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Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. METHODS: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p

Aim Materials and methods Results Conclusion Although immune checkpoint inhibitors (ICPi) for salivary gland cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi.We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high‐grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next‐generation sequencing.ACC and MEChigh showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumors showed a positive correlation with programmed cell death‐ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumors (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumors (r = ‐0.049).The TIME of ACC was the so‐called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune‐inflamed type, and this may support the rationale of ICPi for this pathological subtype. [ABSTRACT FROM AUTHOR]

Our goal was to assess the impact of childhood/adolescent cancer history on overall survival (OS) and disease-specific survival (DSS) in patients with parotid mucoepidermoid carcinoma (MEC). Patients who underwent surgical treatment for primary parotid MEC and those with a second malignancy of parotid MEC were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome variables were OS and DSS. The hazard ratios (HRs) of these survival rates associated with cancer history were analysed using Cox regression models. In total, 2681 patients were included, 263 of whom had a second malignancy. The 10-year OS rates in the primary (72%) and second malignancy groups (59%) were significantly different. Cox regression confirmed that a history of cancer tended to decrease OS (p = 0.062, HR: 1.28, 95% confidence interval: 0.99 to 1.64). Subgroup analyses showed that a history of solid tumour as opposed to haematological cancer predicted worse OS, with central nervous system tumours exhibiting a more significant influence than others (p = 0.030 vs p = 0.088). Cancer history was not related to DSS. A history of childhood/adolescent cancer negatively influenced the prognosis of patients with parotid MEC, and this effect was primarily driven by a history of solid malignancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C‐CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C‐CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC. [ABSTRACT FROM AUTHOR]

Introduction: The main obstacle in treating cancer patients is drug resistance. Lenvatinib treatment poses challenges due to loss of response and the common dose-limiting adverse events (AEs). The Constrained-disorder-principle (CDP)- based second-generation artificial intelligence (AI) systems introduce variability into treatment regimens and offer a potential strategy for enhancing treatment efficacy. This proof-of-concept clinical trial aimed to assess the impact of a personalized algorithm-controlled therapeutic regimen on lenvatinib effectiveness and tolerability. Methods: A 14-week open-label, non-randomized trial was conducted with five cancer patients receiving lenvatinib--an AI-assisted application tailored to a personalized therapeutic regimen for each patient, which the treating physician approved. The study assessed changes in tumor response through FDG-PET-CT and tumor markers and quality of life via the EORTC QLQ-THY34 questionnaire, AEs, and laboratory evaluations. The app monitored treatment adherence. Results: At 14 weeks of follow-up, the disease control rate (including the following outcomes: complete response, partial response, stable disease) was 80%. The FDG-PET-CT scan-based RECIST v1.1 and PERCIST criteria showed partial response in 40% of patients and stable disease in an additional 40% of patients. One patient experienced a progressing disease. Of the participants with thyroid cancer, 75% showed a reduction in thyroglobulin levels, and 60% of all the participants showed a decrease in neutrophil-to-lymphocyte ratio during treatment. Improvement in the median social support score among patients utilizing the system supports an ancillary benefit of the intervention. No grade 4 AEs or functional deteriorations were recorded. Summary: The results of this proof-of-concept open-labeled clinical trial suggest that the CDP-based second-generation AI system-generated personalized therapeutic recommendations may improve the response to lenvatinib with manageable AEs. Prospective controlled studies are needed to determine the efficacy of this approach. [ABSTRACT FROM AUTHOR]

Background: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection. Methods: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis. Results: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)—radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively. Conclusions: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account. [ABSTRACT FROM AUTHOR]

While several studies reported epidermal growth factor receptor (EGFR) expression in salivary gland cancer (SGC), results varied due to a lack of unified definition of EGFR positivity. In this study, we assessed the EGFR expression level using both EGFR positive score and cumulative EGFR score in the patients with SGC. Between January 2010 and April 2021, 102 patients with SGC who underwent surgical resection were reviewed retrospectively by immunohistochemistry. The membrane staining intensity was scored as follows: no staining (0), weak staining (1+), intermediate staining (2+), and strong staining (3+). The cumulative EGFR score was determined on a continuous scale of 0–300 using the formula:1 × (1+: percentage of weakly stained cells) + 2 × (2+: percentage of moderately stained cells) + 3 × (3+: percentage of strongly stained cells). EGFR expression in SGC varied widely even among the same as well as different histopathological types. The average EGFR positive scores were 46.0 %, 55.7 %, 51.6 %, 1.0 %, 26.8 %, 50 %, and 76.8 % for mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma NOS (ACNOS), carcinoma ex pleomorphic adenoma (CAexPA), and squamous cell carcinoma (SqCC), respectively. The average cumulative EGFR scores were 82, 91, 80, 1, 52, 93, and 185 for MEC, SDC, AdCC, AcCC, ACNOS, CAexPA, and SqCC, respectively. EGFR positive scores and cumulative EGFR scores in SGCs varied among the various histological types, and even in the same histological type. These scores may predict the clinical outcome of SGC treated with EGFR-targeting therapies, such as head and neck photoimmunotherapy, and need to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

To determine the indications for radiotherapy in salivary gland cancer and to specify the modalities and target radiation volumes. The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. Postoperatively, radiotherapy to the primary tumor site ± to the lymph nodes is indicated if one or more of the following adverse histoprognostic factors are present (risk > 10% of locoregional recurrence): T3–T4 category, lymph node invasion, extraglandular invasion, close or positive surgical margins, high tumor grade, perineural invasion, vascular emboli, and/or bone invasion. Intensity-modulated radiation therapy (IMRT) is the gold standard. For unresectable cancers or inoperable patients, carbon ion hadrontherapy may be considered. Radiotherapy in salivary gland cancer is indicated in postoperative situations in case of adverse histoprognostic factors and for inoperable tumors. [ABSTRACT FROM AUTHOR]

To determine the indications for neck dissection in the management of parotid, submandibular or minor salivary gland cancers depending on the clinical situation: i.e., clinical lymph node involvement (cN+) or not (cN0); low or high risk of occult nodal metastasis; diagnosis of malignancy before, during or after surgery. The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. In cN+ salivary gland cancer, ipsilateral neck dissection is recommended. In cN0 salivary gland cancer, ipsilateral neck dissection is recommended, except for tumors at low risk of occult nodal metastasis. If definitive pathology reveals a high risk of occult nodal involvement, additional neck treatment is recommended: ipsilateral neck dissection or elective nodal irradiation. The rate of occult lymph node involvement, and therefore the indication for elective neck dissection, depends primarily on the pathologic grade of the salivary gland cancer. [ABSTRACT FROM AUTHOR]

Introduction: The characterization of circulating tumor cells (CTC) and circulating tumor microemboli (CTM) has emerged as both a challenge to the standard view of metastasis, and as a valuable means for understanding genotypic and phenotypic variability shown even within the same cancer type. However, in the case of salivary gland neoplasms, limited data are available for the role that CTCs and CTMs play in metastasis and secondary tumor formation.ru.AQ1 In response to this, we propose that similarities between in vitro clusters of cultured salivary gland cancer cells may act as a surrogate model for in vivo CTCs and CTMs isolated from patients. Materials and Methods: Using techniques in immunofluorescence, immunoblotting, and 2-dimensional migration, we isolated and characterized a group of cohort cells from a commercially available cell line (HTB-41). Results: Here, cells exhibited a hybrid phenotype with simultaneous expression of both epithelial and mesenchymal markers (E-cadherin, vimentin, and α-SMA). Cohort cells also exhibited increased migration in comparison to parental cells. Conclusion: Data suggest that these isolated cell clusters may fucntion as a potential in vitro model of CTCs and CTMs. [ABSTRACT FROM AUTHOR]

This article explores the use of 18F-choline-PET/CT imaging for non-FDG-avid salivary gland cancer. Salivary gland tumors are rare and have diverse characteristics. While cross-sectional imaging with contrast-enhanced CT or MRI is the standard for initial staging, FDG-PET has also been used. However, some tumors do not show high FDG uptake, so the study aimed to assess the potential of the non-FDG tracer 18F-choline. The study included five patients with malignant salivary gland tumors and found promising results. Choline-PET was found to be somewhat superior to FDG-PET for salivary gland cancer, especially for low-grade tumors and adenoid cystic carcinoma. However, the high background uptake of choline affected the evaluation of the primary tumor. The authors concluded that more specific radiopharmaceuticals are needed for certain types of primary salivary gland carcinoma. [Extracted from the article]

Objective: The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. Methods: Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. Results: A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36–4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17–3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. Conclusion: Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC. [ABSTRACT FROM AUTHOR]

Background: Low-grade salivary gland carcinoma is regularly treated with surgical therapy of the salivary gland without elective neck dissection in T1/2 carcinomas, either alone or with adjuvant radiation therapy. However, occult metastasis and locoregional recurrence influence therapy and outcome. Tumor budding is an emerging prognostic pathological factor in many carcinomas, but has not yet been adequately considered in salivary gland carcinomas. Methods: We conducted a retrospective single-center study of 64 patients diagnosed with low-grade carcinoma of themajor salivary glands treated between 2003 and 2017. Pathological risk factors andTNMclassificationwere thoroughly assessed foreach case. All hematoxylin and eosin (HE)-stained histological specimens underwent careful examination, and tumor budding was identified following the guidelines set forth by the International Tumor Budding Consensus Conference in 2016. Results: Tumor budding was not statistically significant concerning 5-year survival rate (5-YSR) (p=0.969) and mean overall survival (log-rank p=0.315). Whereas 5-year disease-free survival rate (5-YDFSR) was 87% in the low tumor budding group and 61.1%in the intermediate and high tumorbuddinggroup(p=0.021). Meandisease-free survival accounted for 100.2 months (CI: 88.6;111.9) in the low budding score group and 58.7months (CI: 42.8;74.6) in the other group (log-rank p=0.032). Notably, pT1/2 showed significantly lower tumor buds than pT3/4 stages (2.43 tumor buds/0.785 mm² vs. 4.19 tumor buds/0.785 mm² p=0.034). Similar findings were noted comparing nodal-positive and nodal-negative patients, as well as patients with and without lymphovascular invasion and perineural invasion (each p<0.05). Conclusions: Tumor budding might be used as an additional prognostic factor for recurrence in low-grade salivary gland carcinoma, seemingly associated with a higher nodal metastasis rate and advanced tumor stages and a worse 5-YDFSR. Consequently, the evaluation of tumor budding in resection specimens of lowgrade salivary gland tumor may prove valuable in decision-making for neck dissection and follow-up strategy. [ABSTRACT FROM AUTHOR]

Introduction: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of 177Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. Methods: An extensive literature search was performed in three different databases using different combinations of the following terms: "Lu-PSMA", "177Lu-PSMA", "preclinical", "mouse", "salivary gland cancer", "breast cancer", "glioblastoma", "solid tumour", "renal cell carcinoma", "HCC", "thyroid", "salivary", "radioligand therapy", and "lutetium-177". The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. Results: A total of four preclinical studies were selected (breast cancer model n = 3/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. Conclusions: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the low incidence, heterogeneous behavior, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This is the first systematic review and meta-analysis to report the cumulative evidence on postoperative radiotherapy (PORT) for SGC of the head and neck. Based on 2962 patients with SGC from 26 studies, this study demonstrated the long-term survival and toxicities of PORT as a local treatment modality for SGC. Considering the suboptimal disease-free survival and distant metastasis-dominant recurrent patterns, however, an intensified treatment strategy is needed. Background: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. Results: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56–66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0–100%), 40% (0–77%), and 31% (0–75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89–94%), 89% (95% CI, 86–93%), and 84% (95% CI, 73–92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70–83%), 67% (95% CI, 60–74%), and 61% (95% CI, 55–67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79–88%), 75% (95% CI, 72–79%), and 68% (95% CI, 62–74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3–14%). Conclusion: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Secretory carcinoma, previously known as mammary analog secretory carcinoma, is a rare malignancy of salivary glands. It has a diversity of microscopic patterns and is similar to other salivary gland tumors. Case Report: This report presents the case of a 32-year-old female patient with a painless swelling of the upper lip and a history of recent surgery for an immature ovarian teratoma. The microscopic sections revealed a circumscribed neoplasm composed of macrocystic, papillary-cystic, and microcystic patterns with bland vesicular nuclei and vacuolated cytoplasm. Tumoral cells were strongly positive for mammaglobin, SOX10, GATA3, S-100, and vimentin. The diagnosis of salivary gland secretory carcinoma was made. After 22 months, there has been no recurrence. Conclusions: As secretory carcinoma is a relatively new entity, it is necessary to understand its characteristics. Although the overall incidence of second primary cancer in patients with salivary gland cancers is low, the possibility of its presence in such patients should be considered. [ABSTRACT FROM AUTHOR]

Epidemiological evidence on myoepithelial carcinoma is rare. This study aimed to investigate the effect of tumor primary site and treatment modality on survival in patients with head and neck myoepithelial carcinoma. Data on adult patients diagnosed with head and neck myoepithelial carcinoma between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Uni- and multivariable Cox proportional hazard models were utilized to evaluate the effects of different tumor primary sites and treatment modalities on overall survival (OS) and cancer-specific survival (CSS), and expressed as hazard ratio (HR) and 95% confidence interval (CI). A total of 415 patients were enrolled. No significant differences in OS and CSS were found between different tumor primary sites (P > 0.05). Compared with partial excision, patients with total excision (HR = 1.65, 95%CI: 1.12–2.42) (partial or total removal of the organ in which the tumor is located and complete removal of the tumor) or no surgery (HR = 3.52, 95%CI: 2.05–6.03) had worse OS. Compared with surgery only, patients with radiotherapy only had poorer OS (HR = 4.69, 95%CI: 2.32–9.46) and CSS (HR = 6.72, 95%CI: 2.59–17.46), while no significant differences in OS (P = 0.120) and CSS (P = 0.847) were found among patients who received surgery combined with radiotherapy. In patients with AJCC III/IV, patients with radiotherapy only (HR = 4.51, 95%CI: 1.61–12.62) had poorer OS compared to those with surgery only, whereas patients who received surgery combined with radiotherapy had better OS (HR = 0.50, 95%CI: 0.29–0.89). The tumor primary site may not affect the prognosis of patients with myoepithelial carcinoma, while the effect of treatment modality on prognosis is related to the primary site and stage of the tumor. • Primary site may not affect the survival of patients with myoepithelial carcinoma. • Total organ excision may be related to worse OS/CSS compared to partial excision. • Surgery plus radiotherapy did not show better survival compared to surgery alone. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We aim to evaluate the role of elective neck dissection (END) and adjuvant radiation on survival in N0 high‐grade mucoepidermoid carcinoma (MEC). Study Design: Retrospective cohort study. Setting: National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods: All patients diagnosed with high‐grade MEC with node‐negative disease (N0) from 2004 to 2018 were included. Demographic, clinicopathologic, treatment, and outcomes were analyzed. Kaplan‐Meier survival curves were used to evaluate 5‐year disease‐specific survival (DSS) and 5‐year overall survival (OS). Multivariate Cox regression analysis was used to control for confounders. Results: A total of 310 patients with high‐grade MEC and N0 (clinical and pathologic) disease were identified. The parotid was the most common primary site (266, 86%). Of included patients, 133 (42.9%) were T3‐T4 tumors and 212 (68%) received adjuvant radiation. END was performed on 223 (71.9%) of cases. END in T3‐T4 high‐grade MEC led to significant improvements in DSS (74.3% vs 34.0%, P <.01) and OS (55.2% vs 20.5%, P <.01) as compared to no END. Subanalysis shows that in patients who received neck dissections and were pathologic N0, adjuvant radiation had no impact on DSS (84.0% vs 72.1%, P =.45) and OS (52.1% vs 55.8%, P =.91). Benefits persisted when controlling for confounders using multivariate Cox proportional regression. Conclusion: Patients with T3‐T4 high‐grade MEC who underwent END and found to be pathologically node‐negative (pN0) had significantly improved 5‐year DSS and 5‐year OS than patients who were cN0 and did not undergo END. Importantly, although 68% of patients received adjuvant radiation, we show no benefit of this treatment modality on outcomes in pN0 high‐grade MEC. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma of minor salivary glands (AdCCmSG) represents a 'rarity in the rarity,' posing a clinical challenge in lack of standardized, evidence-based recommendations. At present, AdCCmSG management is mostly translated from major salivary gland cancers (MSGCs). Ideally, AdCCmSG diagnostic-therapeutic workup should be discussed and carried out within a multidisciplinary, high-expertise setting, including pathologists, surgeons, radiation oncologists and medical oncologists. The present review provides an overview of epidemiology and pathologic classification. Moreover, the most recent, clinically relevant updates in the treatment of AdCCmSG (Pubmed searches, specific guidelines) are critically discussed, aiming to a better understanding of this rare pathologic entity, potentially optimizing the care process, and offering a starting point for reflection on future therapeutic developments. The management of rare cancers is often hindered by limited data and clinical trials, lack of evidence-based guidelines, and hardly represented disease heterogeneity, which cannot be successfully tackled with a 'one-size-fits-all' approach. Our goal is to address these potential pitfalls, providing an easy-to-use, updated, multidisciplinary collection of expert opinions concerning AdCCmSG management as of today's clinical practice. We will also cover the most promising future perspectives, based on the potential therapeutic targets highlighted within AdCCmSG's molecular background. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. Methods Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. Results A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36–4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17–3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. Conclusion Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive cancer-related disease with a dismal clinical course. The patient in this report was a 43-year-old man with metastatic salivary duct carcinoma arising from the parotid gland. Combined androgen blockade therapy was administered started as first-line treatment, but failed after 5 months, followed by docetaxel plus carboplatin therapy as second-line treatment, which failed after 3 months. Genomic profiling revealed a BRAF V600E mutation, and combined BRAF and MEK inhibitor therapy was started as third-line treatment. The cancer remained stable during the first 10 months of third-line treatment, but treatment was subsequently discontinued due to the onset of symptoms of fatigue, myalgia and arthritis. Twenty days after the onset of these symptoms and interruption of third-line treatment, the patient was urgently admitted to hospital with respiratory distress and severe thrombocytopenia. CT images at the time of admission led our radiologist to the possibility of PTTM, but the patient died the day after admission and autopsy findings indicated that PTTM was the cause of death. This report describes a very informative case of PTTM with sequential imaging and detailed autopsy findings were available and provides a literature review. [ABSTRACT FROM AUTHOR]

Objective: This population-based study aims to assess the survival benefits of selective neck dissection (SND) compared to neck observation in patients with T1/T2N0M0 major salivary gland malignancy (MSGC). Methods: We conducted a retrospective review of T1/T2N0M0 MSGC patients who underwent primary tumor surgical extirpation with or without elective neck dissection in the Surveillance, Epidemiology, and End Results database (SEER) from 2004-2015. The impact of SND and clinical variables on overall survival (OS) and disease-specific survival (DSS) was evaluated using Univariate and Multivariate Cox proportional hazards regression models. Kaplan-Meier survival curves were generated, and survival rates were assessed via the log-rank test. Results: Of 3778 post-operative T1-T2N0M0 MSGC patients, 2305 underwent elective neck dissection, while 1473 did not. Median follow-up was 106 months. Univariate and Multivariate analysis identified SND as a prognostic factor for OS in all the study population. After stratified analysis, we found that in the poorly high-grade (differentiated and undifferentiated) patients, the survival showed a significant OS and DSS benefit after receiving SND compared with the neck observations [HR for OS (95%CI): 0.571(0.446-0.731), P<0.001] and [HR for DSS (95%CI): 0.564(0.385-0.826), P=0.003], other than in the well differentiated or moderately differentiated subgroup. Especially, when the pathological is squamous cell carcinoma, the results show that the people underwent SND had better prognosis, not only in OS [HR (95%CI): 0.532 (0.322-0.876), P=0.013], but also in DSS [HR (95%CI): 0.330(0.136-0.797), P=0.014]. The multivariate analysis also yielded encouraging results, compared with neck observation, receiving SND bought about a significant independent OS (adjusted HR, 0.555; 95% CI, 0.328-0.941; P=0.029) and DSS (adjusted HR, 0.349; 95% CI, 0.142-0.858; P=0.022) advantage in high grade squamous cell carcinoma MSGC patients. The Kaplan-Meier survival curves also demonstrated that adjusted SND still had significantly better OS(P=0.029) and DSS(P=0.022) than the observation group in patients with high-grade squamous cell carcinoma of MSGC. Conclusion: Poorly differentiated and undifferentiated T1/T2N0M0 major salivary gland malignancy treated with selective neck dissection demonstrated superior survival compared to neck observation, especially in the pathological subtype of squamous cell carcinoma. These findings suggest the potential benefits of multimodal therapy for appropriately selected patients, emphasizing significant clinical implications. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04–1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16–1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01–1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06–1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72–0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83–0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81–0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC. [ABSTRACT FROM AUTHOR]

Background: Oral cavity malignancies mostly affect older adults and the elderly. Adolescents and young adults (15–39 years) are less affected. However, there is a paucity of studies addressing the epidemiology of oral cavity malignancies in these age groups. Objectives: To describe the epidemiology of oral cavity malignancies in adolescents and young adults in Jordan. Patients and methods: The records of ordinarily resident patients in Jordan aged between 15 and 39 years, with histologically confirmed oral cavity malignancies, between the years 2000 and 2017, were analyzed. The frequency of each type of malignancy, incidence, annual percentage, site, age, sex and trends were analyzed. Results: Between the years 2000 and 2017, 406 adolescents and young adults fulfilled the inclusion criteria. This comprised 2.9% of all cancers in this age category during the same period. The mean age was 28.5 ± 7.6 years. Some 59.4% were male and 40.6% female. Regarding marital status, 34.2% were single, 61.6% married, and 0.7% divorced, while the marital status of 3.4% was unknown. Most (98.3%) were Jordanian nationals. The number of cases increased from 4.7% in 2000 to 6.2% in 2017, with no statistically significant trend. The overall age-adjusted incidence rate was 7.8 per 1,000,000. It decreased from 9.4 in 2000 to 6.2 in 2017, with no statistically significant trend over the study period. Nasopharyngeal cancer was the most common (56.9%), followed by cancers of the salivary gland (16.7%), tongue (10.3%), gums (6.2%), lips (5.2%), hypopharynx (2.7%), other oral cavity and pharynx (1.0%), oropharynx (0.5%), floor of mouth (0.2%), and tonsils (0.2%). Overall, the incidence of cancers of the oral cavity and pharynx was higher in males. The incidence of cancers of the nasopharynx, tongue, and lips was higher in males, while salivary gland cancer was higher in females. The incidence of cancers of the gum, hypopharynx, and pharynx did not differ between the sexes. Conclusions: The incidence of oral malignancies in adolescents and young adults in Jordan is relatively high compared to worldwide estimates but is not increasing. Risk factors for these malignancies should be the target of primary prevention interventions. [ABSTRACT FROM AUTHOR]

Sublingual gland herniation into the submandibular space through a mylohyoid muscle defect is a common anatomical variation; however, salivary gland cancers that arise from a herniated sublingual gland have not been described yet. Here, we report three patients with salivary gland cancers originating from a herniated sublingual gland. All tumors were detected as palpable submandibular masses, located anterior to the submandibular gland, medial to the mandible, and lateral to the mylohyoid muscle, with contact with the sublingual gland through a mylohyoid muscle defect. Intraoperative findings confirmed that the masses were derived from herniated sublingual glands. Pathological examination showed one case of mucoepidermoid carcinoma and two cases of adenoid cystic carcinoma. Imaging findings of the tumor location, in addition to the continuity with the sublingual gland through the mylohyoid muscle defect, are crucial for accurately diagnosing the tumor origin, which is essential for determining the appropriate clinical management. [ABSTRACT FROM AUTHOR]

A risk factor for thyroid cancer (TC) may be a history of former cancer and cancer therapy. The precise risk of a second primary thyroid carcinoma has not yet been revealed. In this study, we evaluated standardized incidence ratios (SIRs) of second primary thyroid cancer (SPTC) with consideration of different conditions and further analyzed the clinicopathological characteristics and survival of these patients. The cohort was selected from the US Surveillance, Epidemiology, and End Results (SEER) Program between 1975 and 2019. The standardized incidence ratios, morbidity risk, clinicopathological features, and survival of second primary thyroid carcinoma were analyzed. Propensity score matching (PSM) was used to balance covariates. Kaplan–Meier method was performed to assess the survival outcomes. Overall, 7066 patients with SPTC and 83,113 patients with primary TC were identified. The SIR of TC in tumor patients was 1.51/10,000, statistically higher than the natural population (0.94/10,000, P < 0.05). The most significant tumors contributing to the increased SIRs of SPTC were acute lymphocytic leukemia (3.49/10,000), Hodgkin's lymphoma-nodal (3.29/10,000), salivary gland cancer (3.23/10,000), and kidney and renal pelvis cancer (3.05/10,000). The incidence of TC increased significantly in tumor patients who received radiotherapy/chemotherapy before age 35. The age at diagnosis of the SPTC was much older than the primary TC (64.01 vs. 49.55 years, p < 0.001). The SPTC had a higher percentage of histological grades 3/4 (23.14% vs. 15.19%, p < 0.001). Survival analyses demonstrated a worse prognosis for the SPTC group compared to the primary TC group. But after PSM, the survival outcomes of the two groups tended to be equivalent (P = 0.584). The SIRs of TC are higher in tumor patients. The most significant factors contributing to the increased risk of SPTC were some specific former tumors and acceptance of radiotherapy/ chemotherapy before age 35. There was no significant difference in survival between SPTC and primary TC. [ABSTRACT FROM AUTHOR]

Acinic cell carcinoma is a rare malignant tumor that accounts for 2%-3% of salivary gland tumors. Acinic cell carcinoma arising from the breast is extremely rare, with only approximately 70 cases reported to date. Owing to its rarity, previous studies have primarily focused on pathological findings. Herein, we present the clinical and radiological features of acinic cell carcinoma of the breast in a 33-year-old woman. [ABSTRACT FROM AUTHOR]

This article presents a global population-based study on the distribution and trends of salivary gland cancer. The study utilized data from the Global Cancer Observatory and the Cancer Incidence in Five Continents Plus. The findings reveal that salivary gland cancer burden is higher in regions with higher Human Development Index (HDI) and is associated with lifestyle factors such as smoking and alcohol consumption. The study also highlights a rising trend of salivary gland cancer among females, possibly linked to hormonal factors. However, the study acknowledges limitations in data availability and classification in low-income countries. Further research is needed to understand the complex relationship between socioeconomic factors and salivary gland cancer burden. [Extracted from the article]