A meta-analysis of the risk of salivary gland tumors associated with mobile phone use: the importance of correct exposure assessment.

OBJECTIVES: To investigate the risk of developing salivary gland tumors associated with the use of mobile phones. CONTENT: There have been a number of epidemiological studies conducted to assess for a possible association between mobile phone usage and the development of intracranial tumours, however results have been conflicting. We conducted an extensive literature search across four different databases was conducted. After selecting the articles relevant to the area of study, a total of seven studies were included in this meta-analysis, with no restrictions set on publication date or language. Studies were qualitatively assessed using the Newcastle-Ottawa scale. No significant association between the use of mobile phones and salivary gland tumors was observed (OR=1.06, 95% CI=0.86-1.32). No evidence for publication bias was detected. SUMMARY AND OUTLOOK: Our findings indicate no significant association between mobile phone usage and salivary gland tumours. However, there were many limitations encountered in these studies, suggesting that the observed result may not be an accurate estimate of the true carcinogenic risk of mobile phones, especially for heavy long-term users. In fact, the studies included in this meta-analysis highlight the need to correctly define exposure assessment in order to ascertain the risk of a certain variable.

Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma.

OBJECTIVES: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC. MATERIALS AND METHODS: Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied. RESULTS: We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression. CONCLUSION: c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC.

Molecular chaperones in tumors of salivary glands.

The salivary glands are key components of the mouth and play a central role in its physiology. Their importance may be appreciated considering their number, occurrence in pairs, and distribution in the mouth: two parotids, two submandibular, two sublingual, and many other small ones scattered throughout the mouth. They produce saliva, without which ingestion of non-liquid nutrients and speech would be practically impossible. Nevertheless, the physiology and pathology of salivary glands are poorly understood. For instance, tumors of salivary glands occur, and their incidence is on the rise, but their etiology and pathogenesis are virtually unknown, although some risk factors have been identified. Likewise, the role of the chaperoning system in the development, normal functioning, and pathology, including carcinogenesis, remains to be determined. This scarcity of basic knowledge impedes progress in diagnosis, disease monitoring, and therapeutics of salivary gland tumors. We are currently involved in examining the chaperoning system of human salivary glands and we performed a search of the literature to determine what has been reported relating to oncology. We found data pertaining to six components of the chaperone system, namely HSP27, HSP60, HSP70, HSP84, HSP86, and GRP78, and to another HSP, the heme-oxygenase H-O1, also named HSP32, which does not belong in the chaperoning system but seemed to have potential as a biomarker for diagnostic purposes as much as the HSP/chaperones mentioned above. The reported quantitative variations of the six chaperones were distinctive enough to distinguish malignant from benign tumors, suggesting that these molecules hold potential as biomarkers useful in differential diagnosis. Also, the quantitative variations described accompanying tumor development, as observed in cancers of other organs, encourages research to elucidate whether chaperones play a role in the initiation and/or progression of salivary gland tumors.

Sjögren Syndrome in Primary Salivary Gland Lymphoma.

OBJECTIVES: Sjögren syndrome (SS) is considered as a major etiologic factor for primary salivary gland lymphoma (SGL). However, the percentage of SGL that is caused by SS (and thus the real impact of SS on SGL epidemiology) is unclear. We aimed to assess the prevalence of SS in patients with SGL through a systematic review and meta-analysis. METHODS: Electronic databases were searched for studies assessing the presence of SS in patients with SGL. Pooled prevalence of SS in SGL was calculated, with a subgroup analysis based on histotype (mucosa-associated lymphoid tissue [MALT] vs non-MALT). RESULTS: Sixteen studies with 665 SGLs were included. Pooled prevalence of SS in SGL was 18.2%, with high heterogeneity among studies. In MALT SGL, the prevalence of SS was 29.5%, with moderate heterogeneity. In non-MALT SGL, the prevalence of SS was 0%, with null heterogeneity. CONCLUSIONS: SS seems to be responsible for a significant but minor portion of SGLs. SS appears involved in MALT-type SGL but not in other histotypes.

Salivary neoplasia in dogs and cats: 1996-2017.

OBJECTIVE: The objectives of this study were to report the contemporary demographical information, provide the incidence of and to assess sex and breed predisposition of salivary gland neoplasia in dogs and cats. MATERIALS AND METHODS: Information was collected from cats or dogs with salivary neoplasia (cases) and controls from the 26 university veterinary teaching hospitals within the Veterinary Medical Data Base. A total of 56 dogs and 24 cats were identified as having been diagnosed with salivary neoplasia. RESULTS: The incidence of salivary neoplasia in this population was calculated to be 15.3 per 100,000 dogs and 26.3 per 100,000 cats. The specific anatomic location of the salivary neoplasia was unable to be determined in 90.8% of cases in both dogs and cats. Results of the univariable conditional logistic regression models revealed no increased risk of salivary neoplasia in dogs or cats of any sex or neuter status (dogs: p = .26; cats: p = .45). There was no breed disposition within the feline species for salivary neoplasia. However, in the conditional logistic regression for dogs, poodles (toy and standard) trended towards significance (p = .075) with an odds ratio of 6.83 (95% CI: 1.16-40.10) compared to mixed breeds. CONCLUSIONS AND CLINICAL RELEVANCE: The present study's results differ from previous conclusions made in regards to predisposed breeds and tumour location. Additional epidemiological studies should be performed to help in determining risk factors for salivary gland neoplasia.

Role of Antioxidants in Minor Salivary Glands Cancer in the Elderly.

BACKGROUND: Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature. METHODS: An electronic search of the English language literature was performed using PubMed and Google scholar (). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands). RESULTS: According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population. CONCLUSIONS: Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.

Brain and Salivary Gland Tumors and Mobile Phone Use: Evaluating the Evidence from Various Epidemiological Study Designs.

Mobile phones (MPs) are the most relevant source of radiofrequency electromagnetic field (RF-EMF) exposure to the brain and the salivary gland. Whether this exposure implies a cancer risk has been addressed in several case-control and few cohort studies. A meta-analysis of these studies does not show increased risks for meningioma, pituitary, and salivary gland tumors. For glioma and acoustic neuroma, the results are heterogeneous, with few case-control studies reporting substantially increased risks. However, these elevated risks are not coherent with observed incidence time trends, which are considered informative for this specific topic owing to the steep increase in MP use, the availability of virtually complete cancer registry data from many countries, and the limited number of known competing environmental risk factors. In conclusion, epidemiological studies do not suggest increased brain or salivary gland tumor risk with MP use, although some uncertainty remains regarding long latency periods (>15 years), rare brain tumor subtypes, and MP usage during childhood.

AHNS series: Do you know your guidelines? Diagnosis and management of salivary gland tumors.

This article is the next installment of the series "Do you know your guidelines" presented by the Education Committee of the American Head and Neck Society. Guidelines for the workup and management of tumors of the major and minor salivary glands are reviewed.

Current State of Knowledge on Salivary Gland Cancers.

Salivary gland cancers (SGCs), categorized as head and neck cancers (HNCs), constitute about 6% of head and neck cancer diagnoses based on estimate by American Head and Neck Society. Salivary gland tumors originate from different glandular cell types and are thus morphologically diverse. These tumors arise from any of the three major and various minor salivary glands. The incidence of SGCs has slowly increased during the last four decades. The etiology of SGCs is mostly unknown; however, specific gene mutations are associated with certain types of salivary tumors. Treatment options include surgical resection, radiation therapy (RT), chemotherapy, and multimodality therapy. HNC patients treated with RT often develop xerostomia and salivary hypofunction due to damaged salivary glands. In this review, we discuss etiology of SGCs, present findings on the role of autophagy in salivary tumorigenesis, review adverse effects of radiation treatment, and examine remedies for restoration of salivary function.

The evaluation of disease activity in Sjögren's syndrome based on the degree of MALT involvement: glandular swelling and cryoglobulinaemia compared to ESSDAI in a cohort study.

OBJECTIVES: To investigate if indicators of a heavier involvement of mucosa-associated lymphoid tissue (MALT) in primary Sjögren's syndrome (pSS), i.e. persistent salivary gland (SG) swelling and cryoglobulinaemia, might better evaluate the lymphoma risk compared to the ESSDAI. Therefore, the current concept of disease activity of pSS should be re-evaluated, based solely on ESSDAI. METHODS: A cohort of 255 pSS patients, including 30 pSS with B-cell lymphoma, was investigated. Three subgroups were distinguished, i.e. pSS developing lymphoma in the follow-up (n=12), pSS with lymphoma at cohort inclusion (n=18), and control pSS not developing lymphoma in the follow-up (n=225). SG swelling, cryoglobulinaemia and ESSDAI were evaluated at baseline, in the follow-up to one year before lymphoma diagnosis, and at lymphoma diagnosis. RESULTS: SG swelling and/or cryoglobulinaemia at baseline were significantly higher (p=0.0003) in pSS patients evolving into lymphoma if compared to pSS controls, while ESSDAI showed no significant difference. Both SG swelling and cryoglobulinaemia persisted and sometimes developed ex novo in the follow-up. SG swelling and cryoglobulinaemia were present in 24/30 (80%) cases the time of lymphoma diagnosis, and lymphoma itself was usually of MALT/marginal zone histotype (90%), leading to peculiar manifestation of lymphoma in pSS. CONCLUSIONS: The autoimmune and lymphoproliferative involvement of MALT is the biological substrate of pSS. If this involvement is heavier, as reflected by SG swelling and cryoglobulinaemia, disease activity may be considered higher, and the risk of lymphoma is increased. The current concept and evaluation of activity of pSS, based solely on the ESSDAI, needs revision.

Cancers of the Major Salivary Gland.

Salivary gland malignancies are rare tumors that comprise multiple histologic entities with diverse clinical behavior. Mucoepidermoid carcinoma is the most frequent primary salivary malignancy, followed by adenoid cystic and acinic cell carcinoma. Although most salivary malignancies are asymptomatic, presentation with a rapidly enlarging mass may be accompanied by pain, functional neurologic deficits, soft-tissue invasion, or nodal enlargement. Assessment of clinical behavior and physical exam greatly contributes to diagnostic workup. Preoperative imaging, to include ultrasound, computed tomography, or magnetic resonance imaging, may assist with surgical planning. Limitations of preoperative fine-needle aspiration cytology mean that, in some cases, definitive histologic diagnosis may not be established until therapeutic surgery is undertaken. Treatment strategies rely on oncologic resection of the primary site with negative margins as well as adjuvant radiotherapy in patients with high-risk features, such as high-grade histology, advanced T class, or perineural invasion. Regional lymphadenectomy is recommended for involved nodal basins. Patients with clinically node-negative disease at high risk for occult nodal metastases may be considered for elective lymphadenectomy or radiotherapy. Use of chemotherapy in the adjuvant setting, in combination with radiotherapy, remains controversial. The rate of objective response to palliative chemotherapy in recurrent or metastatic salivary gland malignancy remains low. In studies that include a significant proportion of adenoid cystic carcinomas, whether disease stability represents an indolent disease process or the true effect of a therapeutic drug may be difficult to discern. Recognition of genetic alterations and protein expression unique to salivary malignancies presents exciting new opportunities for molecularly targeted therapy, although the response to molecularly targeted therapy in studies has been modest thus far.

Mobile phone use and risk for intracranial tumors and salivary gland tumors - A meta-analysis.

Results of epidemiological studies on the association between use of mobile phone and brain cancer are ambiguous, as well as the results of 5 meta-analysis studies published to date. Since the last meta-analysis (2009), new case-control studies have been published, which theoretically could affect the conclusions on this relationship. Therefore, we decided to perform a new meta-analysis. We conducted a systematic review of multiple electronic data bases for relevant publications. The inclusion criteria were: original papers, case-control studies, published till the end of March 2014, measures of association (point estimates as odds ratio and confidence interval of the effect measured), data on individual exposure. Twenty four studies (26 846 cases, 50 013 controls) were included into the meta-analysis. A significantly higher risk of an intracranial tumor (all types) was noted for the period of mobile phone use over 10 years (odds ratio (OR) = 1.324, 95% confidence interval (CI): 1.028-1.704), and for the ipsilateral location (OR = 1.249, 95% CI: 1.022-1.526). The results support the hypothesis that long-term use of mobile phone increases risk of intracranial tumors, especially in the case of ipsilateral exposure. Further studies are needed to confirm this relationship. Int J Occup Med Environ Health 2017;30(1)27-43.

Siringoma Condroide. Presentación de un caso / Chondroid syringoma. Case presentation

Introducción: El Siringoma Condroide o tumor mixto es una neoplasia habitualmente benigna que constituye 0,01 por ciento de los tumores primarios de la piel. Es una entidad análoga al tumor mixto (Adenoma Pleomorfo) de glándulas salivales. El diagnóstico es exclusivamente histopatológico. Objetivo: Presentar una paciente con un diagnóstico poco común de Siringoma Condroide benigno, donde se destaca como diagnóstico diferencial entre los tumores de la piel en cabeza y cuello. Presentación de caso: Presentamos el caso de una paciente femenina, de 45 años de edad, quien acude a consulta por presentar un nódulo subcutáneo en la región geniana derecha, que apareció como un pequeño aumento de volumen debajo de la piel, que fue creciendo gradualmente, asintomático, redondeado, bien delimitado, móvil, de consistencia entre suave y firme, de varios meses de evolución, como única lesión. Clínicamente se interpretó como un quiste epidérmico. Su diagnóstico anatomopatológico fue el de Siringoma Condroide benigno o Tumor mixto de la piel. Conclusiones: Resulta un caso interesante debido a la baja frecuencia de presentación de esta lesión. Es importante tener presente esta entidad en el diagnóstico diferencial de los tumores de la piel en cabeza y cuello. A pesar de ser un tumor benigno es necesario el seguimiento del paciente, pues, aunque es muy raro, se han descrito casos con un comportamiento maligno(AU)

Introduction: Chondroid syringoma or mixed tumour is usually a benign neoplasia, constituting 0.01 percent of primary tumours of the skin. This is analogous to mixed tumour (Pleomorphic adenoma) of salivary gland. The diagnosis is only histopathologically. Objective: To present a patient with a diagnosis not very common of chondroid syringoma, where it is highlighted as differential diagnosis among the head and neck skin tumours. Case presentation: Is presented a case of a female patient; 45 years old, that arrived to the consulting room showing a subcutaneous nodule on the right genial region, it appeared as an asymptomatic slow-growing small mass, rounded, well bounded, mobile of soft and firm consistence, of several months of evolution, as a single lesion. The diagnosis was a chondroid syringoma or skin mixed tumour. Conclusions: It is an interesting case because it has a low frequency. It is important bear in mind this entity in the differential diagnosis of head and neck skin tumours. Despite being a benign tumour it is necessary to monitor patients, because even though it is uncommon, some cases have been reported with a malignant behaviour(AU)

The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC. METHODS: The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP. RESULTS: The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02). CONCLUSION: Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.

Cáncer oromaxilofacial en niños: Parte II tumores odontogénicos y de glándulas salivales malignos / Maxillofacial cancer in children: Part II malignant odontogenic and salivary gland tumors

A nivel mundial, la información acerca de tumores malignos del territorio maxilofacial que afectan a niños es limitada. La mayoría de los resportes consiste principalmente en datos de la población adulta. Las neoplasias malignas originadas del aparato odontogénicos y glándulas salivales son lesiones que con cierta frecuencia pueden afectar a la población infantil. Los tumores odontogénicos malignos son entidades sumamente raras que, correspondiendo a menos del 5 % del total de tumores odontogénicos. Los sarcomas odontogénicos, si bien son poco frecuentes, corresponden a los tumores odontogénicos malignos más comunes en la infancia. Las neoplasias malignas de glándulas salivales corresponden al 35­60 % de los tumores de gándulas salivales en la infancia, siendo el más común de ellos el carcinoma mucoepidermoide. En general, el pronóstico de estas entidades es positivo sobre todo si es acompañado de un diagnóstico oportuno. A pesar de la baja frecuencia que presenta este grupo de patologías, no es menos cierto que es necesario saber con precisión cuales son los tejidos orales desde los cuales se pueden originar neoplasias malignas en los niños y tener una breve referencia diferencial entre ellos.

Globally, information about the maxillofacial malignant tumors affecting children is limited. Most reported data consists mainly of studies in the adult population. Malignant neoplasms arising from odontogenic apparatus and salivary glands are lesions that frequently can affect children. Malignant odontogenic tumors are extremely rare entities, corresponding to less than 5 % of all odontogenic tumors. Odontogenic sarcomas, although they are rare, correspond to the most common malignant odontogenic tumors in childhood. Malignant salivary gland neoplasms correspond to 35­60 % of tumors of salivary glands during childhood and the most common of these is mucoepidermoid carcinoma. In general, the prognosis of these entities is positive especially when there is a timely diagnosis. Despite the low frequency presented by this group of diseases, the fact remains that it is necessary to know precisely what the originating oral tissues are which can cause malignancies in children and have a brief reference differential between them.

HPV Infection, but Not EBV or HHV-8 Infection, Is Associated with Salivary Gland Tumours.

Benign and malignant salivary gland tumours are clinically heterogeneous and show different histology. Little is known about the role of human herpes virus 8 (HHV-8), Epstein-Barr virus (EBV), and human papillomavirus (HPV) infection in salivary gland neoplasms. We investigated the presence of the three viruses in formalin-fixed, paraffin-embedded tissue samples in a cohort of 200 different salivary gland tumours. We performed EBV-LMP-1 and HHV-8 and p16 immunohistochemistry, a specific chip based hybridization assay for detection and typing of HPV and a chromogenic in situ hybridization for EBV analysis. Only one case, a polymorphic low-grade carcinoma, showed HHV-8 expression and one lymphoepithelial carcinoma was infected by EBV. In 17 cases (9%) moderate or strong nuclear and cytoplasmic p16 expression was detected. The HPV type was investigated in all of these cases and additionally in 8 Warthin's tumours. In 19 cases HPV type 16 was detected, mostly in Warthin's tumour, adenoid cystic carcinoma, and adenocarcinoma NOS. We concluded that HHV-8 infection and EBV infection are not associated with salivary gland cancer, but HPV infection may play a role in these tumour entities.

Spectrum of Salivary Gland Lesions in a Tertiary Level Hospital.

Salivary gland tumors are relatively infrequent and account for less than 2% of all human tumors. This study was conducted to see the prevalence of patterns of non neoplastic and neoplastic lesions of salivary glands in greater Mymensingh. It was a retrospective study carried out in the department of Pathology, Community Based Medical College Bangladesh from January 2010 to December 2012. Heamatoxylin and eosin stained sections were studied in all cases. Total 98 cases of salivary gland lesions were retrieved and evaluated. Out of them 55 cases were female and 43 were male. Mean age of the cases were 42 years. Among the salivary gland lesions non-neoplastic lesions 24.48% and neoplastic lesions 75.51%. Among neoplastic lesions benign tumor comprises 91.89% and malignant tumor comprises 8.10%.

Aberrant Activation of the RANK Signaling Receptor Induces Murine Salivary Gland Tumors.

Unlike cancers of related exocrine tissues such as the mammary and prostate gland, diagnosis and treatment of aggressive salivary gland malignancies have not markedly advanced in decades. Effective clinical management of malignant salivary gland cancers is undercut by our limited knowledge concerning the key molecular signals that underpin the etiopathogenesis of this rare and heterogeneous head and neck cancer. Without knowledge of the critical signals that drive salivary gland tumorigenesis, tumor vulnerabilities cannot be exploited that allow for targeted molecular therapies. This knowledge insufficiency is further exacerbated by a paucity of preclinical mouse models (as compared to other cancer fields) with which to both study salivary gland pathobiology and test novel intervention strategies. Using a mouse transgenic approach, we demonstrate that deregulation of the Receptor Activator of NFkB Ligand (RANKL)/RANK signaling axis results in rapid tumor development in all three major salivary glands. In line with its established role in other exocrine gland cancers (i.e., breast cancer), the RANKL/RANK signaling axis elicits an aggressive salivary gland tumor phenotype both at the histologic and molecular level. Despite the ability of this cytokine signaling axis to drive advanced stage disease within a short latency period, early blockade of RANKL/RANK signaling markedly attenuates the development of malignant salivary gland neoplasms. Together, our findings have uncovered a tumorigenic role for RANKL/RANK in the salivary gland and suggest that targeting this pathway may represent a novel therapeutic intervention approach in the prevention and/or treatment of this understudied head and neck cancer.