Potential role of hybrid positron emission tomography in pre-operative assessment of primary salivary gland carcinomas.

OBJECTIVE: The added value of hybrid positron emission tomography is increasingly recognised in head and neck cancer. However, its potential role in salivary gland carcinomas has been scarcely investigated. METHODS: A consecutive cohort of 45 salivary gland carcinoma patients who underwent pre-therapeutic hybrid positron emission tomography and surgical resection was reviewed. This study investigated whether maximum standardised uptake value correlated with tumour phenotype. RESULTS: Tumours of high-grade disease on histology (salivary duct carcinoma, carcinoma ex pleomorphic adenoma) had higher maximum standardised uptake value (Kruskal-Wallis test, p = 0.011) than low-grade tumours (adenoid cystic carcinoma and acinic cell carcinoma). Patients with pathologically confirmed node-positive disease had significantly higher maximum standardised uptake value of the primary tumour than patients with pathologically confirmed node-negative disease (Kruskal-Wallis test, p = 0.012). CONCLUSION: Maximum standardised uptake value of the primary tumour may guide clinical decision-making in patients with salivary gland carcinomas, as a high maximum standardised uptake value is associated with high-grade tumour histology and the presence of lymph node metastases. Clinicians may consider more aggressive surgery for these patients.

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases.

PURPOSE: Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy. METHODS: Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan-Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis). RESULTS: The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards. CONCLUSION: With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.

Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland.

PURPOSE: Early phase clinical studies are ongoing to evaluate the role of immune checkpoint inhibitors in adenoid cystic carcinoma (ACC) despite a paucity of information on the immune microenvironment. This study aims to better characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on tumour infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression. METHODS: Patient characteristics, treatment and outcome data were collected for 24 ACC patients. The CD8+(cluster of differentiation 8) TIL and PD-L1 expression were quantified by immunohistochemistry. Marker expression and survival outcomes were evaluated by Kaplan-Meier analysis. RESULTS: All cases were negative for PD-L1 expression; four cases had focal high, eight cases had focal moderate and 12 cases had low TIL expression. Based on TIL expression, there was no difference in disease-free or overall survival. CONCLUSION: Adenoid cystic carcinoma tumours were found to be associated with a poor immunogenic microenvironment, with absent PD-L1 expression and low CD8+ TILs. There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.

Analysis of Characteristics and Survival of Primary Cutaneous Adenoid Cystic Carcinoma of the Head and Neck.

BACKGROUND/OBJECTIVES: Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare skin tumor. The head and neck (H&N) is the most common anatomical location. Due to limited published cases, its clinical course and management are not well understood. METHODS: The National Cancer Database (NCDB) was queried for all cases of H&N PCACC diagnosed from 2004 to 2016. Kaplan-Meier (KM) and Cox proportional hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. RESULTS: A total of 201 cases were analyzed. The average age of diagnosis was 57.7 years (± SD 15.8). There was a female predilection (57.7%; P < .05) with the most common primary site being the ear (58.2%). The average tumor size was 15.9 mm in diameter. The most common treatment was surgery alone (51.7%) with wide local excision being the common surgery performed (36.3%). 5-year and 10-year OS were 87.0% and 76.0%, respectively. A total of 65.8% of cases were localized (Stage I and II). KM analysis indicated that gender, age, insurance status, Charlson-Deyo Comobordity Score, and stage were significant predictors of OS (P < .05). Cox proportional hazards analysis revealed that patients with both private (HR 0.11, 95%CI [0.019-0.670]; P = .02) and government (HR 0.12, 95%CI [0.019-0.972]; P = .03) health insurance had a significantly decreased hazard of death than patients who were uninsured. Increasing age was associated with an increased hazard of death (HR 1.06, 95%CI [1.016-1.110]; P = .01). CONCLUSION: This study represents the largest cohort of H&N PCACC studied to date and provides important clinicopathologic information for this rare tumor. Additionally, our results emphasize the importance of health insurance as an independent predictor of survival in PCACC.

Cost-effectiveness analysis (CEA) of IMRT plus C12 boost vs IMRT only in adenoid cystic carcinoma (ACC) of the head and neck.

BACKGROUND: Particle therapy provides steep dose gradients to facilitate dose escalation in challenging anatomical sites which has been shown not only to improve local control but also overall survival in patients with ACC. Cost-effectiveness of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost vs IMRT alone was performed in order to objectivise and substantiate more widespread use of this technology in ACC. METHODS: Patients with pathologically confirmed ACC received a combination regimen of IMRT plus C12 boost. Patients presenting outside C12 treatment slots received IMRT only. Clinical results were published; economic analysis on patient-level data was carried out from a healthcare purchaser's perspective based on costs of healthcare utilization. Cost histories were generated from resource use recorded in individual patient charts and adjusted for censoring using the Lin I method. Cost-effectiveness was measured as incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed regarding potentially differing management of recurrent disease. RESULTS: The experimental treatment increased overall costs by € 18,076 (€13,416 - €22,922) at a mean survival benefit of 0.86 years. Despite improved local control, following costs were also increased in the experimental treatment. The ICER was estimated to 26,863 €/LY. After accounting for different management of recurrent disease in the two cohorts, the ICER was calculated to 20,638 €/LY. CONCLUSION: The combined treatment (IMRT+C12 boost) substantially increased initial and overall treatment cost. In view of limited treatment options in ACC, costs may be acceptable though. Investigations into quality of life measures may support further decisions in the future.

Demography, patterns of care and survival outcomes in patients with malignant tumors of trachea: A systematic review and individual patient data analysis of 733 patients.

BACKGROUND: Malignant tumors of the trachea (MTT) account for 0.01-0.4% of all cancer cases. The rarity of the tumor along with different histologies makes it is a great challenge on how to optimally treat tracheal tumors and most of the available data is from small retrospective data series. We performed a systematic review and individual patient data analysis to evaluate the patterns of care and survival outcomes in patient with MTT. METHODOLOGY: A comprehensive search in Pub Med and Google scholar was done to find all possible publications related to malignant tumors of the trachea. The data on patient demograpphy, treatment, survival and recurrence pattern of individual patient was collected from the published data and was entered in a predesigned proforma. Progression free survival [PFS] and overall survival [OS] was calculated from the date of diagnosis to the date of documented progression and death respectively. Kaplan- Meier method was used for survival analysis and uni-variate analysis was performed using log rank test. SPSS v16 was used for all statistical analysis. RESULTS: 733 patients were included in this analysis. The most common histology was adenoid cystic carcinoma (ACC) followed by squamous cell carcinoma (SCC). The gender ratio was 4.43: 1[male: female] in patients with SCC while it was 0.85:1[male: female] in ACC. Smoking and age >50 years were associated with worse OS. The estimated median overall survival for entire cohort was 96 months. Survival was significantly better in patients with ACC than in patients with SCC [165 vs. 14 months, p < 0.001]. The use of definitive surgery was associated with a significantly better survival of 180 months when compared to 48 months with radiation as local therapy, [p < 0.001]. The radiation dose used also affected survival in patients with SCC with a better median OS of 24 months in patients who recieved more than 60 Gy vs 6 months in whom the dose was less than 60 Gy although not statistically significant (p = 0.011). CONCLUSION: ACC and SCC are the most common MTT. ACC has better prognosis compared to SCC. Surgery seems to provide better outcomes than radiation for ACC and sarcoma. Role of definitive radiotherapy versus surgery in SCC needs to be further studied.

Pretreatment assessment of hematologic and inflammatory markers in adenoid cystic carcinoma: neutrophil/lymphocyte ratio is associated with multiple recurrences.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a rare entity of salivary gland cancer. Inflammatory and hematologic markers and their prognostic and predictive value have been intensively studied in several cancer entities. The aim of this study was to investigate the role of such markers in patients with ACC. STUDY DESIGN: This retrospective analysis investigated hematologic and inflammatory markers in patients with ACC in the period between the years 1996 and 2016. We assessed the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, cross-reactive protein and fibrinogen levels. A total of 28 to 31 patients were included, depending on the examined parameter. All markers were evaluated for their effects on outcome and prognostic value. RESULTS: Patients with an elevated preoperative NLR (>2) had a significantly higher multiple recurrence rate (44.4% vs 8.3%; P = .049). Other hematologic markers showed no significant effects on outcome. CONCLUSIONS: This study showed that the NLR may serve as a useful prognosticator for a high risk of multiple recurrences in patients with ACC.

The efficacy of neutron radiation therapy in treating salivary gland malignancies.

OBJECTIVES: Radiation therapy is commonly used to treat head and neck malignancies. While there is abundant research regarding photon radiation therapy, literature on neutron radiotherapy (NRT) and oral complications is limited. This study aims to determine: (1) the 6-year and 10-year locoregional control and survival rates, (2) factors associated with locoregional control and survival and (3) the frequency of oral complications in patients undergoing NRT for salivary gland malignancies. MATERIALS AND METHODS: This is a retrospective cohort study. The sample was composed of patients with salivary gland malignancies treated with NRT between 1997 and 2010. Data were extracted from patient charts, telephone surveys, and social security records. Multivariate competing risk and Cox regression models were used to assess predictors of locoregional control and survival. RESULTS: The sample was composed of 545 subjects with a mean age of 54.2 years (±16). The predominant tumor and location were adenoid cystic carcinoma (47%) and the parotid (56%). Multivariate analysis indicated that positive surgical margins, biopsied/inoperable malignancies, neck involvement, and lymphovascular invasion were prognostic risk factors associated with decreased survival. The 6- and 10-year locoregional control rates were 84% and 79%. The 6- and 10-year survival rates were 72% and 62%. Osteoradionecrosis developed in 3.4% of subjects. CONCLUSIONS: The 6- and 10-year locoregional control and survival rates compare favorably to rates reported for conventional photon radiation. Osteoradionecrosis rates were comparable to that of photon radiation treatment (2-7%). Given the potential benefits of NRT, healthcare professionals should be educated regarding its indications and oral complications.

Assessment of CTNNB1 gene mutations and ß-catenin immunoexpression in salivary gland pleomorphic adenomas and adenoid cystic carcinomas.

ß-Catenin exerts multiple functions in several neoplasms, playing a major role in cell signaling and tumor progression. This study analyzed possible CTNNB1 mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic carcinomas (ACCs), and determined possible differences in ß-catenin immunoexpression in relation to these mutations, as well as histopathological aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of ß-catenin distribution and cellular localization. Furthermore, ß-catenin expression was evaluated using the H-score scoring system. Mutations in CTNNB1 exon 3 were investigated by the single-strand conformational polymorphism test. Diffuse ß-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in ß-catenin cellular localization was observed between these tumors (P = 0.098). Comparisons between PA and ACC cases revealed a higher median H-score in the latter (P = 0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed in 6 PAs and 7 ACCs, with no significant difference in H-scores for ß-catenin according to mutation status (P = 0.135). ß-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence ß-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.

Assessment of p16 expression and HPV infection in adenoid cystic carcinoma of the lacrimal gland.

Purpose: Adenoid cystic carcinoma (ACC) in the lacrimal gland is a rare malignancy. P16 is encoded by the CDKN2A gene, which is recognized as a tumor suppressor due to its inactivation in many types of tumors. However, p16 overexpression is also linked to adverse tumor parameters. These contradictory observations have also been confirmed in ACCs in the salivary glands. Furthermore, evidence of human papilloma virus (HPV) infection is found in a proportion of ACCs in the salivary glands. P16 is often overexpressed in HPV-related squamous cell carcinoma in parallel. To our knowledge, the role of p16 and HPV in ACCs in the lacrimal gland is still unknown. Methods: Twenty-one ACCs in the lacrimal gland and ten matched healthy lacrimal glands were studied. P16 was detected with immunohistochemistry (IHC), and HPV was detected with in situ hybridization (ISH) and PCR in all cases. Other cell cycle proteins were also detected with IHC, including cyclin D1 and Ki67. The methylation status of the p16 promoter was detected with methylation-specific PCR (MSP) to further investigate the regulation of p16 expression. Results: The expression rates of p16 (47.6%, 10/21), cyclin D1 (100%, 21/21), and Ki67 (52.4%, 11/21) were increased in ACCs compared to healthy lacrimal glands (negative). The results showed p16 expression was limited to the inner ductal epithelial cells in the majority of the tubular and cribriform patterns. In solid ACCs, p16 was uniformly positive. HPV was negative in all 21 cases with ISH and PCR. P16 overexpression was associated with cyclin D1 overexpression (p=0.013). Only 13 cases were tested successfully with MSP. The expression rate of p16 methylation was 23.1% (3/13) of the ACCs. Compared with primary ACCs, recurrent ACCs showed higher p16, cyclin D1, and Ki67 expression (p=0.011, p=0.026, p=0.049, respectively). Conclusions: In summary, p16 overexpression was cell-type dependent in ACCs in the lacrimal gland, while HPV infection was negative. P16 overexpression was unrelated to HPV infection. The mechanism of p16 overexpression needs to be further investigated in ACCs in the lacrimal gland.

Longitudinal Perioperative Pain Assessment in Head and Neck Cancer Surgery.

OBJECTIVE: To evaluate perioperative pain in patients undergoing major head and neck cancer surgery and identify associations between preoperative and postoperative pain characteristics. METHODS: Patients undergoing head and neck surgery with regional/free tissue transfer were enrolled. Preoperative pain and validated screens for symptoms (neuropathic pain, anxiety, depression, fibromyalgia) were assessed. Postoperatively, patients completed a pain diary for 4 weeks. RESULTS: Twenty-seven patients were enrolled. Seventy-eight percent had pain prior to surgery, and for 38%, the pain had neuropathic characteristics. Thirteen patients (48%) completed at least 2 weeks of the postoperative pain diary. Patients with moderate/severe preoperative pain report significantly greater pain scores postoperatively, though daily pain decreased at a similar linear rate for all patients. Patients with more severe preoperative pain consumed greater amounts of opioids postoperatively, and this correlated with daily postoperative pain scores. Patients who screened positive for neuropathic pain also reported worse postoperative pain. CONCLUSION: Longitudinal perioperative pain assessment in head and neck patients undergoing surgery suggests that patients with worse preoperative pain continue to endorse worse pain postoperatively and require more narcotics. Patients with preoperative neuropathic pain also report poor pain control postoperatively, suggesting an opportunity to identify these patients and intervene with empiric neuropathic pain treatment.

Cavity theory applications for kilovoltage cellular dosimetry.

Relationships between macroscopic (bulk tissue) and microscopic (cellular) dose descriptors are investigated using cavity theory and Monte Carlo (MC) simulations. Small, large, and multiple intermediate cavity theory (SCT, LCT, and ICT, respectively) approaches are considered for 20 to 370 keV incident photons; ICT is a sum of SCT and LCT contributions weighted by parameter d. Considering µm-sized cavities of water in bulk tissue phantoms, different cavity theory approaches are evaluated via comparison of [Formula: see text] (where D w,m is dose-to-water-in-medium and D m,m is dose-to-medium-in-medium) with MC results. The best overall agreement is achieved with an ICT approach in which [Formula: see text], where L is the mean chord length of the cavity and ß is given by [Formula: see text] (R CSDA is the continuous slowing down approximation range of an electron of energy equal to that of incident photons). Cell nucleus doses, D nuc, computed with this ICT approach are compared with those from MC simulations involving multicellular soft tissue models considering a representative range of cell/nucleus sizes and elemental compositions. In [Formula: see text] of cases, ICT and MC predictions agree within [Formula: see text]; disagreement is at most 8.8%. These results suggest that cavity theory may be useful for linking doses from model-based dose calculation algorithms (MBDCAs) with energy deposition in cellular targets. Finally, based on the suggestion that clusters of water molecules associated with DNA are important radiobiological targets, two approaches for estimating dose-to-water by application of SCT to MC results for D m,m or D nuc are compared. Results for these two estimates differ by up to [Formula: see text], demonstrating the sensitivity of energy deposition within a small volume of water in nucleus to the geometry and composition of its surroundings. In terms of the debate over the dose specification medium for MBDCAs, these results do not support conversion of D m,m to D w,m using SCT.

Facial mimetic, cosmetic, and functional standardized assessment of the facial artery musculomucosal (FAMM) flap.

OBJECTIVE: To objectively assess donor site morbidity after harvesting the facial artery musculomucosal flap. Use of the FAMM-flap in oral cavity reconstruction remains sporadic. This case series describes our newly developed standardized assessment of this flap in a floor of mouth (FOM) reconstructive setting. METHODS: Standardized postoperative assessment of the FAMM flap for donor site wound complications, functional, facial mimetic and oncologic outcomes. RESULTS: There were no wound complications. Oral competence remained intact, tongue mobility was good to excellent, average word articulation score was 98%, and mimetic function excellent in all patients. Three patients experienced ipsilateral upper lip anesthesia, and five patients were noted to have slight dysfunction of the orbicularis oris resulting in a loss of lip height at rest. CONCLUSION: The FAMM flap is a reliable option for reconstruction of ablative defects of the FOM, and should be considered a workhorse flap for oral cavity defects. Unlike the submental island flap, a complete level I dissection may be concurrently performed without compromising the vascular supply to the FAMM flap.

Avaliação da via do c-kit no adenoma pleomórfico e carcinoma adenoide cístico das glândulas salivares: estudo da expressão das proteínas da via, das mutações e da regulação pós-transcricional do gene kit / c-Kit signaling cascade in pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: evaluation of cascade proteins, mutations and post-transcriptional regulation of gene Kit

Introdução: As neoplasias das glândulas salivares têm amplo espectro histológico resultante da múltipla diferenciação celular tumoral. O adenoma pleomórfico (AP) e o carcinoma adenoide cístico (CAC) são as mais comuns neoplasias benignas e malignas provenientes do ducto intercalado, respectivamente, além de serem compostas por estruturas luminais e células mioepiteliais. Em estudo realizado previamente pelo nosso grupo, detectamos que a proteína c-kit está envolvida nos processos da morfogênese das glândulas salivares e no adenoma pleomórfico. A proteína c-Kit tem papel importante no desenvolvimento de muitos processos embrionários, incluindo a gametogênese, melanogênese e hematopoiese, e também na biologia de tumores. Sua ativação induz diversas respostas intracelulares através de cascatas de sinalização de vias como PI3K/AKT e MAPK. Em tumores da glândula salivar ainda há poucos estudos sobre as alterações do gene KIT e das proteínas relacionadas a sua via de sinalização, assim como sua regulação pós-transcricional, realizada principalmente por meio dos microRNAs. O presente estudo avaliou, em APs e CACs (a) a localização das proteínas das vias PI3K/AKT/mTOR e MAPK por meio da técnica de imunoistoquímica; (b) a expressão dos microRNAs 221 e 222, relacionados ao gene KIT (c) a associação dos achados laboratoriais com variáveis clínicas, patológicas e sobrevida. Resultados: Nos casos de AP a proteína c-Kit foi identificada em formações luminais e em raras células isoladas no parênquima tumoral. Já nos CAC, observou-se positividade na membrana das células ductais. Para a via de PI3K/AKT/mTOR, no AP, a proteína PI3K beta mostrou-se parcialmente positiva no citoplasma das células próximas à capsula tumoral, e as proteínas AKT e mTOR fosforiladas, foram expressas especialmente nas células epiteliais e em poucas células mioepiteliais. Já no CAC, a proteína PI3K beta e AKT fosforilada mostraram-se negativas na maioria dos casos, e a proteína mTOR fosforilada foi expressa no citoplasma das células epiteliais e em algumas células mioepiteliais. Para a via MAPK, as proteínas RAS, MEK-1 fosforilada e ERK 1/2 foram negativas na maioria dos AP e CAC; B-Raf e MEK-2 fosforilada foram observadas nas células luminais dos AP. Nos CAC, estruturas luminais neoplásicas foram positivas para a proteína MEK-2 fosforilada; B-Raf foi positivo nas células luminais e mioepiteliais. Além disso, os pacientes que expressaram as proteínas mTOR e MEK-2 fosforilada apresentaram sobrevida câncer-específica significativamente aumentada (p=0,040 e p=0,005, respectivamente). Na análise do microRNAs, a expressão do miR-221 foi variável nas 13 amostras analisadas, tendo baixa expressão em 30,77% dos casos, expressão normal em 38,46 e expressão aumentada em 30,77% dos casos. Já nos APs o miR-221 foi detectado em 19 amostras, sendo 36,84% com baixa expressão, 52,63% com expressão normal e expressão aumentada foi vista em 10,53% dos casos. A expressão do miR-222 foi detectada em 14 CACs, sendo que a maioria dos casos (8 casos ­ 57,1%) a expressão do miR-222 foi semelhante ao observado nas amostras não neoplásicas. Nos APs, o miR-222 foi detectado em 22 amostras, sendo 31,8% com baixa expressão, 31,8% com expressão normal e 36,4% com expressão aumentada. Conclusão: Apesar de a proteína c-Kit ser expressa em ambas as neoplasias ­ AP e CAC, sua influência sobre as vias de sinalização MAPK e PI3K/AKT/mTOR ainda permanece por ser estabelecida. Ainda, os microRNAs 221 e 222 não mostram correlação consistente com a expressão de c-Kit nos tipos tumorais estudados.

Introduction: Salivary gland tumors present broad histological spectrum resulting from multiple tumor cell differentiation. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are the commonest benign and malignant salivary gland neoplasms originated from the intercalated duct region, respectively, and are composed by luminal structures and myoepithelial cells. In a previous study we detected that protein c-kit is involved in the process of salivary gland morphogenesis and PA. c-Kit protein is important during embryogenesis, including gametogenesis, melanogeneis and hematopoiesis as well as in tumorigenesis. Its activation induces various intracellular responses through pathways such as MAPK and PI3K/AKT/mTOR signaling cascades. In salivary gland neoplasms, only a few reports have shown that alterations in KIT gene are present and proteins related to its signaling pathway as well as its post-transcriptional regulation. This study has aimed at evaluating in PA and ACC: (a) the proteins location of PI3K/AKT/mTOR and MAPK pathways using immunohistochemistry (IHC); (b) expression of miR-221 and miR-222, related to KIT gene; and (c) the association of these findings with clinical, pathological and survival data of patients. Results: In PA c-kit was positive in isolated luminal cells; in ACC, neoplastic luminal structures were positive for c-Kit. In PA, PI3K beta protein was shown to be partially positive in the cytoplasm of cells near the tumor capsule and phosphor AKT and phospho mTOR, are specifically expressed in epithelial cells and in a few myoepithelial. In ACC, PI3K and phosphor AKT protein showed to be negative in most of cases. Phospho mTOR protein was expressed in the cytoplasm of epithelial cells and some myoepithelial cells. In MAPK pathway, Ras, ERK1/2 and phosphor MEK-1 proteins were negative in most PAs and CACs; B-Raf and phospho MEK-2 were detected in luminal cells of PA. In ACC neoplastic luminal structures were positive for phospho MEK-2; B-Raf was also positive in myoepithelial and epithelial cells. In addition, cases with expressed phospho-mTOR and phosphor MEK-2 proteins were significantly associated with higher cancer-specific survival (p = 0.040 and p = 0.005, respectively). Moreover, expression of miR-221 was detected in 13 CAC samples and 19 PA samples. In CAC, expression of miR-221 was downregulated in 30,77% of the samples, upregulated in 30,77% samples, and normal in 38,46% samples. In PA, miR-221 expression was downregulated in 36,84% samples, upregulated in 10,53% samples, and normal in 52,63% samples. Expression of miR-222 was detected in 14 CAC samples and 22 PA samples. In the majority of CAC samples, the expression of miR-222 was similar to that observed in non-neoplastic samples. In PA samples, expression of miR-222 was downregulated in 31,8% samples, upregulated in 36,4% samples, and normal in 31,8% samples. Conclusion: Although c-Kit expression is detected in PA and ACC, its influence on the MAPK e PI3K/AKT/mTOR signaling cascades remains to be established. miR-221 e -222 did not show a robust correlation with c-Kit expression in the tumors studied.

Sinonasal carcinomas: epidemiology, pathology, and management.

Sinonasal carcinomas are uncommon neoplasms accounting for approximately 3% to 5% of all upper respiratory tract malignancies. Sinonasal malignancies in most cases do not cause early symptoms and present in an advanced stage of disease. Exact staging necessitates a clinical and endoscopic examination with biopsy and imaging. Tumor resection using an open or endoscopic approach is usually considered the first treatment option. In general, sinonasal carcinomas are radiosensitive, so adjuvant or neoadjuvant radiation treatment may be indicated in advanced disease. Multidisciplinary surgical and medical oncologic approaches, including ablation and reconstruction, have enhanced the survival outcome over the past few decades.

Radiofrequency ablation: a safe and economical modality in treatment of Brooke-Spiegler syndrome.

Brooke-Spiegler syndrome is an uncommon disease. Patients have a predisposition to develop cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas, spiradenomas, trichoblastomas, basal cell carcinomas, follicular cysts, and organoid nevi. Malignant transformation of preexisting tumors also occurs in these individuals. Various techniques have been used for the treatment of trichoepitheliomas and cylindromas including excision, electrocautery, carbon dioxide laser ablation, cryosurgery, and radiotherapy. In our case, cylindromas were ablated by radiofrequency in multiple sittings. Trichoepitheliomas were ablated using coagulation mode with power # 3 to 3.5. Cosmetically acceptable results were obtained in 100 percent of the cylindromas and 70 percent of the trichoepitheliomas (Visual Analog Scale). The radiofrequency ablation technique under different modes can be used in both large tumors as well as smaller ones, especially in developing countries because it is very cost effective and easily accessible.

Immunohistochemical assessment of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors.

OBJECTIVE: The aim of this study was to investigate the presence of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors. METHODS: Twenty-seven minor salivary gland tumors were investigated using immunohistochemistry for CD1a and E-cadherin. RESULTS: A significant difference regarding the mean density of CD1a-positive Langerhans cells was observed between pleomorphic adenomas and malignant tumors studied (P = 0.001). No CD1a-positive cells were detected in most cases (n = 5) of cystic adenoid carcinomas. CD1a-positive cells were detected in one mucoepidermoid carcinoma case, and six low-grade polymorphous adenocarcinomas cases. Comparison of the mean density of CD1a-positive cells between the three malignant tumors showed no significant difference (P = 0.127). No significant difference was observed in the presence of E-cadherin between tumors (P = 0.73), but it was detected in 24 cases. CONCLUSIONS: The lack of CD1a-positive in malignant salivary gland tumors facilitates the neoplastic development and suggests that these cells might be useful as auxiliary diagnostic and prognostic tool in minor salivary gland tumors. Furthermore, it is suggested that E-cadherin mediates cell adhesion in these tumors although we did not demonstrate significance.

Adenoid cystic carcinoma of parotid gland treated with surgery and radiotherapy: long-term outcomes, QoL assessment and review of the literature.

To assess outcomes, toxicity and quality-of-life (QoL) of patients with parotid gland adenoid cystic carcinoma (PGACC) treated by surgery and postoperative radiotherapy. Between 1995 and 2010, 46 patients with PGACC were treated with parotidectomy±neck dissection followed by radiotherapy. Endpoints were loco-regional control (LRC), distant metastasis-free (DMFS), disease-free (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and QoL. After a median follow-up of 58 months (range 4-171), the 5-year Kaplan-Meier estimates of LRC, DMFS, DFS, CSS, and OS were 88%, 78%, 75%, 80%, and 67%, respectively and the 8-year rates were 88%, 75%, 72%, 77%, and 64%, respectively. On multivariate analysis, T-stage, N-stage, tumor grade, and perineural invasion correlate significantly with DMFS and DFS. The overall 5-year cumulative incidence of grade ≥2 late toxicity was 9%. QoL-scores deteriorate during and shortly after treatment but returned in all scales to almost baseline levels within 6 months. Excellent LRC rates were achieved in patients with PGACC treated by surgery and postoperative radiotherapy with low rate of late side-effects and preservation of good QoL. Despite the effective local therapy, 9 of 46 patients (20%) failed distantly. Because effective treatment strategies for this problem are lacking, prospective trials are needed to determine the role of adjuvant systemic or targeted therapy in patients at high risk of DM.