Malignant Salivary Gland Tumors Research Articles

Frequency and pattern of salivary gland lesions at a tertiary care centre

Objective: To analyze the frequency and histo-morphological pattern of non-neoplastic and neoplastic salivary gland lesions at a tertiary care centre. Study Design: Retrospective descriptive cross-sectional study Place and Duration: Histopathology section, Dow Diagnostic Reference and Research Laboratory, Karachi from 1st February 2021 to 31st July, 2021. Methodology: Data of all salivary gland lesions were retrieved from institutional database. All tissue specimens of parotid, submandibular and sublingual salivary glands lesions as well as possible minor salivary glands swellings were included for histopathological analysis. Type of benign or neoplastic lesion along with salivary gland involved were assessed. Results: Out of a total of 739 samples, 28.0% were non-neoplastic whereas 72.0% were neoplastic lesions. Out of 207 non-neoplastic lesions, 55.1% were of inflammatory origin whereas 44.9% were mucoceles. Chronic sialadenitis (61.4%) was the most common non-neoplastic inflammatory lesion. Among mucoceles, those reported with no specification of type predominated (37.6%). Out of total 543 neoplastic lesions, 53.1% were benign whereas 19.3% were malignant. Pleomorphic adenoma (87.1%) was the commonest benign neoplastic lesion, followed by benign epidermal inclusion cysts (3.7%). Of the 127 malignant salivary gland tumors, mucoepidermoid carcinoma (39.4%) was the most common lesion, followed by adenoid cystic carcinoma (29.1%). Conclusion: Chronic sialadenitis was the most common non-neoplastic lesion whereas pleomorphic adenoma was the predominant benign lesion. Moreover, mucoepidermoid carcinoma was the most common malignant lesion followed by adenoid cystic carcinoma. Keywords: Salivary Glands, Neoplastic lesion, Non-neoplastic lesion, Frequency, Sialadenitis, Adenoma, Carcinoma

Clinical and Pathological Features and Outcome of Patients with Salivary Gland Cancer a Single Centre Report

Introduction: Salivary gland tumors are rare tumors that account for 3 to 4% of head and neck neoplasms. These tumors may arise from 6 major and numerous minor salivary glands. This study was designed to investigate the factors affecting the prognosis of salivary gland tumors. Methods: This study is a retrospective descriptive study in which the records of patients with salivary gland tumors referred to the Radiotherapy and Oncology Center of Namazi Hospital from 2005 to 2015 were reviewed. Results: 158 patients were included in this study with a mean age of 55.37 years. 49% of the patients were men. Adenoid Cystic Carcinoma was the most common histological type (30.57%) and Adenocarcinoma with a prevalence of 1.91% had the lowest prevalence rate in this study. 65.19% of salivary gland neoplasms in this study had parotid gland involvement and sublingual gland involvement had the lowest prevalence (3.8%). The results of survival analysis clearly illustrated that surgery, pathology type and stage was statistically significant in survival. Discussion: Clinical, pathological and therapeutic factors in people with malignant salivary gland neoplasms have a significant relationship with their survival. controversies on treatment and outcome continues.

Radiation therapy of malignant salivary gland tumors

Due to their rarity, histologic heterogeneity, and localization, treatment of malignant salivary gland tumors requires an interdisciplinary approach. First-line treatment includes complete tumor resection. Postoperative radiation therapy is advised in patients with risk factors, i.e., incomplete tumor resection, high-grade tumors, or perineural invasion. Definitive radiation therapy is only advised for inoperable tumors because of significantly lower local control and survival rates when compared to combined surgery and radiation therapy. In radiation oncology, modern techniques such as intensity-modulated radiation therapy (IMRT) or particle therapy with heavy ions (i.e., C12) have led to improved outcomes in the treatment of head and neck tumors, especially of adenoid cystic carcinomas. Given the biological and physical benefits of particles, particle therapy, particularly carbon ion radiation, is apromising therapeutic approach for salivary gland tumors that will be further investigated in prospective clinical studies.

Metastatic Pleural Effusion: A Rare Presentation of Salivary Gland Adenoid Cystic Carcinoma

Adenoid cystic carcinoma, an uncommon malignant salivary gland neoplasm, is known for its long clinical course, indolent growth, local recurrence and late distant metastasis. We report an unusual case of adenoid cystic carcinoma of the palate in a 64-year-old woman, undiagnosed for more than 15 years, who presented as malignant pleural effusion.

Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands

Salivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.

Multiplexed single-cell analysis of FNA allows accurate diagnosis of salivary gland tumors.

Diagnosing salivary gland tumors (SGTs) through fine‐needle aspiration (FNA) biopsies is challenging due to the overlapping cytomorphologic features between benign and malignant tumors. The authors developed an innovative, multiplexed cycling technology for the rapid analyses of single cells obtained from FNA that can facilitate the molecular analyses and diagnosis of SGTs. Antibodies against 29 protein markers associated with 7 SGT subtypes were validated and chemically modified via custom linker–bio‐orthogonal probes (FAST). Single‐cell homogenates and FNA samples were profiled by FAST cyclic imaging and computational analysis. A prediction model was generated using a training set of 151,926 cells from primary SGTs (N = 26) and validated on a separate cohort (N = 30). Companion biomarker testing, such as neurotrophic tyrosine receptor kinase (NTRK), was also assessed with the FAST technology. The FAST molecular diagnostic assay was able to distinguish between benign and malignant SGTs with an accuracy of 0.86 for single‐cell homogenate samples and 0.88 for FNA samples. Profiling of multiple markers as compared to a single marker increased the diagnostic accuracy (0.82 as compared to 0.65‐0.74, respectively), independent of the cell number sampled. NTRK expression was also assessed by the FAST assay, highlighting the potential therapeutic application of this technology. Application of the novel multiplexed single‐cell technology facilitates rapid biomarker testing from FNA samples at low cost. The customizable and modular FAST‐FNA approach has relevance to multiple pathologies and organ systems where cytologic samples are often scarce and/or indeterminate resulting in improved diagnostic workflows and timely therapeutic clinical decision‐making.

Could Argyrophilic Nucleolar Organizer Regions count mirror DNA Ploidy in Malignant Salivary Gland Tumors?

Objective:Nucleolar organizer regions (NORs) are DNA coils that transcribe to ribosomal RNA. The NOR-associated protein, termed argyrophilic NOR (AgNOR), was visible within the nucleus by staining with silver nitrate examination via the light microscope. AgNOR counting is a proliferation marker and may help in the diagnosis and prognosis of various neoplastic lesions. Aneuploidy (abnormal DNA content) can predict the progression, survival and prognosis of the tumors. The aim of this study was to evaluate the role of AgNORs, DNA ploidy status, and total S-phase fraction (TSPF) as prognostic parameters in malignant salivary gland tumors (MSGTs). Methods:The current study is a retrospective study on a cohort of MSGTs (N=47), to assess AgNORs using Silver Nitrate stain, DNA index (DI), and TSPF using flow cytometry (FCM). Data including tumor size and site, lymphovascular invasion (LVI), lymph node metastasis (LNM) were collected. Results:The AgNORs count was statistically significant with MSGT type. DI was found to have a significant association with tumor site, tumor size and MSGT type. In addition, TSPF was found to be significantly associated with LVI. A moderate positive correlation was noted between AgNORs count and TSPF. LNM, tumor site, high AgNORs and low DI were all associated with short disease-free survival (DFS) and poor overall survival (OS). Conclusion:The present study revealed that high AgNORs count, DNA aneuploidy and TSPF had a poor influence on MSGTs prognosis.

FAST-FNA molecular diagnostic assay facilitates rapid diagnosis and ntrk biomarker testing of salivary gland tumors.

e18089 Background: Primary epithelial salivary gland tumors (SGTs)are classified into 31 tumor types. Diagnosing SGTs through fine needle aspiration (FNA) biopsies is challenging due to the overlapping cytomorphologic features between benign and malignant tumors. In this study, we developed an innovative, multiplexed cycling technology which allows for the rapid cellular analyses of single cells obtained from FNA which can facilitate the rapid molecular analyses and diagnosis of SGTs. Methods: Antibodies against 29 cell surface markers associated with 7 SGT subtypes were validated and chemically modified via custom linker–bio-orthogonal quencher probes (FAST). Single cell homogenates and a FNA sample set representing 7 SGT subtypes were profiled by FAST cyclic staining, imaging, and automated computational analysis. A prediction model was generated utilizing a training set of 151,926 single cells obtained from primary SGTs (N = 26) and validated on a separate cohort of SGTs (N = 30). Companion biomarker testing, such as NTRK, was also assessed with the FAST technology. Results: The customized FAST-FNA SGT molecular diagnostic and biomarker panel was validated on human cell lines and specificity confirmed by both flow cytometry and clinical immunohistochemical staining on primary SGTs. The FAST molecular diagnostic assay was able to distinguish between benign and malignant SGTs with an accuracy of 0.86 for single-cell suspension samples and 0.88 for FNA samples. Profiling of multiple markers as compared to a single tumor marker increased the diagnostic accuracy of the SGTs, 0.82 as compared to 0.65-0.74, respectively. The results of the assay were highly reproducible and independent of the cell number sampled. NTRK expression in SGTs was also assessed by the FAST assay within hours, highlighting the potential therapeutic application of this technology. Conclusions: High dimensional single-cell profiling and molecular diagnostic testing on FNA samples are feasible at relatively low cost and as a rapid test. Application of the novel multiplexed single cell technology improves the diagnostic accuracy of SGT biopsy and facilitates multiplex biomarker testing from FNA samples. The customizable and modular FAST-FNA approach has relevance to multiple pathologies and organ systems where cytologic samples are often scarce and/or indeterminate resulting in improved diagnostic workflows and timely therapeutic clinical decision making.

Mammary analog secretory carcinoma in adults: A systematic review.

e18076 Background: Mammary analog secretory carcinoma (MASC) is a rare malignant salivary gland tumor of the head and neck region that was first described by Skálová et al. in 2010. It histologically mimics breast secretory carcinoma and parotid acinic cell carcinoma, and characterized by ETV6-NTRK3 fusion gene. This review aims to investigate the clinicopathologic features, treatment, and outcomes of MASC in adults. Methods: PubMed search for MASC adults (18+ years) from data inception through 2021, pooled with a case from our institution. Kaplan-Meier analysis was used to plot survival curves. Results: Of the 254 included cases, female:male ratio 1.02:1 with a mean age at diagnosis (±SD, range) of 50.1 (±16.7, 18–86) years. In terms of location, 143 (56.3%) occurred in the parotid gland, 21 (8.3%) in the submandibular gland, 21 (8.3%) in the lip, 15 (5.9%) in the thyroid gland–all (100%) had a component of classical type papillary carcinoma, 15 (5.9%) were cutaneous, 13 (5.1%) in the buccal mucosa, 12 (4.7%) split between hard and soft palate, 4 (1.6%) in the nasal mucosa, 2 (0.8%) in the lung, and remaining 8 (3.1%) each in the conjunctiva, tongue, minor salivary gland, submaxillary gland, maxillary sinus, ethmoid sinus, upper esophagus, and mandible. Patients mostly presented with swelling or growing mass in 95.4% (out of which, 93.3% were painless), followed by a painful ulcer in 1.8%. Median tumor size was 1.9 cm (range 0.3cm–8.5cm). Median duration of symptoms at time of presentation was 12 (range 1-360) months. Tumors were T1 (49.7%), T2 (23.9%), T3 (20.3%), and T4 (6.1%), N0 (81.9%), N1 (10.7%), N2 (7.4%), M0 (97.4%), and M1 (2.6%). Most patients (70.7%) presented as early stage (I or II) which was associated with a high survival probability based on a log-rank test (p-value: 0.0007). All patients had surgical resection, mostly combined with neck dissection (ND) in11.4%, radiation (RT) in 7.8%, ND+RT in 4.7%, ND with platinum-based chemoradiation in 1.0%, and one case reported use of Crizotinib followed by Entrectinib with disease progression at 4.5 and 7 months, respectively. Among patients with reported outcomes, 92.2% were alive with a median follow-up of 26 (range 1-228) months, and 7.8% deceased with a median time-to-death of 29 (range 1-107) months. Eleven (4.3%) reported a high-grade MASC and 18.5% of patients lived for over five years after their diagnosis. Conclusions: Early stage was a notable predictor of higher survival probability in MASC patients. Its rarity, heterogeneity of clinical behaviors, and variable outcomes make it even more challenging. This review serves as real-world evidence to further our understanding of this rare entity and shed light on prospective clinical trial design.

Evaluation of CD44s, CD44v6, CXCR2, CXCL1, and IL-1β in Benign and Malignant Tumors of Salivary Glands.

Background: Several studies have reported an association between high expression of CD44 in different types of cancer. However, no study has reported a link among CD44 expression, other biomarkers, and the aggressiveness of salivary gland tumors. Methods: A total of 38 specimens were obtained from non-tumorous salivary glands, benign and malignant tumors in salivary glands. Immunohistochemical analyses of CD44s, CD44v6, IL-1β, CXCL1, and CXCR2 were performed, and the area of positive cells was assessed. Results: We found that both CD44s and CXCR2 expression were increased in the benign and malignant groups. CD44v6 was also increased in both groups, but it had the highest level in the malignant group. IL-1β was the only biomarker that increased significantly in the malignant group in comparison to the other two groups. Conclusions: CD44s, CD44v6, CXCR2, and IL-1β expressions were found to be higher in salivary gland tumors. However, IL-1β alone may play a crucial role in the aggressiveness of salivary gland tumors as this cytokine was expressed only in the malignant group with high expression associated with high-grade malignancy.

The anti-tumor effect of proteasome inhibitor MG132 for human adenoid cystic carcinoma: correlate with the emerging role of Nrf2/Keap1 signaling pathway.

BackgroundAdenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Moreover, the unique biological characteristics and complex structures of ACC contribute to its poor survival rates. Recently, proteasome inhibitors have been shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC.MethodsIn this present study, cell counting kit-8 assay and flow cytometry assay were performed to examine the effects of proteasome inhibitor (MG132) on cell viability and apoptosis. We applied western blot and immunofluorescence staining to explore the expression of the Nrf2/Keap1 signaling pathway and P62, additionally Nrf2 inhibitor (ML385) was utilized to evaluate the role of Nrf2/Keap1 signaling pathway in MG132-induced cell apoptosis.ResultsOur data indicated that MG132 significantly suppressed the growth of ACC-83 cells(MG132 10µM P = 0.0046; 40µM P = 0.0033; 70µM P = 0.0007 versus control) and induced apoptosis (MG132 10µM P = 0.0458; 40µM P = 0.0018; 70µM P = 0.0087 versus control). The application of MG132 induced the up-regulation of Nrf2/Keap1 signaling pathway. Furthermore, inhibition of Nrf2 attenuated the therapeutic effects of MG132 for ACC (both ML385 + MG132 10µM P = 0.0013; 40µM P = 0.0057; 70µM P = 0.0003 versus MG132). P < 0.05 was considered statistically significant.ConclusionsOur results revealed that proteasome inhibitors MG132 could inhibit the cell viability and induce the apoptosis of ACC through Nrf2/Keap1 signaling pathway.

Classification of salivary gland tumors in optical coherence tomography images based on deep learning

The diagnosis of oral diseases mainly relies on visual examination by doctors with clinical experience. Histopathological examination is still the gold standard of oral disease diagnosis, but it is invasive and time-consuming. In recent years, optical coherence tomography (OCT) has played an important role in the field of biomedicine with its unique advantages of non-invasiveness, high resolution, real-time and three-dimensional imaging, which can be well applied to the imaging of oral lesions. In this paper, four deep learning (DL) models including LeNet-9, VGG-16, ResNet-18 and ResNet-50 were used to classify oral tumors including two benign and two malignant salivary gland tumors (SGTs), which were imaged by our home-made swept-source OCT. The results indicated that ResNet-18 has the best classification performance, with accuracy, precision, recall (sensitivity), F1 score and specificity all above 98%. Then, we analyzed the visualization process of DL and explored how the DL model extracts features. It is demonstrated that the DL model has a good clinical auxiliary role in the classification of SGTs.

Immunohistochemical Study of Cancer Stem Cell marker, Tight Junction Protein, and Lymphatic Density in Malignant Salivary Gland Tumors

Background: CD117/c-kit, is a powerful stem cell marker for malignant salivary gland tumors in which dysregulation of c-kit is closely associated with impairment of cell adhesion molecules and cancer metastasis.&#x0D; Objective: The main purpose of this work is to evaluate the immunohistochemical expression of c-kit, and claudin-1 and measure the density of lymph vessels (LVD) in common malignant salivary gland tumors by using podoplanin (D2-40) antibody.&#x0D; Materials and Methods: Immunohistochemical staining with streptavidin peroxidase was used to analysis the expression of c-kit, claudin-1 and stained podoplanin (D2-40) lymphatic vessels on fifty archival paraffin blocks of malignant salivary gland tumor (MSGTs) cases included 20 cases of AdCC, 11 cases of MEC, 10 cases of CXPA, 6 cases of AcCC, and 3 cases of PAC.&#x0D; Results: The immunopositivity of c-kit (CD117) was detected in 44/50 (88%) of studied cases, whereas, claudin-1 protein was observed in 35 (70%) of our specimens of MSGTs. Count down of stained lymph vessels between examined cases was, MEC on the top, followed by CXPA, AdCC, PAC and AcCC. A direct correlation was observed between c-kit and lymphatic density, on the other hand, the inverse correlation was found d between c-kit and cld-1, as well as, between cld-1 and lymphatic density&#x0D; Conclusion: Up regulation of cancer stem cell marker c-kit (CD117) expression is associated with decrease of tight junction protein cld-1 and increase the density of stained lymphatic vessels by podoplanin (D2-40) antibody which confirms the using of c-kit inhibitor to improve treatment strategy of malignant salivary gland tumors.

Immunohistochemical expression of pan-Trk in a large cohort of salivary gland neoplasms: preliminary results

<h3>Introduction</h3> Neurotrophic tyrosine receptor kinases (NTRK) represent a group of proteins that actively partici- pate in cell survival, proliferation, and differentiation processes. NTRK gene rearrangements have been identified in several neoplasms, including secretory carcinoma of the salivary glands (ETV6-NTRK3). A newly developed pan-Trk antibody for immunohistochemistry (IHC) was able to identify and differentiate cases of secretory carcinoma from mimics by its nuclear staining. However, different patterns of expression (cytoplasmic and/or membranous) have also been reported in benign and malignant salivary gland neoplasms (SGN). Due to this apparent heterogeneous staining profile, the significance of pan-Trk IHC in SGN is still unclear. <h3>Materials and Methods</h3> Cases of salivary mucoepidermoid carcinoma (MEC), polymorphous adenocarcinoma (PAC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), epithelial-myoepithelial carcinoma (EMC), and secretory carcinoma (SC) were retrieved be- tween 2003 and 2019 from the University of Iowa, College of Dentistry archives. Pan-Trk IHC was performed in tissue microarrays. IHC pattern of expression and intensity (H-score) were assessed. <h3>Results</h3> Patient cohort was comprised of 41 women and 20 men with a median age of 61 years old. The most common location was the palate followed by the buccal mucosa. Pan-Trk is positive predominantly in the nucleus of SC (H-score=23.6), and in the cytoplasm/membrane of PAC (H-score=12.2), MEC (H-score=5.6), AdCC (H-score=13.5), and EMC (Hscore=21.4). How- ever, nuclear staining was also present in a small subset of PAC, MEC, and AdCCs. Notably, Pan-Trk was negative in all ACC samples. <h3>Conclusions</h3> Preliminary data suggests that pan-Trk nuclear staining is not exclusive to SC. Fur- thermore, the cytoplasmic/membranous pattern seen in non-SC neoplasms may indicate the presence of NTRK gene rearrangement. A better understanding about the pan-Trk staining pattern could not only improve its diagnostic value, but also contribute identifying patients that would benefit from targeted-therapies using NTRK inhibitors (<i>e.g.</i> entrectinib, larotrectinib).

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

This paper proposes the effect of contrast-enhanced ultrasound combined with real-time elastic imaging technology in the differential diagnosis of salivary gland tumors. 200 patients were selected, including 120 males and 60 females. The age ranged from 9 to 83 years, with an average of 55.4 years. Among the 200 cases, there were 90 cases of single parotid gland on the right, 77 cases of single parotid gland on the left, 2 cases of bilateral (single parotid gland on each side), 2 cases of multiple parotid gland on the right (2 lesions), 1 case of 2 lesions on the left and 1 lesion on the right, and 1 case of multiple parotid gland on the left (4 lesions). 135 cases were located in the superficial lobe (78%) and 38 cases (22%) in the deep lobe of parotid gland. The ARIETTA 70 color Doppler ultrasound diagnostic instrument is used. The equipment is equipped with high-frequency contrast probe, real-time elastic imaging technology, and related software. The results showed that the detection rate of salivary gland tumors by ultrasound was 100% and the diagnostic coincidence rate was 71% (123/173). Ultrasound can not only identify the tumors in and around the parotid gland but also identify the location, size, and internal structure of the tumors. Combined with CDFI, it can make qualitative diagnosis of most benign and malignant salivary gland tumors and provide help for clinical treatment and operation plan. It is proved that contrast-enhanced ultrasound and real-time elastic imaging technology have advantages over gray-scale ultrasound in differentiating benign and malignant superficial enlarged lymph nodes, and the combined use can effectively improve the diagnostic efficiency.

Tumor blood flow and apparent diffusion coefficient histogram analysis for differentiating malignant salivary tumors from pleomorphic adenomas and Warthin’s tumors

We aimed to assess the combined diagnostic value of apparent diffusion coefficient (ADC) and tumor blood flow (TBF) obtained by pseudocontinuous arterial spin labeling (pCASL) for differentiating malignant tumors (MTs) in salivary glands from pleomorphic adenomas (PAs) and Warthin’s tumors (WTs). We used pCASL imaging and ADC map to evaluate 65 patients, including 16 with MT, 30 with PA, and 19 with WT. We evaluated all tumors by histogram analyses and compared various characteristics by one-way analysis of variance followed by Tukey post-hoc tests. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. There were significant differences in the mean, 50th, 75th, and 90th percentiles of TBF among the tumor types, in the mean TBFs (mL/100 g/min) between MTs (57.47 ± 35.14) and PAs (29.88 ± 22.53, p = 0.039) and between MTs and WTs (119.31 ± 50.11, p < 0.001), as well as in the mean ADCs (× 10−3 mm2/s) between MTs (1.08 ± 0.28) and PAs (1.60 ± 0.34, p < 0.001), but not in the mean ADCs between MTs and WTs (0.87 ± 0.23, p = 0.117). In the ROC curve analysis, the highest areas under the curves (AUCs) were achieved by the 10th and 25th percentiles of ADC (AUC = 0.885) for differentiating MTs from PAs and the 50th percentile of TBF (AUC = 0.855) for differentiating MTs from WTs. The AUCs of TBF, ADC, and combination of TBF and ADC were 0.850, 0.885, and 0.950 for MTs and PAs differentiation and 0.855, 0.814, and 0.905 for MTs and WTs differentiation, respectively. The combination of TBF and ADC evaluated by histogram analysis may help differentiate salivary gland MTs from PAs and WTs.

Indications for fine-needle aspiration and core needle biopsy for diagnosis of salivary gland tumors

Salivary gland malignancies are rare neoplasms of the head and neck area. Preoperative clinical and imaging assessment of salivary gland masses is challenging. However, preoperative identification of malignancy is crucial for further treatment and for the course of the disease. This article presents the advantages and disadvantages of fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB). Additionally, the sensitivity and specificity of both methods for predicting malignancy were analyzed. Furthermore, it is discussed which procedure is suitable for the diagnostic work-up of salivary gland tumors. This current article summarizes important and recent studies in the field of the diagnostic work-up for salivary gland lesions, with discussion of original articles, metanalyses, and systematic reviews concerning FNAC and CNB. The sensitivity and specificity of the predictive ability of FNAC for malignancy is described at between 70.0-80.0% and 87.5-97.9%. The pooled sensitivity and specificity for CNB were 92.0-98.0% and 95.0-100.0%, respectively. Tumor cell seeding or facial nerve palsy are very rare complications of both procedures. If malignancy is suspected based on clinical examination or imaging, FNAC or CNB should be performed. FNAC is easy to perform; however, an onsite cytologist is necessary. CNB has ahigher sensitivity for routine diagnosis of malignancy; tumor typing and grading is facilitated by preserving the histological architecture. In conclusion, CNB is the procedure of choice in the diagnostic work-up for suspected malignant salivary gland tumors.

Immunohistochemical expression of MCM4 and its main regulator in most prevalent benign and malignant salivary gland neoplasms

Immunohistochemical expression of MCM4 and its main regulator in most prevalent benign and malignant salivary gland neoplasms

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

Objective Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MSCs. Materials and Methods In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry. Results Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones. ConclusionMalignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.

Assessment of angiogenesis using endoglin in salivary gland tumors – An immunohistochemical study

Endoglin, a co-receptor of transforming growth factor (TGF)-β1 and TGF-β2, is indispensable for endothelial cell proliferation and modulation of tumor promotion activities of TGF-β1. The assessment of neovascularization using endoglin expression has been considered a potential predictor of prognosis in various solid malignancies. To analyze the expression of endoglin by immunohistochemistry in both benign and malignant salivary gland tumors. Fifteen cases of benign salivary gland tumors and seventeen cases of malignant salivary gland tumors were included in the study, and immunohistochemistry was performed using anti-CD105 antibody using standard protocol. The study demonstrated that there is increased endoglin expression in malignant tumors as compared to their benign counterparts which is suggestive of increased angiogenic activity in tumor areas and could be responsible for the aggressive behavior of the malignancies. The highest density of endoglin-positive blood vessels was observed in the inflammatory tumor stromal areas. Furthermore, a significant increase in endoglin expression was evident as the grade of malignant salivary gland tumor increased. The results of the study indicate that the increased expression of endoglin in high-grade malignancies contributes to their aggressive nature.