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Salivary Gland Cancer

The salivary glands make saliva, which contains a range of enzymes which help digest food and protect against infections of the mouth and throat. There are 3 pairs of major salivary glands and hundreds of minor microscopic salivary glands:

  • Parotid glands: the largest salivary glands,located in front of and just below each ear. Aproximately 80% of salivary gland tumors begin in the parotid glands.
  • Submandibular glands: found below the jawbone. Between 10-15% of salivary gland tumours are found in the submandibular glands
  • Sublingual glands: found under the tongue in the floor of the mouth.
  • Minor salivary glands there are several hundred tiny salivary glands lining parts of the mouth, nose, and larynx.
More than half of all salivary gland tumours are benign (non cancerous). Malignant (cancerous) tumours are designated high-grade or low-grade, depending on how they look under the microsope.

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Latest Research Publications

Information Patients and the Public (6 links)

Information for Health Professionals / Researchers (7 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Israel Y, Rachmiel A, Gourevich K, Nagler R
Kaplan-Meier analysis of salivary gland tumors: prognosis and long-term survival.
J Cancer Res Clin Oncol. 2019; 145(8):2123-2130 [PubMed] Related Publications
PURPOSE: We evaluated the impact of various tumor related parameters on survival probability in a cohort of patients with malignant salivary tumors, using the Kaplan-Meier analysis.
METHODS: We measured patients up to 15 years following therapy, looking at T N M stage, grade perineural invasion and extra-parenchymal spread.
RESULTS: Of 101 patients diagnosed with various salivary malignant tumors in our medical center, 79 patients survived while 22 died with disease (DWD). The impact of distant metastasis (M+) was devastating (survival probability at 60 months and at 180 months dropped from 0.93 (M-) to 0.40 (M+) and from 0.67 to 0.40, respectively, p = 0.0001), the impact of perineural invasion was severe (at 180 months the probability of survival dropped from 0.75 to 0.21, p = 0.002). Higher stage tumor also decreased survival (from 0.82 to 0.53 at 180 months, p = 0.002) as did poor histological grade (from 0.85 to 0.48 at 180 months, p = 0.019). Neck metastasis (N+) impact was quite moderate (at 180 months the probability of survival dropped from 0.69 to 0.58, p = 0.044) while neither tumor size (T) nor extra-parenchymal spread significantly affected survival.
CONCLUSIONS: Salivary tumor location and its potential to infiltrate nerves and blood vessels and to metastasize is the most telling parameter. Systemic therapy aimed at halting distant metastatic spread is the most effective therapeutic goal. Dissection of N0 neck metastasis is not necessarily a valuable treatment.

Zhang D, Liao X, Tang Y, et al.
Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.
Anticancer Res. 2019; 39(6):3213-3217 [PubMed] Related Publications
BACKGROUND: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass.
CASE REPORT: Fine-needle aspiration showed features suggestive of Warthin tumor. Following parotidectomy, grossly there was a 1.6 cm well-circumscribed multilobular mass with focal areas of cystic change. Microscopically, at low magnification it had histological features resembling Warthin tumor, while lining with squamoid cells with scattered mucocytes demonstrating mild cytologic atypia was observed at high magnification. Immunohistochemically, the tumor cells were positive for p40, p63, cytokeratin 5/6, cytokeratin 7, and cancer antigen 125, but negative for discovered on GIST-1 (DOG1). Mucicarmine stain highlighted intracellular mucin within mucocytes. Rearrangement of mastermind like transcriptional coactivator 2 (MAML2) (11q21) gene was shown to be present in tumor cells by fluorescence in situ hybridization, supporting the diagnosis of a low-grade Warthin-like mucoepidermoid carcinoma. The patient was disease-free 12 months after surgery.
CONCLUSION: Warthin-like mucoepidermoid carcinoma has not been widely recognized and can be misdiagnosed as Warthin tumor. Testing for MAML2 rearrangement provides essential support for diagnosis in difficult cases.

Liu C, Jiang YH, Zhao ZL, et al.
Knockdown of Histone Methyltransferase WHSC1 Induces Apoptosis and Inhibits Cell Proliferation and Tumorigenesis in Salivary Adenoid Cystic Carcinoma.
Anticancer Res. 2019; 39(6):2729-2737 [PubMed] Related Publications
BACKGROUND/AIM: Salivary adenoid cystic carcinoma (SACC) is the most common malignancy of the salivary gland with a poor prognosis and survival. The present study aimed to investigate the role of histone methyltransferase WHSC1 in SACC.
MATERIALS AND METHODS: Human SACC specimens were evaluated for WHSC1 expression by RT-PCR and immunohistochemistry. The effects of WHSC1 knockdown on SACC cells proliferation, cell cycle, clone and tumorsphere formation, and apoptosis as well as on the expression of related genes were examined. A xenograft mouse model of SACC was used to evaluate the in vivo effects of WHSC1 knockdown on SACC tumorigenesis.
RESULTS: WHSC1 expression was up-regulated in human SACC tissues (p<0.01). WHSC1 knockdown in SACC cells significantly inhibited cell proliferation, clone and tumorsphere formation (p<0.05). Cell distribution at the S and G
CONCLUSION: Knockdown of WHSC1 inhibited cell proliferation, induced apoptosis and affected tumorigenesis in SACC.

Seok J, Jeong WJ, Ahn SH, Jung YH
The growth rate and the positive prediction of needle biopsy of clinically diagnosed Warthin's tumor.
Eur Arch Otorhinolaryngol. 2019; 276(7):2091-2096 [PubMed] Related Publications
PURPOSE: This study reports the clinical course, including the growth rate, of Warthin's tumor (WT) and evaluates the positive prediction of needle biopsy for WT.
METHODS: The medical records of 182 patients clinically diagnosed with WT were retrospectively reviewed. Tumor growth rates were measured in patients who underwent serial radiologic exams with minimum 6-month time intervals, and the positive prediction value (PPV) of needle biopsy was evaluated in comparison with surgical pathology in patients who underwent surgical excision of the tumors.
RESULTS: Serial radiologic exams were available for growth rate measurement in 31 tumors (size 0.7-9.1 cm) from 25 patients. Among these, 24 tumors increased in size, and 7 were stable. The median follow-up duration was 23.5 months [interquartile range (IQR) 14.8-51.9], and the tumor growth rate ranged from - 0.36 to 2.26 cm per year (median 0.26, IQR 0.07-0.44). Needle biopsy results were available for comparison with postoperative pathology specimens in 147 patients. The PPV was 97.7% for fine-needle aspiration biopsy and 100% for core-needle biopsy. There were no reports of inflammation, facial nerve paralysis, or admission event during the follow-up.
CONCLUSIONS: WT glows slowly and can be predicted by needle biopsy. Therefore, parotid masses diagnosed as Warthin's tumor can be treated or left untreated based on the patient's needs and clinical decision-making.

Li C, Chen Q, Tian Z, et al.
Expression of MIF, Beclin1, and LC3 in human salivary gland adenoid cystic carcinoma and its prognostic value.
Medicine (Baltimore). 2019; 98(20):e15402 [PubMed] Free Access to Full Article Related Publications
Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy with a poor long-term prognosis. Clinical reports show the high rates of local recurrences and distant metastases. This study aimed to investigate the expression of MIF, Beclin1, and light-chain 3 (LC3) in salivary adenoid cystic carcinoma (SACC).Tissue specimens were obtained from 48 salivary glands adenoid cystic carcinoma (SACC) patients and 15 oral squamous cell carcinoma (OSCC) patients. Immunohistochemical staining was performed to estimate the level of LC3, Beclin1, and MIF. All SACC patients were followed up. The Kaplan-Meier method was used to compare the prognosis of patients after treatment.The 3-year, 5 year-, and 10 year-survival rates of the SACC patients were 83.9%, 69.9%, and 46.6%, respectively. MIF, LC3, and Beclin1 in SACC were all obviously over-expressed. MIF showed an increased tendency in cases with advanced TNM stages, and at the same time, there was an inversely proportional relationship between MIF and LC3, Beclin1.The long-term survival of SACC patients is poor. MIF might be a risk factor for SACC patients, whereas, LC3 and Beclin1 might be an effective strategy for treatment of SACC.

Stodulski D, Mikaszewski B, Majewska H, Kuczkowski J
Parotid salivary duct carcinoma: a single institution's 20-year experience.
Eur Arch Otorhinolaryngol. 2019; 276(7):2031-2038 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The aim of the study was to assess the treatment results of the parotid gland salivary duct carcinoma (SDC).
MATERIAL AND METHODS: A retrospective clinicopathological analysis of 40 patients treated for parotid SDC in 1996-2015 was performed. The impact of following factors on 5-year disease-free survival (DFS) and overall survival (OS) was studied: age, sex, preoperative 7th nerve palsy, skin infiltration, pT, pN, surgical margin, type of parotidectomy and neck dissection, histology (SDC de novo vs. SDC ex pleomorphic adenoma, SDCexPA), intra/periparotid lymph nodes metastases, perineural invasion (PNI), extraparenchymal extension (EPE), and overexpression HER2.
RESULTS: The average age of the patients was 62 years (ranged from 39 to 81). Males predominated (57.5%). Patients with the clinical stage IV predominated (82.5%). In 1/3 of patients preoperative, 7th nerve palsy occurred. All patients were treated surgically, and all but one had supplementary radiotherapy. In 28 patients (70%), total radical parotidectomy was performed. A neck dissection was performed in all patients. In 19 cases (47.5%), SDCexPA was diagnosed. Negative microscopic surgical margin was obtained in 60% of patients. The follow-up for the whole analyzed group ranged from 2 to 22 years, average was 11.6 years. In 23 patients (57.5%), the disease recurred. Local recurrence was observed in 10 (25%) and distant metastases in 15 (37.5%) cases. 20 patients (50%) died of cancer. 5-year DSF and OS were 42.5% and 41%, respectively. Univariate analysis proved that the significant influence on the survival had 7th nerve palsy (p = 0.024 and p = 0.017, respectively), higher pT-stage (p < 0.001), radical parotidectomy (p = 0.024 and p = 0.022), radical treatment of the neck (p = 0.001 and p = 0.002), EPE (p = 0.040 and p = 0.028), and histology SDCexPA and PNI (p = 0.036 and 0.048). Multivariate analysis showed that independent prognostic factors were the 7th nerve palsy and the histology SDCexPA, which worsened 5-year DFS, respectively, 3.61 and 3.94 times (p = 0.033 and p = 0.026). On the other hand, on 5-year OS, only 7th nerve palsy had an influence (3.86 times worse prognosis, p = 0.033).
CONCLUSIONS: SDC is a clinically aggressive cancer with high risk of local recurrence and distant metastases, however, with a chance of curing of around 40%. In the majority of patients, a radical surgical treatment is necessary due to the high clinical stage of disease. Worse prognosis have patients with preoperative 7th nerve palsy and in whom SDC develops in pleomorphic adenoma.

Niu X, Fang Q, Liu F
Role of intraparotid node metastasis in mucoepidermoid carcinoma of the parotid gland.
BMC Cancer. 2019; 19(1):417 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prognostic factors for parotid mucoepidermoid carcinoma (MEC) usually include disease grade, tumor stage, node stage, perineural invasion, and lymphovascular invasion. But the role of intraparotid nodes (IPNs) remains unclear, therefore, the study aimed to analyze the significance of IPNs in predicting recurrence in parotid MEC.
METHODS: One hundred and ninety patients were included for analysis finally. Data regarding demography, pathological characteristics, IPN metastasis, TNM stage, follow up was collected and evaluated. The recurrence-free survival (RFS) was the main study endpoint.
RESULTS: A total of 47 (24.7%) patients had IPN metastasis, and the IPN metastasis was significantly related to tumor stage, pathologic N stage, lymph-vascular invasion, perineural invasion, and disease grade. Recurrence occurred in 34 (17.9%) patients. For patients without IPN metastasis, the 10-year RFS rate was 88%, for patients with IPN metastasis, the 10-year RFS rate was 54%, the difference was significant (p < 0.001). Further Cox model analysis confirmed the independence of IPN metastasis in predicting the prognosis.
CONCLUSION: The IPN metastasis is relatively common in parotid MEC, it is significantly related to tumor stage and disease grade, IPN metastasis means worse recurrence-free survival.

Okada T, Saotome T, Nagao T, et al.
Carboplatin and Docetaxel in Patients With Salivary Gland Carcinoma: A Retrospective Study.
In Vivo. 2019 May-Jun; 33(3):843-853 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: The aim of this study was to evaluate the efficacy and safety of carboplatin/docetaxel combination therapy in patients with locally advanced and/or recurrent/metastatic (LA/RM) salivary gland carcinoma (SGC).
MATERIALS AND METHODS: This was a retrospective analysis of 24 patients that included six patients with AR-positive salivary duct carcinoma (SDC) after progressive disease treated with combined androgen blockade (CAB). Carboplatin (AUC5) and docetaxel (70 mg/m
RESULTS: The overall response rate was 42%, the median progression-free survival was 8.4 months, and the median overall survival was 26.4 months. Among the six patients with CAB-resistant SDC, two achieved a partial response and two long-term stable disease. Grade 3/4 neutropenia and anemia were observed in 20-30% of the patients; all adverse events were manageable.
CONCLUSION: Carboplatin/docetaxel combination therapy may be a chemotherapeutic option for patients with LA/RM SGC, and a valuable second-line chemotherapy for CAB-resistant, AR-positive SDC.

Wei Y, Jin X, Kong T, et al.
The endocytic pathways of carbon dots in human adenoid cystic carcinoma cells.
Cell Prolif. 2019; 52(3):e12586 [PubMed] Related Publications
OBJECTIVES: This study aimed at investigating cellular uptake pathways of carbon dots (CDs) in human adenoid cystic carcinoma cell line ACC-2.
MATERIALS AND METHODS: We synthesized CDs using a hydrothermal method with citric acid and polyethylenimine (PEI, Mw = 25 000). The CDs incubated with the ACC-2 cells showed their bioimaging capabilities using a confocal microscopy test. Flow cytometry was used to analyse cellular uptake pathways of CDs in ACC-2 cells.
RESULTS: Our findings indicated that CDs possessed good biocompatibility in ACC-2 cells. CDs were endocytosed mainly via micropinocytosis and energy-dependent pathways.
CONCLUSIONS: In general, these findings suggested that CDs had excellent biomedical imaging properties for ACC-2 cells and there was a potential opportunity to develop biomedical applications.

Garrett SL, Trott K, Sebastiano C, et al.
Sensitivity of Fine-Needle Aspiration and Imaging Modalities in the Diagnosis of Low-Grade Mucoepidermoid Carcinoma of the Parotid Gland.
Ann Otol Rhinol Laryngol. 2019; 128(8):755-759 [PubMed] Related Publications
OBJECTIVE: To determine the diagnostic accuracy of fine-needle aspiration (FNA) and imaging modalities for low-grade mucoepidermoid carcinoma (MEC) of the parotid gland.
METHODS: Retrospective chart review of patients diagnosed with low-grade MEC of the parotid gland following surgical excision between January 2010 and June 2018. Imaging from patients with MEC were randomly mixed with imaging from patients with benign pathology and reviewed in a blinded fashion. Main outcome measure was sensitivity.
RESULTS: A total of 24 patients were confirmed to have had low-grade MEC on final pathology, with a total of 31 FNAs performed between them. Twelve of 31 FNAs were positive for low-grade MEC, with a sensitivity of 39%. A total of 27 imaging studies were reviewed, which included 16 patients with low-grade MEC and 11 patients with benign pathology. Of these 27 imaging studies, 10 were declared indeterminate. Of the remaining 17 imaging studies, 13 were reviewed as malignant (11 true positive and 2 false positive) and 4 as benign (4 true negative). Overall magnetic resonance imaging (MRI) sensitivity for low-grade MEC was 100% (9/9) with 95% CI (0.66-1.0) when considering indeterminate results as positive for malignancy.
CONCLUSION: This study reaffirms that for low-grade MEC, sensitivity of FNA is poor. MRI provides an important diagnostic tool in the evaluation of salivary gland neoplasms, due to its increased sensitivity for low-grade MEC when considering indeterminate results as positive. This provides confidence in the diagnosis of benign tumors and allows appropriate counseling of all options to the patient, including observation. Imaging and low threshold of excision should be considered despite an inflammatory or benign FNA.

Fu JY, Wu CX, Shen SK, et al.
Salivary gland carcinoma in Shanghai (2003-2012): an epidemiological study of incidence, site and pathology.
BMC Cancer. 2019; 19(1):350 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Salivary gland carcinoma ranks the sixth in head and neck cancers while it is relatively rare in its incidence. Epidemiological studies have been based mostly on institutional data, leading to selection bias in incidence evaluation. Most population-based cancer registries have grouped cancers of the minor salivary glands with oral cancer instead of with salivary gland carcinoma as a whole, because of the international disease coding. Thus, the incidence of salivary gland carcinoma has not been well assessed. The aim of the study is to evaluate the incidence of both minor and major salivary gland cancers in Shanghai during the years 2003-2012, and to analyse the site and histological distributions.
METHODS: Data from the Shanghai Cancer Registry system were extracted for patients diagnosed with malignancies of the major or minor salivary glands for the year 2003 to 2012. Pertinent socio-demographic data were obtained from the Shanghai Municipal Bureau of Public Security. The age-standardized incidence rates were calculated directly according to the world standard population. The change in incidence during the study period was analysed by comparing the rates during the first and next five years. The distributions of anatomic subsites and histology were also analysed.
RESULTS: A total of 1831 cases were identified, representing 0.35% of all malignancies during the study period. The median age was 59 and 57 years for men and women, respectively. The age-standardized incidence was 7.99 per 1,000,000 person-year, with a male-to-female ratio of 1.10. There was no significant change in the incidence during the 10-year period. The anatomic distribution confirmed the 4:1:2 rule for the parotid, submandibular, and minor glands. In men, adenocarcinoma not otherwise specified was the most common histological type followed by mucoepidermoid; in women, the mucoepidermoid was the most common histotype, followed by the adenoid cystic.
CONCLUSION: Salivary gland carcinoma is relatively rare in incidence. However, the variations in age and sex distribution in sites and histology types suggest differences in aetiology which warrants further investigation.

Wu JS, Li ZF, Wang HF, et al.
Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma.
Int J Oncol. 2019; 54(4):1233-1244 [PubMed] Free Access to Full Article Related Publications
Cathepsin B (CTSB) has been reported to be involved in cancer metastasis by altering extracellular matrix (ECM) remodeling and facilitating invasion. However, the contribution of CTSB to collective cell invasion in salivary adenoid cystic carcinoma (SACC) and the underlying mechanisms remain unclear. The present study demonstrated that collective cell invasion is commonly observed in SACC without a complete epithelial‑mesenchymal transition signature. CTSB was found to be overexpressed in the invasive front of SACC compared to the tumor center, and was associated with a poor prognosis of patients with SACC. Subsequently, a 3D spheroid invasion assay was established in order to recapitulate the collective cell invasion of SACC and the results revealed that CTSB was only expressed in leader cells. The knockdown of CTSB by siRNA inhibited the migration and invasion of SACC‑83 cells and impaired the formation of leader cells. CTSB knockdown also disrupted cytoskeletal organization, altered cell morphology and inhibited ECM remodeling by downregulating matrix metalloproteinase‑9, focal adhesion kinase and Rho/ROCK function. Therefore, the present study provides evidence that CTSB may define leader cells in SACC and is required for collective cell invasion as a potential key regulator of ECM remodeling.

Wang HF, Wang SS, Zheng M, et al.
Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial-mesenchymal transition in salivary adenoid cystic carcinoma.
Cell Prolif. 2019; 52(3):e12600 [PubMed] Related Publications
OBJECTIVES: To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved.
MATERIALS AND METHODS: Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT-PCR were used to detect the effect of hypoxia on VE-cadherin and VEGFA expression. And pro-vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E-cadherin, N-cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF-1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF-1α level were analysed.
RESULTS: Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE-cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N-cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E-cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF-1α expression.
CONCLUSIONS: VEGFA played an important role in hypoxia-induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.

Miesbauerová M, Tommola S, Šteiner P, et al.
Cytopathological features of secretory carcinoma of salivary glands and ancillary techniques in its diagnostics: impact of new Milan system for reporting salivary gland cytopathology.
APMIS. 2019; 127(7):491-502 [PubMed] Related Publications
Secretory carcinoma (SC) of salivary glands is a newly described low-grade malignancy characterized by the presence of ETV6 rearrangement. Only a few cases and very small series with cytomorphology were reported so far. Six cases of fine-needle aspirations (FNAs) from afterward histologically, immunohistochemically and genetically confirmed SCs were retrieved from the archives of the authors. Ancillary immunocytochemistry (ICC) and translocation detection were performed on cell blocks (CBs). All aspirates were sufficiently cellular and cells were arranged in more or less cohesive groups with only mild nuclear polymorphism. The cytoplasm was eosinophilic, granulated and vacuolated, especially in CBs. Secretory material within the microcystic spaces was periodic acid-Schiff (PAS) positive. Triple positivity of immunomarkers S-100 protein, mammaglobin and vimentin was present. The proliferation index was low. Ancillary techniques suggested the possibility of SC in a few cytology cases; nevertheless, the final diagnosis was based on histomorphology, immunohistochemistry and genetics. The SC of salivary glands is detectable pre-operatively using ICC and genetics. The presence of the diagnostic ETV6 rearrangement increases the accuracy of FNA to the maximum. According to the Milan system, cases genetically not confirmed should be categorized as Suspicious for Malignancy or Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP), both requiring surgery.

Cheng NM, Hsieh CE, Liao CT, et al.
Prognostic Value of Tumor Heterogeneity and SUVmax of Pretreatment 18F-FDG PET/CT for Salivary Gland Carcinoma With High-Risk Histology.
Clin Nucl Med. 2019; 44(5):351-358 [PubMed] Related Publications
PURPOSE: Previous studies have shown that SUVmax on F-FDG PET/CT predicts prognosis in patients with salivary gland carcinoma (SGC). Here, we sought to evaluate whether texture features extracted from F-FDG PET/CT images may provide additional prognostic information for SGC with high-risk histology.
METHODS: We retrospectively examined pretreatment F-FDG PET/CT images obtained from 85 patients with nonmetastatic SGC showing high-risk histology. All patients were treated with curative intent. We used the fixed threshold of 40% of SUVmax for tumor delineation. PET texture features were extracted by using histogram analysis, normalized gray-level co-occurrence matrix, and gray-level size zone matrix. Optimal cutoff points for each PET parameter were derived from receiver operating characteristic curve analyses. Recursive partitioning analysis was used to construct a prognostic model for overall survival (OS).
RESULTS: Receiver operating characteristic curve analyses revealed that SUVmax, SUV entropy, uniformity, entropy, zone-size nonuniformity, and high-intensity zone emphasis were significantly associated with OS. The strongest associations with OS were found for high SUVmax (>6.67) and high SUV entropy (>2.50). Multivariable Cox analysis identified high SUVmax, high SUV entropy, performance status, and N2c-N3 stage as independent predictors of survival. A prognostic model derived from multivariable analysis revealed that patients with high SUVmax and SUV entropy or with the presence of poor performance status or N2c-N3 were associated with worse OS.
CONCLUSIONS: A prognostic model that includes SUVmax and SUV entropy is useful for risk stratification and supports the additional benefit of texture analysis for SGC with high-risk histology.

Elmokadem AH, Abdel Khalek AM, Abdel Wahab RM, et al.
Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging for Differentiation Between Parotid Neoplasms.
Can Assoc Radiol J. 2019; 70(3):264-272 [PubMed] Related Publications
PURPOSE: This study was designed to evaluate the role of multiparametric magnetic resonance imaging (MRI) for differentiation of parotid gland neoplasms.
METHODS: Prospective study was conducted upon 52 consecutive patients (30 men, 22 women; aged 24-78 years; mean, 51 years) with parotid tumours that underwent multiparametric MRI using combined static MRI, dynamic contrast enhanced (DCE) MRI, and diffusion-weighted imaging (DWI). The static MRI parameter, time signal intensity curves (TIC) derived from DCE-MRI, and apparent diffusion coefficient (ADC) values of parotid tumours were correlated with histopathological findings.
RESULTS: Static MRI revealed a significant difference between both benign and malignant lesions in regards to margin definition (P < .001) and T2 hypointensity (P < .013), with a diagnostic accuracy 95% and 78.33% respectively. Study of the TIC type on DCE-MRI revealed statistically significant difference between benign and malignant lesions (P < .001) and diagnostic accuracy 96.55%. There was no statistically significant difference (P = .181) between the ADC values of benign and malignant lesions. ROC curve analysis revealed that by using ADC cut-off value of 1 × 10
CONCLUSION: Multiparametric MRI can be used for differentiation of malignant from benign parotid tumours and characterization of some benign parotid tumours.

Ma S, An F, Li LH, et al.
Expression of Mucin 1 in salivary gland tumors and its correlation with clinicopathological factors.
J Biol Regul Homeost Agents. 2019 Mar-Apr,; 33(2):563-569 [PubMed] Related Publications
This study aimed to detect the expression of Mucin 1 (MUC1) in acinic cell carcinoma (AciCC) of salivary gland and to explore the relationship between MUC1 and clinicopathological factors of AciCC of salivary gland. Patients with salivary gland tumors who were treated at our hospital were enrolled in this study. The pathological sections collected from all subjects were classified by histological examinations. In addition, 40 cases of primary salivary gland AciCC tissues were selected and classified into experimental group, whereas 40 cases of normal salivary gland (NSG) tissues were selected and classified into control group. MUC1 positive cells in both experimental and control groups were detected by immunohistochemistry assays, while all clinical data were analyzed statistically. The results showed that MUC1 was only expressed in the ductal epithelium of NSG and distributed at the apical side of the cell membrane. In primary salivary gland AciCC tissues, scattered expressions of MUC1 were found both on the cell membrane and in the cytoplasm of tumor cells, and sometimes even in the cell nuclei, thus completely eliminating the polarized distribution of MUC1 expressions. The percentage of MUC1 positive cells in experimental group was significantly higher than that in control group (P < 0.05). In addition, the expression of MUC1 in salivary gland AciCC was correlated with gender, age, histological type, lesion location, cervical lymph node metastasis, local recurrence, and distant metastasis. In conclusion, MUC1 is related to the occurrence and development of salivary gland AciCC. Therefore, MUC1 may be used as a novel tumor marker in the clinical diagnosis and treatment of salivary gland AciCC.

Lubin D, Song S, Zafar HM, Baloch Z
The key radiologic and cytomorphologic features of oncocytic and oncocytoid lesions of the salivary gland.
Diagn Cytopathol. 2019; 47(6):617-636 [PubMed] Related Publications
Oncocytic and oncocytoid lesions represent a distinct subset of salivary gland lesions. True oncocytic lesions of the salivary gland are entirely composed of oncocytes. These are characterized by the presence of abundant eosinophilic granules due to the presence of abundant cytoplasmic mitochondria. Oncocytic lesions of the salivary gland include oncocytosis, oncocytoma, and oncocytic carcinoma. In addition to the true oncocytic lesion, there exists another group of salivary gland lesions, which demonstrate cells with abundant and occasionally granular cytoplasm. These are often termed as "oncocytoid" lesions. The recently proposed Milan System for reporting salivary gland cytology clearly states that fine-needle aspiration specimens representing oncocytic/oncocytoid lesions of salivary gland cannot effectively distinguish between a nonneoplastic lesion, benign and malignant neoplasms. Therefore, most lesions lacking classic cytomorphologic features will be classified under the umbrella diagnostic term of "Salivary Gland Neoplasm of Uncertain Malignant Potential" (SUMP). In this review, we discuss and illustrate key clinicopathologic and radiologic features that can help the practicing cytopathologist narrow down the differential and provide the best management based diagnosis.

Cardoso CM, de Jesus SF, de Souza MG, et al.
Is HIF1-a deregulated in malignant salivary neoplasms?
Gene. 2019; 701:41-45 [PubMed] Related Publications
BACKGROUND: There is significant controversy in the literature regarding the relationship between hypoxia and salivary gland neoplasms (SGNs).
OBJECTIVE: The current study aims to investigate levels of hypoxia markers in both benign and malignant salivary neoplasms.
PATIENTS AND METHODS: The current study sample is comprised of a total of 62 samples. HIF-1α expression was evaluated by immunohistochemistry. Additionally, HIF-1α mRNA and miR-210 levels were assessed using qRT-PCR.
RESULTS: No differences in HIF-1α expression were observed among the control group, benign and malignant SGNs. Similarly, HIF-1α mRNA levels were similar between benign and malignant SGNs. Also, there was no difference in miR-210 expression between case and control groups.
CONCLUSION: The angiogenic markers, miR-210 and HIF-1α, do not appear to distinguish malignancy in salivary glands.

Cavalieri S, Platini F, Bergamini C, et al.
Genomics in non-adenoid cystic group of salivary gland cancers: one or more druggable entities?
Expert Opin Investig Drugs. 2019; 28(5):435-443 [PubMed] Related Publications
INTRODUCTION: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignant tumors arising from either major or minor salivary glands. Among SGCs patients, adenoid cystic carcinoma (ACC) is the most frequent histotype and its genetic aberrations are well known even though they are generally uncommon. Non-ACC subtypes are rarer and more heterogeneous than ACC from a histological and genomic point of view. In non-ACC, some altered molecular pathways [e.g. BRAF or RET mutations, Androgen Receptor (AR)] are potentially targetable with specific drugs.
AREAS COVERED: A literature search was performed to summarize the main druggable genomic aberrations involving non-ACC SGCs. An overview of the genomics of non-ACC salivary gland malignancies is discussed. We describe the pattern of potentially targetable genomic alterations in non-ACC salivary gland malignancies according to their frequency rather than to the single non-ACC histotype.
EXPERT OPINION/COMMENTARY: The genetic profiling through in-depth molecular analyses [e.g. Next-generation sequencing (NGS)] is advised in all patients affected by recurrent and/or metastatic non-ACC SGCs to find any potentially druggable target. Some histotypes may carry driving mutations that must be investigated and defined. For the rare cancers, access to a referral center is recommended to optimize the management of these patients.

Xu LH, Zhao F, Yang WW, et al.
MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma.
Int J Oncol. 2019; 54(5):1579-1590 [PubMed] Free Access to Full Article Related Publications
The incidence of recurrent t(6;9) translocation of the MYB proto‑oncogene to NFIB (the gene that encodes nuclear factor 1 B‑type) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. A total of 50 fresh‑frozen SACC tissues and 41 fresh‑frozen normal submandibular gland (SMG) tissues were collected to measure MYB mRNA expression, and to analyse the associations between MYB and epithelial‑mesenchymal transition (EMT) markers. Compared with normal SMG tissue, SACC tissues demonstrated significantly increased MYB expression, with a high expression rate of 90%. Interestingly, MYB tended to be negatively correlated with CDH1 [the gene that encodes cadherin‑1 (E‑cadherin)] and positively correlated with VIM (the gene that encodes vimentin), suggesting that MYB is associated with SACC metastasis. To explore the role of MYB in SACC, the authors stably overexpressed and knocked down MYB in SACC cells. The authors of the current study demonstrated that MYB overexpression promoted SACC cell proliferation, migration and invasion, whereas its knockdown inhibited these activities. Additionally, when MYB was overexpressed, CDH1 expression was downregulated, and CDH2 (the gene that encodes cadherin‑2), VIM and ACTA2 (the gene that encodes actin, aortic smooth muscle) expression was upregulated. Then, the effect of MYB on lung tumour metastasis was investigated in vivo in non‑obese diabetic/severe combined immunodeficiency mice. MYB overexpressing and control cells were injected into the mice through the tail vein. The results revealed that MYB promoted SACC lung metastasis. Collectively, these results demonstrated that MYB is aberrantly overexpressed in SACC tissues, and promotes SACC cell proliferation and metastasis, indicating that MYB may be a novel therapeutic target for SACC.

Thompson JD, Avey GD, Wieland AM, et al.
Auriculotemporal Nerve Involvement in Parotid Bed Malignancy.
Ann Otol Rhinol Laryngol. 2019; 128(7):647-653 [PubMed] Related Publications
OBJECTIVE: To identify and evaluate patients with parotid bed malignancy demonstrating radiographic findings of auriculotemporal (AT) nerve involvement.
METHODS: A retrospective review of patients with parotid bed malignancy was performed to identify patients with imaging findings of AT nerve involvement and record associated clinical findings, symptoms, and pathology information. Independent, blinded review of radiographic images by a senior neuroradiologist was performed to identify imaging characteristics and categorize patients into highly likely or possible involvement groups.
RESULTS: Of 547 patients identified with parotid bed malignancy, 23 patients exhibited radiographic findings suggestive of AT nerve involvement. Thirteen patients met criteria for highly likely involvement, and 10 patients met criteria for possible involvement. Cutaneous malignancy with metastasis to the parotid bed accounted for 11 of 23 patients, and the most common histology was squamous cell carcinoma (9 patients). Primary parotid malignancy accounted for 12 of 23 patients, and the most common histology was salivary ductal carcinoma (3 patients). All 13 highly likely patients reported periauricular pain, and 11 of 13 demonstrated facial weakness. Features suggesting advanced disease included radiographic findings of intracranial involvement (10/23 patients), nonsurgical primary treatment (13/23 patients), and positive margins on pathology report (7/10 patients).
CONCLUSION: AT nerve involvement is an uncommon but important phenomenon that often occurs in the setting of advanced disease and is commonly associated with periauricular pain and coexisting facial weakness. Awareness of the associated clinical features and imaging patterns can allow for appropriate identification of this pattern of spread and help to optimize treatment planning.

Ogino A, Onishi K, Nakamichi M, Okaneya T
Use of Parotid Gland Fascia in the Prevention of Frey Syndrome After Parotidectomy.
J Craniofac Surg. 2019; 30(4):1009-1011 [PubMed] Related Publications
BACKGROUND: Superficial parotidectomy is standard surgical procedure for parotid gland tumor, and Frey syndrome and depressed deformity of the region are often seen as complications. In this study, we performed prevention of Frey syndrome by covering the residual parotid gland defect with the parotid gland fascia flap.
METHOD: The subjects were 5 patients with parotid gland tumor. Tumor was localized in the inferior and superior poles of the parotid gland in 3 and 2 patients, respectively, and it was confirmed on preoperative diagnostic imaging that the tumor and parotid gland fascia were not present in close proximity. Through Lazy-S incision, main trunk of facial nerve was identified and conserved following the surgical procedure of normal superficial parotidectomy, and the superficial parotid gland containing tumor was elevated. A parotid gland fascia flap with a pedicle on the nasal side was prepared and the defect after superficial parotidectomy was covered with it.
RESULTS: The facial nerve and resected parotid gland stump could be sufficiently covered with the parotid gland fascia flap in all patients. The mean duration of postoperative follow-up was 36 months (10 months-4 years and 5 months), and there were no complications such as tumor recurrence, Frey syndrome, salivary gland fistula, or severe concavity in the parotid region.
CONCLUSION: Although application of the present procedure is limited to patients in whom the parotid gland fascia and tumor are not located in close proximity, it may be useful to prevent Frey syndrome because extension of incision is not necessary, the surrounding tissue is not sacrificed, the flap can be easily elevated, and the parotid gland stump can be sufficiently covered.

Jo MG, Lee DJ, Cha W
A modified V-shaped incision combined with superficial musculo-aponeurotic system flap for parotidectomy.
Acta Otolaryngol. 2019; 139(2):178-183 [PubMed] Related Publications
BACKGROUND: V-shaped incision (VSI) for parotidectomy had been introduced for cosmetic purpose. Despite having aesthetic superiority, it required excessive retraction or an additional hairline incision for adequate surgical exposure. To overcome these problems, we conceptualized a modified VSI approach combined with a separate superficial musculo-aponeurotic system flap.
AIMS: This study aimed to propose this approach and evaluate its technical feasibility and efficacy for excision of parotid tumors.
MATERIALS AND METHODS: This is a prospective, nonrandomized study involving 74 patients with small-to-medium (<4 cm), benign parotid tumors located superficially. The patients were divided into two groups based on the incision techniques used: modified VSI and modified Blair incision (MBI). The clinical outcomes of both approaches for parotidectomy were analyzed.
RESULTS: Thirty-four patients underwent modified VSI approach, while 40 underwent MBI. All parotidectomies with modified VSI were successfully completed without any further incision, and no facial nerve injury or intraoperative tumor rupture complication was reported. There were no significant differences in the complications between both approaches, such as hematoma, infection, wound dehiscence, skin necrosis, sialocele, or sensory disturbance. The modified VSI group showed better cosmetic satisfaction results than did the MBI group (9.2 and 7.8, respectively; p < .001).
CONCLUSIONS AND SIGNIFICANCE: The modified VSI approach is safe and feasible for small-to-medium benign parotid tumors. This approach could be a possible option for patients with a high cosmetic demand.
STUDY DESIGN: Prospective pilot study.

Wang KY, Yang Z, Wang WL, et al.
Autologous Free Fat Graft for Repair of Concave Deformity After Total Parotidectomy.
J Craniofac Surg. 2019 May/Jun; 30(3):834-837 [PubMed] Related Publications
OBJECTIVE: Resectioning of giant maxillofacial tumors has been shown to cause facial depression deformity, representing a persistent challenge for surgeons. Here, the authors review their experience using autologous free fat grafts to repair total parotidectomy defects. This review aims to encourage the surgical field to pay more attention to this century-old treatment technique.
METHODS: Patients were included who underwent free fat transfer for tissue reconstruction after total parotidectomy at the Affiliated Stomatology Hospital of China Medical University between 2012 and 2018. Patients with bleeding disease or postoperative follow-up less than 6 months were excluded.
RESULTS: Twenty-three patients between the ages of 35 and 68 were included in this analysis. Ten patients (6 males, 4 females) underwent fat grafting at the time of total parotidectomy, and a control group of 13 patients (9 males, 4 females) underwent total parotidectomy without correction of concave deformities. There were significant differences between fat graft group and control group in terms of age (44.9 ± 9.0117 years versus 56.385 ± 8.9586 years; P = 0.006), Frey syndrome questionnaire score (1 ± 0 versus 2.385 ± 1.0439; P = 0.00), blood loss (195.7 ± 54.8777 mL versus 107.769 ± 22.8916 mL; P = 0.001), postoperative drainage (319.8 ± 103.1803 mL versus 230.385 ± 53.5701 mL; P = 0.027), duration of postoperative drainage (122.4 ± 23.8663 hours versus 90.462 ± 22.2434 hours; P = 0.003), and satisfaction questionnaire score (8.5 ± 0.8498 versus 3 ± 1.1547; P = 0.00). The difference in operation time between the fat graft group and control group was not significant (417 ± 108.0062 min versus 351.538 ± 91.7475 min; P = 0.131).
CONCLUSION: Autologous free fat grafting resulted in more blood loss as well as an increased volume and duration of postoperative drainage. Remarkably, however, patients had superior satisfaction, lower Frey syndrome scores, and similar operation times with use of free fat grafting after parotidectomy. The authors recommend such grafting be utilized to repair concave deformities secondary to total parotidectomy.

Oteri G, Lentini M, Cicciù M, et al.
Role of Antioxidants in Minor Salivary Glands Cancer in the Elderly.
J Craniofac Surg. 2019 May/Jun; 30(3):823-828 [PubMed] Related Publications
BACKGROUND: Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature.
METHODS: An electronic search of the English language literature was performed using PubMed and Google scholar (). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands).
RESULTS: According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population.
CONCLUSIONS: Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.

Gottlieb JB, Joachim M, Leiser Y, et al.
Polymorphous Low-Grade Adenocarcinoma: A Proposed Reconstruction Protocol Based on Past Surgical Experience.
J Craniofac Surg. 2019; 30(4):1228-1230 [PubMed] Related Publications
BACKGROUND: To propose a reconstructive protocol based on surgical management experience of polymorphous low-grade adenocarcinoma (PLGA) and the location of the primary lesion.
METHODS: Data on the surgical management and the reconstructive technique of 14 histologically conformed patients with PLGA, all treated by the same surgeon, were analyzed and evaluated.
RESULTS: Mean follow-up period in our series was 6.2 years. Mean age at diagnosis was 55.5 years and female to male ratio was 2.2:1. The most common presenting sign was a nonpainful lump or mass in an intraoral location. Most patients were managed by wide local excision and reconstruction method varied from primary closure to the use of radial forearm graft. Recurrence appeared in one of the patients in this series, while 2 required further radiation therapy. A protocol for reconstruction of intraoral patients with PLGA is suggested based on our analysis.
CONCLUSION: Surgical management is the gold standard for PLGA treatment. Neck dissection is recommended only in patients with presurgery fine-needle aspiration confirmed lymph node involvement. The reconstruction depends mainly on location and size of the primary lesion.

Cho WK, Roh JL, Cho KJ, et al.
Lymph node ratio predictive of recurrence, distant metastasis, and survival in submandibular gland carcinoma patients.
J Cancer Res Clin Oncol. 2019; 145(4):1055-1062 [PubMed] Related Publications
PURPOSE: Submandibular gland (SMG) carcinoma has an unfavorable clinical course and a low survival rate. Specific tumor and nodal findings might help predict posttreatment recurrence and survival in SMG carcinoma patients. This study evaluated factors predictive of posttreatment recurrence and survival in SMG carcinoma patients.
METHODS: This study enrolled 99 consecutive patients with previously untreated SMG carcinoma. All patients underwent tumor and metastatic lymph node resection along with or without radiation/chemo-radiation. The predictive clinical and pathological factors for disease-free survival (DFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were determined using univariate and multivariate Cox proportional hazards regression analyses.
RESULTS: The median tumor size was 2.7 cm and 53 patients (53.5%) had high-grade tumors. The rates of initial nodal and distant metastasis at initial presentation or follow-up were 45.5% and 42.4%, respectively. The actuarial 5-year DFS, DMFS, DSS, and OS rates were 46.4%, 55.9%, 61.5%, and 59.7%, respectively. The independent factors associated with poor DFS, DMFS, DSS, and OS outcomes (all p < 0.05) were T3-T4 classification and lymph node ratio. A histological high-grade tumor was an independent prognostic factor predictive of poor DMFS, DSS, and OS outcomes (all p < 0.05).
CONCLUSIONS: A high rate of distant site failure is associated with SMG carcinoma, resulting in a poor survival rate. Lymph node ratio might help predict recurrence, distant metastasis, and death due to SMG carcinoma.

Jaafari- Ashkavandi Z, Khademi B, Malekzadeh M, Shahmoradi Z
Serum Levels of Zinc, Copper and Ferritin in Patients with Salivary Gland Tumors
Asian Pac J Cancer Prev. 2019; 20(2):545-548 [PubMed] Related Publications
Background: Variation in serum levels of trace elements including zinc, copper and ferritin has been reported in cancer patients. The aim of this study was to evaluate these trace elements in the patients’ sera with benign and malignant salivary gland tumors (SGTs) and compare them with normal individuals. Methods: In this cross-sectional study, 60 patients with SGTs including 16 pleomorphic adenoma and 44 malignant SGTs, as well as 28 healthy controls, were enrolled. Serum levels of zinc, copper and ferritin were determined by atomic absorption and ELISA methods. Data were analyzed using one way ANOVA, Chi-square, Kruskal-Wallis and Mann- Whitney tests. Results: The mean concentration of zinc, copper, ferritin was1.5± 2 ppm, 1.2± 0.5 ppm, and 96.7± 65.7 ng/ml in PA, 1.5± 1.4,1.3± 0.4, and 111.2± 112 in malignant SGTs, and1.1±0.3, 1.2± 0.23 and 124±135.8 in normal control groups. There was no statistically significant difference between the patients and control groups, and between benign and malignant SGTs (P>0.05). Conclusion: The serum levels of trace elements in SGTs were not different from normal individuals. The results might have been affected by some interventional factors. Therefore, designing cohort complementary studies might result in obtaining more accurate data.

Suzuki M, Nakaegawa Y, Kobayashi T, et al.
The role of frozen section biopsy for parotid gland tumour with benign fine-needle aspiration cytology.
J Laryngol Otol. 2019; 133(3):227-229 [PubMed] Related Publications
OBJECTIVES: This study focused on parotid gland tumours diagnosed as benign by fine-needle aspiration cytology and investigated the necessity of frozen section biopsy.
METHODS: There were 104 cases of parotid gland tumour where fine-needle aspiration cytology was benign and frozen section biopsy was subsequently performed, between April 2006 and June 2016. In this retrospective study, the results of frozen section biopsy were analysed and compared with the final histological diagnosis.
RESULTS: Among the 104 cases diagnosed as benign by fine-needle aspiration cytology, 102 cases and 2 cases were diagnosed as benign and malignant, respectively, by frozen section biopsy. The final histological diagnoses showed that 98 cases were benign and 6 cases were malignant. The sensitivity and specificity values of frozen section biopsy in detecting malignant tumours were 33 per cent and 100 per cent, respectively.
CONCLUSION: The necessity of frozen section biopsy in cases with benign fine-needle aspiration cytology may be low in parotid gland surgery.

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