Incurable advanced salivary gland tumours: a retrospective analysis and peek into the perplexing clinical and molecular intricacies from a tertiary care centre in India.

Background: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.

Palatal Swellings: A Proposed Classification and a Case Report of Pleomorphic Adenoma of Minor Salivary Gland of the Palate.

Palatal swellings are a commonly encountered diagnostic entity. They can be infectious, neoplastic, odontogenic, vascular, congenital or secondary manifestation of a systemic disease. While individual palatal lesions are well documented in the literature, there is lack of a comprehensive classification of such entities. Proper classification helps in prompt and accurate diagnosis, facilitating proper management. This article proposes a comprehensive classification of palatal swellings based on their location, clinical findings and aetiology, and describes a case report of pleomorphic adenoma of the minor salivary gland of the palate.

Adenoid Cystic Carcinoma of the Oral Cavity- A Case Report Comparing the Differences and Similarities Between a Child and an Adult Patient.

Adenoid cystic carcinoma is a malignant neoplasm primarily of the salivary gland, which can also involve lacrimal glands and other exocrine glands. Adenoid cystic carcinoma rarely presents in the buccal mucosa and young children, and among the major salivary glands, it rarely occurs in the sublingual gland. We are presenting two cases of Grade 1- adenoid cystic carcinoma. One in the buccal mucosa of an eight-year-old boy and another in the sublingual gland of a 50-year-old female patient. The site and age of occurrence can make a huge difference in diagnosis and treatment planning due to the unpredictability of the lesion. Proper diagnosis, treatment planning, and appropriate treatment help improve the lesion's prognosis. Even though such lesions rarely occur, awareness among the Oral and maxillofacial fraternity is very important in providing proper patient care.

Survival in Patients with Primary Parotid Gland Carcinoma after Surgery-Results of a Single-Centre Study.

This study aims to analyse a single-centre cohort series of patients who underwent parotidectomy for primary malignant parotid tumours. A retrospective chart review of 64 consecutive patients treated from November 2010 to March 2022 was performed. Outcomes were analysed by Kaplan-Meier curves. Sixty-four patients with a primary parotid malignancy were included in the study, with one bilateral case in this cohort. Patients were classified as stage I-II in 39 cases and stage III-IV in 26 cases. The five-year overall survival (OS), disease-specific survival (DSS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 78.4%, 89%, 92.5%, and 87.1%, respectively. Univariate analysis showed that high-risk histology, stage IV disease, lymphovascular invasion, perineural invasion, node metastasis, skin involvement, facial nerve involvement, and positive or close margins were risk factors associated with poorer outcomes. At present, the best evidence suggests that radical surgery should be the standard approach, and adjuvant therapy, in terms of radiotherapy/chemoradiotherapy, is recommended in patients with risk factors.

Outpatient parotidectomy with or without the use of a post-operative drain: A retrospective bi-institutional study.

OBJECTIVE: Parotid surgery is historically performed as an inpatient procedure and suctions drains are predominantly used during surgery. Recent literature provides evidence that outpatient parotid surgery is safe and effective. Our study aims to describe the results of drainless outpatient parotidectomy and outpatient parotidectomy with drain placement and compare their outcomes. DESIGN: Retrospective cohort study. SETTING: Bi-institutional retrospective cohort study. PARTICIPANTS: Patients that underwent outpatient drain-less parotidectomy and patients that underwent outpatient parotidectomy with post-operative drain placement. MAIN OUTCOME MEASURES: Complication rates, unplanned post-operative visits, unplanned prolonged stay. RESULTS: Three hundred eighty patients underwent outpatient parotidectomy with drain placement and 31 patients underwent outpatient drainless parotidectomy in two different hospitals. The incidence of haematoma (drain: 3.1% vs. drainless: 0%, p = 1), infection (drain: 14.3% vs. drainless: 13.8%, p = 1) and salivary fistula (drain: 5.6% vs. drainless: 3.4, p = 1) were comparable between both groups. Seroma or sialocele was more frequently seen in the drain-less group (27.6% vs. 6.2%, p < .001), but were all managed conservatively. Within 10 days after surgery, unplanned visits seemed more frequent in the drain group, although the difference was not statistically significant (14.9% vs. 3.4%, p = .16). CONCLUSIONS: Outpatient parotid surgery with or without the use of a post-operative drain is safe, practical and feasible. Same-day discharge with and without drain placement yield comparable outcomes. However, the results need to be interpreted cautiously as this study was limited by a small cohort of parotidectomies without drain placement. Future studies should further compare both approaches.

A Rare Case of a Nasopharyngeal Pleomorphic Adenoma Mimicking a Nasopharyngeal Carcinoma.

Pleomorphic adenoma is the most common benign pathology of the major salivary gland but rare in the minor salivary gland, especially in the nasopharynx, with only a few cases reported in the literature. A 76-year-old lady presented with bilateral nasal blockage for one year secondary to a nasopharyngeal mass. Histopathological examination reported it to be nasopharyngeal carcinoma, but the mass persisted after a course of chemotherapy combined with radiotherapy. Upon repeat biopsy, the mass was found to be a pleomorphic adenoma. The patient underwent nasopharyngectomy without complications and no evidence of recurrence after 18 months of follow-up.

Acinic cell carcinoma of the parotid gland: Timeo Danaos et dona ferentes? A multicenter retrospective analysis focusing on survival outcome.

OBJECTIVES: To analyze the demographic data, surgical and adjuvant treatment data and the survival outcomes in adult patients affected by acinic cell carcinoma of the parotid gland (AciCC). METHODS: A retrospective multicenter analysis of patients treated for AciCC of the parotid gland from 2000 to 2021 was performed. Exclusion criteria were pediatric (0-18 years) patients, the absence of follow-up and patients with secondary metastatic disease to the parotid gland. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: The study included 81 adult patients with AciCC of the parotid gland. The median age was 46.3 years (SD 15.81, range 19-84 years), with a gender female prevalence (F = 48, M = 33). The mean follow-up was 77.7 months (min 4-max 361, SD 72.46). The 5 years overall survival (OS) was 97.5%. The 5 years disease-free survival (DFS) was 60%. No statistical differences have been found in prognosis for age (< 65 or ≥ 65 years), sex, surgery type (superficial vs profound parotid surgery), radicality (R0 vs R1 + Rclose), neck dissection, early pathologic T and N stages and adjuvant therapy (p > 0.05). CONCLUSION: This study did not find prognostic factor for poorest outcome. In contrast with the existing literature, our results showed how also high-grade tumours cannot be considered predictive of recurrence or aggressive behaviour.

Bone Formation in Pleomorphic Adenoma: A Case Report.

Pleomorphic adenoma is a benign tumour with variable cytomorphological and architectural elements. It is the most common salivary gland tumour in children and adults. We report a case of a 32-year-old Malay woman who presented with a slow-growing, painless, firm, and mobile nodule of 1 cm x 1 cm in size at the angle of her mandible on the right side which could be palpated bimanually. Intraorally, this nodule could be palpated at the retromolar area. On excisional biopsy, this nodule was reported as a pleomorphic adenoma with predominant chondroid stromal elements and a large area of bone formation in the stroma. We discuss the possible pathogenesis, differential diagnosis, and clinical significance of this exceptionally rare phenomenon of bone formation in pleomorphic adenoma in minor salivary glands with the literature review. The clinical significance and relevance on treatment outcome for pleomorphic adenoma with bone formation is currently uncertain as there are only a few cases reported in the literature. A good follow-up study is recommended to assess the clinical significance of pleomorphic adenoma with extensive bone formation.

Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation.

Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron-microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC-positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC-positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC-positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Synchronous Multifocal Canalicular Adenomas.

Canalicular adenoma (CAD) is an uncommon benign tumor of minor salivary glands with predilection for the upper labial mucosa. An 80-year-old female presented with nine submucosal nodules of the upper labial mucosa and bilateral buccal mucosa. Histopathologic examination revealed multifocal circumscribed tumor islands with a tubular growth pattern within a loose hypocellular myxoid background stroma. Interconnecting rows of columnar tumor cells imparted a canalicular morphology. In addition to the characteristic histopathologic findings, a comprehensive immunohistochemical panel supported a final diagnosis of multifocal CAD. Synchronous multifocality in CAD is an infrequent finding and this sine qua non clinicopathologic correlation article exemplifies such a case.

Endobronchial sialolipoma. Case report.

BACKGROUND: A 52-year-old woman presented with shortness of breath and cough. An endobronchial sialolipoma was found at the left entrance of the main bronchus. Sialolipoma is an exceedingly rare type of lipoma reported of the minor salivary glands, especially within the bronchus. CASE PRESENTATION: A 52-year-old woman presented with shortness of breath and cough with 6 months´ evolution. Endobronchial endoscopy revealed a tumour at the left entrance of the main bronchus. The entire removal of the tumour was removed using a cryoprobe device. Pathological examination showed a tumour consistent with the diagnosis of sialolipoma due to the presence of mature adipose cells blended with acinar, ductal, basal, and myoepithelial cells. The patient had a favourable outcome. CONCLUSION: The infrequent tracheobronchial presentation of this tumour can be challenging for correct diagnosis.

Intracapsular carcinoma ex basal cell adenoma of the parotid gland.

Malignant transformation of basal cell adenoma is extremely rare. We report the case of a 63-year-old Chinese woman, who had noticed a slowing growing mass in her right parotid gland with slight pain for 1 month. Based on physical and ultrasound examinations, a diagnosis of benign salivary gland tumour was made before the surgery. A frozen biopsy was performed, and the diagnosis was basal cell adenoma, with the tumour cells infiltrating the capsule. Routine histopathological examination was performed after the surgery, and a final diagnosis of intracapsular basal cell adenocarcinoma ex basal cell adenoma was made. The patient received a further total parotidectomy and recovered well without any evidence of facial nerve palsy. This case suggests that during frozen biopsy, adequate sectioning including the capsule should be made. With regard to the treatment, we suggest a complete excision of the tumour with tumour-free margins, without any additional auxiliary therapy.

Intraparotid node metastases in adults with parotid mucoepidermoid cancer: an indicator of prognosis?

We have retrospectively analysed the predictive value of intraparotid nodal metastases in patients having neck dissection for parotid mucoepidermoid cancer. The main outcomes were intraparotid nodal metastases, a new system for staging metastatic parotid nodes, and recurrence-free survival. The overall rate of intraparotid metastasis was 30/122 (25%), and seven patients had deep parotid nodal metastases. This metastasis was significantly related to tumour stage, neck disease, perineural invasion, lymphovascular invasion, and pathological tumour grade. The sensitivity of intraparotid nodal metastases in predicting neck disease was 50%, and the specificity of them predicting neck disease was 89%. The stages of the intraparotid nodes were as follows: P0 (n=92 patients), P1 (n=10), P2 (n=16), and P3 (n=4). A Cox's model analysis confirmed that the stage of the intraparotid nodes was an independent prognostic factor for recurrence, so the presence of intraparotid nodal metastases is associated with a higher risk for recurrence of disease.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Nerve growth factor-induced migration in oral and salivary gland tumour cells utilises the PI3K/Akt signalling pathway: Is there a link to perineural invasion?

OBJECTIVES: The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of PI3K/Akt pathway. MATERIALS AND METHODS: Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS-H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter/scratch assays. RESULTS: Nerve growth factor triggered the PI3K/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent. CONCLUSIONS: Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.

Finding a Mass Within the Oral Cavity: What Are the Common Causes and How Should A GP Manage them?

@#A 24-year-old male presented with worsening right buccal pain and numbness of the anterior right tip of the tongue. A fixed, hard, non-tender mass was found on the right floor of the mouth. Subsequently, maxillofacial surgery evaluation, MRI scan of the head and neck, and biopsy confirmed a low-grade hyalinising clear cellcarcinoma, likely of salivary gland origin. This clinical encounter led to a review for the variety of masses that can occur in each site in the oral cavity and the commonmasses that may present to a GP. A suggested management approach is presented. In addition,common salivary gland pathologies are highlighted, andsalivary gland tumours as was present in this patient are further discussed.

Hyalinizing Clear Cell Carcinoma: Base of Tongue.

Hyalinizing clear cell carcinoma (HCCC) is a low grade, rare neoplasm originating from the minor salivary glands. It usually follows an indolent course and the main treatment modality is surgery. The prognosis of these tumours are good, hence it needs to be differentiated from other carcinomas with clear cells. Here we report a pathologically proven HCCC of the base of tongue.

Sialolipoma of Parotid Gland a Rare Histological Presentation.

Sialolipoma is a rare tumour found within both major and minor salivary glands, it is recently described as a variant of salivary gland lipoma. Sialolipoma was first described by Pusiol et al. (Indian J Pathol Microbiol 52(3):379-382, 2009). Sialolipoma is well circumscribed and contains mature adipose tissue admixed with benign salivary gland component. We report a case of 62 years old female who presented with the complaint of swelling in the right parotid region for 5 years duration. Apart from cosmetic reason she had no other complain. All specific investigations done were inconclusive and suggested a benign tumor. Histopathological examination after superficial parotidectomy suggested sialolipoma. As newly described tumor type, care should be taken to distinguish oncocytic sialolipoma from other salivary gland neoplasms such as simple lipoma, pleomorphic adenoma, or oncocytoma.

Pleomorphic Adenoma of the Cheek: A Case Report.

Pleomorphic adenoma (PA) is the most common benign tumor affecting both major and minor salivary glands. Parotid gland is the most commonly affected major salivary gland. Among minor salivary glands, palate is the most commonly affected site followed by lips, cheeks, gingiva, floor of the mouth, and tongue. PA of buccal minor salivary glands is a very rare occurrence both in adults and children. In this report, we present a case of PA of buccal minor salivary gland in an adult patient who was successfully treated by wide local surgical excision, and after a follow-up period of one year there was no recurrence. A review of literature of PA of cheek is also presented.