Adenoid Cystic Carcinoma, Clinical Presentation, Current Treatment and Approaches Towards Novel Therapies.

Adenoid cystic carcinoma (AdCC) is a rare cancer originating from secretory glands with unknown aetiology. It is one of the most dominant malignant salivary tumours (MST). However, it can arise in other areas of the head and neck region and in secretory glands outside this area. It occurs at all ages, but is more frequent between 50-70 years of age and more common in females than in males. The symptoms of AdCC are generally unspecific and the clinical diagnosis of AdCC maybe challenging, partially due to its heterogenous histopathology and indolent growth. Moreover, there is a lack of good prognostic markers, and due to its rarity, it is difficult to predict which therapeutic methods are the most optimal for each patient, especially since very late recurrences occur. This review presents some major characteristics of AdCC and some current treatments for this disease.

Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020.

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.

Salivary gland carcinoma: Towards a more personalised approach.

Salivary Gland carcinomas (SGCs) are rare tumors accounting for less than 1% of all cancers with 21 histologically diverse subtypes. The rarity of the disease presents a challenge for clinicians to conduct large size randomized controlled trials. Surgery and radiotherapy remain the only curative treatment for localized disease, whereas treatments for recurrent and metastatic disease remain more challenging with very disappointing results for chemotherapy. The different histological subtypes harbor various genetic alterations, some pathognomonic with a diagnostic impact for pathologists in confirming a difficult diagnosis and others with therapeutic implications regardless of the histologic subtype. Current international guidelines urge pathologists to identify androgen receptor status, HER-2 expression that could be determined by immunohistochemistry, and TRK status in patients with non-adenoid cystic salivary gland carcinoma that are eligible to initiate a systemic treatment, in order to offer them available targeted therapies or refer them to clinical trials based on their mutational profile. A more advanced molecular profiling by next generation sequencing would offer a larger panel of molecular alterations with possible therapeutic implications such as NOTCH, PI3K, BRAF, MYB, and EGFR. In the following review, we present the most common genetic alterations in SGCs as well as actionable mutations with the latest available data on therapeutic options and upcoming clinical trials.

Prognostic factors for sublingual gland carcinoma: a population-based Surveillance, Epidemiology and End Results database study.

OBJECTIVE: To identify the clinical features and prognostic factors for sublingual gland carcinoma. METHODS: This was a case-control study. Patients with surgically treated sublingual gland carcinoma were retrospectively included in the Surveillance, Epidemiology and End Results database and divided into adenoid cystic carcinoma (ACC) and non-ACC groups. Primary outcome variables were disease-specific survival (DSS) and overall survival (OS). Prognostic factors for each group were analyzed using Cox models. RESULTS: We included 251 patients (115 men and 136 women). Compared with the non-ACC group, the ACC group had a larger average tumor size and received more adjuvant radiotherapy. In patients with ACC, the pathologic grade had an independent impact on DSS and OS, and patients who were undergoing adjuvant chemotherapy had worse DSS than those who were not receiving chemotherapy. In the non-ACC group, pathologic grade IV, lymph node metastasis, and adjuvant chemotherapy were associated with poor DSS and OS, and tumor extension predicted worsening DSS. CONCLUSIONS: In sublingual gland carcinoma, the pathologic grade and adjuvant chemotherapy were the most important prognostic factors, whereas lymph node metastasis had a negative impact in non-ACC patients but not in ACC patients.

[Salivary gland neoplasms]. / Tumeurs des glandes salivaires.

SALIVARY GLAND NEOPLASMS. Salivary gland tumors represent a heterogeneous group of lesions, with various anatomical locations. The most frequent site of involvement is the parotid, and the most frequent histology is pleomorphic adenoma, a benign tumor with the potential for recurrence and malignant transformation. Approximately one third of tumors are malignant, and the prognosis depends on the tumor histology and histoprognostic criteria. The diagnostic strategy focuses on determining the benignity or malignancy of these lesions to choose appropriate treatment. It is based on multiparametric magnetic resonance imaging (MRI) [associating morphological images with diffusion and perfusion sequences], and on fine needle aspiration. Surgery is almost always indicated to allow histological confirmation and treatment of the disease. The extent of resection, the need for elective neck dissection, and the indication of adjuvant therapy (postoperative radiotherapy) depend on the tumor histology.

TUMEURS DES GLANDES SALIVAIRES. Les tumeurs des glandes salivaires représentent un groupe hétérogène de lésions, de localisations anatomiques variées. L'atteinte la plus fréquente est parotidienne, et l'histologie est le plus souvent l'adénome pléomorphe, tumeur bénigne avec un potentiel de récidive et de transformation maligne. Environ un tiers des tumeurs sont malignes ; le pronostic dépend alors de l'histologie tumorale et de critères histopronostiques. La démarche diagnostique s'attache à déterminer la bénignité ou la malignité de ces lésions pour un choix thérapeutique adapté. Elle se fonde sur l'imagerie par résonance magnétique (IRM) multiparamétrique (associant des images morphologiques à des séquences de diffusion et de perfusion) et sur la cytoponction à l'aiguille fine. La chirurgie est presque toujours indiquée pour permettre la confirmation histologique et traiter la maladie. L'étendue de la résection, la réalisation d'un curage cervical et d'un traitement adjuvant (radiothérapie postopératoire) dépendent de l'histologie tumorale.

Treatment and outcomes of minor salivary gland cancers of the larynx and trachea: a systematic review.

Objectives: Malignant minor salivary glands carcinomas (MiSGC) of the larynx and trachea are rare tumours and published evidence is sparse. We conducted a systematic review to describe shareable treatment strategies and oncological outcomes of these neoplastic entities. Methods: Full text English manuscripts published from January 1st 2000 to December 14th 2022 were included. Data on demographics, treatments and outcomes were collected. A pooled analysis of 5-year overall survival (OS) was performed. Results: Seventeen articles and 365 patients met the inclusion criteria. The most common subsites involved were subglottic and distal trachea. Adenoid cystic carcinoma was, by far, the most frequent histotype. The first-choice treatment strategy was surgery (86.8%), while adjuvant treatments were delivered in 57.4% of patients. Only 12.9% were treated with definitive radiotherapy with/without chemotherapy. The mean follow-up was 68.3 months. One hundred nine (34.9%) deaths were recorded and 62.4% were cancer-related. Five-year OS ranged from 20% to 100% and, at pooled analysis, it was 83% (range, 78-87%). Conclusions: In case of MiSGC of the larynx and trachea, surgery remains the mainstay of treatment. Adjuvant treatments are frequently delivered. Survival estimates are good overall, but highly heterogeneous.

NUT carcinoma of the submandibular gland: A case report.

BACKGROUND: NUT carcinoma (NUTc) is a rare and aggressive malignant epithelial tumor characterized by rearrangement of the NUT gene on chromosome 15q14. METHODS: In this article, we present the fifth case worldwide of a young woman affected by a NUTc arising from a submandibular gland, presenting as a rapidly evolving mass. She underwent a right scialoadenectomy and received the initial diagnosis of high-grade mucoepidermoid carcinoma. Due to evidence of local recurrence at magnetic resonance imaging 1 month later, a subsequent right radical neck dissection was performed. The patient then sought a second opinion at our cancer center and finally received the correct diagnosis of NUT carcinoma. Given the well-known aggressive behavior of this neoplasm, as well as clinical and radiological features, she underwent adjuvant chemo-radiation (intensity-modulated radiotherapy + concurrent chemotherapy with cisplatin). RESULTS: After a disease-free interval of 2.6 months, a widespread metastatic disease led to rapid deterioration of performance status and patient death in a few weeks after metastatic onset. CONCLUSIONS: We presented a case of NUTc arising from salivary gland aiming to improve the knowledge of this rare malignancy. First, we pointed out that in the setting of rare tumors like salivary gland cancers, the diagnosis should be obtained by expert pathologists, and patients should be referred to tertiary cancer centers for their clinical management. Second, molecular profiling may help to identify possible druggable targets that may be exploited to treat patients suffering from this aggressive malignancy. Sharing the molecular data provided in this case will be useful for further research.

The evolving landscape of salivary gland tumors.

Salivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.

Management and outcome of adenoid cystic carcinoma of the major salivary glands: the 22-year experience of a single institution.

BACKGROUND: Prognostic factors and survival rate are difficult to determine for adenoid cystic carcinoma(AdCC) of salivary glands. AIMS/OBJECTIVES: To clarify the clinical characteristics of AdCC and examine factors associated with recurrence and prognosis by histopathological grade classification. MATERIALS AND METHODS: Twenty-five patients with AdCC of the parotid gland and 10 patients with AdCC of the submandibular gland were included. We classified AdCC histopathologically by the proportion of solid components. Clinical features, fine-needle aspiration cytology (FNAC), and patient outcomes were examined according to grade. Factors associated with local recurrence and distant metastases were examined. RESULTS: Age was significantly higher in the grade III group than in the grade I group. The grade III group had significantly higher proportions of patients with cN+, pN+, and perineural invasion. In FNAC, lower-grade groups showed higher rates of correct histopathological type. Five-year disease-specific survival and disease-free survival rates were significantly lower in the grade III than in the grade I. Distant metastases were more common among patients with high-stage and perineural invasion. CONCLUSIONS: Five-year survival is significantly worse in patients with grade III.

Clinicopathological study and survival outcomes of sialoblastoma: A systematic review.

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.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

BACKGROUND: Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. METHODS: We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. RESULTS: In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival. CONCLUSION: CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

Pediatric primary salivary gland tumors.

OBJECTIVES: To characterize the presentation and treatment of children presenting with primary salivary gland neoplasms. METHODS: A retrospective review of primary salivary tumor patients presenting to Children's Hospital Colorado between January 2000 and August 2020. RESULTS: Fifty children were identified with primary salivary gland tumors, comprising of 39 (78 %) benign and 11 (22 %) malignant lesions. Pleomorphic adenoma was the most common benign tumor (36/39, 92 %), while acinic cell carcinoma was the most common malignancy (7/11, 64 %). The parotid gland was the most common site, followed by the submandibular gland (66 % vs. 34 %). No tumors were found in the sublingual glands. Benign neoplasms accounted for 70 % of parotid lesions and 94 % of submandibular tumors. No significant differences in age (13.6 years, SD 4 vs. 13.0 years, SD 4.3) were noted between patients with benign and malignant disease, but tumors in females were more frequently malignant (M:F 1:1.3 vs. 1:2.7 for benign and malignant tumors, respectively). Neck dissection and/or facial nerve sacrifice were required in 27 % (3/11) and 9.1 % (1/11) of malignancies, respectively. Local recurrence was observed in 7.7 % (3/39) of benign cases and 9.1 % (1/11) of malignant cases. No salivary malignancies required chemotherapy, though one patient with neurofibromatosis received imatinib prior to resection. Two patients with locoregional malignancy received adjunctive radiation. The average duration of follow up for benign and malignant disease were 12.6 ± 25 and 45.1 ± 32 months, respectively. CONCLUSIONS: This study presents one of the larger single institutional experiences of pediatric primary salivary neoplasms in the past 20 years, identifying pleomorphic adenoma and acinic cell carcinoma as the most common benign and malignant etiologies, respectively. While this review found most neoplasms presented as a localized mass effectively managed with conservative surgical resection, aggressive tumors required multidisciplinary care.

[Salivary gland cancer: new therapeutic approaches]. / Cancers des glandes salivaires : nouvelles approches thérapeutiques.

Salivary gland carcinomas are rare, characterized by a diversity of histological subtypes associated with variable clinical behavior and prognosis with usually a poor response to chemotherapy. In this context, molecular alterations have been identified and represent potential therapeutic targets: overexpression of human epidermal growth factor receptor 2 (HER2) and androgen receptors in salivary duct cancer, NOTCH mutations in adenoid cystic carcinoma, NTRK gene fusion in secretory carcinoma. Screening for these molecular alterations is mandatory in all patients with recurrent or metastatic salivary gland cancer as it may allow an individualized treatment.

Les carcinomes des glandes salivaires sont rares et se caractérisent par une grande diversité de sous-types histologiques associés à des comportements cliniques différents, à un pronostic variable et à une réponse habituellement médiocre à la chimiothérapie. Dans ce contexte, des altérations moléculaires ont été identifiées et représentent de nouvelles cibles thérapeutiques : surexpression du récepteur 2 du facteur de croissance épidermique humain (HER2) et des récepteurs aux androgènes dans le cancer des canaux salivaires, mutations activatrices de NOTCH dans le carcinome adénoïde kystique, fusion de gène NTRK dans le carcinome sécrétoire notamment. Ces altérations moléculaires doivent être recherchées chez tous les patients présentant un cancer des glandes salivaires récidivant ou métastatique et permettent d'individualiser sa prise en charge.

Clinical features of tumours and tumour-like pathologies involving the buccal fat pad.

This study aimed to investigate the clinical, radiological, and pathological characteristics of pathologies involving the buccal fat pad (BFP) and to explore the treatment protocols. The cases of 109 patients with primary pathologies involving the BFP (pBFP) diagnosed between January 2013 and September 2021 were assessed. The patients' clinical presentations and radiological and histopathological findings were analysed retrospectively, and their treatment outcomes were evaluated. The 109 pBFP were categorized as benign tumours (n = 17), malignant tumours (n = 29), vascular malformations (n = 38), and inflammatory masses (n = 25). Of the 17 benign tumours, seven were lipomas, five were pleomorphic adenomas, three were solitary fibrous tumours, and two were other tumours. The 29 malignant tumours included five adenoid cystic carcinomas, six mucoepidermoid carcinomas, three synovial sarcomas, and 15 other tumours. Of the 38 vascular malformations, 37 were venous and one was arteriovenous. Regarding the inflammatory masses, the lesions appeared after cosmetic facial botulinum toxin injection in 13 cases and after other cosmetic facial procedures in five. The upper body of the BFP was the most frequently involved site (79/109), while other frequently involved sites were the lower body (67/109) and the masseteric (41/109), temporal (32/109), and pterygopalatine (30/109) extensions.

Pathological nodal status as a main predictive factor of survival and treatment outcomes of submandibular salivary gland cancers: A 25-year single center experience.

INTRODUCTION: Aim of this study was to explore the survival predictive factors and treatment outcomes in a cohort of SGC patients treated at a single center over a period of 25 years. MATERIALS AND METHODS: Patients who had received primary treatment for SGC were enroled. Outcomes evaluated were: overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DFS). RESULTS: A total of 40 patients with SGC were enroled in the study. The most common tumor was the adenoid cystic carcinoma (60% of cases). Cumulative OS for 5-and 10-year follow up period was 81% and 60%, respectively. Thirteen patients (32.5%) developed distant metastases during follow-up. Nodal status, high-grade histology, tumor stage and adjuvant radiation-therapy (RT) were significant variables on multivariate analysis for survival and treatment outcomes. CONCLUSIONS: Submandibular gland carcinomas represent rare and heterogenous tumor group regarding histological appearance and locoregional and distant metastatic potential. Tumor histological grade, AJCC tumor stage and nodal status were the strongest predictive factors for survival and treatment outcomes. RT improved OS and locoregional treatment outcome, but not DFS. Elective neck dissection (END) could be beneficial for selected cases of SGC. Superselective neck dissection of levels I-IIa may be the level of dissection for END. Distant metastases were the main cause of death and treatment failure. Prognostic factors for poor DMFS were AJCC stage III and IV, high tumor grade and nodal status.

Malignant salivary gland tumours: treatment outcomes from a tertiary referral centre in the UK.

Salivary gland malignant tumours are a complex and highly variable pathological group. Their diagnosis can be challenging, and management is guided by multidisciplinary teams. This project aimed to establish clinicopathological and sociodemographic features that significantly impacted overall disease-free or progression-free survival in patients diagnosed with malignant salivary gland disease between 2010 and 2019 in a tertiary referral centre. In total, 86 patients were included for analysis, with a female:male gender ratio of 1.3:1. Mean age at diagnosis was 57.7 years. Mucoepidermoid carcinomas constituted almost 25% (n = 20) of all cases, with adenoid cystic carcinomas (20%, n = 17) and acinic cell carcinomas (17.5%, n = 15) being the next most frequently diagnosed. The parotid gland was the most frequently affected site (80.2%, n = 69). Perineural and lymphovascular invasion, and a maximum tumour dimension of ≥4 cm were highly associated with the decision to provide a neck dissection as part of treatment. Involved margins, extracapsular spread, and lymphovascular and perineural invasion were associated with the need for adjuvant treatment. However, no factors remained statistically significant on multivariate analysis. This retrospective service evaluation demonstrates the difficulty of predicting treatment outcomes for patients diagnosed with malignant salivary gland disease.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.