Salivary Gland Tumors : A Clinicopathologic Study of 366 Cases in Southern Iran

Salivary gland tumors (SGTs) are a heterogeneous group of neoplasms in the maxillofacial area with complex morphologic appearance and different clinical behavior. These tumors are relatively uncommon, comprising 3-6% of all head and neck neoplasms in various reports (Ansari, 2007; Jones et al., 2008). However, they are an important issue in the science of head and neck pathology, due to their difficult diagnosis, management and unpredictable clinical course of disease. Etiologic factors of this group of neoplasms have not been recognized exactly however; Ionizing radiation, sunlight, chemotherapy, smoking and vitamin A deficiency have been pointed out in the literature (Licitra et al., 2003; Hashemi et al., 2007). These tumors have inconsistent characteristics in different countries and it seems that geographic location and ethnic factors may affect clinicopathologic profile of these tumors (Kayembe et al., 2002; Shishegar et al., 2011). Clinical data such as patient’s age and gender, site of involvement and the relative incidence are imperative for accurate diagnosis and management. We found only limited number of reports of large group of cases in Iranian population. This research analyzes a large group of patients in southern Iran


Introduction
Salivary gland tumors (SGTs) are a heterogeneous group of neoplasms in the maxillofacial area with complex morphologic appearance and different clinical behavior.These tumors are relatively uncommon, comprising 3-6% of all head and neck neoplasms in various reports (Ansari, 2007;Jones et al., 2008).However, they are an important issue in the science of head and neck pathology, due to their difficult diagnosis, management and unpredictable clinical course of disease.Etiologic factors of this group of neoplasms have not been recognized exactly however; Ionizing radiation, sunlight, chemotherapy, smoking and vitamin A deficiency have been pointed out in the literature (Licitra et al., 2003;Hashemi et al., 2007).These tumors have inconsistent characteristics in different countries and it seems that geographic location and ethnic factors may affect clinicopathologic profile of these tumors (Kayembe et al., 2002;Shishegar et al., 2011).Clinical data such as patient's age and gender, site of involvement and the relative incidence are imperative for accurate diagnosis and management.We found only limited number of reports of large group of cases in Iranian population.This research analyzes a large group of patients in southern Iran female (M/F 1.02:1).The age range was from 5-83 years with mean age of 41.8±16.7.Out of all SGTs, 249 were benign and 109were malignant.Pleomorphic adenoma (PA) was the most common tumor comprising 54.3% all SGTs followed by adenoid cystic carcinoma (ACC) (15%) and mucoepidermoid carcinoma (MEC) (9.2%).

Benign tumors
These neoplasms constituted 248 (67.8%) of all tumors and involved 121 males and 127 females (M/F: 1:1.05).The mean age of patients was 37.7±14.9.Table 1 shows details of this group.PA and Warthin's tumor were the first and the second most common benign tumor, respectively.These neoplasms tend to involve parotid and submandibular glands more frequently.

Malignant tumors
Out of all samples, 118 (32.2%) neoplasms were malignant (Table 2).M/F was 1.2:1 in this group.ACC with 55 cases (46.6%) and MEC with 35 cases (29.6%) were the first and the second most common type respectively (Table 2).Parotid and minor salivary glands showed the most frequent involvement with this tumor.

Anatomic variations
Parotid gland: 57.5% (n=210) of all SGTs located in this location.Benign to malignant ratio was 4:1.PA and MEC were the most common tumors in this area.
Submandibular gland: 48 cases (13.1%) located in these glands that 73% were benign.PA and ACC achieved the first place in benign and malignant groups.
Sublingual gland: Only 3 cases of ACC were found in this area.
Minor salivary glands: These glands were involved by 28.5%( n=105) of all SGTs and most of these neoplasms were malignant (56%).PA and ACC were the most common benign and malignant entities.Palate was the most frequent site of involvement.5.2% of tumors involved intra-osseous glands in maxilla and mandible (Figure1).
Figure 2 shows the relative frequency of benign and malignant tumors in various anatomic locations.

Discussion
SGTs probably are the most complex human neoplasia (Dardick et al., 1992), accounting for 3-10% of all head and neck tumors (Ansari, 2007;Jones et al., 2008).During 2005-2009, we discovered that 2.7% of all biopsied materials and 39% of oral and maxillofacial tumors were SGTs.This high rate of reported cases attributes to the nature of study situation (Khalili hospital) that is the largest referral center for the maxillofacial tumors in southern Iran.Although increasing sun-exposure might be a cause.The benign/ malignant ratio was 2.1:1 with prominent involvement of major glands.This ratio varies from 1.1:1 in Africa to 5.6:1 in European reports (Ma`aita et al., 1999;Satko et al., 2000;Vuhahula, 2004;Ito et al, 2005;Lima et al., 2005;Li et al., 2008;Subhashraj, 2008).Ansari has reported this ratio 2.2:1 in western Iran (Ansari, 2007).All these reports have confirmed greater involvement of major glands with parotid gland being the greatest.The majority of tumors in parotid glands were benign and there was a reverse relation between size of the major glands and the rate of malignancy.The minor salivary glands were the second common site of involvement, engaged in 28.5% of all tumors.In minor salivary glands, palatal area was the region with more involvement.Other studies in Iran and other countries also reported that 9-23% of all SGTs arise from minor glands, majority of them in the palate (Spiro, 1986;Rahrotaban et al., 1995;Valizadeh and Mohagheghi, 1995;Ansari, 2007;Atarbashi-Moghadam et al., 2010;Vaidya et al., 2012).The tumors arising from minor glands had a tendency to become malignant.This finding also was seen in the large series of minor SGTs in Tehran,Iran center (Daneshvar et al., 2011).However data from Pennsylvania, USA and California have shown predominance of benign tumors (Yih et al., 2005;Buchner et al., 2007;Pires et al., 2007).These different results are attributable to the racial factors, as well the place where cancer had registered, whether hospital or dental school.
PA undoubtedly is the most common SGTs.As, similar to the present study, all researchers from other parts of Iran and worldwide have noticed that this neoplasm stands for 40.4-89.9% of all SGTs (Valizadeh and Mohagheghi, 1995;Ma`aita et al., 1999;Satko et al., 2000;Vargas et al., 2002;Vuhahula, 2004;Ito et al, 2005;Lima et al., 2005;Otoh et al., 2005;Ansari, 2007;Li et al., 2008;Subhashraj, 2008;Atarbashi-Moghadam et al., 2010).Warthin's tumor was the second common benign tumor denoted 10.5% of all cases with Male to Female ratio of 10: 3. Other studies in Denmark and Pennsylvania reported a high incidence of this tumor (about 30% of parotid tumors), however some populations such as Africans were affected rarely (Poulsen et al., 1987;Monk and Church, 1992;Vuhahula, 2004).Male/ female is decreasing during recent years.As smoking is a risk factor for development of this neoplasm, most probably increasing female smokers is the cause (Monk and Church, 1992).
ACC was the most common malignant tumor followed by MEC.This finding is consistent with researches in Brazil, India, Africa and Bratislava (Satko et al., 2000;Vuhahula, 2004;Lima et al., 2005;Subhashraj, 2008).Also, authors have reported ACC being the most common malignancy in a large group of patients in Iran center (Khalili and Salamat, 2009).
However, most of the studies on Brazilian, Libyan and Chinese populations and also those enrolled in western and center Iran have shown that MEC occurs with more frequency (Ma`aita et al., 1999;Vargas et al., 2002;Ito et al, 2005;Otoh et al., 2005;Ansari, 2007;Li et al., 2008;Daneshvar et al., 2011).Attarbashi et al in south of Iran, have demonstrated that MEC and ACC were the most common malignant tumors arising from major and minor salivary glands, respectively (Atarbashi-Moghadam et al., 2010).These data indicate a racial and geographic variation in relative incidence of SGTs.
The mean age of patients in benign neoplasms was 37.7 years.This result is similar to the other studies which have reported a range from 33.5-47.7 (Rahrotaban et al., 1995;Satko et al., 2000;Vargas et al., 2002;Vuhahula, 2004;Ansari, 2007;Li et al., 2008).Malignant tumors showed a mean age of 50.7 years which was 13 years higher than benign tumors.The difference between mean age of patients with benign and malignant tumors have been reported from 3 years in Chinese to 10 years in African population (Luukkaa et al., 2005;Li et al., 2008), but Vargas et al. have found an almost equal average of age in malignant and benign neoplasms in Brazil (Vargas et al., 2002).This difference that was noticeable in our study is related to the lower age of our patients with benign tumors.Also, earlier studies in China and Sri Lanka have shown a lower age range in malignant group in comparison with our results (Li et al., 2008;Tilakaratne et al., 2009).
The malignant tumors occurred in males 1.2 times more than females.Also, overall male predominance was observed.This result is consistent with Li's et al study in China (Li et al., 2008).Malignant tumors also had a tendency to males in Brazil, Fanland, India and other studies in Iran (Rahrotaban et al., 1995;Luukkaa et al., 2005;Hashemi et al., 2007;Li et al., 2008;Subhashraj, 2008;Atarbashi-Moghadam et al., 2010;Daneshvar et al., 2011) while Some studies have indicated opposite results (Al-Khateeb and Ababneh, 2007;Tilakaratne et al., 2009;Atarbashi-Moghadam et al., 2010).Moreover, Licitro et al stated an equal gender involvement (Licitra et al., 2003).With a comprehensive review of large series of SGTs in various reports from Iran and worldwide, it seems that benign tumors occurs more commonly in females, but malignant entities have a propensity to involve male patients.
In conclusion, although SGTs, in this study, demonstrated many similarities in clinical course to the other parts of the world and other parts of Iran, our study has come to a few individual results: Overall incidence was higher than earlier studies.A slightly tendency to males was seen, although benign tumors affected female patients with more frequency.ACC was more observable in southern Iran and malignant neoplasms were detected at least one decade later than benign ones.These data exhibited a special clinical profile of SGTs in southern Iran in comparison with reports from other countries and other parts of Iran.Authors hope that this silhouette could help physician, surgeons and pathologists for more accurate diagnosis, management and early treatment.

Figure
Figure 1.Incidence of Benign and Malignant Tumors in Various Anatomic Locations

Table 1 . Distribution of Benign Salivary Gland Tumors According to Tumor Type, Age and Gender
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