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Background: Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities., Methods: Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt., Results: Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds of primary surgery (0.89, 0.84, 0.94), radiotherapy (0.91, 0.85, 0.97, p = 0.003) for SGCs. Trends were differentially correlated with SES, ML, HH, and HT-vulnerabilities., Conclusions: Through quantifying SDoH-derived SGC-disparities, the SVI can guide targeted initiatives against SDoH that elicit the most detrimental associations for specific sociodemographics., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs., Methods: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing., Results: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies., Conclusion: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objective: This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA)., Materials and Methods: We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis., Results: Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways., Conclusion: This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways., (© 2024 Wiley Periodicals LLC.)

Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient-derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common MYB::NFIB or MYBL1::NFIB translocations. We have developed the conditions for the generation of both 2D and 3D tumour organoid patient-derived ACC models that retain MYB expression and can be used for drug studies. Using these models, we show in vitro and in vivo sensitivity of ACC cells to the bromodomain degrader, dBET6. Molecular studies show a decrease in BRD4 and MYB protein levels and target gene expression with treatment. The most prominent effect of dBET6 on tumours in vivo was a change in the relative composition of ACC cell types expressing either myoepithelial or ductal markers. We show that dBET6 inhibits the progenitor function of ACC cells, particularly in the myoepithelial marker-expressing population, revealing a cell-type-specific sensitivity. These studies uncover a novel mechanistic effect of bromodomain inhibitors on tumours and highlight the need to impact both cell-type populations for more effective treatments in ACC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: This study aimed to evaluate the diagnostic performance of serum inflammatory biomarkers in salivary gland tumors with dubious results following cytological analysis., Methods: A retrospective analysis of 239 cases following surgery between January 2011 and June 2022 was performed. Receiver Operating Characteristic curves were drawn and areas under the curves were computed to evaluate the diagnostic performance of the inflammatory biomarkers (SII, SIRI, PLR, and NLR). Optimal cut-offs for each marker were determined by maximizing the Youden index., Results: Analysis showed that among the major biomarkers examined, SIRI performed an AUC of 0.77. The best SIRI cut-off was 0.94 with an accuracy of 79.9%. The accuracy, sensitivity, and specificity of cytological analysis were 77.8%, 59.6%, and 90.7% respectively. By combining SIRI with cytological analysis we demonstrated an increase in sensitivity to 82.8%., Conclusions: Inflammatory biomarkers could be evaluated to support the diagnosis and treatment of salivary gland tumors in difficult cases., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The comparative impact of histologic variants and grade has not been well described., Methods: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival., Results: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73)., Conclusion: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems., (© 2023 Wiley Periodicals LLC.)

Sialoblastoma is a rare malignant salivary gland tumor. The aim of this study was to review the available published data on sialoblastoma in a comprehensive analysis of its clinicopathologic characteristics, treatment, and outcomes. An unrestricted electronic search was performed in the following databases: MEDLINE/PubMed, EMBASE, Scopus, Web of science, and gray literature databases. Eligibility criteria included publications with sufficient clinical, imaging, and histopathological information to confirm the diagnosis of sialoblastoma. Data were evaluated descriptively and analytically. A total of 52 studies met the eligibility criteria. In total, 62 patients were evaluated. There was no gender predilection, with the parotid being the most affected primary site (n = 28; 45.2%). In the log-rank test, there was a significant increase in disease-associated survival in patients younger than 1 year of age (82.8% vs. 44.4%; p = 0.003), individuals with lesions in major salivary glands (79.4% vs. 38.5%; p = 0.005), patients without metastases (77.8% vs. 14.3%; p = 0.011), encapsulated lesions (85.7% vs. 0%; p < 0.0001), congenital lesions (83.3% vs. 25.0%; p < 0.0001), and lesions that do not show perineural invasion (89.5% vs. 40%; p = 0.035). Kaplan-Meier curves estimated overall survival and disease-free survival at 5 years of 95.5% and 68.1%, respectively. In the multivariate Cox regression model, only the presence of metastasis was identified as an independent prognostic factor (hazard ratio [HR] = 9.81; p = 0.010). Although sialoblastoma presents good prognosis, the tumor has a high recurrence rate., (© 2023 Wiley Periodicals LLC.)

Salivary gland carcinomas (SGC) are a rare and variable group of head and neck cancers with historically poor response to cytotoxic chemotherapy and immunotherapy in the recurrent, advanced, and metastatic settings. In the last decade, a number of targetable molecular alterations have been identified in SGCs including HER2 upregulation, androgen receptor overexpression, Notch receptor activation, NTRK gene fusions, and RET alterations which have dramatically improved treatment outcomes in this disease. Here, we review the landscape of precision therapy in SGC including current options for systemic management, ongoing clinical trials, and promising future directions., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies., Methods: The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses., Results: Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34)., Conclusions: Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy., (© 2022 Wiley Periodicals LLC.)

Objectives: To evaluate the clinical diagnostic value of contrast-enhanced ultrasound (CEUS) for focal benign and malignant lesions of the salivary glands, as well as for common benign lesions., Methods: A total of 91 patients with focal lesions of the salivary glands were included in this study. In this study, CEUS was used to study the differential diagnosis of focal benign and malignant lesions of the salivary gland and the most common benign tumors, that is, pleomorphic adenoma (PA) and adenolymphoma., Results: The differences between focal benign and malignant lesions in the salivary glands were statistically significant (P < .05) in terms of qualitative CEUS indicators, enhancement pattern, enhancement homogeneity, enhancement margin, and enhanced lesion size, whereas the differences were not statistically significant (P > .05) in terms of wash-in and wash-out pattern, enhancement degree. Blurred margins and increased size of the lesion after enhancement are two CEUS features independently associated with focal malignant lesions of the salivary gland. The differences between salivary gland PA and adenolymphoma were statistically significant (P < .05) in terms of wash-in pattern, enhancement degree, enhancement homogeneity, and enhancement pattern, but not in terms of wash-out pattern, enhancement margin, and enhanced lesion size (P > .05)., Conclusions: As an economical, convenient, and safe imaging method, CEUS has important clinical value in distinguishing benign and malignant salivary glands., (© 2022 American Institute of Ultrasound in Medicine.)

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty-five patients underwent salvage surgery (20.1%) and their 5-year mortality rate, overall survival and disease-free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow-up., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC., Methods: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes., Results: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases., Conclusions: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Milan system for reporting salivary gland cytopathology (MSRSGC) was introduced to standardize reporting of salivary gland cytopathology., Methods: A retrospective review of ultrasound-guided fine needle biopsy of salivary gland lesions was performed between January 2018 and May 2021 at a community otolaryngology practice. Diagnostic accuracy and rate of diagnostic sialoadenectomy were calculated., Results: A total of 203 FNAs (fine needle aspiration) were performed in 184 patients. MSRSGC was utilized in 87/203 cytopathology reports, with a diagnostic accuracy of 84%. Descriptive reporting was used in 115 FNAs, with a diagnostic accuracy of 89% (p = 0.68). Sialoadenectomy rate was 41% for MSRSGC compared to 36% in descriptive cytopathology (p = 0.48)., Conclusions: MSRSGC is as accurate as descriptive cytopathology and the rate of diagnostic sialoadenectomy between both groups is similar in our community. The MSRSGC brings uniformity and standardization to the FNA reporting process., (© 2022 Wiley Periodicals LLC.)

We defined the occult nodal metastasis (ONM) rate of clinical node-negative salivary gland malignancies and examined the role of elective neck dissection (END). Meta-analysis querying four databases, from inception of databases to March 25th, 2020. Fifty-one studies with 11 698 patients were included. ONM rates were 64% for salivary ductal carcinoma (SDC), 51% for undifferentiated carcinoma, 34% for carcinoma ex-pleomorphic adenoma (CXPA), 32% for adenocarcinoma not otherwise specified (ANOS), 31% for lymphoepithelial carcinoma (LE), 20% for mucoepidermoid carcinoma, 17% for acinic cell carcinoma, and 17% for adenoid cystic carcinoma. T3/T4 tumors had a 2.3 times increased risk of ONM than T1/T2 tumors. High-grade tumors had a 3.8 times increased risk of ONM than low/intermediate-grade tumors. ONM rates were exceedingly high for T3/T4, high-grade, and undifferentiated, SDC, ANOS, CXPA, and LE tumors, indicating the potential role of END., (© 2021 Wiley Periodicals LLC.)

Background: Using a population-based database, this study investigates the risk factors, epidemiology, and outcomes of basal cell adenocarcinoma (BCAC) of the head and neck., Methods: The Surveillance, Epidemiology, and End Results database was analyzed for all patients with BCAC of the head and neck from 1973 to 2015., Results: Three hundred and twenty-two cases of BCAC of the head and neck were identified. Mean age of diagnosis was 64.1 years. 52.5% were male and 77.3% were white. The most common primary site was the parotid gland (71.7%). Most patients underwent surgery alone (51.9%). Five-year disease-specific survival (5Y-DSS) was 95.6%, and 10Y-DSS was 90.3%. Highest survival was seen with surgery alone followed by combined surgery and radiation (10Y-DSS: 93.9% vs. 88.9%, p = 0.001). Age, primary site, T-classification, grade, and treatment type significantly affected survival., Conclusions: BCAC of the head and neck presents most frequently in the parotid glands. Surgery alone is associated with highest survival., (© 2021 Wiley Periodicals LLC.)

Background: The aim of the present study was to establish a competing risk nomogram to predict parotid gland cancer-specific mortality (PGC-SM)., Methods: Seven thousand nine hundred and sixty-two patients extracted from SEER database were randomly categorized into training and validation sets. The competing risk model was used to identify factors associated with PGC-SM. The nomogram was evaluated via concordance indexes (C-indexes), calibration plots, and decision curve analysis (DCA)., Results: Male, elderly, white, widowed, larger tumor, no surgery, advanced tumor grade, lymph node (LN) metastasis, adenocarcinoma (ADC), and higher TNM stage were associated with higher incidence of PGC-SM. Calibration plots showed that the nomogram was well calibrated. C-indexes for nomogram were 0.84 (95% CI: 0.81-0.86) and 0.84 (95% CI: 0.82-0.86) in training and validation sets, respectively. DCA demonstrated the clinical usefulness of nomogram., Conclusions: The competing risk nomogram shows high performance in predicting PGC-SM, which might enable clinicians formulate suitable treatment protocols for patients with parotid gland carcinoma (PGC)., (© 2021 Wiley Periodicals LLC.)

Background: Parotid gland mucoepidermoid carcinoma (MEC) has published five-year cancer-specific survival (CSS) rates of 77%-97%, with variance related to grade., Methods: Patients receiving primary surgery for parotid gland MEC from 1995 to 2014 at a tertiary medical center underwent clinical review, histopathologic review, and cytogenetic analysis. Survival outcomes were evaluated., Results: Among 58 patients, T/N/M classification was as follows: T1 in 35 patients, T2 in 14, T4a in 9, N0 in 53, N1 in 2, N2b in 3. Histologic grade was low in 27, intermediate in 17, and high in 12 patients with 98% MAML2 positivity. All patients underwent parotidectomy, and seven patients received adjuvant radiation therapy. CSS was 100% at 5 years and 94.1% at 10 and 15 years. Two patients experienced locoregional recurrence., Conclusions: Treatment with adequate surgical resection and adjuvant radiation therapy for high-grade or advanced-stage tumors yields excellent survival, independent of clinical stage or pathologic grade., (© 2021 Wiley Periodicals LLC.)

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., (© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Elective neck dissection (END) in patients with salivary gland carcinoma is controversial and there are no universally accepted guidelines., Methods: Patients were identified from the Danish Head and Neck Cancer Group. Between 2006 and 2015, 259 patients with primary salivary gland carcinoma were treated with END. Variables potentially associated with regional metastases were analyzed using logistic regression. Neck recurrence-free survival was calculated using the Kaplan-Meier method., Results: Occult metastases were found in 36 of the patients treated with END (14%) and were particularly frequent among patients with T3/T4 tumors and high-grade histology tumors. In multivariate analyses, high-grade histology and vascular invasion were associated with occult metastases., Conclusion: We recommend END of levels II and III for patients with high-grade or unknown histological grade tumors, and for T3/T4 tumors. Levels I, II, and III should be included in END in patients with submandibular, sublingual, or minor salivary gland carcinomas., (© 2021 Wiley Periodicals LLC.)

Background: This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC)., Methods: This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS)., Results: In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P < .05). Our new N classification proposed three categories: N0 (0 LN+), N1 (1 LN+), and N2 (≥2 LN+ or ENE). The C-index of our N classification showed improvement in OS prediction (0.768) compared with the AJCC seventh (0.743) and eighth (0.756) edition N classifications., Conclusions: Our proposed N classification incorporating LN+ number and ENE may improve prediction of post-treatment survival and recurrence in patients with SGC., (© 2020 Wiley Periodicals, Inc.)

Background: Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non-ACC., Methods: Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed., Results: Twenty-six patients (50% were male; 6 ACC, 20 non-ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression-free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent., Conclusions: This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature., (© 2019 Wiley Periodicals, Inc.)

Background: The role of molecular markers in salivary gland carcinoma (SGC) is not well understood. We evaluated molecular marker expression and their prognostic value., Methods: Immunohistochemical analysis of 124 tumor specimens was performed to determine expression of androgen (AR), estrogen (ER), and progesterone (PR) receptors and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 receptor (PD-L1), and PD-L1 in tumor-infiltrating mononuclear cell (TIMC). Survival outcomes (disease-free survival [DFS] and overall survival [OS]), pT and N classification, margin status, and treatment failure were assessed., Results: Most patients (78; 62.9%) had early-stage SGC. AR positivity and EGFR positivity were detected in 21.0% and 78.6%, respectively, of tumors. AR positivity and PD-L1 negativity were associated with locally advanced disease. PD-L1-negativity was associated with higher recurrence (38.5% vs 0%; P < .001) and worse DFS. OS and DFS were worse in patients with AR+ or HER2+ disease., Conclusions: Several molecular markers-AR and HER2 positivity and PD-L1 negativity-were associated with worse clinical outcomes. Prospective, multi-institutional trials are needed to determine the prognostic value of these markers., (© 2019 Wiley Periodicals, Inc.)

Background: Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. Apoptosis plays an important role in organogenesis of glandular structures, and aberrations of apoptotic mechanisms is associated with a wide array of pathologic conditions., Methods: The immunoexpression of proteins associated with apoptosis and proliferation was evaluated in 40 mucoepidermoid carcinoma cases., Results: Par-4, Survivin, MUC1, PHLDA1, Fas, and Ki-67 were predominantly expressed in mucoepidermoid carcinoma. FasL was rarely expressed, and Caspase-3 expression was observed in almost 50% of the cases. SPARC expression was associated with low-grade tumors, and Ki-67 expression was associated with lymph node metastasis. Expression of Fas and decreased expression of Ki-67 and Caspase-3 were associated with better overall cancer-specific survival rates., Conclusions: The association of SPARC and Ki-67 expression with pathological features and the association of Fas, Caspase-3, and Ki-67 with survival probabilities suggest that these proteins may be useful prognostic markers for mucoepidermoid carcinoma., (© 2019 Wiley Periodicals, Inc.)

Background: We aimed to investigate the prognostic role of examined (dissected) lymph nodes (ELNs), negative LNs (NLNs), and positive (metastatic) LNs (PLNs) counts and LN ratio (LNR = PLNs/ELNs×100) in patients with major salivary gland cancer (SGC)., Methods: Data were retrieved for major SGC patients diagnosed between 1988 and 2011 from Surveillance, Epidemiology, and End Results program., Results: We have included 5446 patients with major SGC. Most patients had parotid gland cancer (84.61%). Patients having >18 ELNs, >4 PLNs, and >33.33% LNR were associated with a worse survival. Moreover, older age, male patients, grade IV, distant stage, unmarried patients, submandibular gland cancer, and received chemotherapy but not received surgery were significantly associated with a worse survival., Conclusions: We demonstrated that patients with >18 ELNs and >4 PLNs counts, and >33.33% LNR were high-risk group patients. We strongly suggest adding the ELNs and PLNs counts and/or LNR into the current staging system., (© 2019 Wiley Periodicals, Inc.)

Background: Fine-needle aspiration of a salivary gland lesion is a well-established diagnostic procedure that aids management decisions. Recently, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) classification has been proposed in order to improve the reproducibility and communication in the management of salivary gland lesions., Methods: A total of 375 patient's cytological reports collected between January 2010 and December 2017 were reviewed and reclassified according to MSRSGC and a risk of malignancy was calculated for each of the category., Results: The rate of malignancy in MSRSGC classification was 19.0%, 11.8%, 25.0%, 5.5%, 50.0%, 71.4%, and 94.6% for each of the category (I, II, III, IVa, IVb, V, and VI), respectively., Conclusion: The MSRSGC classification is a valuable tool in everyday practice. The modified version of MSRSGC aims to improve the surgical relevance and facilitate uniform management., (© 2019 Wiley Periodicals, Inc.)

Background: The prognostic relevance of extranodal extension (ENE) for salivary gland carcinoma (SGC) remains unclear. The present study is undertaken to investigate the predictive significance of pathological nodal parameters in surgically treated patients with nodal metastatic SGC., Methods: This multicenter cohort included 114 patients with pathologically proven node-positive SGC between 2000 and 2014. Possible correlations of clinicopathological parameters and outcomes were examined., Results: The median follow-up was 69 months (range, 11-173 months). The multivariate analysis identified metastatic node number (1-2 vs 3-6; 1-2 vs ≥7) as an independent predictor for regional control (P = 0.005; P = 0.02), locoregional control (P = 0.008; P = 0.04), distant metastasis-free survival (P = 0.17; P = 0.006), disease-free survival (P = 0.05; P = 0.002), and overall survival (P = 0.18; P = 0.009), whereas ENE was not associated with survival outcomes., Conclusions: Metastatic node number, not ENE, is an independent node-related prognosticator for SGC. Integration of ENE into the American Joint Committee on Cancer 8th edition staging criteria may not improve prognostic performance., (© 2019 Wiley Periodicals, Inc.)

Background: The role of elective neck dissection in the management of major salivary gland adenoid cystic carcinoma is unclear., Methods: Data were retrospectively extracted from the National Cancer Center Database. The study cohort included 1504 patients with adenoid cystic carcinoma of major salivary glands with clinical N0 necks who were treated with surgery between 2004 and 2014. The cohort was divided into four groups based on number of lymph nodes (LNs) examined on pathology: 0, 1-8, 9-17, and ≥18 LNs., Results: The rate of occult nodal metastasis was 9.0%. Number of LNs removed was not associated with survival (Reference, 0 LNs; HR = 0.98, 95% CI 0.73-1.32 for 1-8 LNs; HR = 1.22, 95% CI 0.80-1.88 for 9-17 LNs; HR = 0.94, 95% CI 0.61-1.46 for ≥18 LNs) after adjusting for important covariates., Conclusions: LN sampling is not associated with survival in cN0 major salivary gland ACC., (© 2019 Wiley Periodicals, Inc.)

Background: Our aim was to identify the number of cases of secretory carcinoma (SC) of the major salivary gland in a population-based cohort and review its clinical behavior with long-term follow-up., Methods: All malignant salivary gland tumors (MSGTs) diagnosed between 1980 and 2014 were assessed for histological features compatible with SC and 140 were selected for further analysis., Results: Twenty two new cases of SC were identified, 19 of which were originally classified as acinic cell carcinoma, and 3 as adenocarcinoma, not otherwise specified (NOS). Lymph node involvement was less common in SC tumors (5%) than in the control group (11%). Disease recurrence was seen less frequently in SC (9%) than the control group (20%). Mean disease-free survival was 192 months for SC compared with 162 months for controls (P = 0.15)., Conclusion: The clinical course of SC is typically indolent with a low risk of relapse not significantly different from other low-grade MSGT., (© 2018 Wiley Periodicals, Inc.)

The aim of this meta-analysis is to evaluate myeloblastosis (MYB) as a prognostic marker for patients with adenoid cystic carcinoma (ACC) with respect to MYB gene fusion, MYB protein expression, and tumor sites. We comprehensively searched PubMed, Embase, Web of Science, and Cochrane libraries. Ten studies concerning the prognostic comparisons between MYB positivity and negativity were included. The combined positive rates of MYB gene fusion and protein expression were 57.2% and 62.3%, respectively. Overall, no significant prognostic differences were observed between MYB-positive and MYB-negative ACCs. When further divided into MYB gene fusion and MYB protein expression subgroups, no significant differences were observed for any survival outcome (overall survival, disease-free survival, and local control rate). Moreover, MYB also demonstrated no prognostic value in head and neck ACCs. In conclusion, the current studies reveal that MYB is not a good prognostic marker for ACC., (© 2019 Wiley Periodicals, Inc.)

Background: Salivary gland neoplasms are relatively rare and comprise only 1%-4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown., Method: We generated an inducible Tet-MAP3K8::MMTV-rTA mouse model by crossing the MAP3K8 transgenic mice with MMTR-rTA transgenic mice to express MAP3K8 in the salivary gland., Results: MAP3K8 overexpression in the murine salivary glands of Tet-MAP3K8::MMTR-rTA transgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC)., Conclusion: MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type., (© 2019 Wiley Periodicals, Inc.)

Background: The purposes of this study were to describe the characteristics of a prospective multicenter series of patients with salivary duct carcinoma and to investigate prognostic factors., Methods: Patients included for salivary duct carcinoma between 2009 and 2016 in the Réseau d'Expertise Français des Cancers ORL Rares (REFCOR) database were selected. Immunohistochemical analyses were performed., Results: Sixty-one patients were included in this study. The primary site was the parotid gland in 90% of the cases. Fifty-seven percent of the tumors were stage IV, 65% of patients had lymph node involvement, and 10% had metastases. Tumors showed androgen receptor (89%) and human epidermal growth factor receptor 2 (HER2)/neu (36%). Ninety-four percent of patients underwent surgery and 86% had postoperative radiotherapy. Six patients were treated with targeted therapies. The 3-year overall survival (OS) was 74% and the 3-year disease-free survival (DFS) was 44%. Tumor stages III to IV reduced DFS (hazard ratio [HR] 4.3; P = .04). The N2/3 class reduced distant metastasis-free survival (HR 7.3; P = .007)., Conclusion: Salivary duct carcinoma prognosis is poor and is correlated with tumor stage and lymph node classification. Androgen receptor and HER2/neu should be tested as they offer the possibility of targeted therapies., (© 2018 Wiley Periodicals, Inc.)

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend considering postoperative radiotherapy (PORT) for completely resected T1/2N0M0 salivary mucoepidermoid carcinomas when they show tumor spillage, perineural invasion, or intermediate/high-grade histology. CRTC1/3-MAML2 fusions have been associated with a favorable clinical outcome., Methods: Forty-seven T1/2N0M0 mucoepidermoid carcinoma cases positive for CRTC1/3-MAML2 fusions were completely resected and were not treated with PORT., Results: Pathologically, none of the cases showed tumor spillage or perineural invasion. Cases with intermediate/high-grade histology numbered 9 (19%) to 26 (55%) with the currently used 3 different grading systems. During the follow-up (median 60 months), locoregional tumor recurrence occurred in 4 cases, which were treated with surgery alone. At the last follow-up (median 60 months; 7-160), all patients were alive with no evidence of disease., Conclusion: An excellent prognosis may be achieved without PORT in T1/2N0M0 mucoepidermoid carcinoma patients positive for CRTC1/3-MAML2 fusions when the tumors are completely resected without tumor spillage., (© 2018 Wiley Periodicals, Inc.)

Background: Alterations in the human epidermal growth factor receptor-2 (HER2) pathway have been identified in a subset of salivary duct carcinomas. Dual HER2 inhibition with trastuzumab and pertuzumab has superior antitumor efficacy to trastuzumab monotherapy in HER2-positive breast cancer, yet its efficacy in HER2-positive salivary duct carcinoma is unknown., Methods: We report 2 cases of exceptional responses of HER2-positive salivary duct carcinomas to dual HER2 blockade and docetaxel combination and their molecular characteristics., Results: A 54-year-old man with recurrent metastatic HER2 expressing salivary duct carcinoma of the parotid gland after definitive concurrent chemoradiation achieved a complete response (CR) after 6 cycles of trastuzumab, pertuzumab, and docetaxel (TPH). A 42-year-old woman with HER2-positive salivary duct carcinoma of the parotid gland with bone and liver metastases had CR with TPH and remains in remission on maintenance trastuzumab and pertuzumab., Conclusion: Dual HER2 blockage resulted in CR in patients with HER expressing salivary duct carcinoma and warrants further evaluation in this patient population., (© 2018 Wiley Periodicals, Inc.)

Background: Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors., Methods: A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure., Results: Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06)., Conclusion: Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival., (© 2018 Wiley Periodicals, Inc.)

Background: Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features., Methods: A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted., Results: Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705)., Conclusion: Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to investigate the performance of the Memorial Sloan Kettering Cancer Center salivary carcinoma nomograms predicting overall survival, cancer-specific survival, and recurrence with an external validation dataset., Methods: The validation dataset comprised 123 patients treated between 2010 and 2015 at our institution. They were evaluated by assessing discrimination (concordance index [C-index]) and calibration (plotting predicted vs actual probabilities for quintiles)., Results: The validation cohort (n = 123) showed some differences to the original cohort (n = 301). The validation cohort had less high-grade cancers (P = .006), less lymphovascular invasion (LVI; P < .001) and shorter follow-up of 19 months versus 45.6 months. Validation showed a C-index of 0.833 (95% confidence interval [CI] 0.758-0.908), 0.807 (95% CI 0.717-0.898), and 0.844 (95% CI 0.768-0.920) for overall survival, cancer-specific survival, and recurrence, respectively., Conclusion: The 3 salivary gland nomograms performed well using a contemporary validation dataset, despite limitations related to sample size, follow-up, and differences in clinical and pathology characteristics between the original and validation cohorts., (© 2018 Wiley Periodicals, Inc.)

Background: This study examined the microtubule inhibitor eribulin in recurrent/metastatic salivary gland cancers (RMSGCs), a disease where no therapeutic standard exists., Methods: This phase II clinical trial treated patients with progressive recurrent/metastatic salivary gland cancers with eribulin 1.4 mg/m 2 i.v. on days 1 and 8 of a 21-day cycle until disease progression/unacceptable toxicities. The primary endpoint was the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 objective response rate., Results: Between May 2012 and August 2015, 29 patients were enrolled in this study. The median age was 63 years (range 34-75 years) and 20 of the subjects were men (69%). The most common histologies were adenoid cystic carcinoma (ACC; n = 11) and adenocarcinoma (n = 4). Neutropenia was the most common toxicity (grade 3; n = 5; 17% and grade 4 n = 3; 10%). The objective responses were observed in 3 of 29 patients (10%), 20 of 29 patients (69%) demonstrated a decrement in tumor size, and disease control was observed in 26 of 29 patients (90%)., Conclusion: Although the objective responses to eribulin were uncommon, disease control was observed in the majority of patients., (© 2017 Wiley Periodicals, Inc.)

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT)., Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care., Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02)., Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017., (© 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.)

Background: The purpose of this study was to investigate the efficacy and safety of vinorelbine plus cisplatin chemotherapy in patients with recurrent and/or metastatic salivary gland cancer of the head and neck., Methods: In this single-arm phase II study, patients with recurrent and/or metastatic salivary gland cancer were treated with i.v. vinorelbine (25 mg/m 2 ) on days 1 and 8 plus cisplatin (80 mg/m 2 ) on day 1 every 3 weeks for 4 or 6 cycles. The primary endpoint was the objective response rate. Progression-free survival (PFS), overall survival (OS), and adverse events were also assessed., Results: Between September 2008 and November 2014, 40 patients with recurrent and/or metastatic salivary gland cancer received vinorelbine plus cisplatin chemotherapy. The objective response rate was 35.0%, including 1 complete response. Median PFS and OS rates were 6.3 months and 16.9 months, respectively. No treatment-related deaths occurred., Conclusion: Administering vinorelbine plus cisplatin chemotherapy to patients with recurrent and/or metastatic salivary gland cancers is safe and effective., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to establish an effective prognostic nomogram for carcinoma ex pleomorphic adenoma (Ca-ex-PA) of the salivary gland., Methods: The nomogram was based on a retrospective study on 223 patients who underwent surgical operation for Ca-ex-PA from 2001 to 2010. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling and a prospective study on 111 patients operated on from 2011 to 2012., Results: On multivariate analysis of the primary cohort, independent factors for disease-specific survival (DSS) were age, tumor diameter, degree of capsule invasion, lymph node metastasis, and the interaction between tumor site and histological subtype, which were all selected into the nomogram. The C-index of the nomogram for predicting DSS was 0.90 and 0.86 in the primary cohort and validation cohort, respectively., Conclusion: The proposed nomogram resulted in more accurate prognostic predictions for patients with Ca-ex-PA., (© 2017 Wiley Periodicals, Inc.)

Background: Mammary analog secretory carcinoma of the salivary glands (MASC SG ) is a newly introduced malignant tumor of the salivary glands. For decades, it has been confused with acinic cell carcinoma (ACC) of the salivary glands., Methods: All reported cases of MASC SG were surveyed from 2010 until January 2017. The collected data was compiled and computationally processed to describe the clinical parameters of MASC SG . Its epidemiology was also mapped. Moreover, inaccurate data was highlighted., Results: Clinically implicating, this article tackles simply the several clinical findings of MASC SG so that our contemporary nosology, at 7 years after description, can be updated. The cytogenetic, histologic, and immunohistochemical details are also defined., Conclusion: The available data about MASC SG is sufficient enough to diagnose it with no need to investigate the ETV6-NTRK3 translocation. Although high-grade malignancy and distant metastases were rarely reported, a rapt attention should be paid both to the nature of this tumor and to the indicated close follow-up of such cases, especially when necrosis, increased mitotic activity, and other classic caveats are conspicuous. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1243-1248, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported., Methods: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data., Results: Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rβ were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rβ expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively., Conclusion: High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1145-1154, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to test the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting recurrence risk of major salivary gland carcinoma in an Asian cohort., Methods: We retrospectively enrolled 149 patients who had undergone intended curative resections for major salivary gland carcinoma between 2007 and 2012. The performance of the MSKCC nomogram and the American Joint Committee on Cancer (AJCC) seventh staging system in predicting recurrence risk was compared., Results: The MSKCC nomogram and the AJCC staging system both accurately predicted the 5-year recurrence probabilities, with the concordance index (c-index = 0.82; 95% confidence interval [CI], 0.75-0.89 vs c-index, 0.77; 95% CI, 0.68-0.87; p = .45) in patients with major salivary gland carcinomas after curative surgeries. Comparing to the actual observed events, the calibration plot indicated that the MSKCC nomogram accurately estimated the recurrence in low-risk groups but tended to overestimate in high-risk groups. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the prediction was very good for patients with AJCC stages I and II disease (c-index = 0.92 and 0.90, respectively) and modest for those of AJCC stages III and IVa (c-index = 0.51 and 0.62, respectively)., Conclusion: The MSKCC nomogram and the AJCC staging system each had its value in predicting recurrence of major salivary gland cancers. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the MSKCC nomogram was more accurate in predicting recurrence risks in those patients with AJCC stage I and II diseases than those with late-stage diseases. © 2017 Wiley Periodicals, Inc. Head Neck 39: 860-867, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: Salivary ductal carcinoma and carcinoma ex pleomorphic adenoma (CEPA) are aggressive salivary gland cancers with poor prognosis. The standard of care is resection with or without radiotherapy, and there are no established systemic therapy options., Methods: We describe 1 patient with metastatic CEPA and 1 patient with metastatic recurrent salivary duct carcinoma whose tumors were evaluated by comprehensive genomic profiling. Testing identified human epidermal growth factor receptor 2 (HER2) amplification in both patients, and an additional activating HER2 mutation in the CEPA case., Results: Both patients were treated with the HER2-targeting monoclonal antibody trastuzumab (herceptin) plus chemotherapy and experienced rapid responses. Subsequently, both patients were given single-agent maintenance trastuzumab and continue to experience durable disease control., Conclusion: Given the poor prognosis for salivary gland cancers and the limited treatment options upon recurrence or metastasis, patients should be tested for all classes of HER2 alterations. In cases with HER2 overexpression or activation, targeted therapies, such as trastuzumab are promising. © 2016 Wiley Periodicals, Inc. Head Neck 39: E40-E44, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: Hyalinizing clear cell carcinoma (HCCC) is a rare malignancy, characterized by EWSR1-ATF1 gene fusion, whose behavior is poorly understood, as it was for many years considered a diagnosis of exclusion., Methods: All available salivary gland carcinomas (n = 594) from our institution were reviewed. Diagnosis of HCCC was confirmed by fluorescence in situ hybridization (FISH) for EWSR1. Literature review was performed., Results: We found 15 patients with HCCCs (10 women, 5 men), 13 with EWSR1 rearrangement. Median age at diagnosis was 57 years (range, 31-87 years). Oral cavity (n = 9) and base of tongue (n = 4) were the most frequent primary sites. Combining our cases with those identified in literature review, the 10-year risk of local recurrence and locoregional nodal metastasis were 49% and 15%, respectively., Conclusion: Molecularly confirmed HCCC accounted for 2.5% of salivary gland malignancies at our institution. HCCCs are indolent tumors with a propensity for locoregional recurrence. © 2016 Wiley Periodicals, Inc. Head Neck 39: 503-511, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: The purpose of this study was to present our preliminary exploration of safety and efficacy of postoperative low-dose-rate brachytherapy for the early clinical stages of minor salivary gland carcinomas of the lip and buccal mucosa., Methods: Twenty-seven patients with the early stages of minor salivary gland carcinomas of the lip and buccal mucosa received postoperative 125 I seed interstitial brachytherapy from March 2005 to May 2015. Actuarial likelihood estimates for local control, overall survival, and disease-free survival were calculated by Kaplan-Meier method., Results: The actuarial 3-year, 5-year, and 10-year local control rates were 94.7%, 82.9%, and 82.9%, respectively. The actuarial 3-year, 5-year, and 10-year overall survival rates were 93.3%, 93.3%, and 77.8%, respectively. No patient experienced toxicity above grade 2., Conclusion: Postoperative 125 I seed interstitial brachytherapy is an alternative to radical surgery for early stages of minor salivary gland carcinomas of the lip and buccal mucosa, which offers satisfactory cosmetic and functional outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 572-577, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: Salivary duct carcinoma is a rare, aggressive tumor entity first described by Kleinsasser et al in 1968, as a group of malignant salivary gland tumors characterized by duct formation and central necrosis. A case with an unusual localization in the nasal cavity and maxillary sinus is being described in our report., Methods: A 60-year-old patient presented with difficulty of nasal breathing and recurrent episodes of epistaxis from the left nasal cavity over the previous 3 months. On endoscopy, a vulnerable lesion in the left inferior nasal meatus could be seen. Biopsy showed salivary duct carcinoma. Treatment consisted of tumor resection by means of a combined endoscopic-osteoplastic surgical approach to the maxillary sinus, bilateral neck dissection, partial parotidectomy, and adjuvant radiochemotherapy., Results: The patient is 6 months after completion of treatment and is free of disease., Conclusion: As salivary duct carcinoma of the sinonasal tract is extremely rare, no therapeutic standards have been developed and treatment essentially is based upon experience with ductal adenocarcinoma of the salivary glands. Surgery therapy should be radical, aiming at eradicating locoregional disease with the role of adjuvant radiotherapy lying in the management of cases with negative prognostic factors. © 2016 Wiley Periodicals, Inc. Head Neck 38:E2464-E2466, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Malignant salivary gland neoplasms are rare in children. The purpose of this study was to present our experience in the treatment of primary and recurrent salivary gland neoplasm and contribute to the fractional available data., Methods: All patients <18 years, treated between June 2005 and April 2014 were included in this study., Results: The parotid gland was the most common site for both primary (n = 18) and recurrent (n = 6) tumors and mucoepidermoid carcinoma, low or intermediate grade, main histological type. Surgical excision was performed in all patients, of which 13 patients received radiotherapy. Lymph node metastasis was present in 3 patients with primary tumor, which were assessed accurately on frozen section examination. Local recurrence occurred in 1 patient with primary tumor and all patients are alive., Conclusion: Surgery is the prime modality of treatment for malignant salivary gland neoplasm and is associated with excellent outcomes. The role of lymph node sampling and frozen section examination needs further evaluation in identifying lymph node metastasis. © 2015 Wiley Periodicals, Inc. Head Neck 38: 852-856, 2016., (© 2015 Wiley Periodicals, Inc.)

Objectives: This study aimed to assess multiple factors influencing the outcomes of ultrasound (US)-guided fine-needle aspiration (FNA) of salivary gland lesions., Methods: From 2008 to 2013, a single radiologist performed US-guided FNA of salivary gland lesions in 243 patients. With the exclusion of pure cysts, poor image quality, and insufficient static image cases, 218 salivary gland lesions in 218 patients were included. The composition, size, location, and vascularity of the lesions were retrospectively investigated on the basis of sonographic findings by the same radiologist. The relationship between sampling adequacy and multiple factors was compared, and the diagnostic accuracy of US-guided FNA of salivary gland lesions was calculated by using the final diagnosis as a reference standard., Results: The sampling adequacy rate for US-guided FNA of the 218 salivary gland lesions was 96.8% (211 of 218). A significant difference was observed in the composition and vascularity of the lesions (P < .0001), whereas there was no significant difference in the patient age and sex, lesion size, lesion location, and needle size. The rate of inadequate sampling increased in predominantly cystic lesions compared with solid lesions as well as in low-vascularity lesions compared with high-vascularity lesions. Of the 218 lesions, 178 (81.7%) were ultimately diagnosed, and most were benign (162 of 178 [91.0%]). When 3 cases with indeterminate cytologic results were excluded, the sensitivity, specificity, positive and negative predictive values, and accuracy of US-guided FNA of salivary gland lesions were 64.3%, 98.8%, 81.8%, 97.0%, and 96.0%, respectively., Conclusions: When using US-guided FNA to diagnose salivary gland lesions, sampling adequacy depends on the composition or vascularity of the lesions., (© 2016 by the American Institute of Ultrasound in Medicine.)