Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands

Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow-up time and (for SGC patients) histological subtype. The mean follow-up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow-up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow-up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%-4.7% and 2.6%-4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19-2.09) higher in the SGC-cohort than expected based on incidence rates in the general population. SGPA-patients showed a 1.48 times (95%CI 1.16-1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening

The tubarial salivary glands:A potential new organ at risk for radiotherapy

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results. Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V

Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands

Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow-up time and (for SGC patients) histological subtype. The mean follow-up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow-up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was

Natural history of recurrent pleomorphic adenoma: implications on management

Background: Treating recurrent pleomorphic adenoma (RPA) aims to reduce risk of malignant transformation (MT) while avoiding facial nerve injury. Our objective was to systematically investigate this natural history of RPA and address the current rational for its treatment. Methods: The follow-up data of two nationwide series of PA was pooled with a focus on risk of MT and analyzed against the literature. Results: The combined nationwide data (n = 9003 PA patients) showed 3.1% with first recurrence of which 6.2% were malignant. In the literature first RPA rate was >7% at 20 years follow-up. MT occurred in 0% to 7%, and facial nerve damage increased from with each surgery 3% to 16% at first RPA to 18% to 30% at second RPA. Conclusions: RPA showed a characteristic course with surgery being unreliable and damage to the facial nerve. The risk of MT was low. This might give flexibility towards a more conservative approach of management

Interpretation of treatment outcome in the clinically node-negative neck in primary parotid carcinoma: A systematic review of the literature

BACKGROUND: Critical evaluation of outcome of primary parotid carcinoma treatment is limited by pathologic diversity and low incidence numbers. Scientific evidence for the optimal management of the N0-neck is scarce and was, therefore, investigated in a systematic literature review. METHODS: The articles included were published in English between 1997 and 2007 and describe populations with the definitive pathology, staging, and treatment. Of 1104 articles, 19 were selected, describing 2703 patients. RESULTS: Of eligible populations, 83% were clinically N0. Pathology reporting of elective lymph node dissection (ELND) had limitations, but 23% showed occult metastases. Regional recurrence occurred in 5% of patients. CONCLUSION: The discrepancy between the relatively high percentage of occult metastases and reported low regional recurrence rates may indicate the efficacy of treatment, being either ELND or radiotherapy of the neck. Pooling, standardized collection, and reporting of data are essential in comparing outcomes in populations to determine optimal treatment. © 2009 Wiley Periodicals, Inc. Head Neck, 201

Prostate-specific membrane antigen positron emission tomography/computed tomography as a potential tool to assess and guide salivary gland irradiation

Evaluation of salivary gland damage after head and neck radiotherapy (RT) is difficult with current tools, such as subjective patient-reported outcome measures. We demonstrate the use of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) as an objective non-invasive tool to visualize damage to salivary glands resulting from RT. In three clinical cases, the PSMA-ligand distribution correlates to the RT dose distribution including intra-gland dose gradients and matches patient-reported toxicity, suggesting a dose-response relation. These findings support further exploration of PSMA PET/CT to guide and evaluate RT, with the ultimate aim to reduce salivary gland toxicity. Keywords: Salivary glands, Toxicity, PSMA, Radiotherapy, Case series, Head and neck neoplasm

Malignant transformation of salivary gland pleomorphic adenoma

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for a

Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also have high PSMA-ligand uptake. This study aimed to describe physiologic PSMA-ligand uptake distribution characteristics in the head and neck to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging. Study Design: Thirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUVmax) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intraindividual variations were reported. Results: All gland locations had increased tracer uptake. The mean SUVmax ± standard deviation varied: parotid 12.3 ± 3.9; submandibular 11.7 ± 3.5; sublingual 4.5 ± 1.9; soft palate 2.4 ± 0.5; pharyngeal wall 4.3 ± 1.3; nasal mucosa 3.4 ± 0.9; supraglottic larynx 2.7 ± 0.7; and lacrimal 6.2 ± 2.2. The parotid had the largest overall variation in SUVmax (5.2-22.9), and the sublingual glands had the largest mean intraindividual difference (18.1%). Conclusions: Major and minor salivary and seromucous glands consistently have high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or lutetium-177-PSMA radionuclide treatment

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck

Background: Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck. Methods: One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis. Results: PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p =.04). Conclusions: PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail