Search Results (100)

Objective: Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mainly arises in the head and neck area. We aimed to compare the long-term survival of patients with ACC based on their geographic regions within the United States using the Surveillance, Epidemiology, and End Results (SEER) registry data. Methods: We queried the SEER database to evaluate the geographic distribution of ACC patients based on inpatient admissions. The states included in the study were divided into four geographical regions (Midwest, Northeast, South, and West) based on the U.S. Census Bureau-designated regions and divisions. Demographic and clinical variables were compared between the groups. Kaplan–Meier curves and Cox regression were used to assess late mortality. Results: A total of 5150 patients were included (4.2% from the Midwest, 17.2% from the Northeast, 22.5% from the South, and 56.1% from the West regions). The median follow-up was 12.3 (95% CI: 11.6–13.1 years). Median overall survival was 11.0 (95% CI: 9.2-NR years), 14.3 (95% CI: 12.4–16.4 years), 11.3 (95% CI: 9.7–14.8 years), and 12.0 (95% CI: 11.3–13.0 years) for Midwest, Northeast, South, and West regions, respectively. In multivariable analysis, older age, male sex, thoracic cancer, the presence of regional and distal disease, receiving chemotherapy, not undergoing surgical resection, and being treated in the West vs. Northeast region were found to be independent predictors of poor survival. We identified a significant survival difference between the different regions, with the West exhibiting the worst survival compared to the Northeast region. Conclusions: In addition to the well-known predictors of late mortality in ACC (tumor location, stage, and treatment modalities), our study identified a lack of social support (being unmarried) and geographic location (West region) as independent predictors of late mortality in multivariable analysis. Further research is needed to explore the causal relationships. Full article

There is currently no effective treatment strategy for recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts, unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but NOTCH1 and KDM6A frameshift and CTCF splice site mutations (no MYB/L fusion) with a low tumor mutational burden (TMB), microsatellite stable (MSS) and negative programmed death ligand 1 (PD-L1) were observed. We recommended an anti-programmed cell death protein 1 (anti-PD-1) plus anti-Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) combination based on TMB 2-fold greater-than-median TMB in ACC, tumor harboring multiple immunogenic frameshift or splice site mutations, and PD-L1 negativity. Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in “immune-cold” cancer types. Full article

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. Full article

In the case of any pathologies arising in the hard palate, it is always important to exclude their possible odontogenic origins. Cone-beam computed tomography is mandatory. In cases where a possible non-teeth-related pathology is confirmed, each clinician should remember possible differential diagnostics. Many small salivary glands between the mucosa and bone are present in this palatal area. Both benign and malignant tumors arising from the small glands, and mucosa of the hard palate, might occur. The case presented here mimics a solid tumor because of the nodule consistency. Because of a healthy palatal mucosa without any erosions or irritations with firm attachment to the submucosal nodule, a possible malignant tumor of small salivary gland origins was suspected in this case. When the tumor diameter is small, an excisional biopsy is required to collect good and representative material for further histopathological evaluation. In most cases, bulky nodules present on the palate are hard on palpation, non-movable, and covered with healthy mucosa. Possible bone infiltrations with mucous membrane ulcerations could manifest a more expansive character of the lesion. In the presented case, an unusual occurrence of a traumatic neuroma without any past traumatic etiology of the palate was first differentiated from the occurrence of adenoid-cystic carcinoma (ACC), pleomorphic adenoma, other benign/malignant small gland tumors, or atypical, fibroma/schwannoma of the palate. This paper presents treatment options for this rare oral neural tumor occurrence in the palate and differential diagnosis between hard palate tumors in a 42-year-old male patient, furthermore highlighting the role of an excisional biopsy as a good source for a tissue sample. Full article

Background: Recent studies have suggested using positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals for the detection of salivary gland malignancies (SGM), particularly adenoid-cystic carcinoma (ACC). Methods: The authors conducted an extensive review of the scientific literature to examine the potential diagnostic role of PET/CT using PSMA-targeting radiopharmaceuticals in salivary gland malignancies (SGMs) and adenoid cystic carcinoma (ACC). This study included newly diagnosed SGM patients and those with disease recurrence in their imaging evaluation. Results: This updated systematic review included a total of six studies that examined the diagnostic performance of PSMA-targeted PET/CT in ACC. The articles provided evidence of a high detection rate of PSMA-targeting PET/CT in ACC across all clinical contexts examined. SGMs other than ACC exhibited poorer diagnostic performance. Conclusions: PSMA-targeted PET/CT seems promising in detecting ACC lesions; moreover, PSMA appears to be a suitable potential target for radioligand therapy. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting radiopharmaceuticals in ACC, as both diagnostic and theragnostic agents. Full article

Salivary glands tumors are uncommon neoplasms with variable incidence, heterogenous histologies and unpredictable biological behaviour. Most tumors are located in the parotid gland. Benign salivary tumors represent 54–79% of cases and pleomorphic adenoma is frequently diagnosed in this group. Salivary glands malignant tumors that are more commonly diagnosed are adenoid cystic carcinomas and mucoepidermoid carcinomas. Because of their diversity and overlapping features, these tumors require complex methods of evaluation. Diagnostic procedures include imaging techniques combined with clinical examination, fine needle aspiration and histopathological investigation of the excised specimens. This narrative review describes the advances in the diagnosis methods of these unusual tumors—from histomorphology to artificial intelligence algorithms. Full article

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim. Full article

Background and Objectives: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods: Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results: A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma (p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands (p = 0.000). Conclusions: Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours. Full article

Tumor-infiltrating lymphocytes (TILs) represent a subset of immunological constituents within the tumor microenvironment that can influence cancer growth. We retrospectively evaluate the density and pattern of CD3 and CD20 expression in salivary gland tumors and their relation to clinical pathologic parameters. A total of 44 formalin-fixed paraffin-embedded blocks of salivary gland tumors were included. These tumors were stained immunohistochemically with CD3 and CD20. The chi-square test was used to relate immune scoring, intensity, and clinical pathological parameters to different salivary tumors. p-value < 0.05 was considered statistically significant. The intra-tumoral CD3 infiltrating count was high and diffused in (71.4%) of pleomorphic adenomas (PAs) followed by mucoepidermoid carcinomas (MECs) (66.7%). At the same time, adenoid cystic carcinomas (AdCCs) exhibited significantly low infiltration (71.4%) (p = 0.046). The three types of tumors exhibited high tumor-infiltrating counts diffused in peripheral areas with significant differences between malignant tumors (p = 0.047). The intra-tumoral CD20 infiltrating count significantly differed among the tumors (p = 0.002); it was low in all PAs and AdCCs, while MECs showed an equal percentage of expression. However, in the peripheral area, PAs and MECs exhibited significantly (p = 0.007) high infiltrating counts (69.2% and 84.6), and the lowest infiltrating count was predominantly found for AdCCs. The two markers had a significant positive correlation between the mean of CD3 in the intra-tumoral and peripheral regions and CD20 in the peripheral zone across the total samples. In conclusion, the density of CD3 expression is notably higher than CD20 across tumor types. PAs and MECs showed high-density scores, while AdCCs were characterized by low scores. TIL expression was found to be significantly associated with patients’ outcomes in the intra-tumoral area. Full article

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin. Full article

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3–4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT. Full article

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0–33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials. Full article

The MYB protein is a pivotal player in the cellular transcriptional network, influencing major important processes such as cell proliferation, differentiation, and apoptosis. Because of its role in oncogenesis, MYB is now a compelling target for therapeutic interventions in cancer research. This review summarizes its molecular functions and current therapeutic approaches aiming to inhibit its oncogenic activity. Full article

Adenoid cystic carcinoma (ACC) is a rare neoplasm known for its indolent clinical course, risk of perineural invasion, and late onset of distant metastasis. Due to the scarcity of samples and the tumor’s rarity, progress in developing effective treatments has been historically limited. To tackle this issue, a high-throughput screening of epigenetic drugs was conducted to identify compounds capable of disrupting the invasive properties of the tumor and its cancer stem cells (CSCs). ACC cells were screened for changes in tumor viability, chromatin decondensation, Snail inhibition along tumor migration, and disruption of cancer stem cells. Seven compounds showed potential clinical interest, and further validation showed that Scriptaid emerged as a promising candidate for treating ACC invasion. Scriptaid demonstrated a favorable cellular toxicity index, effectively inhibited Snail expression, induced hyperacetylation of histone, reduced cell migration, and effectively disrupted tumorspheres. Additionally, LMK235 displayed encouraging results in four out of five validation assays, further highlighting its potential in combating tumor invasion in ACC. By targeting the invasive properties of the tumor and CSCs, Scriptaid and LMK235 hold promise as potential treatments for ACC, with the potential to improve patient outcomes and pave the way for further research in this critical area. Full article

Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mostly occurs in minor glands, especially in the palate. Intraosseous adenoid cystic carcinoma (IACC) is rarer. There is no clear conclusion on the clinical, radiologic and pathological characteristics of IACC because of few reported IACC cases, leading to insufficient understanding of IACC. We reviewed 52 previous reports of primary IACC (PIACC) and analyzed the clinical features of those patients involved, attempting to provide a better understanding of PIACC. Moreover, we present a case of primary PIACC and a case of recurrent IACC (RIACC). The two patients showed similarities in clinical and pathological results, along with slight differences in radiological and immunohistochemical results. The patient of case 1 seemed to display a worse prognosis, which can only be proved after long term follow-up. Full article