Negative prognostic behaviour of PD-L1 expression in tongue and larynx squamous cell carcinoma and its significant predictive power in combination with PD-1 expression on TILs.

BACKGROUND: Biomarkers that can predict outcome will improve the efficacy of treatment for HNSCC patients. In this regard, we retrospectively evaluated the prognostic effect of PD1, PD-L1, and CD45RO in tongue and larynx squamous cell carcinomas. METHODS: FFPE tissue blocks of 63 larynx and 40 tongue squamous cell carcinoma samples were selected, cut into 3 µm sections, and immunohistochemically stained for PD1, PD-L1, and CD45RO. The slides were evaluated by an expert pathologist, and results were analysed using Chi-square, univariate, and multivariable Cox regression methods. RESULTS: TC-PD-L1 expression (P = 0.001) and its expression intensity (P = 0.002) were significantly correlated with a higher percentage of PD-1 + tumor infiltrating lymphocytes. In univariate survival analysis, TC-PD-L1 and its expression intensity had a significant impact on both DFS (HR: 0.203; P = 0.003 and HR: 0.320; P = 0.005) and OS (HR: 0.147; P = 0.002 and HR: 0.322; P = 0.005). Based on the multivariate analysis, PD1 (DFS: HR: 3.202; P = 0.011, OS: HR: 2.671; P = 0.027) and TC-PD-L1 (DFS: HR: 0.174; P = 0.006, OS: HR: 0.189; P = 0.009) were found to be independent prognostic markers. In the second part, scoring systems were defined based on the expression status of PD1 and PD-L1. Patients with higher scores were expected to have longer DFS and OS. In multivariate analysis, the PD1/TC-PD-L1 (DFS: P = 0.001, OS: P = 0.003) scoring systems showed superior prognostic effects. Interestingly, at the highest levels of this score, none of the patients experienced recurrence or cancer-caused death. CONCLUSION: Collectively, this study suggests negative prognostic behaviour for TC-PD-L1 protein and introduces the PD-1/TC-PD-L1 scoring system as a strong prognostic marker in OS and DFS prediction of tongue and larynx HNSCC patients.

Association of Complications During and After Carotid Body Tumor Resection with Tumor Size and Distance to the Base of Skull.

BACKGROUND: Depending on the size and location of the tumor, carotid body tumor (CBT) resection can come with various complications, mostly intraoperative bleeding, and cranial nerve injuries. In the present study, we aim to evaluate 2 fairly new variables, tumor volume, and distance to the base of the skull (DTBOS), with operative complications of CBT resection. METHODS: Patients who underwent CBT surgery in Namazi hospital from 2015 to 2019 were studied using standard databases. Tumor characteristics and DTBOS were measured via computed tomography or Magnetic resonance imaging. Outcomes, including intraoperative bleeding and cranial nerve injuries, along with perioperative data were collected. RESULTS: A total of 42 cases of CBT were evaluated with an average age of 53.21 ± 12.8 and mostly female (85.7%). Based on Shamblin scoring, 2 (4.8%) were classified as group I, 25 (59.5%) as group II, and 15 (35.7%) as group III. The amount of bleeding significantly increased with an increase in the Shamblin scores (P = 0.031; median: I: 45 cc; II: 250 cc, III: 400 cc). Also, there was a significant positive correlation between the size of the tumor and the estimated amount of bleeding (correlation coefficient = 0.660; P < 0.001), and also a significant reverse correlation with between bleeding and DTBOS (correlation coefficient = -0.345; P = 0.025). During the follow-up of the patients, 6 (14.3%) had abnormalities in their neurological evaluation. Receiver operating characteristic curve analysis revealed the size of tumor cutoff level 32.7 cm3 (3.2 cm radius) to be most predictive of postoperative neurological complication with an area under the curve = 0.83, sensitivity = 83.3%, specificity = 80.6%, a negative predictive value = 96.7%, and positive predictive value of 41.7%, and an accuracy of 81.0%. Furthermore, based on the predictive power of the models in our study, we demonstrated that a combination model including the tumor size, DTBOS, along with the Shamblin score had the most predictive power for neurological complications. CONCLUSIONS: By evaluating CBT size and DTBOS, paired with the use of the Shamblin classification, a better, more insightful understanding of possible risks and complications of CBT resection can be obtained, leading to deserved levels of patient care.

Modulation of semaphorin 3C & 4D expression in cancerous tissues from individuals with laryngeal squamous cell carcinoma.

BACKGROUND OBJECTIVES: Semaphorins were initially characterized as axon guidance factors but were subsequently implicated in the regulation of immune responses, angiogenesis, organ formation and a variety of other physiological and developmental functions. Various semaphorins enhance or inhibit tumour progression through different mechanisms. The objective of this study was to assess the expression of various semaphorins and vascular endothelial growth factor (VEGF) gene transcripts as well as the serum level of Sema3A in individuals with laryngeal squamous cell carcinoma (LSCC). METHODS: Tissue expression of Sema3A, Sema3C, Sema4D, Sema6D and VEGF was determined in both tumour tissues and tissues around the tumour from 30 individuals with pathologically confirmed LSCC using quantitative real-time PCR. Furthermore, the serum level of Sema3A in these individuals was assessed using enzyme-linked immunosorbent assay. RESULTS: Sema3C gene transcript showed a significant increase (P=0.001), while Sema4D was observed with a significant decrease in tumour samples compared to non-tumoural tissues (P≤0.01). The expression of the Sema3C gene was found to be associated with the stage of LSCC tumour as it was statistically significant for tumours with stage IV (P<0.01). The serum level of Sema3A was not found to be significant between cases and controls. INTERPRETATION CONCLUSIONS: Increased expression of Sema3C but decreased expression of Sema4D in tumour tissue of LSCC may introduce these two growth factors as crucial mediators orchestrating tumour growth in individuals with LSCC. This result could open a new vision for the treatment of this malignancy.

Evaluation of recurrence, mortality and treatment complications of oral squamous cell carcinoma in public health centers in Shiraz during 2010 to 2020.

INTRODUCTION: Oral Squamous cell Carcinoma (OSCC) is the most common oral cancer and is treated with surgery, radiotherapy and chemotherapy. Various complications of treatment include xerostomia, mucositis, and trismus, which affect patients' quality of life. The aim of this study is to evaluate the mortality, recurrence rate and prevalence of oral complications in treated patients. METHOD AND MATERIALS: This cross-sectional study reviewed 326 cases of patients with OSCC who were referred to public health centers in Shiraz (Khalili Hospital and Dental School) from 2010 to 2020. All patients were contacted, and the survivors were called and examined by an oral physician. A medical record was created for them, including demographic information, location of the lesion, type of treatment, history of recurrence, metastasis and oral complications. RESULTS: 53.5% of patients were male and 46.5% were female. The mean age of patients was 58.68 years. Mortality and recurrence rate was respectively 49.8% and 17.8%. The most common location of the lesion was tongue (64%). Surgery was done for all patients. 97.4% of patients complained of xerostomia, 46.2% of mucositis and 44.3% of trismus. CONCLUSION: The most common complications of treatment are xerostomia, mucositis, and trismus, respectively. Frequent and regular follow-ups and supportive therapies reduce these complications and improve patients' quality of life.

Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck.

BACKGROUND: A crucial role for the immune system has been proposed in the establishment and progression of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the cytokine and regulatory profiles of T cells in tumor draining lymph nodes (TDLNs) of patients with HNSCC. RESULTS: The frequencies of CD4+TNF-α+ and CD4+TNF-αhi negatively were associated with poor prognostic factors such as LN involvement (P = 0.015 and P = 0.019, respectively), stage of the disease (P = 0.032 and P = 0.010, respectively) and tumor size (P = 0.026 and P = 0.032, respectively). Frequencies of CD8+IFN-γ+ and CD8+IFN-γ+ TNF-α+ T cells showed negative relationship with tumor grade (P = 0.035 and P = 0.043, respectively). While, the frequencies of CD4+IL-4+, CD8+IL-10+, CD8+IL-4+T cells were higher in advanced stages of the disease (P = 0.042, P = 0.041 and P = 0.030, respectively) and CD4+IFN-γ+TNF-α-, CD8+IL-4+ and CD8+IFN-γ+TNF-α- T cells were higher in patients with larger tumor size (P = 0.026 and P = 0.032, respectively). Negative associations were found between the frequencies of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3+CD127low/- Treg cells and cancer stage (P = 0.015 and P = 0.059). CONCLUSION: This study shed more lights on the changes in immune profile of T cells in TDLNs of HNSCC. Larger tumor size and/or LN involvement were associated with lower frequencies of CD4+TNF-α+, CD8+IFN-γ+ and CD8+IFN-γ+TNF-α+ but higher frequency of CD4+IL-4+ T cells. Moreover, Foxp3+Tregs correlated with good prognostic indicators.

Evaluating a semi-nested PCR to support histopathology reports of fungal rhinosinusitis in formalin-fixed paraffin-embedded tissue samples.

BACKGROUND: Fungal rhinosinusitis (FRS) encompasses a various spectrum of diseases. Histopathology is the "reference method" for diagnosing FRS, but it cannot determine the genus and species. Moreover, in more than 50% of the histopathologically proven cases, the culture elicited no reliable results. This study was an attempt to evaluate the diagnostic efficiency of semi-nested polymerase chain reaction (PCR) from formalin-fixed paraffin-embedded (FFPE) functional endoscopic sinus surgery (FESS) in FRS patients. METHODS: One hundred ten specimens were subjected to DNA extraction and histopathology examination. The amplification of the ß-globin gene by conventional PCR was used to confirm the quality of extracted DNA. The semi-nested PCR was performed using ITS1, ITS2, and ITS4 primers during two steps. Sequencing the internal transcribed spacer region (ITS1-5.8S-ITS2) to identify causative agents was performed on PCR products. RESULTS: Sixty-four out of 110 samples were positive by histopathology evidence, of which 56 samples (87.5%) were positive by PCR. Out of 46 negative samples by histopathological methods, five samples (10.9%) yielded positive results by PCR. Sensitivity, specificity, positive predictive value, and negative predictive value of the semi-nested PCR method were reported 87.5%, 89.2%, 92.7%, and 85.2%, respectively. The kappa factor between PCR and histopathological methods was 0.76, indicating substantial agreements between these two tests. CONCLUSION: Due to the acceptable sensitivity and specificity of the present method, it might be used to diagnose fungal sinusitis infections along with microscopic techniques. This method is recommended to confirm the diagnose of suspected fungal sinusitis with negative histopathology results.

KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.

BACKGROUNDS: Our previous study has suggested that KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with head and neck squamous cell carcinoma (HNSCC) development. The purpose of the current study was to investigate the possible association of killer cell immunoglobulin like receptors (KIRs) gene with the clinicopathological features of patients. METHODS: We reviewed the pathological reports of 285 pathologically confirmed cases of HNSCC and analyzed the association of KIR system with pathological characteristics. RESULTS: A significant increase was demonstrated in the carrier frequency of KIR2DS4 in conventional than basaloid type and a higher frequency of lymph node metastasis (LNM) in carriers of KIR2DL2 and individuals possess 5 inhibitory KIRs (iKIRs). We also observed a higher proportion of patients with advanced stage of HNSCC in carriers of KIR2DL2 and deleted variant of KIR2DS4. CONCLUSION: In HNSCC, KIR2DL2 is positively while KIR2DS4 is negatively associated with advanced stage. The higher proportion of LNM in carriers of KIR2DL2 and carriers of 5 iKIRs, suggested that inhibitory KIRs are associated with metastatic risk.

Orbital mucormycosis in immunocompetent children; review of risk factors, diagnosis, and treatment approach.

BACKGROUND: Orbital mucormycosis is a rare but potentially severe and troublesome invasive fungal infection that could be occurred even in healthy individuals. The initial clinical presentation is similar to bacterial pre-septal or septal cellulitis, especially in early stages. CASE PRESENTATION: Herein, we describe the successful management of a series of five cases presenting with orbital mucormycosis in previously healthy children. CONCLUSIONS: Orbital mucormycosis is extremely rare in healthy children and maybe life-threatening when diagnosis delayed given a similar clinical presentation with bacterial septal cellulitis. Intravenous antifungal therapy with amphotericin B and timely surgical drainage is live-saving.

PD-1 Haplotype Combinations and Susceptibility of Patients to Squamous Cell Carcinomas of Head and Neck.

INTRODUCTION: Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of head and neck and the sixth most common malignancy worldwide. Programmed cell death 1 (PD-1) is an immune inhibitory molecule which through interaction with its ligands recruits protein phosphatase resulting in immune response inhibition. Expression of PD-1 ligands on tumor cells is considered as one of the crucial immune evasion mechanisms. This study aimed to investigate the association of PD-1 gene polymorphisms at positions PD1.3 (rs11568821), PD1.5 (rs2227981) and PD1.9 (rs2227982) with susceptibility to HNSCCs. SUBJECTS AND METHODS: 150 patients pathologically confirmed to suffer from HNSCCs and 150 age-sex matched healthy controls were recruited in this study. Genomic DNA was extracted from white blood cells of all participants. Restricted fragment length polymorphisms (RFLP)-PCR was performed using site specific primers to determine the genotypes in each position. RESULTS: Statistical analyses indicated no significant differences in the frequencies of genotypes, alleles as well as haplotypes between patients and controls (P > 0.05), however, haplotype combination differed significantly between two groups. GCC/GCT, GCC/GCC and GCT/GCC were higher in the HNSCC patients than the control group (P < 0.05). On the other hand, in the controls, GCT/GCT, GCT/ACC, GCT/ACT and ACC/GCT were more frequent. No significant association was found with various HNSCC clinicopathological characteristics. DISCUSSION: Our results suggested that although PD-1 gene polymorphisms at three investigated positions are not solely associated with susceptibility to HNSCCs, haplotype combinations emerged from these three loci may render susceptibility.

Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading incident cancer worldwide. In this study, we aimed to investigate the possible association of OX40 gene polymorphisms, rs17568G/A and rs229811A/C, with susceptibility to HNSCC and its clinicopathological features. Two hundred and two HNSCC patients and 200 healthy age-sex matched individuals were enrolled. rs17568G/A and rs229811A/C polymorphisms in OX40 gene were genotyped using RFLP-PCR method. We observed more than 2 times increased risk for squamous cell carcinoma development in nose and paranasal sinuses among individuals who inherited GG genotype at rs17568 region (OR 2.29; CI 1.01-5.20; P = 0.035). Considering rs2298211 SNP, AA genotype was also observed with higher frequency, in comparison with other two genotypes (AC or CC), among patients with HNSCC originated from these regions (P = 0.003). Besides, we observed that patients with C allele at this locus (AC and CC genotypes) have tumors with significantly higher histological grade (P = 0.042). Our findings suggest the possible association of rs17568 GG genotype, as well as rs2298211 AA genotype with susceptibility to develop squamous cell carcinoma in the nose and sinonasal cavities.

Assessing whether EORTC QLQ-30 and FACT-G measure the same constructs of quality of life in patients with total laryngectomy.

BACKGROUND: The European Organization for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and the Assessment of Cancer Therapy-General (FACT-G) are the two most widely used measures of cancer-specific health-related quality of life (HRQOL). This study aims to assess whether the two instruments measure the same constructs of HRQOL in patients with total laryngectomy. METHODS: The EORTC QLQ-30 and the FACT-G was completed by 132 patients with total laryngectomy. Convergent, discriminant, and construct validity of the EORTC QLQ-C30 and the FACT-G were assessed by Spearman's correlation and explanatory factor analysis. RESULTS: The results of factor analysis showed that the EORTC QLQ-C30 and the FACT-G measure different aspects of HRQOL. Moreover, both instruments showed excellent convergent and discriminant validity, except for nausea and vomiting symptom subscale in the EORTC QLQ-C30 questionnaire. The internal consistency was close or greater than 0.7 for all domains of both instruments except for functional wellbeing in FACT-G. CONCLUSIONS: This study revealed that neither of the two instruments can be replaced by the other in the assessment of HRQOL in Iranian patients with total laryngectomy. Accordingly, clinicians should exactly define their research questions related to patient-reported outcomes before choosing which instrument to use.

Clinical implication of CD166 expression in salivary gland tumor.

CD166 is a glycoprotein of immunoglobulin superfamily of adhesion molecules which is overexpressed in many tumors. However, no published literature was found concerning CD166 expression in salivary gland tumor. The purpose of this study was to examine the CD166 expression in the salivary gland tumor by an immunohistochemical approach, to examine the clinical implication of this marker in the prognosis and diagnosis of the salivary gland tumor. In this study, 45 samples of salivary tumors from Khalili Hospital archive including 15 cases of pleomorphic adenoma, 16 cases of mucoepidermoid carcinoma, 14 cases of adenoid cystic carcinoma, and 15 normal salivary glands were selected for immunohistochemistry (IHC) method staining for CD166. CD166 immunoreactivity in malignant tumors (adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC)) (56.7 ± 14.05) was significantly higher than that of pleomorphic adenoma (PA) (34.3 ± 17.07) (P < 0.000) and higher in the PA than normal salivary gland (13.2 ± 12.1) (P = 0.001). CD166 expression was significantly higher in the high-grade tumors (90.3 ± 11.07) compared to low-grade (65.11 ± 27.08) malignant tumors (P = 0.002). CD166 expression showed a significant association with tumor size and the clinical stage (P < 0.001). In conclusion, an overexpression of CD166 was detected in the benign and malignant salivary gland tumors and its expression in the malignant tumor was associated with the aggressive behavior and tumor progression. For this reason, CD166 may be one of the potential biomarkers for predicting tumor behavior in the prognosis of this disease.

Fine-needle aspiration cytological diagnosis of neck masses.

BACKGROUND: Fine-needle aspiration (FNA) is a simple, safe, inexpensive, and acceptable method for diagnosing masses, especially at superficial areas. Therefore, we decided to evaluate the accuracy of FNA cytological diagnosis in nonthyroidal, nonsalivary gland neck masses and compare the results with histopathological diagnosis. MATERIALS AND METHODS: In this retrospective study, all cases with FNA cytological diagnosis of nonthyroidal, nonsalivary gland neck masses from April 2009 to July 2013 were retrieved. The procedure was done by pathologists, and all cytological and histopathological slides of the existing 46 cases were reviewed by 3 pathologists. The values of sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. RESULTS: SN, SP, PPV, NPV, and accuracy in this study were 79, 100, 100, 73, and 86%, respectively. We had 6 false-negative and no false-positive cases. CONCLUSION: The FNA procedure is a reliable method as the first step for the diagnosis of nonthyroidal, nonsalivary gland neck masses. To increase the diagnostic value of cytology, careful examination of all cytological slides, repetition of the FNA procedure and good history taking are helpful.

Upregulation of serum vascular endothelial growth factor and matrix metalloproteinase-3 in patients with oral squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is known as a fundamental regulator of angiogenesis that accelerates cellular proliferation, vascular permeability, and endothelial cell migration and is an inhibitor of apoptosis. Extracellular matrix degradation by matrix metalloproteinase (MMP) is necessary for endothelial cell proliferation, migration, and metastasis. Accordingly, the objective of the present study was to determine the circulating levels of VEGF and MMP3 and their relation in patients with oral squamous cell carcinoma. Using an ELISA kit, the circulating levels of VEGF and MMP-3 in the sera of 45 patients with oral squamous cell carcinoma (OSCC) and 45 healthy controls were assessed. Mean VEGF levels in the sera of patients with OSCC (122.4 ± 36.1) were significantly higher than those in controls (65.3 ± 23.4); however, no relation was found between VEGF levels and clinicopathologic factors. The serum MMP-3 level in OSCC patients was significantly higher (9.45 ± 4.6 ng/ml, n=45) than that in healthy controls (5.9 ± 3.6 ng/ml, n=45). There was no correlation in serum MMP-3 concentration with clinicopathologic features such as tumor stage, tumor size, nodal status, and histological grade. A significant relationship was found between serum levels of VEGF and MMP3. This study concludes that VEGF and MMP3 may have a potential role in the pathogenesis of OSCC but cannot be used as a tool for monitoring tumor progression. Moreover, the role of VEGF in the regulation of angiogenesis is in part due to activation of MMP-3.

Serum levels of osteopontin as a prognostic factor in patients with oral squamous cell carcinoma.

Osteopontin (OPN) is a multifunctional glycophosphoprotein that was detected in many carcinomas, and it may have a prognostic role. The aim of this study was to determine osteopontin serum levels in patients with oral squamous cell carcinoma (OSCC) and investigated its correlation with clinicopathological features of tumor. Using an ELISA kit, we assessed and compared the circulating levels of OPN in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. The serum osteopontin level in patients with OSCC was significantly higher (145.8 ± 14.6 ng/ml, n = 45) compared with the healthy controls (53.9 ± 9.6 ng/ml, n = 45, p < 0.001). Mean serum osteopontin level was significantly higher in patients with nodal metastasis (p = 0.03) and higher stage (p = 0.02). Findings of the present study suggest that OPN may have a potential role in pathogenesis of OSCC and it may be used as a tool for monitoring tumor progression.

Intracellular CTLA4 and regulatory T cells in patients with laryngeal squamous cell carcinoma.

To explore if the increased percentages of Regulatory T (Treg) cells, as well as, overexpression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) are involved in laryngeal-squamous cell carcinoma (SCC), 45 patients with laryngeal-SCC and 27 healthy controls were enrolled. Flow cytometry was performed to investigate, in the peripheral blood, the prevalence of CD4+CD25+FoxP3+ Treg cells, as well as, surface and intracellular expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). The results indicated intracellular (In)CTLA4 with considerable higher expression in the CD8+ lymphocytes among patients with laryngeal-SCC compared with the control group (8.2 ± 8.7 versus 2.3 ± 3.5, P = 0.001). The mean percentage of InCTLA4+CD4+ and InCTLA4+CD19+ lymphocytes was also significantly higher in patients (8.7 ± 7.8 versus 4.4 ± 4.2, P = 0.018 and 0.6 ± 0.8 versus 0.2 ± 0.2, P = 0.024, respectively). With respect to surface (Sur)CTLA4, the difference between patients and controls was, however, significant only in the case of CD8+ lymphocytes (0.7 ± 0.6 versus 0.3 ± 0.3, P = 0.003, respectively). The percentage of Treg cells was observed to be significantly higher in patients (7.5 ± 6.3 and 3.2 ± 1.9, P < 0.0001). Furthermore, association analysis revealed the association of Treg cell increase with the higher tumor-size and lymphnode stage (P < 0.005). These data collectively suggest that patients with laryngeal-SCC may benefit from immunotherapy targeting CTLA4 and Treg cells.

Anaplastic Solitary plasmacytoma of mandible, masquerading as sarcoma.

Plasma cell neoplasm is characterized by a monoclonal neoplastic proliferation of plasma cells and solitary plasmocytoma of bone (SPB) is a localized form. It usually occurs in vertebrae and secondarily in long bones. Its presence in mandible is extremely rare event. A 48-year-old man consulted to our clinic with a chief complaint of pain in his mandible. Radiography revealed a destructive lesion in body and ramus. The initial pathologic evaluation revealed a high grade pleomorphic neoplasm. The diagnosis was confirmed by immunohistochemical markers. Overall, plasmacytoma with anaplastic features can be confused with high grade sarcoma clinically and histologically.

Serum Level of Vitamin D in Patients with Salivary Gland Tumors.

Introduction: The active vitamin D metabolites have anticancer effects on many human neoplasms. The vitamin D receptors have been detected in salivary glands tissue. This study aimed to evaluate the serum level of vitamin D in patients with malignant and benign salivary gland tumors. Materials and Methods: In this retrospective and cross-sectional study, 151 participants, including 42 patients with benign, 42 malignant salivary gland tumors, and 67 healthy subjects, participated. The serum level of vitamin D was measured using an enzyme-linked immunosorbent assay (ELISA). Results: The mean serum level of vitamin D was 42.7 ng/mL in patients with benign tumors, 40 ng/mL in malignant tumors, and 36.7 ng/mL in the control group. There was no significant difference between the mean vitamin D level and vitamin D status in patients with salivary gland tumors and normal controls (P=0.2). There was a significant positive correlation between vitamin D level and age in the control group (P=0.04). Conclusions: The results showed a high prevalence rate of vitamin D deficiency/insufficiency in salivary gland tumors and normal subjects, with no significant difference. Therefore, the serum level of vitamin D might not play a significant role in the pathogenesis of these tumors, similar to many human cancers. However, further prospective studies are recommended focusing on specific tumors and considering other interventional factors.

Epidemiological Profile of Salivary Gland Tumors in Southern Iranian Population: A Retrospective Study of 405 Cases.

Aims: Salivary gland tumors (SGTs) are a rare and diverse group of tumors that account for 3 to 10% of all head and neck malignancies. We aimed to conduct a comprehensive epidemiological analysis of SGTs in the south of Iran and compare the findings with previous reports from Iran and other parts of the world. Methods: Using a retrospective study, 405 patients diagnosed with SGTs were observed over an eight-year period between April 2013 and October 2021 in Shiraz, Iran. Patients' demographic and clinicopathological features were obtained from patients' records. Quantitative and descriptive data analysis was performed using SPSS software. Results: There were 302 benign (74.5%) and 103 (25.4%) malignant SGTs. Pleomorphic adenoma and Warthin's tumors were the most common benign SGTs (70.5% and 21.5%, respectively). The most common malignant SGTs were mucoepidermoid carcinoma and adenoid cystic carcinoma (26.2% and 22.3%, respectively). There was a statistically significant association between tumor origin and its malignancy status (p < 0.001). In addition, the results indicated that benign tumors were most commonly detected in the parotid gland (p < 0.05). The benign tumors were more frequently observed among the younger population (p = 0.006). Conclusion: In summary, the findings of the current study were mainly consistent with the previous reports from Iran and the rest of the world. Benign tumors were the most prevalent type of SGTs, and the parotid gland was the most common site. While the majority of cases that developed from the major salivary glands were benign, all the minor SGTs were malignant. Older patients were more likely to develop malignant tumors compared to younger ones. This study provides insights into the prevalence, age-related incidence, gender distribution, and geographic variation of salivary gland tumors. This can be instrumental to develop a guideline for screening, diagnosis, and determining an optimal treatment.

Simultaneous Expression of PD-1 and PD-L1 in Peripheral and Central Immune Cells and Tumor Cells in the Benign and Malignant Salivary Gland Tumors Microenvironment.

BACKGROUND: To investigate the differential expression of PD-1 and PD-L1 in salivary gland tumors (SGTs, malignant and benign subtypes) and determine their association with the clinicopathological characterization of the patients. METHODS: The immunohistochemistry was used to examine PD-1 and PD-L1 expression in specimens from 83 patients with primary SGTs including salivary ductal carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), warthin's tumors (WT), poleomorphic adenoma (PA) and other subtypes. RESULTS: The expression of PD-1 in peripheral and central immune cells (ICs) of MEC, and peripheral ICs of ACC was significantly higher than those with AdCC (P = 0.02, P = 0.02, P = 0.03, respectively). Interestingly, the expression of PD-1 was also observed in peripheral and central malignant tumor cells (TCs), particularly in SDC and ACC. Despite no significant difference in PD-L1 expression of TCs among malignant subtypes, the peripheral and central ICs of ACC and MEC were revealed to express PDL-1 significantly more than those with AdCC (P < 0.05). WTs were rich in PD-1/PD-L1 expressing ICs. However, the tumor microenvironment of PA generally had low levels of PD-1/PD-L1 expression. In general, the expression of PD-1 in peripheral and central TCs was found to be significantly higher in malignant tumors than in benign ones (P = 0.002 and P = 0.003, respectively). CONCLUSION: The simultaneous presentation of PD-1 and PD-L1 in TCs and ICs of SGTs, their significant association with disease severity as well as the positive correlation between these immune checkpoints may suggest the therapeutic potential of anti-PD-1 and anti-PDL-1 combinational immunotherapy for SGTs.