J Bagh College Dentistry Vol. 26(1), March 2014 Salivary gland Oral Diagnosis 88 Salivary gland tumors: A review of 171 cases, with particular reference to histological types, site, age and gender distribution Faris I. Al-Khiro, M.B.Ch.B., F.I.C.M.S., E.B.P. (1) ABSTRACT Background: Salivary tumors are uncommon, being of low incidence worldwide. This study aimed to assess cases collected in this series of salivary gland tumors in regard to histopathological typing, in relation to age, site and gender. Materials and methods: This is a retrospective study; cases were collected from public and private laboratories. A total number of 171 cases were collected. The slides were reviewed and reclassified for histopathological typing according to WHO classification 2005. Results: Benign tumors were more common than malignant tumors. The most common histological type was benign mixed tumor, followed by Warthin’s tumor. The most common malignant tumor was adenoid cystic carcinoma. One hundred twenty three cases out of 171 cases developed in the parotid, the most common site for salivary tumors, with a low risk for malignancy, while minor salivary glands show higher risk for malignancy. Salivary tumors developed in females more than males with a ration 1.4:1, the peak incidence in the sixth and seventh decades for both benign and malignant tumors. There was no significant difference between right and left tumors, bilateral tumors were uncommon. Conclusions: The results of this study reveal similarity to the findings of other studies on salivary tumors done in Iraq and the neighboring countries. Keywords: Salivary gland tumors. (J Bagh Coll Dentistry 2014; 26(1):88-91). INTRODUCTION Salivary gland tumors are uncommon, accounting for about 3-6% of head and neck neoplasms1. Most of tumors develop in major salivary glands, so 43-90% occurs in the parotid gland, 8-19.5% in submandibular gland, uncommon in sublingual glands and only 14-22% occurs in minor salivary glands 2. Salivary tumors show marked variation and morphological overlap, which resulted in repeated new classifications 3-6, the first classification was done by Foote et al in 19543. Currently, the most widely used classification is the World Health Organization (WHO) classification, which primarily stresses distinction into benign and malignant tumors7. In most studies, salivary tumors are generally more common in females in their 3rd to 5th decades of life8,9 . They are rare in pediatric age group, the most common tumors seen are benign mixed tumors, but the ratio of malignancy is higher than in adults10. Most of salivary gland tumors are unilateral, with no significant difference between right and left. Bilateral tumors are uncommonly seen, and occur mostly with Warthin’s tumors 11. Benign salivary gland tumors are more common than malignant tumors; the most common type is the benign mixed tumor or pleomorphic adenoma. These vary greatly in morphologic features, composed basically of epithelial and mesenchymal elements, they have a potential to recur 12, because they are partially (1) Pathology Department, Al Yarmouk Teaching Hospital. encapsulated and difficult to excise completely in many cases. Malignant transformation is uncommon. However, it has been reported to occur more in submandibular gland tumors13,14. Warthin’s tumor, also called cystadenoma lymph- omatosum papilliferum, seen almost exclusively in major glands 15. The tumor has a higher risk for bilateralality16, and it's incidence is higher in smokers17.Other benign salivary adenomas are collectively much less common; the least uncommon are canalicular adenomas and basal cell adenomas. It has been reported in most studies that Mucoepidermoid carcinomas are the most common malignant tumor in the parotid gland18. Acinic cell carcinomas and adenocarcinoma are less common, while adenoidcystic carcinomas are the most common malignancy in the minor salivary glands11. Malignant lymphoma can be seen as part of a systemic disease, or more commonly a primary neoplasm. Most of the cases are B cell type, often seen on a background of Miculisz disease or other autoimmune diseases 19. Immunohistochemistry can be useful as an ancillary aid in diagnosis of specific histologic types of salivary gland tumors 20,21, particularly in uncommon adenomas and in malignant tumors: These tumors are uncommon in general pathology practice, and because these tumors frequently show morphological overlap. Therefore, This retrospective study is aimed to assess collected series of cases of salivary gland tumors, in regard to histological typing, site, age and gender. J Bagh College Dentistry Vol. 26(1), March 2014 Salivary gland Oral Diagnosis 89 MATERIALS AND METHODS Cases were collected from private and public laboratories. The total number of cases collected was 171 cases. For all cases, the slides were collected and reviewed. The cases were histologically classified according to the WHO classification7 . The following parameters were evaluated and analyzed: age incidence and distribution versus histological type, histological type versus various salivary gland anatomical sites, and the reverse relationship of anatomical sites versus histological typing laterality. Ultimately, results were compared to other national and abroad studies. RESULTS The total number of collected cases was 171. Benign tumors made up 141 cases, or 82.5% of total number of cases, while malignant cases were 30 cases, constituted 17.5 % of cases. Age incidence is shown in (Table 1), where age was higher in females over males with a ratio of 1.4:1, both benign and malignant tumors, with a ratio of 1.3:1 and 2.3:1 respectively. The peak incidence for benign tumors was in the sixth decade and for malignant tumors in the seventh decades for both males and females. No case in this series developed in the pediatric age group, age range was 15-91 years. There was no significant difference in the incidence of right versus left salivary gland tumors. Two cases were bilateral, both were Warthin’s tumor. In regard to benign tumors, benign mixed tumor was the most common tumor type, with 102 cases, making up 59.7% of cases, the mean age was 49.4 years (Table 2).Age range was between 15 and 90 years. Eighty one cases developed in the parotid, 13 in the submandibular and 8 in minor salivary glands. Warthin’s tumor was the second most common benign salivary tumor, with 27 cases (15.8%), mean age 67.2 years, age range 49-91. All other benign tumor types were 12 cases (7%), the mean age 64.8 years and age range 44-77. Seven cases were in the parotid gland and 5 in minor salivary glands. The most common was basal cell adenoma with 8 cases; all were females, with a mean age of 66 years. Five cases were in the parotid and 3 in the minor salivary glands. Other benign tumors included 3 cases of oncocytoma and 1 case of canalicular adenoma. The most common malignant tumor was adenoidcystic carcinoma 7 cases (Table 3), 5 of them were in the minor salivary glands, while 2 cases were submandibular. No cases were seen in the parotid gland. Five cases of acinic cell carcinoma were seen, 4 of them in the parotid. Also five cases of pleomorphic low grade adenocarcinoma, all were in the minor salivary glands. Three cases of mucoepidermoid carcinoma and 4 cases of malignant lymphoma were seen. Other types of malignancy collectively accounted for 6 cases. The parotid gland was the most common site of salivary tumors, with 123 cases (Table 4). However, only 9 cases (7%) in this series were malignant. According to Table-4, Benign tumors were 114 cases, or 93%, the most common type was pleomorphic adenoma, 81 cases (66%), followed by Warthin’s tumor 26 cases (21%). Other benign tumors were rare. Submandibular gland tumors were 20 cases in this series, 13 benign, all pleomorphic adenomas, and 7 malignant, so malignant risks is higher than the parotid gland. Sublingual gland tumors were rare, 2 cases were diagnosed, both malignant. While minor salivary gland tumors were 26 cases, malignancy 12 cases, most commonly adenoidcystic carcinoma and pleomorphic low grade adenocarcinoma. Table 1: Age and gender distribution and percentage of salivary gland neoplasm Age(years) Benign Malignant Males Females Total Males Females Total 11-20 3 4 7(5.0%) 0 0 0 21-30 5 4 9(6.4%) 0 2 2(6.7%) 31-40 7 7 14(9.9%) 0 1 1(3.3%) 41-50 10 11 21(14.9%) 2 1 3(10%) 51-60 14 20 34(24.1%) 3 5 8(26.7%) 61-70 11 19 30(21.3%) 4 7 11(36.6%) 71-80 9 10 19(13.4%) 0 5 5(16.7%) 81-90 3 3 6(4.3%) 0 0 0(0%) 91-100 0 1 1(0.7%) 0 0 0(0%) Total 62(44.0%) 79(56.0%) 141(100%) 9(30%) 21(70%) 30(100%) J Bagh College Dentistry Vol. 26(1), March 2014 Salivary gland Oral Diagnosis 90 Table 2: Tumor types mean age, standard deviation and age range, with anatomical site distribution Sal. gland anatomical site Age Range Mean Age±S.D. Number Tumor types Minor Sublingual Submand Parotid 81 13 --- 8 15-90 49.4±17.3 102(59.7%) Pl.Ad. 26 --- --- 1 49-91 67.2±7.7 27(15.8%) Warthin's 7 --- --- 5 44-77 64.8±8.4 12 (7.0%) Benign 9 7 2 12 24-80 59.9±13.2 30(17.5%) Malignant 123 20 2 26 15-91 55.1±14.4 171(100%) Total Table 3: Malignant salivary gland tumors: Histological types vs. age, sex and anatomical site Minor Sublingual Submand Site Parotid Sex F:M Mean Age Case Number Tumor type 5 --- 2 ---- 5:2 60 7(23.3%) Adenoidcystic 1 4 4:1 55 5(16.7%) Acinic 1 2 1:2 70 3(10.0%) Mucopeidermoid 5 4:1 53 5(16.7%) PLGA 2 0:2 58 2(6.7%) Pl. adenoca. 1 0:1 59 1(3.3%) Basal cell ad. 1 1:0 69 1(3.3%) Epi.myoep. ca. 1 1:0 26 1(3.3%) Adenoca.NOS 2 2 4:0 74 4(13.4%) Lymphoma 1 1:0 60 1(3.3%) Metastastatic 12 2 7 9 21:9 30(100%) Total Table 4: Salivary gland tumor case distribution according to gland site Total Tumor types and % per site Salivary Gland Malignant Benign Warthin Pl.adenoma 123(100%) 9(7.3%) 7(5.7%) 26(21.1%) 81(65.9%) Parotid 20(100 %) 7(35%) ----- ----- 13(65%) Submandibular 2(100%) 2(100%) ----- ----- ---- Sublingual 26(100%) 12(46.2%) 5(19.2%) 1(3.8%) 8(30.8%) Minor 171(100%) 30(17.5%) 12(7.0%) 27(15.8%) 102(59.7%) Total DISCUSSION Salivary gland tumors are interesting, because of their uncommon incidence in the routine pathology practice and their varied histology. This variation resulted in their complex and constantly changing classifications. Currently, the WHO classification is most widely used, which stresses mainly on the distinction between benign and malignant tumors7. Age incidence showed peak value in the sixth and seventh decades (Table 1), which is slightly higher than other studies, with no significant difference. Incidence was higher in females than males in most of salivary tumor types. The exception was Warthin’s tumor, more common in males. This is in concordance with other studies9. Histological typing of this series revealed that benign tumors were much more common, the most common type in our series was pleomorphic adenoma, 102 cases of total 171 cases collected(or 59.7%), most of the cases are in the parotid gland. The second most common tumor was Warthin’s tumor with 15.8% (27 cases); cases were seen almost exclusively in the parotid gland. The same result was seen in other studies 3,5,15. Other benign tumors were much less common, so a total of 12 cases (7%) were collected, 8 cases were basal cell adenoma. There is some variation between studies in regard to the incidence of benign salivary tumors, and which of the types are more common, whether canalicular11 or basal cell adenomas22. A probable cause for this discrepancy is the low incidence rate of these tumors resulting in small number of cases in many of the studies, including ours. Malignant tumors were 17.5%(30 cases), most commonly adenoidcystic carcinoma, matching some studies 8, and pleomorphic low grade carcinoma. Cases of mucoepidermoid carcinoma were seen less in this series. The parotid gland was the most common site of salivary gland tumors, with 123 cases, which outweigh the mere size and weight difference11. Most of the tumors were benign, as most other studies 4,9. Pleomorphic adenoma was the most J Bagh College Dentistry Vol. 26(1), March 2014 Salivary gland Oral Diagnosis 91 common tumor type, then Warthin’s tumor and other benign tumors. Malignant tumors were seen in 9 cases, slightly less than other studies. The most common parotid malignant tumors in our series were acinic cell carcinoma, mucoepidermoid carcinoma and adenocarcinoma, matching other studies. Submandibular gland tumors were less common, mostly benign. Minor salivary gland tumors were also less common, but with 46% malignancy. Immunohistochemical markers were used in most of the malignant tumors and some of the less common benign tumors, to help in the differential diagnosis and to confirm diagnosis. The most commonly used markers were AE1/AE3, actin, S-100, CK-5/6, CK -7, CD-117 and Ki-67. Other uses of markers in cases of specific diagnoses as in suspected lymphoma or metastatic tumors. 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