 (9/9), and DOG-1 (9/10) highlighted the acinar component. Six of 7 cases showed a focal acinar predominant NR4A3 expression. MAML2 fluorescence in situ hybridization was positive in all cases, in both acinar and mucoepidermoid components. Two cases tested by next generation sequencing showed standard CRTC1-MAML2 fusions. MSANTD3 and NR4A3 fluorescence in situ hybridization on the other hand were negative. Evidence thus suggests that mucoacinar carcinoma represents an acinar variant morphology in MEC, rather than a true MEC-acinic cell carcinoma hybrid, or collision tumor. The acinar differentiation, SOX-10, DOG-1, and even focal NR4A3 reactivity may thus be diagnostic pitfalls.

Objective To evaluate the safety and utility of core needle biopsy (CNB) for diagnosis of salivary gland lymphoma in Sjogren's syndrome (SS). Methods We analyzed data from consecutive SS patients who underwent ultrasound-guided major salivary gland CNB for lymphoma diagnosis and determined whether CNB yielded an actionable diagnosis without need for further intervention. Results CNB were performed in 24 patients to evaluate discrete parotid (n=6) or submandibular (n=2) gland masses or diffuse enlargement (n=16; 15 parotid). One patient had 3 CNB of the same mass. Of the 26 CNB, 24 included flow cytometry using CNB and/or fine needle aspirate material and 14 targeted sonographically-identified focal lesions. No patient reported complications. In the 23 patients with one CNB, final diagnoses were marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT; n=6), atypical lymphoid infiltration (n=3), benign lymphoepithelial sialadenitis (BLEL, n=9), normal gland tissue (n=4), and lymphoepithelial cyst (n=1). In the patient with serial CNB, the initial one without flow cytometry was benign but the next two showed atypical lymphoid infiltration. Monoclonal lymphoid infiltration was detected in 12 patients: six with MALT lymphoma, three benign and three atypical lymphoid infiltration. Of the latter three, one was treated with rituximab and two with expectant observation. The diagnosis changed from atypical lymphoid infiltration to MALT lymphoma in one patient following biopsy of inguinal adenopathy 6 months post-CNB. CNB provided actionable results and avoided open excisional biopsies in all cases. Conclusion CNB is safe and useful in the evaluation of suspected salivary gland lymphoma in SS.

Carcinoma adenoide cistico. Un tumore indolente ma aggressivo. Parte A: dalla eziopatogenesi alla diagnosi.Il carcinoma adenoide cistico (ACC) è un tumore relativamente raro ad origine dalle ghiandole salivari minori e maggiori. È poco frequente nella parotide mentre lo è molto di più nella ghiandola sottomandibolare, nelle ghiandole salivari minori e in quelle mucinose del cavo orale, orofaringe e seni paranasali. Esso può anche insorgere nelle ghiandole secretrici localizzate in altri tessuti come l’albero tracheo-bronchiale, l’esofago, la mammella, il polmone, la prostata, la cervice uterina, la cute, le ghiandole lacrimali e quelle del Bartolini. La sua storia naturale è caratterizzata da una lenta crescita, da rare metastasi linfonodali e da frequenti metastasi a distanza. Dal punto di vista istologico esso è stato tradizionalmente suddiviso in tre forme (cribriforme, tubulare e solido). Alcuni studi hanno dimostrato che i tumori con una prevalente componente solida hanno una prognosi peggiore rispetto a quelli con prevalente componente cribriforme o tubulare ma altri studi hanno contestato questa affermazione. Il proposito di questa review è quello di analizzare il grande numero di pubblicazioni (talvolta contraddittorie) sul carcinoma adenoide cistico. In questa prima parte saranno discusse l’eziologia, l’epidemiologia, l’istopatologia, la presentazione clinica e l’iter diagnostico.Adenoid cystic carcinoma (ACC) is a relatively rare tumour of the minor and major salivary glands. It is uncommon in the parotid gland while it is much more frequent in the submandibular gland and in minor salivary and mucinous glands (oral cavity, oropharynx, and paranasal sinuses). ACC may also arise in secretory glands located in other tissues, such as in the tracheobronchial tree, oesophagus, breast, lungs, prostate, uterine cervix, lachrymal and Bartholin’s glands, and skin. The natural history of ACC is characterised by an indolent growth rate, a relatively low probability of regional lymph node metastases and a high likelihood of haematogenous dissemination. ACC has been traditionally subdivided into three histological groups (cribriform, tubular, and solid) based on solid components of the tumour. Some studies have shown that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component, but other studies have failed to correlate growth patterns with clinical course. The purpose of this review is to analyse the very large number of studies (sometimes contradictory) on ACC. In this first part, the aetiology, epidemiology, histopathology, clinical behaviour and diagnostic workup are examined.

Bilateral sagittal split osteotomy is a routine procedure with predictable and well-known complications. The authors report a thitherto unreported complication of bilateral sagittal split osteotomy presenting as a postoperative sialocele of submandibular salivary gland tissue in the floor of the mouth. The sialocele was probably caused by overinstrumentation and injury to sublingual salivary tissues or Wharton's duct during bicortical drilling or screw fixation. This iatrogenic sialocele was managed conservatively with multiple aspiration and compression dressings. Although rare and unreported so far this complication may be included in the preoperative consent process.

Sialoendoscopic, orthodontic, and surgical interventions within the floor of the mouth require precise knowledge of the topography of the Wharton's duct orifices which is still lacking for the pediatric population. We aimed to establish a normative database for the topography of these orifices in children.The prospective cross-sectional analytic study was performed during January to December 2021. The distances between the mandible gonions and each orifice and the lingual frenulum were defined as primary outcome variables. The secondary outcome variables were the inter-position of the orifices and their location against the base of the tongue and the mandibular alveolar ridge. The segments of the cohort were classified by sex and age groups (4 to 7, 8 to 14, 15 to 17 years old) as the primary predictor variables. The data were evaluated by a 3-way ANOVA for analysis of selected distances with the level of significance at P ≤ .05. The correlation analysis between sex and locations of the orifices was performed using χThe study involved 3,000 healthy children from 4 to 17 years of age. The orifices were symmetrical (89.3%), frenulum-independent (78.0%) openings that were usually located in the middle part of the floor of the mouth. The distance between the orifices varied from 0 mm in the frenulum-attached cases to 4.6 ± 1.8 mm for 4 to 7 years old, 7.6 ± 1.9 mm for 8 to 14 years old, and 9.1 ± 2.6 mm for 15 to 17 years old individuals. The orifices were attached to the frenulum (5.7%), were frenulum-related (16.3%), and frenulum-independent (78.0%). The sagittal asymmetry of the orifices was noted in 10.7%, and in 1.6% the lateral asymmetry was detected. No statistically significant sex-related differences were noted.In the pediatric population, the Wharton's duct orifices are usually symmetrical frenulum-independent openings that are located in the middle part of the floor of the mouth. The distance between the orifices normatively varies according to sex and age. The size of the mandible does not influence the positions of the orifices. The position of the duct orifices must be established prior to submandibular sialoendoscopy, orthodontic interventions, frenotomy, and other oral surgeries.

Radiation damage to salivary gland is inevitable in head and neck cancer patients receiving radiotherapy. Safe and effective treatments for protecting salivary glands from radiation are still unavailable. Mitochondrial damage is a critical mechanism in irradiated salivary gland; however, treatment targeting mitochondria has not received much attention. Nicotinamide is a key component of the mitochondrial metabolism. Here, we investigated the effects and underlying mechanisms of nicotinamide on protecting irradiated submandibular gland.Submandibular gland cells and tissues were randomly divided into four groups: control, nicotinamide alone, radiation alone, and radiation with nicotinamide pretreatment. Cell viability was detected by PrestoBlue cell viability reagent. Histopathological alterations were observed with HE staining. Pilocarpine-stimulated saliva was measured from Wharton's duct. Cell apoptosis was determined by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Nicotinamide phosphoribosyl transferase was examined with immunofluorescence. The levels of nicotinamide adenine dinucleotide, mitochondrial membrane potential, and adenosine triphosphate were measured with the relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy.Nicotinamide significantly mitigated radiation damage both in vitro and in vivo. Also, nicotinamide improved saliva secretion and reduced radiation-induced apoptosis in irradiated submandibular glands. Moreover, nicotinamide improved nicotinamide phosphoribosyl transferase and the levels of nicotinamide adenine dinucleotide/adenosine triphosphate and mitochondrial membrane potential, all of which were decreased by radiation in submandibular gland cells. Importantly, nicotinamide protected the mitochondrial ultrastructure from radiation.These findings demonstrate that nicotinamide alleviates radiation damage in submandibular gland by replenishing nicotinamide adenine dinucleotide and maintaining mitochondrial function and ultrastructure, suggesting that nicotinamide could be used as a prospective radioprotectant for preventing radiation sialadenitis.

Background Debate surrounding the morphological evolution of the submandibular gland (SMG) with aging, and the uncertain influence of patient demographics, has led to hesitancy about incorporating targeted interventions of the SMG into clinical practice. Objectives The aim of this study was to determine whether SMG ptosis, hypertrophy, or both is the primary etiology behind the increase in submandibular volume with age. Methods MRI segmentation was used to calculate the total and inframandibular (IM) volume and height of the SMG. Adult subjects with previous MRIs of the head and neck were used for analysis. Those with pathology or artifact compromising the SMG were excluded. Subjects were divided into 4 age-defined cohorts, for clinical applicability. Results The study included 129 patients (65 females; 64 males) with a mean age of 52.3 years (range, 20-85 years). No significant change in total SMG volume was observed between the reference group and all cohorts. The IM-SMG volume of the reference cohort was 5.77 cm3. All 3 cohorts had a greater IM-SMG volume than the reference group. The 45- to 54-year cohort had a mean volume of 6.7 cm3 (P = 0.4), the 55- to 64-year cohort, 7.5 cm3 (P = 0.01), and the ≥65-year cohort, 7.2 cm3 (P = 0.01). Male sex and overweight or obese BMI were associated with significantly larger total and IM-SMG volumes. Conclusions The novel finding of a significantly larger IM-SMG volume with no change in total volume provides evidence for SMG ptosis rather than hypertrophy as a significant contributor to age-related submandibular fullness. The lack of any significant difference in total volume or height with aging emphasizes the role of glandular descent.