Incidence and profile of benign epithelial tumors of salivary glands from a single center in Northeast of Brazil

Background Benign tumors of the salivary glands are a group of lesions with varied histopathological and clinical spectrum. The aim was to determine the incidence and clinicopathological characteristics of benign salivary gland neoplasms diagnosed between 2007 and 2016 in a single center located in northeastern Brazil. Material and Methods Records regarding sex, age, anatomical location, histopathological subtype and treatment were retrieved, and data were analyzed using the Stata/IC software (version 12.0). Results There were above 7,100 cases of neoplasms in the head and neck region, of which 403 corresponded to salivary gland neoplasms. Of these, 238 (59%) were benign, being pleomorphic adenoma (PA) the most frequent neoplasm (n=178; 74.8%), followed by Warthin's tumor (WT) (n=23; 9.7%). Overall, most cases occurred in females (n=136; 57.1%) and age ranged from 11 to 83 years. The parotid gland (n=188; 79%) was the most common anatomical site, and all patients were treated by surgical excision. Of the cases diagnosed as PA, malignant transformation to carcinoma ex-pleomorphic adenoma (CAEXPA) occurred in 7 (3.9%) cases. Conclusions The present study confirmed the clinical and demographic profile of benign salivary gland neoplasms, which contributes to the continuous knowledge of current data about these lesions. Key words:Salivary gland, benign neoplasms, epidemiology.

As for their nature, usually more than 50% are benign, reaching a prevalence up to 86% (7). Most cases occur between the fourth and seventh decades of life and women are more affected (2)(3)(4)(5)(6)(7). Pleomorphic adenoma (PA) is the most common benign salivary gland neoplasm, comprehending about 50% of the cases, and Warthin's tumor (WT) is the second one, representing 4 to 15% of all salivary gland neoplasms (2)(3)(4)(5)(6)(8)(9)(10)(11). Furthermore, benign neoplasms with enduring evolution and history of recurrences can undergo malignant transformation. For instance, PA can evolve to carcinoma ex-pleomorphic adenoma (CAEXPA), which diminishes the survival of the patient (12). Epidemiological studies that assess the incidence and characteristics of these tumors help to update scientists and health professionals worldwide. Thus, this retrospective study aimed to analyze the cases of benign salivary gland neoplasms in a referral hospital in northeastern Brazil in order to keep data renewed.

Material and Methods
The study was evaluated and approved by the local Research Ethics Committee (REC/HCP -no 2.774.008). Medical records of patients attended between 2007 and 2016 at the Cancer Hospital of Pernambuco were retrieved, and for those diagnosed with benign salivary gland neoplasm, clinicopathological characteristics (sex, age, anatomical location, histopathological subtype and treatment performed) were collected. Records had to report histopathological diagnosis of salivary gland neoplasm and all clinical data to be included in the study. The cases diagnosed as benign salivary gland neoplasms were re-assessed by an oral and maxillofacial pathologist in order to confirm and adequate final histological diagnosis with the current WHO classification (1). For this, 5μm sections of each case were stained with hematoxylin and eosin and evaluated under light microscopy. Nomenclature and criteria used to reclassify the cases were based on the descriptions summarized by the current WHO classification of salivary gland tumors (1). When in doubt about the diagnosis, a second pathologist was consulted. There were no disagreements related to the reclassification and no case was excluded. After histological evaluation, 3 cases previously denominated "oxyphilic adenoma" were renamed as oncocytoma, and 9 cases diagnosed as "monomorphic adenoma" were reclassified to canalicular adenoma (1 case) and the other 8 to basal cell adenoma. In addition, 6 cases of PA were reclassified to myoepithelioma. Database was mounted and analyzed using the Stata/IC software (version 12.0; StataCorp, CollegeStation, TX), with a descriptive analysis of the sex, age, anatomical location and treatment. The results obtained were assigned to a table with their respective absolute and relative frequencies.

Results
In nine years, approximately 230,635 lesions were diagnosed in the referred hospital. Of these, approximately 7,100 were cases of head and neck neoplasms, of which 403 (5.7%) were of salivary gland neoplasms. There were 238 cases of benign salivary gland neoplasm, which corresponded to 59% of all salivary gland neoplasms and 3.3% of the head and neck tumors. Most cases were diagnosed in females (n=136; 57.1%) and age varied between 11 and 83 years, with an average of 48 years-old (SD±16). PA was the most frequent neoplasm (n=178; 74.8%), followed by WT (n=23; 9.7%) (   topathological analysis. Mucoepidermoid carcinoma, adenoid cystic carcinoma and unspecified adenocarcinoma were the definitive diagnoses. As for the tumors located in the minor salivary glands, incisional biopsy was conducted for diagnosis prior to surgical excision. All patients diagnosed with benign salivary gland neoplasms performed a non-radical surgical excision. Preservation of the facial nerve was maintained for all surgeries of the parotid gland. Of the 178 cases diagnosed as PA, malignant transformation to CAEXPA occurred in 7 cases (3.9%). These cases had a history of PA with one or two recurrences before the transformation and no case was initially diagnosed as malignant (primary CA-EXPA). Evolution time until the diagnosis of CAEXPA ranged from 2 to 10 years. Table 3 shows that for previous studies conducted in Brazil the rate of malignant transformation of PA varied from 0-10.8% in several diagnostic centers.
Patients with lesions in the major salivary glands were submitted to fine-needle aspiration prior to surgical treatment, in order to obtain the diagnosis. Seven cases diagnosed as PA and 2 cases diagnosed as WT were considered malignant after surgical resection and his-

Discussion
In the studied hospital, benign salivary gland neoplasms (n=238; 59%) represented the majority of the cases, being in agreement with worldwide literature (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Furthermore, other studies conducted in Brazil also confirm our findings (3,5,7,14,16,17). In the present study, the average age was 48 years-old (SD ± 16), with a range from 11 to 83 years. Most cases occurred in females and the parotid gland was the most frequent site representing 79% of the cases. Gao et al. (6) and Da Silva et al. (7) found similar results to ours were most cases of benign salivary gland neoplasm occurred in the 5th decade of life, females and parotid gland. In contrast, two studies conducted by Tian et al. (2) and Wang et al. (4) found that the male gender was most affected by salivary tumors. This indicates that some divergence may be found in the literature, reinforcing the importance to perform epidemiological studies worldwide and compare their results. PA was the most common benign neoplasm, representing about 75% of cases, followed by WT with 9.7%. Corroborating these findings, other studies showed similar results (2)(3)(4)(5)(6)(8)(9)(10)(11)(14)(15)(16). Nevertheless, in a multicenter study conducted in Brazil, Da Silva et al. (7) observed basal cell adenoma was the second most prevalent tumor followed by cystadenomas and myoepitheliomas. According to this author, WT may be even more scarce than indicated by the literature. Furthermore, apart from this referred study, other two conducted in Brazil, showed WT is not always the second most frequent tumor showing some discrepancy even in the same coun-try (Table 3). Associated with this, we believe that there is a strong tendency that, when affected, the sublingual gland is mainly a site of malignant tumors. Benign neoplasms in minor glands were more prevalent on the palate, followed by the buccal mucosa. PA was the most frequent lesion at both sites, being reported similar results by Wang et al. (4) and Gao et al. (6). Studies that exclusively addressed tumors in minor salivary glands are also in agreement with our results regarding the most common anatomical site and histological diagnosis. However, they showed variations regarding the second most common anatomical site in which they reported being the lips or tongue instead of the buccal mucosa (16,19,20 Table 3, studies in Brazil show variation in the percentage of CAEXPA, however, the transformation rate in general is between 1 and 5% (3,7,17,(23)(24)(25). In our analysis, of the 178 cases diagnosed as PA, there was malignant transformation in 7 patients, representing 3.9% of the cases. History of recurrences of PA prior to the transformation was noted confirming an important characteristic associated with the development of CAEXPA (12). An important aspect to consider is that the tumors analyzed derived from a medical pathology center (general pathology service), instead of an oral pathology service. It has been shown (3,25) that in medical services the most common location for benign salivary gland neoplasms is the parotid gland in which PA and WT are the most frequent tumors as we observed in the present study. In the other hand, in an oral pathology laboratory most lesions diagnosed are from the minor salivary glands, especially the palate, evidencing a different distribution profile. Furthermore, PA is also the most common tumor in this location, followed by other tumors such as canalicular adenoma, myoepithelioma and basal cell adenoma. The fact that this study was conducted in a medical center also indicates that WT was the second most common tumor as it occurs almost exclusively in the parotid gland as already discussed. Thereby, when analyzing the distribution of salivary gland tumors, the pathology service (general or oral) the lesions were evaluated has to be taken into consideration as it influences the clinicopathological profile of these tumors.