Malignant Salivary Gland Research Articles

Adenoid cystic carcinoma of soft palate

Adenoid cystic carcinoma is a slow growing and relentless salivary gland malignancy composed of epithelial and myoepithelial neoplastic cells that form various patterns, including tubular, cribriform, and solid forms. It is a rare tumor constitutes for less than 1% of head and neck malignancies and 10% of all salivary gland tumors. Palate is the most common site to be involved in the oral cavity followed by parotid gland and submandibular gland. They are usually asymptomatic, characteristically shows infiltrative growth and perineural invasion. In this paper a case of adenoid cystic carcinoma of soft palate in 52 year old male is presented.

Microcribriform Adenocarcinoma of Salivary Glands: A Unique Tumor Entity Characterized by an SS18::ZBTB7A Fusion.

The landscape of salivary gland carcinomas is ever-changing, with a growing list of new tumors and newly elucidated variants of well-known tumor entities. The routine use of next-generation sequencing has been instrumental in identifying novel fusions and tumor entities, which has helped bring the classification to a more objective and evidenced-based model. However, morphology remains critical in assessing the validity of these novel molecular findings, and most importantly, in assessing which of these findings will have an impact on the prognosis and treatment decisions for patients. The recognition of microsecretory adenocarcinoma (MSA) as a distinct low-grade malignancy of salivary glands, underpinned by MEF2C::SS18 , and a single possibly related case of SS18::ZBTB7A , recently expanded this growing list of distinctive tumors. It was not until now, however, that the morphology of the latter case was known to be unique and reproducible. The authors have now seen 4 of these distinctive tumors that show a combination of distinctive oncocytic cells forming compact glandular growth as well as amphophilic cells forming tubular growth, and suggest the appellation "microcribriform adenocarcinoma" (MCA). So far, these tumors appear to preferentially occur in nonoral sites (2 parotid, 1 submandibular gland, and 1 bronchial seromucous glands). By immunohistochemistry, they express S100 and SOX-10 with focal outer myoepithelial cells marked by circumferential p63, p40, and smooth muscle actin staining around some of the nests and tubules. The tumors show infiltrative growth within a hyalinized and myxoid stroma. Cytologically, they appear generally low grade, similar to MSA. The morphologic and molecular uniformity of these 4 microcribriform adenocarcinoma cases warrants their recognition, and while related to MSA, they are sufficiently different to be classified as a distinct tumor. So far, in limited follow-up, these tumors appear to be relatively indolent.

PSMA-Directed Imaging and Therapy of Salivary Gland Tumors: A Single-Center Retrospective Study.

We analyzed the diagnostic performance of prostate-specific membrane antigen (PSMA) PET/CT and the dosimetry, efficacy, and safety of 177Lu-PSMA-617 radioligand therapy (RLT) in salivary gland malignancies (SGMs). Methods: We identified 28 SGM patients with PSMA PET/CT from our database. CT and PSMA PET/CT images were evaluated separately by 3 masked readers in joint reading sessions. Pathologic findings were grouped into 6 TNM regions, and lesion-based disease extent was classified as no disease (n = 1, 4%), unifocal (n = 2, 7%), oligometastatic (n = 9, 32%), multifocal (n = 3, 11%), or disseminated (n = 13, 47%). For each region, the SUVmax of the lesion with the highest uptake was measured and the visual PSMA expression score was evaluated on a per-patient basis using PROMISE criteria. The association between PSMA expression and clinical and histopathologic markers was tested using the Student t test. Five patients underwent PSMA RLT with intratherapeutic dosimetry. Response was assessed using RECIST 1.1, and adverse events were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events. Results: Compared with CT, PSMA PET/CT demonstrated additional metastatic lesions in 11 of 28 (39%) patients, leading to upstaging of TNM and lesion-based disease extent in 3 (11%) and 6 (21%) patients, respectively. PSMA PET/CT detected CT-occult local tumor, regional lymph nodes, nonregional lymph nodes, and bone metastases in 1 (4%), 4 (14%), 2 (7%), and 4 (14%) patients, respectively; no additional lesions were detected in the other predefined regions. PSMA expression level was higher than liver in 6 patients (25%). A significantly higher SUVmax was observed in male than female patients (15.8 vs. 8.5, P = 0.007) and in bone than lung lesions (14.2 vs. 6.4, P = 0.006). PSMA RLT was discontinued after 1 cycle in 3 of 5 patients because of insufficient tumor doses. No adverse events of grade 4 or higher occurred. Conclusion: In SGMs, PSMA PET/CT demonstrated a superior detection rate and led to upstaging in about one third of patients when compared with CT. The male sex and the presence of bone metastases were associated with significantly higher PSMA expression. PSMA RLT was well tolerated, but most patients did not have more than 1 cycle because of insufficient tumor doses.

Adenoid cystic carcinoma of trachea presenting as a medical emergency- A case report

Adenoid cystic carcinoma is a chief histologic type of malignancy of minor salivary glands. Primary malignant Tracheal neoplasms are rare <0.1%, with Adenoid Cystic Carcinoma being very rare. It arises from mucous secreting cells of salivary glands and upper respiratory tract. After Squamous Cell Carcinoma it is second most common Primary tracheal malignancy. Diagnosis can be done by Computed Tomography or Magnetic Resonance Imaging. But histopathology remains gold standard of diagnosis.

Management of Lymphoepithelial Carcinoma of the Parotid Gland with Liver Metastasis: A Case Report

Objective: Lymphoepithelial carcinoma (LEC) is rarely found as one type of salivary gland malignancy, especially the parotid gland. Based on data only covers 0.86% of all cases of salivary gland malignancies with an annual incidence rate of 0.01 cases per 100,000 population. Liver metastasis from this type of cancer is very uncommon. Methode: We reported a 64-year-old female patient who presented with a lump in the left neck which enlarged within four years. Total parotidectomy and modified radical neck dissection were done and the diagnosis of lymphoepithelial carcinoma of the parotid gland was establishes based on pathology examination. The patient was then given adjuvant radiotherapy. Five months after initial treatment, the patient shows no locoregional recurrence. However, the patient developed multifocal liver metastases which were deemed inoperable. Results: Liver metastases in the case of lymphoepithelial carcinoma have a worse prognosis than other types of cancer because it usually manifests in multiple and disseminated lesions rather than solitary.

P53 Inhibits Bmi-1-driven Self-Renewal and Defines Salivary Gland Cancer Stemness.

Mucoepidermoid carcinoma (MEC) is a poorly understood salivary gland malignancy with limited therapeutic options. Cancer stem cells (CSC) are considered drivers of cancer progression by mediating tumor recurrence and metastasis. We have shown that clinically relevant small molecule inhibitors of MDM2-p53 interaction activate p53 signaling and reduce the fraction of CSC in MEC. Here we examined the functional role of p53 in the plasticity and self-renewal of MEC CSC. Using gene silencing and therapeutic activation of p53, we analyzed the cell-cycle profiles and apoptosis levels of CSCs in MEC cell lines (UM-HMC-1, -3A, -3B) via flow cytometry and looked at the effects on survival/self-renewal of the CSCs through sphere assays. We evaluated the effect of p53 on tumor development (N = 51) and disease recurrence (N = 17) using in vivo subcutaneous and orthotopic murine models of MEC. Recurrence was followed for 250 days after tumor resection. Although p53 activation does not induce MEC CSC apoptosis, it reduces stemness properties such as self-renewal by regulating Bmi-1 expression and driving CSC towards differentiation. In contrast, downregulation of p53 causes expansion of the CSC population while promoting tumor growth. Remarkably, therapeutic activation of p53 prevented CSC-mediated tumor recurrence in preclinical trials. Collectively, these results demonstrate that p53 defines the stemness of MEC and suggest that therapeutic activation of p53 might have clinical utility in patients with salivary gland MEC.

Correlation between Current Histopathological Grading and Anatomical Location of Mucoepidermoid Carcinoma of Salivary Glands

Introduction: Mucoepidermoid carcinoma (MEC) is a kind of salivary cancer with a wide range of biologic activity. Mucoepidermoid tumors are the only kind of cancer where histologic grading and clinical behavior features are linked. Given the relative rarity of this disease, while being the most prevalent of the salivary gland malignancies, this is a common problem in the MEC literature. The aim of the study was to observe the correlation of MEC histopathological grading and anatomical location. Methods: This observational descriptive cross-sectional multi-center study was conducted at the Department of Oral and Maxillofacial Surgery, Dhaka Dental College Hospital, Dhaka, Department of Otolaryngology &Head Neck Surgery, Dhaka Medical College Hospital, Dhaka, and Department of Otolaryngology-Head Neck Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh The study duration was 1.5 years, from July 2011 to December 2012. A total of 20 patients attending the study centers with diagnosed case of mucoepidermoid carcinoma of salivary glands was selected for the study following inclusion and exclusion criteria. Result: 40% of the participants were from the age group of 31-40 years, while another 30% were under the age of 21 years. 70% of the participants were female. Histological grading of the participants revealed 9 low grade, 8 intermediate grade, and 4 high-grade MEC tumor cases. High-grade tumor MEC had an association with increasing age and male gender. The swelling was a common clinical feature among all the participants, whereas ulceration was observed in 75% of high-grade tumor patients. Parotid gland was the most common location at 45%, followed by 30% tumors occurring at the palate. Among the 9 parotid gland carcinomas, 55.6% were from MEC intermediate grade, 33.3% from low grade and the remaining 11.1% from MEC high grade by histological grading. Among the 6 carcinomas of the palate, 50% were low grade, 33.3% were intermediate grade, ..........

PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

Simple SummaryPositron emission tomography/computed tomography (PET/CT) has an increasingly relevant role in the management of oncological patients. It consists of the administration of a radioactive molecule (tracer) which localizes in tumour cells due to specific cellular features (e.g., a receptor expressed by a specific cell population). PET/CT has a variety of applications in oncology, including staging, therapeutic response assessment and restaging in various types of tumours through the administration of different tracers. Among them, prostate-specific membrane antigen (PSMA) radioligands are a relatively novel compound widely employed in prostate cancer diagnostics and therapy. Besides their prostate cancer applications, PSMA radioligands have been shown to be a promising instrument to evaluate the stage and the aggressiveness in several types of cancer, since they allow us to study tumour neoangiogenesis. This review provides an overview of the applications of PSMA radioligand PET/CT in various types of tumours other than prostate cancer.Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.

1053 Primary Acinic Cell Carcinoma in a Young Female: A Case Report

Abstract Background Acinic cell carcinoma (ACC) is a rare, low-grade tumour, accounting for about 5% of all primary salivary gland malignancies. ACCs predominate in the parotid gland, seen in the fifth and sixth decades of life and has a female predilection. Well-differentiated and low-grade tumours are associated with a favourable prognosis. Case Description We report a case of a 16-year-old female, presenting with a right parotid lump, slowly increasing over the last year. Clinical examination revealed a 1.5cm right parotid nodule with no facial nerve involvement and presence of cervical lymphadenopathy. Past medical history was unremarkable. Findings Radiological investigations revealed a well-circumscribed lobulated lesion in the anterior right parotid gland with presence of reactive lymph nodes bilaterally. Differential diagnoses included Warthin's tumour, which would have been unusual in this age group, and the patient underwent a right partial parotidectomy. Histological examination showed a multinodular appearance with some marked granular cytoplasm with oncolytic and lymphoid infiltrate. Immunohistochemistry was negative for S100, positive with DOG-1. There were widespread PAS-D-resistant granules throughout the tumour cells, with ki67 proliferation index of approximately 5%. Results The tumour was completely excised, and the patient made a full recovery and considered to have a good long-term prognosis. Conclusion This is an unusual case of ACC seen in this age group and gender, where less than 4% of cases of ACC have been reported in patients younger than 20. It is important to consider differential diagnoses of salivary gland pathology, such as ACC in the young female patient.

DIAGNOSIS, TREATMENT, AND FOLLOW-UP OF MINOR SALIVARY GLAND CANCER IN A YOUNG PATIENT

Mucoepidermoid carcinoma is the most common subtype of salivary gland malignancy and displays distinct histological features. A 17-year-old female patient, with nothing noteworthy in her medical history, was referred to our service for evaluation of a lesion located on the palate. According to the patient, the lesion appeared 4 months prior to consultation. Intraoral examination showed a purplish nodule on the right side of the hard palate measuring 1 × 1 cm, with a fibroelastic consistency and painful symptoms. Computed tomography revealed a nodular lesion with well-defined limits and absence of bone involvement. A biopsy was performed, and histopathologic examination revealed a cystic structure with mucus-secreting and epidermoid cells, characterizing a mucoepidermoid carcinoma. The patient was treated by surgical excision under general anesthesia and is being followed by our team. At 12-month follow-up, she is in good general health and has no evidence of tumor recurrence.

PLEOMORPHIC ADENOMA OF PAROTID GLAND: A CASE REPORT

Pleomorphic adenoma is the most common benign tumor of the salivary glands. It occurs mostly in the parotid gland in middle-aged women. It arises commonly as a painless, slow-growing, and firm swelling. This study reports a case of pleomorphic adenoma in the parotid gland. A 67-year-old female presented with 20-year history of painless swelling in the right parotid gland region. Surgical excision of the tumor was performed under general anesthesia. The lesion was excised with a partial parotidectomy and a compressive dressing. Histopathologic examination of the surgical specimen confirmed the diagnosis of pleomorphic adenoma. The postoperative course was uneventful, and no recurrence was observed after 10 months of follow-up. Surgical excision is the best treatment for pleomorphic adenomas because it improves the prognosis and decreases the risk of recurrence. Appropriate treatment is necessary to avoid future complications, such as malignant transformation into carcinoma ex pleomorphic adenoma, an aggressive salivary gland malignancy.

Surgical management of pediatric salivary malignant tumors-A single-center cohort study.

The purpose of this study was to report incidence, clinicopathologic behavior, management, and outcome of pediatric patients treated surgically for salivary gland (SG) malignancies. Patients who underwent surgery for SG malignancies from 1985 to 2015 were identified. Clinical, pathological, treatment and outcomes data were collected. Disease-specificsurvival (DSS), recurrence-free survival (RFS), and overall survival (OS) were calculated using Kaplan-Meier method. Twenty-eight pediatric patients were included. The most common histopathological types were mucoepidermoid (n = 18, 64.3%), acinic cell (n = 7, 25.0%), adenoid cystic (n = 2, 7.1%), and adenocarcinoma (n = 1, 3.6%). Surgical approach varied and ranged from superficial parotidectomy (n = 11, 39.3%) to partial maxillectomy (n = 6, 21.4%). Nine patients (32%) required postoperative radiotherapy. DSS, OS, and RFS probability at 5 years were 96.4%, 96.4%, and 89.3%, respectively. Pediatric SG malignancies are rare and have favorable outcome at 5 years. Larger, multi-institutional studies are required to better understand the natural history of these rare tumors.

AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.

Comprehensive Molecular Profiling of Oncocytic Salivary Gland Malignancies.

Oncocytic histologic features can be seen in a variety of salivary gland carcinomas. We performed a comprehensive molecular profiling of 15 salivary gland malignancies with oncocytic features (diagnosed as oncocytic carcinoma, carcinoma NOS with oncocytic features, or salivary duct carcinoma with oncocytic features). We reveal multiple novel molecular alterations that have not been previously described in other salivary gland malignancies, including, but not limited to, KEL amplification (13.3%, 2/15), PARP1 amplification (13.3%, 2/15), and EPHB4 amplification (13.3%, 2/15). Alterations in KMT2C (13.3%, 2/15), ERBB3 (13.3%, 2/15), CTNNA1 (13.3%, 2/15), and SMAD4 (20%, 3/15) were also found in this series and have been reported in other salivary gland malignancies. Alterations that have been reported in salivary duct carcinoma were also identified, including TP53 (40%, 6/15) , ERBB2 mutations (13.3%, 2/15) , ERBB2 amplification (13.3%, 2/15), PIK3CA (26.7%, 4/15) , PTEN (20%, 3/15), BRCA2 (20%, 3/15), BRAF (20%, 3/15), CDKN2A/B (20%, 3/15), CDH1 (13.3%, 2/15), and HRAS (13.3%, 2/15). Oncocytic salivary gland malignancies are a molecularly heterogenous group of tumors with partial overlap with salivary duct carcinoma subtypes.

Long‐term evolution of mucoepidermoid carcinoma: Report of two cases

AbstractIntroductionMucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, which mainly affects the major salivary glands. Its prognosis is associated with clinical and histopathological factors.AimThis article reports two long‐term evolution cases of MEC.Case ReportTwo cases of MEC in female patients, duration of 8 years (case 1) and 24 years (case 2). Clinical and histopathological features were analysed in order to predict the long‐term survival of patients.ConclusionsIn addition, possible differential diagnoses are discussed, as well as the results of a histochemical and immunohistochemical analysis performed to assist the accurate diagnosis of the two cases.

ERBB2 amplification status in 67 salivary duct carcinomas assessed by immunohistochemistry, fluorescence in situ hybridization, and targeted exome sequencing

AbstractSalivary duct carcinoma (SDC) is an aggressive salivary gland malignancy with poor survival. Approximately 30% SDC harbor HER2 amplification and response to trastuzumab has been reported. However, a systematic approach for HER2 status assessment in this tumor type has not been established. A total of 67 tumor samples were evaluated for HER2 protein overexpression or ERBB2 gene amplification using at least 2 methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and/or targeted exome next-generation sequencing (NGS). NGS assessed ERBB2 copy number fold change (FC) and total copy number (TCN). HER2 status was first determined by IHC/FISH according to the 2018 ASCO/CAP breast cancer guidelines. FISH results, the “gold standard”, were compared with the NGS results. All (15/15) IHC positive, 35% (6/17) equivocal, and no (0/19) IHC negative SDC were HER2 amplified by FISH. HER2 FISH signal/cell showed a good correlation with FC (Spearman correlation: 0.708, R2: 0.501, p < 0.0001) and TCN (Spearman correlation: 0.763, R2: 0.582, p < 0.0001). Receiver operating characteristics curve estimation showed an area under curve (AUC) of 0.975 for ERBB2 FC. FC cutoff of ≥1.8 corresponded to an accuracy of 95.2% for ERBB2 amplification (Youden's index: 0.84, sensitivity: 89.47%, specificity: 100%). FC < 1.3 could be reliably classified as ERBB2 not amplified and FC ≥ 1.3 and <1.8 as equivocal. TCN estimation showed AUC of 0.981. TCN cutoff of >6.0 corresponded to an accuracy of 92% for HER2 amplification (Youden's index: 0.81, sensitivity: 81.2%, specificity: 100%). TCN < 4 could be reliably classified as ERBB2 not amplified and TCN ≥ 4.0 and ≤6.0 as equivocal. FC and TCN were binarized with respective cutoffs of ≥1.8 and ≥6.0 and the proportion of agreement with FISH were 95% and 92%, respectively. The assessment of ERBB2 copy number by NGS is accurate and reliable with FC or TCN nearly equivalent to FISH in identifying HER2 amplified SDC.

Salivary duct carcinoma- Role of accurate diagnosis for an accurate therapy

Salivary duct carcinoma is an aggressive subtype of primary salivary gland carcinoma with advanced stage at presentation, high rates of metastasis and recurrence. It is most commonly seen in parotid gland of older men with microscopic resemblance to high-grade breast ductal carcinoma. Salivary duct carcinoma mainly affects men over 50 years of age and accounts for 5% to 10% of all salivary gland malignancies. Characteristic histomorphology and immunohistochemical expression of Androgen Receptor (AR) aids the diagnosis of salivary duct carcinoma. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma. Heterologous alterations have been recognized in oncogenes and tumor suppressor genes such as TP53, HRAS, PIK3CA, PTEN, and BRAF as well as AR and HER2. Targeted therapy against these genes may help in broadening treatment options for salivary duct carcinoma. Salivary Duct Carcinoma is one of the most aggressive salivary malignancies with 33% local recurrence and 45% metastasis. We report a case of a 75 years old female patient, who presented with a swelling obliterating the retromandibular groove. FNAC &amp; histopathology confirmed the diagnosis of salivary duct carcinoma.&#x0D;

Sinonasal Acinic Cell Carcinoma: A Review of the National Cancer Database.

Acinic cell carcinoma (ACC) is a salivary gland malignancy that rarely can involve the sinonasal cavity. There are limited outcomes data available to guide management. We sought to use the National Cancer Database (NCDB) to characterize treatment outcomes in sinonasal ACC. A retrospective analysis of the NCDB from 2004 to 2016 for patients with ACC involving the sinonasal cavity was conducted. Demographic, treatment, and survival information were obtained. Unadjusted Kaplan-Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival (OS). A total of 28 patients were included in the analysis with an average age of 58.6 ± 15.5 years. Half the patients (n = 14, 50%) were male, mostly white (n = 23, 82.1%), and with private insurance (n = 16, 57.1%). The nasal cavity was the most common subsite (n = 18, 64.3%), followed by the maxillary sinus (n = 5, 17.9%). Most patient received surgery alone (n = 17, 60.7%), with the remaining patients undergoing surgery followed by radiation (n = 8, 28.6%), radiation alone (n = 1, 3.6%), and no treatment (n = 2, 7.1%). The 1-, 5-, and 10-year survival in this cohort was 100% (95% CI: 100%-100%), 84.3% (95% CI: 71.2%-99.7%), and 72.2% (95% CI: 55%-94.8%), respectively. On multivariate analysis, older age was associated with worse OS (hazard ratio (HR): 1.27; 95% CI: 1.11-1.46, P < .001). Disease of the sphenoid sinus correlated with worse survival (HR: 198, 95% CI: 10.4-3,739, P < .001) and large tumor size was associated with worse OS on log-rank test, but not on multivariate analysis. Sinonasal ACC is a rare entity with relatively good long-term outcomes. Older age and primary disease of the sphenoid sinus are associated with worse outcomes. Most patients are treated with surgical resection. Future research is needed to assess the optimal timing and indications for radiation therapy.

National analysis of positive surgical margins in oropharyngeal salivary gland malignancies

ObjectivePositive surgical margins (PSM) are associated with worse survival in oropharyngeal salivary gland malignancies (OPSGM), but existing literature is limited to small series. Our objective was to identify risk factors for PSM using the national cancer database (NCDB), including a transoral robotic surgical (TORS) approach. MethodsNCDB was queried for patients with T1-T4a OPSGM undergoing resection between 2010 and 2017. Risk factors for PSM were determined using logistic regression. Overall survival (OS) was analyzed using Kaplan-Meier and Cox proportional hazards models. ResultsOf 785 patients, 165 (21.0 %) had PSM. Age, stage T4a tumors (OR 2.00, 95 % Confidence Interval [CI]: 1.03–3.88), adenoid cystic carcinoma (OR 2.02, 95 % CI: 1.29–3.18), and treatment at lower volume institutions (OR 1.68, 95 % CI: 1.09–2.59) were all independently associated with PSM. TORS versus a non-robotic approach was not associated with PSM (23.9 % vs 20.4 %, p 0.358), respectively. Positive margins were independently associated with a worse OS than negative margins (HR 1.63, 95 % CI: 1.03–2.59). Adjuvant radiation therapy was associated with improved survival in high grade tumors with positive margins. ConclusionThis study represents the largest review assessing risk factors for positive margins in OPSGM. Histologic type (adenoid cystic carcinoma), age, T4a tumor stage and treatment at a lower volume institution were all predictive of positive margins. With increasing use of TORS over the last decade, there does not appear to be a greater risk of positive margins using this modality in select patients.Level of evidence: N/A.

Single-cell immune mapping of adenoid cystic carcinoma (ACC) reveals potential therapeutic targets for the aggressive solid subtype.

6090 Background: ACC is a common salivary gland malignancy for which there is no FDA approved therapies. Despite a quiet genome, ACC has significant tumoral heterogeneity, which may facilitate the metastatic relapse. Studies focusing on the deep profile of ACC tumor microenvironment (TME) are lacking. Here we explored the TME of ACC using imaging mass cytometry (IMC) and assessed TME attributes and its association with histology and clinical outcomes. Methods: Two tissue microarrays from 62 ACC patients (pts) were built and stained with 37 metal-tagged markers. IMC was performed with the Fluidigm Helios CyTOF instrument utilizing the Hyperion Imaging System Laser ablation. Tissue and cell segmentation and multiplex imaging analysis were performed with Visiopharm software using pre-trained artificial intelligence algorithms. Comparison of cell types and markers densities among histology sub-groups were analyzed with Wilcoxon signed-rank test and its association with overall survival (OS) with log-rank and Cox Proportional Hazards. Results: Of 62 pts, 37% (23/62) had solid histology, 19% (12/62) were metastatic at diagnosis, and 55% (30/54) had disease recurrence during follow-up. With a median follow-up of 7.9 y, the median OS was 9.3y (CI 95%, 7.8-NR). Pts with solid subtype had poorer OS than non-solid histology (5.2 vs 14.6 y, p = 0.004). The IMC final dataset comprised 507,524 single-cells. No significant differences were found in cell subpopulations density between solid and non-solid histology. The most represented cell population in the stroma were macrophages, followed by CD8+ T cells, and fibroblasts. A higher percentage of M2-macrophage was associated with poor survival (p = 0.001), whereas, a higher percentage of M1-macrophage (M1:M2 ratio) was associated with better prognosis. No other immune cell type, fibroblasts or immune cell functional markers (TIGIT, TIM3, granzyme B, and PD-L1) correlated with survival. Regarding tumor markers, a higher expression of BCL-2, B7-H4, and Ki67 in the tumor cells were associated with worst survival; and remained statistically associated after adjustment for histology and staging (all p &lt; 0.001). Solid histology had a significantly higher density of tumor cells expressing B7-H4, BCL-2, and Ki67 compared to cribriform and tubular histology. A higher expression of myoepithelial marker (p63+) were associated with a better survival when compared with tumors with low p63 expression. Conclusions: ACC’s TME is composed mainly of macrophages. Despite having no significant differences in cellular composition, a higher density of tumor cells expressing BCL-2, B7-H4 and Ki67 were found in the solid histology and these markers were independent predictors of poor prognosis. The overexpression of BCL-2 and B7-H4 in the solid histology provides a scientific rationale for BCL-2 and/or B7-H4 targeting for the most aggressive ACC.