Malignant Salivary Gland Tumors Research Articles

Atypical and worrisome histological features in pleomorphic adenoma: challenging and potentially significant diagnostic pitfall.

Pleomorphic adenoma (PA), the most prevalent salivary gland tumor, exhibits a diverse histological spectrum characterized by epithelial, myoepithelial, and mesenchymal patterns, and secretory products. However, a subset of PAs presents microscopic features suggestive of malignancy, leading to challenging and potentially significant diagnostic pitfalls. A comprehensive retrospective analysis was conducted on the Salivary Gland Tumor Registry, compiled by the authors. A total of 104 cases diagnosed between 1960 and 2023 were retrieved. Clinical findings, pathological features, and molecular genetic results were analyzed. In the study of 104 PA cases, 23 (22.1%) presented features suggestive of pseudoinvasion, with satellite nodules being the most common (43.5%) along with capsular penetration, irregular growth, pseudopodia, lipomatous changes, and vascular permeation. Features of pseudomalignant cytomorphology were found in 97 cases (93.3%), characterized by increased cellularity, cellular atypia, heightened proliferative activity, oncocytic metaplasia, and necrosis. Additionally, 30 cases (28.8%) displayed features resembling other defined malignant salivary gland tumors, particularly myoepithelial carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma. Despite PA's generally straightforward diagnosis, cases with these features may be mistakenly interpreted as malignant tumors. The shared morphocytological features underscore the complexity of anaccurate diagnosis, emphasizing the need for meticulous examination and a comprehensive assessment, incorporating morphological, molecular, and immunohistochemical analyses to differentiate between benign and malignant salivary gland tumors, in selected cases.

Aurora kinase A expression in pleomorphic adenoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands: an immunohistochemical study

BackgroundAurora kinase A (AurkA) plays a vital role in mitosis and is therefore critical in tumors development and progression. There are a few studies on AurkA expression in salivary gland tumors. The aim of the present study was to evaluate the expression pattern of AurkA in the most common benign and malignant salivary gland tumors by immunohistochemistry.MethodsIn this retrospective cross-sectional study, 68 cases including 25 pleomorphic adenomas (PAs), 21 adenoid cystic carcinomas (ADCa), 15 mucoepidermoid carcinomas (MEC), and 7 normal salivary glands (NSG) were enrolled from the archive of the Department of Pathology of Shiraz School of Dentistry, Iran. The expression of AurkA in the tissue samples was assessed by immunohistochemical method and was analyzed using statistical analysis (p < 0.05).ResultsOf total cases analyzed, the majority of benign and malignant tumors were found to involve minor salivary glands compared to major salivary glands (p < 0.001). In addition, all lesions studied expressed AurkA. More than half of the tumor tissues showed AurkA staining percentages between 26 and 50% and 76–100% compared to NSG (p = 0.08). In 44.1% of cases, cells had a weak staining score, 27.9% a moderate score and the rest (27.9%) a strong score (p = 0.64).ConclusionAlthough AurkA was observed to be expressed in all tumor tissues, further studies are needed to clearly understand the role of AurkA and the possibility of using it as a diagnostic, prognostic and therapeutic factor.

Malignant Salivary Gland Tumors in a Tertiary University Hospital in Northern Spain

(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.

TRPS1 Immunohistochemistry in Salivary Gland Neoplasms: Analysis on Cytology Cell Blocks and Surgical Follow-Up Correlation.

In this study we aim to analyze the TRPS1 immunostaining of salivary gland tumors (SGT) on cytology cell blocks and compare the staining pattern on subsequent surgical resections. Malignant SGTs, oncocytomas and basal cell adenomas diagnosed on fine needle aspiration were retrieved from 2019 to 2021 database. Cases with surgical follow-up were selected. TRPS1 staining was performed on cytology cell blocks and surgical specimens. Scoring was interpreted by two pathologists independently. Our cohort comprised of 58 cases: 45 malignant and 13 benign. TRPS1 scoring was interpreted for 44 cytology and 51 surgical cases. 14 cytology cases lacked tumor cells on deeper levels. For 7 cases, surgical blocks were not retrievable. TRPS1 positivity for cytology and surgical cases were 52% and 47% respectively. In the malignant cohort, TRPS1 was positive in 21/32 (66%) cytology cases and 21/43 (56%) surgical cases. All cases of basal cell adenocarcinoma, carcinoma ex pleomorphic adenoma and salivary duct carcinoma were TRPS1 positive on cytology. All cases of adenoid cystic carcinoma and acinic cell carcinoma were TRPS1 positive on surgical resections. In the benign cohort, TRPS1 was positive in 2/12 (17%) cytology cases; however, none of the surgically resected benign cases showed reactivity (0/8). Cytology-surgical correlation of TRPS1 staining was done in 37 cases. We found 21 concordant and 16 discordant cases. Discordance was highest in mucoepidermoid carcinoma. TRPS1 is not an entirely specific marker for breast carcinoma. TRPS1 positivity was noted in a substantial number of salivary gland malignant neoplasms. Cases demonstrating discordance in TRPS1 staining pattern on cytology-surgical correlation warrant further exploration.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, with systemic symptoms such as fever being uncommon. Adult-onset Still’s disease (AOSD) is an autoinflammatory condition characterized by high-grade fever, rash, and polyarthritis. The co-occurrence of AS and AOSD is extremely rare and presents significant diagnostic challenges. This case report outlines the complexities involved in identifying and

Background: Adenoid cystic carcinoma is one of the most common malignant neoplasms of salivary glands, characterized by aggressive behavior, recurrence, metastasis to distant organs, and relative radio resistance, rendering local control challenging to achieve. Objective: The goal of this work is to shed light on the role of c-KIT in the pathogenesis of salivary adenoid cystic carcinoma at the gene and protein levels. Materials and Methods: c-KIT protein expression and gene levels were determined by real-time immunohistochemistry (IHC) and polymerase chain reaction (PCR) in a total of fifty-two specimens of salivary adenoid cystic carcinoma. Results: The immunoreactivity for c-KIT antibody was observed among all of the studied cases, whereas, thirteen cases tested for c-KIT gene mutations by DNA sequencing showed no detection of genetic mutation despite being positive for immunohistochemistry. Conclusion: Although c-KIT immunopositivity is high in salivary adenoid cystic carcinoma, the absence of gene mutation renders target therapy ineffective.

Gallium-67 SPECT/CT and diffusion-weighted MRI in the palatal tumor: report of a rare case with adenocarcinoma not otherwise specified

BackgroundAdenocarcinoma not otherwise specified (NOS) is an uncommon malignant minor salivary gland tumor. We report gallium-67 SPECT/CT and diffusion-weighted MRI (DWI) in the palatal tumor, especially a rare case with adenocarcinoma NOS.Case presentationAn 85-year-old female patient presented with swelling on the palate within 3 months. DWI and apparent diffusion coefficient (ADC) maps indicated high and low signal intensities on the lesion, respectively. ADC value of the lesion was 0.58 × 10–3 mm2s−1. Gallium-67 SPECT/CT showed increased uptake on the lesion and no metastasis. The maximum SUV for the palatal lesion was 7.36. Histopathological diagnosis by a biopsy was adenocarcinoma NOS.ConclusionThe gallium-67 SPECT/CT and DWI should be effective for assessment of the palatal tumor.

Radiomic and Clinical Model in the Prognostic Evaluation of Adenoid Cystic Carcinoma of the Head and Neck.

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. 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). 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. 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.

An Institutional Experience of Core Needle Biopsy with Cooperative Implementation by Pathologists and Head and Neck Oncologists in Salivary Gland Carcinoma.

A major problem in establishing treatment strategies for salivary gland carcinomas is the difficulty of preoperative histologic subtyping. Core needle biopsy (CNB) allows the collection of a small, intact specimens from the tumor center for detailed analysis. We evaluated the efficacy and limitations of preoperative diagnosis with CNB specimens collected using a newly developed 20-gauge needle designed to popularize its use. Paired preoperative CNB and surgical specimens from 41 patients with malignant salivary gland tumors were retrospectively reviewed. A histologic typing platform, including morphologic and immunohistochemical evaluation and fluorescence in situ hybridization, was evaluated using CNB specimens. Biopsy specimen quality, diagnostic accuracy, and immunohistochemistry concordance rates between biopsy and surgical specimens were analyzed. In 39 of the 41 patients, CNB provided high-quality specimens, enabling adequate morphologic, immunohistologic, and genomic analyses. In two patients, high-quality CNB specimens could not be obtained due to cystic fluid and tumor firmness. The overall accuracy of correct preoperative diagnosis was 75%. The success rate of histologic subtyping and HER2 immunostaining concordance between CNB and surgical specimens was lower in carcinoma ex-pleomorphic adenoma (CXPA) than in de novo carcinoma (histologic subtyping; CXPA vs de novo carcinoma 50% vs 89%, p = 0.016, HER2 concordance; salivary duct carcinoma [SDC] ex-PA vs de novo SDC 16% vs 100%, p = 4.66E-03). No recurrence occurred due to tumor seeding after CNB. Highly accurate histologic subtyping of salivary gland carcinomas can be performed by preoperative CNB; however, specificity can be more challenging in pathologically heterogenous tumors.

Pitfalls in Diagnosis of Myoepithelial Carcinoma of Salivary Glands: A Study of 3 Cases with Cytologic-histologic Correlation and Molecular Analysis.

Myoepithelial carcinoma (MECA) represents < 1% percent of salivary gland (SG) tumors with a mean age of 55 years. These tumors can arise de novo or in association with pre-existing pleomorphic Adenoma (PA). The cytologic features of MECA overlap with other SG neoplasms including the more common benign entities like PA and myoepithelioma and can pose a diagnostic challenge. A database search for MECA was performed spanning 10 years. 3 cases qualified with available cyto-histologic correlation. All were morphologically MECA with one case diagnosed as MECA ex-PA. The cases were subjected to a comprehensive immunohistochemical and molecular evaluation (Case#1 has been previously reported and published in head and neck pathology in 2021). A comparative analysis of these cases is presented in Table1. All three cases were initially diagnosed as PA on cytology. On review of cytology slides, presence of metachromatic stromal fragments and bland myoepithelial cells was found to be the most common diagnostic pitfall. S100 was positive in all cases while myosin, p63, and GFAP were variably positive. Molecular analysis revealed novel, previously undescribed mutations in the three cases. Additionally, two of three cases expressed PD-L1, suggesting a role for immunotherapy in treatment. Cytomorphology of MECA is poorly described in literature and can pose a diagnostic challenge due to overlapping features with salivary gland benign neoplasms. A conclusive diagnosis on cytology is often not possible. However, a high cellularity, predominant oncocytoid/ myoepithelial cell population on smears and cell block, along with a strong clinical and radiologic suspicion for malignant salivary gland tumor, should alert the cytopathologist and help avoid an erroneous benign diagnosis on cytology.

A Case Series of a Rare Parotid Gland Oncocytic Mucoepidermoid Carcinoma

Abstract Introduction/Objective We analyzed two cases of oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland which highlight the diagnostic challenges of oncocytic salivary gland neoplasms. OMEC’s are a rare type of salivary gland tumor commonly arising from the parotid gland that can easily be mistaken as benign. Proper pathologic diagnosis of these masses is critical, as it guides therapeutic intervention and has prognostic significance. Methods/Case Report In this case series, two patients were analyzed retrospectively for unilateral parotid masses. Results (if a Case Study enter NA) In a 67-year-old female, an MRI and biopsy were performed. Only a differential diagnosis could be provided, which favored oncocytoma or oncocytic carcinoma. Due to this uncertainty, a complete excision of the mass was performed. Considering the cytomorphology, immunohistochemistry (CK5/6 and P63 in oncocytes), and mucicarmine special stain highlighting scattered mucocytes, the patient was diagnosed with a low- grade OMEC. In our second case, an 80-year-old female, FNA of a posterior left ear mass 1 year prior revealed a low- grade oncocytic proliferation. With the presence of a left parotid mass one year later, additional imaging was performed and showed increased T2 hyperintensity on MRI, which caused concern for the clinicians. A superficial limited parotidectomy was performed and a differential of oncocytoma versus oncocytic variant of mucoepidermoid carcinoma was rendered. Further tumor characterization with fluorescence in situ hybridization (FISH) demonstrated a MAML2 translocation which guided diagnosis of OMEC. Conclusion With approximately 30% of all malignant salivary gland tumors being constituted by mucoepidermoid carcinoma, the ability to accurately diagnose even this rare subtype, oncocytic mucoepidermoid carcinoma, is of significant importance and relevance to pathologists in many practice settings. Herein we demonstrate the utility of H&amp;E morphology, immunohistochemistry, and MAML2 FISH in diagnosing OMEC in the setting of oncocytic salivary gland lesions. Future avenues, including tumor molecular profiling, will aid in elucidating clinicopathologic characteristics of this entity.

Bronchial Sialadenoma Papilliferum in a 10-Year-Old Boy.

Sialadenoma papilliferum (SP) is a rare salivary gland tumor mostly reported in the oral cavity. Here we describe a bronchial SP in the left upper lobe bronchus of a 10-year-old boy. At bronchoscopy, a well-circumscribed polypoid lesion protruding into the bronchial lumen was identified. The tumor was excised, but eventually, the patient had to undergo a sleeve resection after 2 recurrences. Pathology revealed a papillocystic lesion with exophytic and endophytic components. The cells lining the exophytic surface and papillary structures were columnar and squamous, and the cells lining endophytic cystic and papillary structures were cuboidal to columnar, all of which were diffusely reactive with antibodies to SOX10 protein. The presence of basal cells was demonstrated by p63 immunoreactivity. The cells failed to immunohistochemically express BRAF V600E. Fluorescence in situ hybridization analysis revealed no MAML2 or RET gene rearrangement. The patient is alive 24 years after resection with no additional recurrences. Bronchial SP needs to be recognized and distinguished from other benign and malignant salivary gland and pulmonary neoplasms so that patients can receive appropriate treatment and follow-up.

Expression of β-Catenin in Salivary Gland Tumors.

Salivary gland tumors are an important group of neoplasms in the head and neck region. This study aims to assess the significance of β-catenin expression in both benign and malignant salivary gland tumors. We included 80 reported cases of benign and malignant salivary gland tumors and employed β-catenin stain on tumor blocks. A consultant histopathologist interpreted the β-catenin expression, and a score of 0, 1, 2, 3 was given based on intensity as completely absent, mild, moderate, or intense. Intracellular localization ofβ-catenin stain was interpreted as the percentage of membranous, cytoplasmic, or nuclear expression. Expression in benign and malignant classes of salivary gland tumors differs in intensity and localization.The benign category of tumors exhibited primarily membranous expression, and all cases of Warthin tumor showed intense membranous expression (p ≤ 0.05). Malignant tumors manifested chiefly cytoplasmic expression, andamong the malignant category, adenoid cystic carcinoma showed intense cytoplasmic localization (p ≤ 0.05). None of the tumors showed nuclear expression. Decreased membranous and increased cytoplasmic expression could predict malignant behavior and invasive potential.

Perplexing Intraoral Swellings: A Cross-Sectional Study On Minor Malignant Salivary Gland Tumors

Background: This study aims to assess the prevalence and correlation between age, gender, and site of malignant minor salivary gland tumors among patients attending a tertiary healthcare centre in Trivandrum from 2015 to 2022. A total of 26 cases were reviewed, with mucoepidermoid carcinoma (MEC) being the most prevalent, followed by adenoid cystic carcinoma (ACC) and polymorphous adenocarcinoma (PAC). Our findings suggest a slight female predilection overall, though certain tumor types showed gender-specific trends. The study highlights important epidemiological insights that can help future research and clinical practice inmanaging malignant minor salivary gland tumors.

COMPARISON OF IMMUNOHISTOCHEMICAL EXPRESSION OF INSULIN LIKE GROWTH FACTOR 1 RECEPTOR (IGF-1R) IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS

Objectives: To evaluate the difference in immunohistochemical expression of insulin-like growth factor-1 receptor (IGF-1R) in diagnosed cases of benign and malignant salivary gland tumors.Materials and Methods: This Comparative Cross-Sectional Study was conducted at the department of Pathology, Peshawar Medical and Dental College, Peshawar. A total of 100 Salivary Gland Tumors from 56 male and 44 female patients were included in the study, with an average age of 43.50 ± 15.21. The Immunohistochemical Expression of Insulin-like Growth Factor 1 Receptor was determined on both benign and malignant salivary gland tumors using the Bio SB Polyclonal IGF-1R antibody (rabbit, BT-AP04398). The collected data were analyzed using SPSS version 25.Results: For the immunohistochemical expression of IGF-1R on benign and malignant salivary gland tumors, the Allred Scoring method was utilized. P value of &lt;0.05 was considered significant, but no positive signifi cance was found between the expression of IGF-1R and salivary gland tumors.Conclusion: IGF1R expression was positive in various SGTs but no statistically significant difference was seen in multiple histopathological types of benign and malignant SGT

Machine Learning on Ultrasound Texture Analysis Data for Characterizing of Salivary Glandular Tumors: A Feasibility Study.

Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors. 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. Representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use a t-test to test the significance and use the receiver operating characteristic curve method to find the optimal cut-point for these significant features. After splitting 80% of the data into a training set and 20% data into a testing set, we use five machine learning models, k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANNs) and supportive vector machine (SVM), to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors. This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign and malignant tumors (p < 0.05). In ML, the overall accuracy rates are 74.3% (95%CI: 59.8-88.8%), 94.3% (86.6-100%), 72% (54-89%), 84% (69.5-97.3%) and 73.5% (58.7-88.4%) for kNN, Naïve Bayes, Logistic regression, a one-node ANN and SVM, respectively. US texture analysis with ML has potential as an objective and valuable tool to make a differential diagnosis between benign and malignant salivary gland tumors.

Update of newly-recognized salivary gland neoplasms: molecular and immunohistochemical findings and clinical importance.

With the advancement of molecular testing and the routine use of immunohistochemical stains, salivary gland tumours previously categorized as adenoma or adenocarcinoma, not otherwise specified, are being reclassified with distinct diagnoses. Newly recognized benign entities include: sclerosing polycystic adenoma, keratocystoma, intercalated duct hyperplasia and adenoma, and striated duct adenoma. Newly recognized malignant salivary gland tumours include: microsecretory adenocarcinoma, sclerosing microcytic adenocarcinoma, and mucinous adenocarcinoma. Additionally, rare subtypes of mucoepidermoid carcinoma have been described, including Warthin-like and oncocytic. Understanding of intraductal carcinoma continues to evolve. Correctly distinguishing these lesions from mimickers can be crucial for appropriate patient care and prognostication, as well as future conceptualization of salivary disease.

Clinical Behavior and Molecular Insights of Secretory Carcinoma of Salivary Glands, a Single Center Experience

Objective: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. Methods: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. Results: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. Conclusion: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes.

Mucoepidermoid carcinoma: A comparative analysis of histological grading systems

: Salivary gland carcinomas comprise of only 3-5% of all head and neck malignancies. Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. The morphologic diversity of MEC can pose diagnostic challenges hence, various histological grading systems have been proposed based on the quantitative and qualitative analysis. This proves to be greatly consequential in the management and prognosis of patients with MEC.To compare histologic grading methods in MEC of major &amp; minor salivary glands.20 histopathologically diagnosed cases of MEC (10 each major &amp; minor salivary gland) will be analysed using following methods: Qualitative Method: 1) Modified Healey 2) Memorial Sloan-Kettering Cancer Center method. Quantitative method: 1) Armed force Institute of Pathology (AFIP) 2) Brandwein method Histological findings were evaluated. In our study AFIP grading system, 50% Cases were classified as low grade, 35% as intermediate grade and 15% as high graded. According to Brandwein grading system20% of cases were categorized as low, 35% cases as intermediate, 45% cases as high grade MEC. Modified Healey grading system of MEC showed 50%, 40%, 10% cases as low, intermediate and high grade MEC respectively. MSKCC grading system revealed as 55%, 30% and 15% cases as low, intermediate and high grade MEC respectively. Our finding indicated that MSKCC grading system was the most favourable histological grading system as percentage of agreement found to be 85%.Careful microscopic examination is the most important parameter in the grading of MEC. This meticulous microscopic examination emerges as the cornerstone in grading MEC. Both MSKCC and Modified Healey grading methods exhibits effectiveness in evaluating MEC. Our finding indicated that Memorial Slon Kettering Cancer Center (MSKCC) was the most favourable histological grading system as percentage of agreement found to be 85%. However, further longer studies are imperative to substantiate this finding and for establish of universally accepted grading system for Mucoepidermoid carcinoma.

MiR-26a and miR-191 are upregulated while PLAG1 and HIF2 are downregulated in pleomorphic adenomas of the salivary glands compared to Warthin tumors.

Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR-26a, miR-26b, and miR-191), and three pro-oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers. This cross-sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction. All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR-26a And miR-191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH. The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR-26a, miR-191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers.

PD-L1 and PD-L2 Expression in Different Tumor Stages and Types of Malignant Salivary Gland Neoplasms: A Single-center Experience.

There is a limited amount of data on the role of programmed cell death ligand (PD-L) -1 and PD-L2 in salivary gland carcinomas. We aimed to evaluate the prognostic value of PD-L1 and PD-L2 expressions, which are closely related to immune mechanisms, with respect to salivary gland tumor types and stages. Data from patients with salivary gland masses surgically removed between 2006 and 2021, diagnosed with a malignant salivary gland neoplasm, were retrospectively analyzed. Immunoreactivity for PD-L1 and PD-L2 was performed on resection materials. The mean age of 90 patients was 52.1±18.8 and 46.7% were male. Overall, 55.6% of patients were diagnosed with adenoid cystic carcinoma (ACC), 23.3% with mucoepidermoid carcinoma (MEC), 16.7% with acinic cell carcinoma (AciCC), 3.3% with ductal carcinoma (DC), and 1 patient with pleomorphic adenoma ex carcinoma (PA-ex-CA). In all, 52% of ACC, 12% of AciCC, 24% of MEC, and 12% of DC cases were at stage IV. The tumor diameter, frequencies of lymphovascular invasion, metastasis, positive surgical margin, recurrence, and mortality rates of patients at stages III and IV were significantly larger than those at stages I and II ( P <0.05). The percentages of tumor cell score (TCS) and immune cell score (ICS) for PD-L1 were significantly higher among patients with MEC compared with those with other types of tumors ( P =0.0011). However, the percentages of combined score (CS) for PD-L1 and tumor cell score for PD-L2 were comparable among tumor types ( P >0.05). No significant difference was found in these scores for PD-L1 between tumor stages ( P >0.05), but for PD-L2, all patients at stage I had TCS <1% for PD-L2, while all patients at stages II and III, and 92% of patients at stage IV had TCS ≥1% ( P <0.0001). High expression of PD-L1 was mostly observed in MEC cases ( P =0.0016), while all patients with AciCC had a low PD-L1 expression level ( P =0.0206). The mean tumor diameter, rate of lymphovascular invasion, perineural invasion, metastasis, positive surgical margin, recurrence, type of treatment, mortality, and TILs ratio did not differ significantly according to PD-L1 expression level ( P >0.05). The percentage of tumor-infiltrating lymphocytes was comparable among negative and positive PD-L1 scores according to both 1% and 5% threshold values ( P >0.05). High PD-L1 expression is rare in AciCC, while PD-L1 expression is high in MEC. Our findings underline the importance of future screening for PD-L1 and PD-L2 before patients undergoing immunotherapies in all salivary gland tumors.