Search Results (115)

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article

Notch-mediated signaling pathways represent a system that is conserved from an evolutionary point of view, demonstrating a key role in determining cell fate in development; in fact, Notch operates at multiple levels during tissue and organ organization, intervening in the key processes of organogenesis. As a consequence of this, a dysregulation of the Notch-mediated pathways leads to the onset of various pathological conditions such as autoimmune diseases or tumors. The activation of Notch-mediated molecular pathways has also been demonstrated in the development of salivary glands (SGs) and in associated pathologies. Although the numerous advances made in recent years have clarified various aspects of the activation of transductional cascades involving Notch in SGs development and diseases, there are still many aspects that require experimental investigation. In this review, we report, for therapeutic purposes, what is present in the literature relating to the mechanisms regulating the development of Notch-mediated SGs and the most recent discoveries relating to SGs pathologies that derive from alterations of the Notch-mediated pathways. Full article

Background and Clinical Significance: This article explores the complexity of large-cell neuroendocrine carcinoma (LCNEC) by presenting a clinical case involving a 17-year-old admitted for persistent wheezing, with no history of respiratory toxin exposure, a background of atopy, and a suspected diagnosis of bronchial asthma. Given the patient’s age and the nature of the symptoms, the condition was initially diagnosed as asthma, leading to the initiation of maximum inhalation therapy. Case Presentation: Despite proper adherence and correct administration, symptoms persisted, necessitating the use of oral corticosteroids. Imaging revealed an extensive inhomogeneous mass in the cervical esophagus and trachea, along with a similar tumor in the right hilum, prompting bronchoscopy. The diagnosis of LCNEC was confirmed through imaging, histopathological findings, and a detailed immunohistochemical profile. Initially misdiagnosed as adenoid cystic carcinoma, this case highlights the diagnostic challenges and the importance of rigorous evaluation. Conclusions: It emphasizes that recurrent wheezing in adolescents is not always indicative of asthma and requires careful differential diagnosis to uncover less common causes. Full article

Background: While intratumoral microbiota have been identified in various cancers, their presence and clinical significance in lacrimal gland tumors remain largely unexplored. This study investigates the existence, composition, and potential clinical significance of intratumoral bacteria in lacrimal gland tumors. Methods: High-throughput 16S rDNA sequencing was performed on tumor DNA extracted from 89 paraffin-embedded tissues from patients with lacrimal gland tumors. Diversity analysis and LEfSe differential analysis were conducted to identify tumor-type-specific bacterial taxa. LASSO regression and the Cox proportional hazards models were used to analyze the relationship between intratumoral microbiota and prognosis. Results: Significant differences in the β diversity of intratumoral microbiota were observed across adenoid cystic carcinoma (ACC), carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA), and IgG4-related disease (IgG4-RD) patients. After FDR correction, Garicola, Prevotella, Polaribacter, and Helicobacter were notably enriched in the tumors of ACC, CXPA, PA, and IgG4-RD patients, respectively. Importantly, patients with malignant lacrimal gland tumors who experienced relapse, distant metastasis, or death had significantly higher α diversity within their tumors. Furthermore, specific genera, such as Roseburia and Alloprevotella, were particularly associated with poorer prognosis in patients with malignant lacrimal gland tumors. Conclusions: This study provides a comprehensive analysis of microbial profiles in lacrimal gland tumors, highlighting distinct microbial characteristics across tumor types. Our findings suggest that intratumoral bacterial diversity and specific genera may serve as potential prognostic markers for malignant lacrimal gland tumors. Full article

Background/Objectives: Salivary adenoid cystic carcinoma (ACC) is a rare but aggressive neoplasm that predominantly arises from the salivary glands, accounting for a significant proportion of salivary gland cancers. The aim of this literature review is to illustrate the current insights on ACC with regards to related genes and molecular pathways by analyzing original research articles from the period 2015–2025. Methods: An electronic search of literature was performed between January and February 2025 to identify all articles investigating the current insights on salivary gland adenoid cystic carcinoma and its related genes and molecular pathways. The search was conducted using MEDLINE (National Library of Medicine)-PubMed with restrictions concerning the date of publication. In particular, we focused on the period 2015–2025 using the following keywords: Salivary gland adenoid cystic carcinoma AND genes AND molecular pathways. This was followed by a manual search, and references were used to identify relevant articles. Results: In total, 41 articles were identified through the keywords. After the implementation of the time frame 2015–2025, 31 articles remained. Subsequently, by reading the titles and abstracts and thereby excluding non-original research articles and articles written in a language other than English, 23 articles remained. Conclusions: These studies identified 23 relevant genes or pathways whose analysis yielded the most recent data regarding their function. The classification of ACC is multifaceted, encompassing distinct histological subtypes that are crucial for determining prognosis and treatment approaches. Current oncological practices classify ACC based on these histological features alongside emerging genetic and molecular markers that promise to enhance our understanding of the disease’s biology. Diagnostic strategies have evolved, leveraging techniques such as biopsy and molecular diagnostics, which have significantly improved the detection and characterization of ACC. Regarding treatment, the management of ACC remains a challenge due to its propensity for local invasion and metastasis, with surgery, radiation, and chemotherapy being the mainstays of therapy. The development of targeted therapies based on ACC’s molecular profile will allow for a better prognosis and an enhanced quality of life of patients. Full article

Rare breast malignancies represent a challenge for treatment decision making given the lack of evidence-based guidelines. As a particularly uncommon tumor, adenoid cystic carcinomas are especially challenging. Although, histopathologically, they share the same tumor molecular profile as hormone receptor-negative and HER2 nonamplified carcinomas with aggressive physiology, adenoid cystic carcinomas generally have a favorable prognosis. Thus, there is evidence to suggest that more aggressive treatment regimens may not provide better therapeutic effects. In this review, we discuss ACCB with the goal of highlighting pathophysiology, clinical features, and treatment strategies. Existing data support consideration for adjuvant radiation with the omission of axillary staging and systemic therapies. Full article

Primary cutaneous adenoid cystic carcinoma (PCACC) isa rare skin malignancy first reported in the 1970s with limited number of cases found in the literature. These neoplasms are typically identified in middle-to-older-age individuals and are mostly located in the scalp and neck region but can identified throughout the body. We describe the case of a 67-year-old male patient that presented to our department with a slow-growing nodule in the left gluteal region that turned out to be a PCACC and analyze the differential diagnosis, radiology, histopathological findings and successful treatment with a wide local excision. Current literature on the subject is also presented and discussed. Full article

Background: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignancies, accounting for approximately 5% of head and neck cancers. Despite their rarity, advances in molecular profiling have revealed a variety of genetic and molecular pathways, many of which are potentially actionable with targeted therapies. Methods: We reviewed the current literature involving the molecular landscape of SGCs, encompassing the diagnostic and prognostic value of tissue and liquid biomarkers and the potential therapeutic targets across various histological subtypes. Results: Our review highlights key molecular diagnostic findings such as the CRTC1-MAML2 fusion in mucoepidermoid carcinoma and MYB-NFIB rearrangements in adenoid cystic carcinoma, but also targetable alterations such as HER2 and AR positivity in salivary duct carcinoma and ETV6-NTRK3 fusion in secretory carcinoma. Liquid biopsy (both blood- or salivary-based), including circulating tumor DNA, circulating tumor cells, and miRNAs, offers novel, noninvasive approaches for disease monitoring and personalized treatment. Emerging therapies such as HER2 inhibitors, androgen deprivation therapy, and TRK inhibitors underscore the shift towards precision oncology in managing these malignancies. Conclusions: Despite promising advances, challenges remain due to the rarity and phenotypic heterogeneity of SGCs, emphasizing the need for molecularly stratified clinical trials. This review presents an overview of tissue and liquid biomarkers, focusing on molecular targets and therapeutic innovations that lay the foundation for improved diagnostic and treatment strategies for SGCs. Full article

Episiotomy is a perineal incision enlarging the vaginal opening during labor, preventing severe perineal/vaginal/ano-rectal lacerations. We performed a systematic literature review (PRISMA guidelines; Pubmed, Scopus and Web of Science databases) of primary malignant tumors arising from the episiotomy site. Thirteen primary carcinomas were reported, mainly endometriosis-related histotypes (77%) (nine clear cell, CCC; one endometrioid, EC) with only two vulvar invasive squamous cell carcinomas and one adenoid cystic carcinoma of Bartholin’s gland. No sarcomas, melanomas or malignant trophoblastic tumors were described. Endometriosis was associated with tumors or reported in history (62%). Malignant transformation occurred 3 to 27 (mean 16) years after diagnosis of endometriosis. Patients were usually post-/peri-menopausal (eight cases, 61%) (age range: 31–70 years, mean 50). Imaging should exclude distant (0% in our series) or lymph node metastases (three cases, 23%), looking for potential invasion of vagina (five cases, 39%), anus (including sphincter) (four cases, 31%) and/or other deep pelvic soft tissues (five cases, 39%). All patients underwent surgery, except for a CCC-patient (only chemoradiation) subsequently progressing and dying of disease. Adjuvant chemotherapy and/or radiotherapy were administered to five (39%) cases, neoadjuvant therapy to four cases (31%). Globally, three (23%) cases recurred or progressed, and two-thirds (15%) died of disease (1 CCC, 1 EC). Radical surgery with lymph node status evaluation and eventual excision should be performed when possible. Chemotherapy and/or radiotherapy can be considered in an adjuvant and/or neoadjuvant setting (or as only treatment in inoperable patients). However, the role of different treatments should be studied in further larger multicenter series. Full article

Background/Objectives: Salivary gland carcinomas encompass a broad group of malignant lesions characterized by varied prognoses. Stem cells have been associated with the potential for self-renewal and differentiation to various subpopulations, resulting in histopathological variability and diverse biological behavior, features that characterize salivary gland carcinomas. This study aims to provide a thorough systematic review of immunohistochemical studies regarding the expression and prognostic significance of stem cell markers between different malignant salivary gland tumors (MSGTs). Methods: The English literature was searched via the databases MEDLINE/PubMed, EMBASE via OVID, Web of Science, Scopus, and CINHAL via EBSCO. The Joanna Briggs Institute Critical Appraisal Tool was used for risk of bias (RoB) assessment. Meta-analysis was conducted for markers evaluated in the same pair of diseases in at least two studies. Results: Fifty-four studies reported the expression of stem cell markers, e.g., c-KIT, CD44, CD133, CD24, ALDH1, BMI1, SOX2, OCT4, and NANOG, in various MSGTs. Low, moderate, and high RoB was observed in twenty-five, eleven, and eighteen studies, respectively. Meta-analysis revealed an outstanding discriminative ability of c-KIT for adenoid cystic carcinoma (AdCC) over polymorphous adenocarcinoma [P(LG)A] but did not confirm the prognostic significance of stem cell markers in MSGTs. Conclusions: This study indicated a possible link between stem cells and the histopathological heterogeneity and diverse biological behavior that characterize the MSGTs. c-KIT might be of diagnostic value in discriminating between AdCC and P(LG)A. Full article

(1) Background: Salivary gland tumors (SGTs) are a rare and diverse group of neoplasms arising in the parotid, submandibular, sublingual, and minor salivary glands distributed throughout the upper aerodigestive tract. Given the rarity and complexity of MSGTs, understanding their epidemiology across diverse populations is crucial for improving diagnostic and therapeutic strategies. (2) Methods: A retrospective analysis involving 45 patients diagnosed with malignant salivary gland tumors and treated with curative intention between 1 July 2016 and 1 July 2021 in a tertiary academic hospital was performed. (3) Results: Histologically, the most common subtype was adenoid cystic carcinoma in 12 (26.7%) cases, followed by carcinoma ex-pleomorphic adenoma in 7 (15.6%) cases, mucoepidermoid carcinoma in 6 (13.3%) cases, and adenocarcinoma in 6 (13.3%) cases. The majority of tumors were located in the parotid gland in 28 cases (62.2%). The three-year overall survival rate was 80% and the three-year specific survival rate was 86.7%. Tumor grade was significantly associated with local recurrence and the appearance of distant metastasis during the follow-up period (p = 0.04). We also evidenced a worse survival in patients with advanced T-Stage (p = 0.038) and positive nodes in the neck (p = 0.015). (4) Conclusions: Overall, our study reinforces the prognostic significance of tumor grade, T-Stage and N-Stage while challenging the conventional understanding of factors such as PNI, LNM, and margin status. Full article

Background/Objectives: Adenoid Cystic Carcinoma (AdCC) is a rare malignant salivary gland tumor, with high rates of recurrence and distant metastasis. This study aims to stratify patients Relapse-Free Survival (RFS) using a combined model of clinical and radiomic features from preoperative MRI. Methods: This retrospective study included patients with primary AdCC who underwent surgery and adjuvant radiotherapy. Segmentations were manually performed by two head and neck radiologists. Radiomic features were extracted using the 3D Slicer software. Descriptive statistics was performed. A Survival Random Forest model was employed to select which radiological feature predict RFS. Cox proportional hazards models were constructed using clinical, radiological variables or both. Synthetic data augmentation was applied to address the small sample size and improve model robustness. Models were validated on real data and compared using the C-index and Prediction Error Curves (PEC). Results: Three Cox models were developed: one with clinical features (C-index = 0.67), one with radiomic features (C-index = 0.68), and one combining both (C-index = 0.77). The combined clinical-radiomic model had the highest predictive accuracy and outperformed models based on clinical or radiomic features. The combined model also exhibited the lowest mean Brier score in PEC analysis, indicating better predictive performance. Conclusions: This study demonstrate that a combined radiomic-clinical model can predict RFS in AdCC patients. This model may provide clinicians a valuable tool in patient’s management and may aid in personalized treatment planning. Full article

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