Diagnosis Of Salivary Gland Tumors Research Articles

Comparison of Peptidomes Extracted from Healthy Tissue and Tumor Tissue of the Parotid Glands and Saliva Samples.

Salivary gland tumors are highly variable in clinical presentation and histology. The World Health Organization (WHO) classifies 22 types of malignant and 11 types of benign tumors of the salivary glands. Diagnosis of salivary gland tumors is based on imaging (ultrasound, magnetic resonance imaging) and fine-needle aspiration biopsy, but the final diagnosis is based on histopathological examination of the removed tumor tissue. In this pilot study, we are testing a new approach to identifying peptide biomarkers in saliva that can be used to diagnose salivary gland tumors. The research material for the peptidomic studies was extracts from washings of neoplastic tissues and healthy tissues (control samples). At the same time, saliva samples from patients and healthy individuals were analyzed. The comparison of the peptidome composition of tissue extracts and saliva samples may allow the identification of potential peptide markers of salivary gland tumors in patients' saliva. The peptidome compositions extracted from 18 tumor and 18 healthy tissue samples, patients' saliva samples (11 samples), and healthy saliva samples (8 samples) were analyzed by LC-MS tandem mass spectrometry. A group of 109 peptides was identified that were present only in the tumor tissue extracts and in the patients' saliva samples. Some of the identified peptides were derived from proteins previously suggested as potential biomarkers of salivary gland tumors (ANXA1, BPIFA2, FGB, GAPDH, HSPB1, IGHG1, VIM) or tumors of other tissues or organs (SERPINA1, APOA2, CSTB, GSTP1, S100A8, S100A9, TPI1). Unfortunately, none of the identified peptides were present in all samples analyzed. This may be due to the high heterogeneity of this type of cancer. The surprising result was that extracts from tumor tissue did not contain peptides derived from salivary gland-specific proteins (STATH, SMR3B, HTN1, HTN3). These results could suggest that the developing tumor suppresses the production of proteins that are essential components of saliva.

Novel Detection of Pleomorphic Adenomas via Analysis of 68Ga-DOTATOC PET/CT Imaging.

Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues.

Current Developments in Diagnosis of Salivary Gland Tumors: From Structure to Artificial Intelligence.

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.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study.

Diagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine-needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures. Cytological specimens (n=106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated. Of n=63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential. Molecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine-needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

Differentiation of salivary gland tumors using diffusion-weighted image-based virtual MR elastography: A pilot study.

Differentiation among benign salivary gland tumors, Warthin tumors, and malignant salivary gland tumors is crucial to treatment planning and predicting patient prognosis. However, differentiation of those tumors using imaging findings remains difficult. This study evaluated the usefulness of elasticity determined from Diffusion-weighted image (DWI)-based virtual MR elastography (MRE) compared with conventional MRI findings in differentiating the tumors. This study included 17 benign salivary gland tumors, six Warthin tumors, and 11 malignant salivary gland tumors scanned on neck MRI. The long and short diameters, T1 and T2 signal intensities, tumor margins, ADC values, and elasticity from DWI-based virtual MRE of the tumors were evaluated. The interobserver agreement in measuring tumor elasticity and the ROC curves were also assessed. The long and short diameters and the T1 and T2 signal intensities showed no significant difference among the three tumor groups. Tumor margins and the mean ADC values showed significant differences among some tumor groups. The elasticity from virtual MRE showed significant differences among all three tumor groups and the interobserver agreement was excellent. The area under the ROC curves of the elasticity were higher than those of tumor margins and mean ADC values. Elasticity values based on DWI-based virtual MRE of benign salivary gland tumors, Warthin tumors, and malignant salivary gland tumors were significantly different. The elasticity of Warthin tumors was the highest and that of benign tumors was the lowest. The elasticity from DWI-based virtual MRE may aid in the differential diagnosis of salivary gland tumors.

Diagnosis of Salivary Gland Tumors Using Transfer Learning with Fine-Tuning and Gradual Unfreezing.

Ultrasound is the primary tool for evaluating salivary gland tumors (SGTs); however, tumor diagnosis currently relies on subjective features. This study aimed to establish an objective ultrasound diagnostic method using deep learning. We collected 446 benign and 223 malignant SGT ultrasound images in the training/validation set and 119 benign and 44 malignant SGT ultrasound images in the testing set. We trained convolutional neural network (CNN) models from scratch and employed transfer learning (TL) with fine-tuning and gradual unfreezing to classify malignant and benign SGTs. The diagnostic performances of these models were compared. By utilizing the pretrained ResNet50V2 with fine-tuning and gradual unfreezing, we achieved a 5-fold average validation accuracy of 0.920. The diagnostic performance on the testing set demonstrated an accuracy of 89.0%, a sensitivity of 81.8%, a specificity of 91.6%, a positive predictive value of 78.3%, and a negative predictive value of 93.2%. This performance surpasses that of other models in our study. The corresponding Grad-CAM visualizations were also presented to provide explanations for the diagnosis. This study presents an effective and objective ultrasound method for distinguishing between malignant and benign SGTs, which could assist in preoperative evaluation.

Application of the Milan System for Reporting Salivary Gland Lesions and Its Cytohistological Correlation for Risk Stratification: A Single-Institution Experience.

Salivary gland tumors are known to have a heterogeneous profile with variable clinical presentation and a wide variety of histological subgroups of prognostic significance. Immunocytochemical markers that aid in the diagnosis and characterization of the cell type of origin are critical for this heterogeneous group of malignancies. To study the application of The 'Milan System' for Reporting Salivary Gland Cytology and the diagnostic utility of a panel of immunocytochemical markers in the diagnosis of salivary gland neoplasms and their cytohistological correlation for their risk stratification. This was a prospective study carried out in which a total of 60 patients were enrolled in the study. Fine-needle aspiration cytology (FNAC) smears and cell blocks were prepared with standard techniques and staining procedures. Immunocytochemistry (ICC) was performed on cell block sections by immunoperoxidase procedure. Immunocytochemical (ICC) stains were used for the differentiation of the lesions in cell blocks. Histopathology was also studied if the patient underwent excision of salivary gland lesions. Almost 60 cases were studied under FNAC and cell block evaluation, as well as ICC, among those five (8.33%) samples were inadequate, eight (13.3%) were non-neoplastic, 27 (45%) were benign, one (1.7%) was neoplasmwith uncertain malignancy potential, one (1.7%) was suspected of malignancy, and 19 (31.7%) were malignant.The histopathological diagnosis was confirmed in 47 cases. Of these, 24 (51.1%) were benign and 23 (48.9%) were malignant. The malignancy rate for Milan Categories I, II, III, IVa, IVb, V, and VI was 0%, 0%, 100%, 24%, 50%, 80%, and 84.6%, respectively. The study showed that malignancy risk stratification could be further improved by using cell block with immunocytochemistryas a complementary diagnostic modality. The present study was carried out to assess the usefulness of the Milan system to report salivary gland cytology results. Thus, the findings of the present study showthat the Milan system is helpful in stratifying the risk of malignancy in salivary gland tumors.

Diagnostic value of shear wave elastography quantification combined with conventional ultrasound in salivary gland tumors.

The histopathological classification of salivary gland tumors is extremely complex. The imaging manifestations of some tumors are nonspecific. It is particularly important to improve the value of ultrasound in the diagnosis of salivary gland tumors. This study aimed to analyze the diagnostic value of different parameters of shear wave elastography (SWE) in the quantitative diagnosis of salivary gland tumors, and to evaluate the value of SWE combined with conventional ultrasound. The study was conducted retrospectively. Patients who underwent salivary gland tumor resection from April 2021 to November 2022 in the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine were randomly recruited to the study. A total of 305 masses were divided into an elastography group (150 cases) and a control group (155 cases). The control group underwent conventional ultrasonography, whereas the elastography group underwent conventional ultrasonography and elastography. The Young's modulus E of the mass was quantitatively measured in the elastography group, including maximum cross-sectional area (S), maximum Young's modulus (Emax), mean Young's modulus (Emean), and Young's modulus standard deviation (SD). Pathologic diagnosis was used as the reference standard to determine the cut-off of shear wave elastography of salivary gland tumors, and the diagnostic performance of the 2 groups was compared. In the elastography group, the diagnostic value of Emax·S (the product of the maximum Young's modulus of the mass and the maximum cross-sectional area of the mass) in the differential diagnosis of malignant tumors (MT) and non-malignant tumors (NMT) was the highest, with a sensitivity and specificity of 72.0% and 80.0%, respectively. The diagnostic value of Emax/D (the quotient of the maximum Young's modulus of the mass and the maximum diameter of the mass) in the differential diagnosis of pleomorphic adenoma (PA) and adenolymphoma (AL) was the highest, with a sensitivity and specificity of 62.3% and 82.4%, respectively. The receiver operating characteristic (ROC) curves for the diagnosis of salivary gland tumors were compared between the elastography group and the control group. The area under the curve (AUC) of the elastography group was 0.915, the sensitivity, specificity, and Youden index were 84.0%, 88.0%, and 0.720, respectively. The AUC of the control group was 0.906, the sensitivity, specificity, and Youden index were 76.0%, 90.0%, and 0.660, respectively, which is the main finding of the study. SWE can be used as a complementary method for the diagnosis of salivary gland tumors, which has certain value in improving the diagnostic performance. As a result, the sensitivity is improved but the specificity is worsened by addition of SWE to B-mode ultrasound and color Doppler flow imaging (CDFI).

Reliability of Fine Needle Aspiration Cytology for Salivary Gland Tumours Meta-Analytical Study

Abstract Background Fine needle aspiration (FNA) cytology is a safe, reliable, minimally invasive and cost- effective technique for the diagnosis of salivary gland lesions. Aim and objectives to assess the accuracy, sensitivity and specificity of FNAC for diagnosis of salivary gland tumors in comparison with biopsy as definite diagnostic tool for these tumors. Subjects and methods This is a Retrospective and prospective studies, was carried out on Patients diagnosed with salivary gland tumors, treated with surgical management. Result FNA was associated with statistically significant fewer nondiagnostic results, Pooled analysis of all studies (n = 3605) revealed that rate of nondiagnostic results is 2.992% with 95% CI of rate 91.10–95.09 with absence of publication bias. Conclusion Fine needle aspiration biopsy is an important diagnostic tool for evaluating parotid gland tumors. It is more accurate in detecting benign tumors. In tumors greater than 2 cm and extending to the deep lobe, the sensitivity of fine needle aspiration biopsy is high. The use of fine needle aspiration biopsy in conjunction with clinical and radiological evaluation may help to reduce false positive and false negative results Funding Sources This research received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Fine-Needle Aspiration Cytology in the Diagnosis of Salivary Gland Tumors Before the Milan System: A Ten-Year Experience From a Tertiary Care Center in Greece.

Objective The objective of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) for salivary gland tumors. Methodology A retrospective file analysis of patients with salivary gland pathology, attending the Department of Oral and Maxillofacial Surgery of a tertiary care center in Athens, Greece, over a 10-year-long period, was conducted. Sensitivity, specificity, accuracy, positive prognostic value (PPV), and negative prognostic value (NPV) of FNAC for benign and malignant tumors separately were assessed and compared with histology. Results A total of 82 patients (46 male and 36 female) with salivary gland tumors, submitted to both FNAC and histology, were included. The mean age was 55 years. A total of 73 tumors were histologically diagnosed as benign and nine as malignant. FNAC identified 62 benign and seven malignant tumors but was inconclusive in 13 cases. The most common diagnosis of both histology and FNAC was pleomorphic adenoma. FNAC sensitivity, specificity, accuracy, PPV, and NPV were 98.3% and 100%, 87.5% and 100%, 97.1% and 100%, 98.3% and 100%, and 87.5% and 100% for benign and malignant tumors, respectively. Conclusions FNAC is highly sensitive but moderately specific for the preoperative identification of benign salivary gland tumors. Its use as an initial diagnostic modality is warranted, thanks to its safeness, rapidity, and lack of pain.

Comparison Study of FNAC Using the Milan System Cytopathology versus Definitive Histology for the Diagnosis of Salivary Gland Tumors

Introduction: Salivary gland tumors (SGT) represent 6 to 8 percent of head and neck tumors. The cytologic diagnosis of SGT is performed by fine-needle aspiration cytology (FNAC) with variable sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes the cytological results and provides the risk of malignancy (ROM). The aim of our study was to evaluate the cytological findings with the definitive pathological findings to assess the sensitivity, specificity, and diagnostic accuracy of FNAC in SGT according to MSRSGC classification. Method: An observational, retrospective, single-center study was carried out at a tertiary referral hospital over a period of 10 years. Patients that underwent FNAC for major SGT and that have undergone surgery to remove the tumor were included. A histopathological follow-up was performed on the surgically excised lesions. Results from the FNAC were categorized into one of the six MSRSGC categories. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of FNAC for determining benign and malignant cases were calculated. Results: A total of 417 cases were analyzed. The cytological prediction of ROM was 10% in nondiagnostic, 12.12% in non-neoplastic, 3.58% in neoplasm benign group, 60% in AUS and SUMP groups, and 100% in suspicious and malignant group. The statistical analysis of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for determining benign cases was 99%, 55%, 94%, 93%, and 94%, respectively, and for determining malignant neoplasm was 54%, 99%, 93%, 94%, and 94%, respectively. Conclusion: In our hands, MSRSGC is highly sensitive for benign tumors and highly specific for malignant tumors. The low sensitivity to differentiate malignant from benign cases makes it necessary to apply an adequate anamnesis, physical examination, and imaging tests to consider surgical treatment in most cases.

Diagnosis of salivary gland tumors: Does the triple diagnosis method have value?

Appropriate clinical management of salivary gland lesions requires a determination as to whether a salivary gland nodule is benign or malignant. Approximately three-quarters of all salivary gland nodules represent benign neoplasms. Separation of salivary gland carcinomas from benign lesions can be diagnostically challenging. The Milan System for Reporting Salivary Gland Cytopathology recommends the correlation of cytologic diagnoses with imaging and clinical findings creating a diagnostic triplet. How often the "Triple Diagnosis" method is used and its accuracy in separating salivary gland nodules into benign and malignant groups are unknown. An electronic records search of cytology files at the University of Missouri was performed for fine needle aspirates of the salivary gland obtained between September 2018 and August 2022. Chart review was performed for preoperative clinical and imaging diagnoses. Diagnostic "Triplets" constructed from cytologic, clinical, and imaging diagnoses were correlated with final surgical pathology diagnosis. One hundred and thirty-six FNAs were identified. Eighty-seven cases had preoperative imaging with 52 of these cases having clinical diagnoses. Due to the lack of a definitive clinical or imaging diagnosis for a nodule as benign or malignant, only 12 (23%) cases had definitive "Triplets." Nine (17%) "Triplets" were benign and three (6%) were malignant. Accuracy of concordant triplets was 100% for the prediction of malignancy and 89% for the prediction of a benign result as determined by final histologic diagnoses. While highly accurate in predicting the benign or malignant nature of a salivary gland nodule, concordant triplets made up only 23% of cases limiting their clinical utility.

Liquid-based cytology (LBC) with immunocytochemical staining improves fine-needle aspiration cytology (FNA) performance for salivary gland tumors

BackgroundLiquid-based cytology (LBC), now used globally for the head and neck region, has been used at our hospital since 2011. This study was designed to analyze the efficacy of LBC with immunocytochemical staining on preoperative diagnosis of salivary gland tumors. MethodsThis retrospective analysis of fine-needle aspiration (FNA) performance for salivary gland tumors was conducted at Fukui University Hospital. Salivary gland tumor operations conducted during April 2006 – December 2010 (84 cases) were classified as the Conventional Smear (CS) group, which were diagnosed morphologically by Papanicolaou and Giemsa staining. Those done during January 2012 – April 2017 (112 cases) were classified as the LBC group, which were diagnosed using LBC samples with immunocytochemical staining. The FNA results and pathological diagnosis of both groups were analyzed to calculate the FNA performance. ResultsCompared to the CS group, cases of inadequate and indeterminate FNA sample were not reduced significantly by LBC with immunocytochemical staining. As for FNA performance, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CS group were, respectively, 88.7%, 53.3%, 100%, 100%, and 87.0%. Those of LBC group were all 100%, representing significant improvement over the CS group. ConclusionsAnalysis results indicated the usefulness of LBC with immunocytochemical staining for preoperative diagnosis of salivary gland tumors.

Support Tools in the Differential Diagnosis of Salivary Gland Tumors through Inflammatory Biomarkers and Radiomics Metrics: A Preliminary Study

The purpose of this study was to investigate how the systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), and radiomic metrics (quantitative descriptors of image content) extracted from MRI sequences by machine learning increase the efficacy of proper presurgical differentiation between benign and malignant salivary gland tumors. A retrospective study of 117 patients with salivary gland tumors was conducted between January 2015 and November 2022. Univariate analyses with nonparametric tests and multivariate analyses with machine learning approaches were used. Inflammatory biomarkers showed statistically significant differences (p < 0.05) in the Kruskal-Wallis test based on median values in discriminating Warthin tumors from pleomorphic adenoma and malignancies. The accuracy of NLR, PLR, SII, and SIRI was 0.88, 0.74, 0.76, and 0.83, respectively. Analysis of radiomic metrics to discriminate Warthin tumors from pleomorphic adenoma and malignancies showed statistically significant differences (p < 0.05) in nine radiomic features. The best multivariate analysis result was obtained from an SVM model with 86% accuracy, 68% sensitivity, and 91% specificity for six features. Inflammatory biomarkers and radiomic features can comparably support a pre-surgical differential diagnosis.

Efficacy of Ultrasound Shear Wave Elastography in the Diagnosis of Salivary Gland Tumors

Diagnostic accuracy of fine-needle aspiration cytology (FNAC) as the ability to discriminate between the target condition and health in the evaluation of salivary gland tumors is not perfected yet and false-negative results are possible. The purpose of the present study was to measure and compare the diagnostic accuracy of FNAC performed with conventional B-mode ultrasound and ultrasound with shear wave elastography (SWE) FNAC navigation. The investigators implemented a single-blind randomized study (sealed envelope method). The study population was composed of all patients presenting for evaluation and management of suspected benign or malignant tumors of the major salivary glands between July 2013 and December 2020. The involvement of SWE navigation was the primary predictor variable affecting FNA targeting. The method involved analysis of redistribution of SWE values within the affected gland expressed in kilopascals (kPa) and the four-point ES1 (soft tissue) to ES4 (stiff) scoring. The primary outcome variable was the success in obtaining diagnostic tissue resulting in a histologically confirmed FNAC diagnosis and coded as yes/no. Age and sex of the patients and topographical locations of lesions were covariates. Descriptive and bivariate statistics were computed and the P value was set at .05. The sample included 132 subjects (male/female 59/73; mean age 54±11years; 144 tumors). SWE+Group (n=66) consisted of patients presurgically diagnosed with salivary tumors SWE-guided FNAC and SWE- Group (n=66) was diagnosed with tumors by conventional ultrasound-(B-mode)-guided FNAC. The SWE-guided FNAC statistically significantly reduced the incidence of false-negative results (n=0; P=.001) and nondiagnostic cases (n=3 SWE FNAC vs n=7 B-mode US FNAC; P=.04). For SWE+Group, the FNAC diagnosis was confirmed by postsurgical histology in 95.5% with 91.0% sensitivity (confidence interval [CI] 0.62 to 0.97) and 84.4% specificity (CI 0.58 to 0.96). For SWE- Group, 81.8% confirmation was obtained (P=.05) with 82.3% sensitivity (CI 0.54 to 0.90) and 74.0% specificity. SWE can increase success in obtaining diagnostic tissue when used for FNAC navigation purposes. We suggest combining both SWE and standard B-mode US methods when the FNAC procedure is performed.

Retracted: Application of Contrast-Enhanced Ultrasound Combined with Elastic Imaging Technology in Differential Diagnosis of Salivary Gland Tumors.

[This retracts the article DOI: 10.1155/2022/4600751.].

Results of anationwide survey on the treatment of salivary gland diseases in German hospitals

Salivary gland diseases are an important part of the work of ENT physicians in hospitals. The treatment strategies depend, among other things, on the doctrine at the respective location. The aim of this questionnaire-based study was to assess the current diagnostic workup and therapeutic strategies for salivary gland diseases in German otorhinolaryngology departments. Asurvey was performed using a 25-question online questionnaire sent to all German otorhinolaryngology department directors. The questionnaire was answered by92 of 175otorhinolaryngology departments (52.6%). In the diagnosis of salivary gland tumors, adominance of sonography and MRI was shown. Fine- and core-needle aspiration were not performed by more than 50% of the clinics. The dominant technique for parotidectomy was under microscopic control (82%). In 99% of clinics, EMG was used during resection of the parotid gland for intraoperative monitoring of the facial nerve. There was atrend towards performing partial parotidectomies (85%), lateral parotidectomies (70%), and extracapsular dissections (57%) for benign tumors of the parotid gland. The treatment concepts for malignant tumors were inconsistent. In particular, the treatment strategy and extent of surgery for benign and malignant salivary gland tumors differed depending on location. The choice of palliative (drug) therapy was also diverse. Prospective multicenter studies could help to develop evidence-based treatment strategies.

A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors.

Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.

Salivary gland tumors exhibit distinct miRNA signatures involved in Wnt/β-Catenin signaling in formalin fixed paraffin embedded tissue samples.

Advances in high-throughput genomic technologies have enabled the identification of numerous selective tumor markers. However, adapting these newly identified markers to clinical practice is not always possible because most RNA molecules, including mRNAs of protein-coding genes and long non-coding RNAs, are not stable under laboratory conditions, making their testing a major challenge. In contrast to long RNA molecules, miRNAs offer a great advantage in that they are relatively stable due to their small size. Accordingly, herein we aimed to determine the expression levels of miRNAs that are involved in Wnt/β-catenin signaling pathway in formalin fixed paraffin embedded (FFPE) tissue samples of patients with salivary gland tumors. A total of 42 patients with salivary gland tumors were included in the study. The miRNA expression signatures were evaluated using the RT-qPCR. As a result, β-catenin positivity was observed in all salivary gland tumors without distinguishing between benign and malignant phenotypes. Remarkably, we found that miR-200a and miR-373 were significantly upregulated whereas miR-30c were downregulated in tissues of patients with salivary gland tumors, compared to adjacent healthy tissue samples. In addition, distinct expression signatures of these miRNAs were significantly associated with the clinicopathological findings of patients such as perineural invasion and lymph node metastasis. Additionally, miR-145 and miR-30a were found to be specifically downregulated in a mucoepidermoid carcinoma. Also, miR-26b was selectively increased in pleomorphic adenomas of the salivary gland. Collectively, our findings suggest that these miRNAs may play chief roles in the differential diagnosis of salivary gland tumors.

Two Extremely Rare Case of Carcinosarcoma Ex Pleomorphic Adenoma.

Carcinosarcoma ex pleomorphic adenoma (CCPA), also known as true mixed malignant tumor, is an extremely rare high-grade aggressive tumor. The histopathologic examination is the gold standard for diagnosis and radiologic imaging also plays an important role. CCPA should be considered in the differential diagnosis of salivary gland tumors when there are findings suggestive of malignancy such as necrosis and diffusion limitation on imaging.