A clinicopathological study of salivary gland tumors

Background: To evaluate tumors involving major and minor salivary glands, histopathology is an essential diagnostic method and is the gold standard. This study was carried out to know the incidence of salivary gland tumors, their clinical presentation and diverse morphological patterns. Materials and Methods: A prospective cross-sectional descriptive study was carried out over a period of two years in the department of pathology, Yenepoya Medical College hospital, Mangalore.Data regarding patient demographicswas also recorded.All the epithelial salivary gland tumors were classified according toWHO (2005) histological classification. Results: In the present study, a total of 65 cases of salivary gland tumours was found and an age range of 10-79 years was observed. The most common site affected was the parotid gland 47 (72.31%).Among the 48 (73.85%) benign tumors, pleomorphic adenoma 40 (61.54 %) was most commontumor and remaining 17(26.15%) cases were malignant, of which mucoepidermoid carcinoma 8 (12.31%) was frequently observed. Conclusion: This study highlights the usefulness of histopathologicalstudy of salivary gland tumors with various morphological patterns of benign and malignant salivary gland tumors, which are of utmost value in planning the further management of the patient.


Introduction
Salivary gland tumors show diverse morphological patterns between various tumor types and on rare occasions with in the same tumor, thus causing interpretation challenges among the pathologists [1].
Studies from different countries have shown geographic variations in the relative incidence andclinicopathological discrepancies between benign and malignant salivary gland tumors [2]. The annual incidence worldwide ranges from 0.4 to 13.5 cases per 1,00,000 people. Majority of salivary gland tumors show a female preponderance [3].
Although the aetiology of salivary gland tumors is unknown, literature reports certain risk factors implicated in causation of these tumors. Among  Patients exposed to head and neck radiation for treatment showed increased incidence. Certain occupations such as asbestos mining, manufacturing of rubber products and plumbing (exposure to metals) and working in the automobile are other risk factors [4,5,6]. Clinically, salivary gland tumors present as a slow growing mass, however, rapid growth, pain, nerve involvement and fixation to skin or underlying muscles indicate malignancy [7].
Benign tumors commonly occur in the age group of 30-70years whereas peak incidence of malignant tumors is in the 6th to 7th decades. Malignant tumors are more frequent in women than men [8]. Among the pediatric age group, 35% of salivary gland tumors are considered malignant [2].
Majority of Epithelial tumors are benign (75%) among which pleomorphic adenoma is the most common tumor and constitutes about 65% of all salivary gland neoplasms. Among the malignant neoplasms, mucoepidermoid carcinoma is the commonest. Of the major salivary glands, parotid gland isfrequently involved [4,5].

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 533 | P a g e The distribution of salivary neoplasm's between sites has followed a rule of 100:10:10:1 ratio for parotid, submandibular, minor salivary glands and sublingual tumors, respectively [9].

Aims & Objectives
• To study the age, sex and site distribution of the salivary gland tumors regarding their origin from major and minor salivary glands.
• To study histomorphology of salivary gland lesions and to classify benign and malignant lesions according to World Health Organisation (WHO) 2005 Classification [3].

Material and Methods
Study design: A prospective cross-sectional descriptive study was carried out over a period of two years in thedepartment of pathology, Yenepoya Medical College from patients admitted to Yenepoya Medical College, hospital Mangalore.

Sample size calculation
Formula for calculation of sample size [10] Estimate sensitivity: ≥

Results
A total of65specimens of salivary gland tumors werereceived during the study period of which, 48 (73.84%) were benign tumors and 17 (26.15 %) were malignant tumors. The age incidence of salivary gland tumors in the present study ranged from 10 to 79 years and the male to female ratio of distribution of salivary gland tumors was 1:1.03 (Table 1). Male to female ratio in adenomas and carcinomas was 1:1.25 and 1:0.5 respectively.
History of tobacco chewing (30.36%), alcohol consumption (29.23%) and smoking (23.07%) was noted. The most common presenting complaint was a localised swelling. Only a small percentage (18.46%) of patients also presented with pain along with swelling.
The parotid gland 47 (72.31%) was the commonest site for various tumors, notable exception being adenoid cystic carcinoma, adenocarcinoma NOS, clear cell carcinoma NOS, which showed predilection for the minor salivary glands 15 (23.08%). Two cases (4.62%) involvedthesubmandibular gland. However, no case was seen in the sublingual gland. Histology of Pleomorphic adenoma revealed classical histological features. Five cases showed squamous metaplasia of the ducts with epithelial pearl formation (figure 1) and one case showed adenoid cystic -like areas.
Seven cases of warthin'stumor accounted for 10.77% of total, occurring in an age range of 50 and 59 years, frequent in males. In the present study, one case of oncocytoma was found in a 40 year female patient involving the parotid gland and showed typical histological features.

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 534 | P a g e    Eight cases of mucoepidermoid carcinoma accounted for 12.31% of total, occurring in an age range of 50-59 years with a male predominance. Parotid gland was the commonest site followed by minor salivary glands and showed typical histological features ( figure 1). There was a higher incidence of low grade tumors and only one tumor with intermediate grade showed lymph node metastasis. Four cases of adenoid cystic carcinoma accounted 6.15% of total,with an age range of 50-59 years and involving mainly males and minor salivary glands. Microscopically, cribriform arrangement was the predominant pattern observed and two cases showed perineural invasion and one case showed muscle invasion.
One case of Acinic cell carcinoma was observed in a 45 year female affecting the parotid gland with characteristic morphological features. One case of clear cell carcinoma, NOS was observed in a 52 year male, involving the minor salivary gland with lymph node metastasis and one case of salivary duct carcinoma was seen in a 60 year male affecting theparotid gland.
A 58 year male, presented with morphological features of adenocarcinoma, NOS involving theminor salivary gland. A rare case of squamous cell carcinoma arising in warthintumor was seen in a 65 year male, involving the parotid gland. Microscopically, the tumorshowed two components, the first component showed cystic spaces and papillae lined by double layered cuboidal to columnar epithelium with benign cytological features. The second component showed nests and sheets of pleomorphic cells with moderate amount of eosinophilic cytoplasm and centrally placed pleomorphic nuclei (figure 2).

Discussion
The mean incidence of salivary gland tumorsper year at our hospital was 33 cases which is similar to the study by Vuhahula EAM [9] however, lower incidence of these tumorswas reported in the literature [1,3] [2,11] wherein malignant tumors were predominant.
The mean age observed was 40 years with an age range of 10 to 79 years. Benign tumors were common in age group of 40 to 49 years and the peak age incidence for malignant tumors was 50 to 59 years; which is in accordance with the observation by Chatterjee et al [1] wherein benign tumors occurred at a lower age group as compared to malignant tumors. A slight female preponderance (33 cases among 65) with a sex ratio of 1:1.03 was noted. Our findings were in similar to the previous studies [15].
A female predominance was observed among benign tumors supporting the findings of previous studies [9,15]. However; other authors [16,17] have observed a male predominance. A male predominance was seen in malignant tumors of salivary glands in our study which was similar to the previous studies [8,11,12].

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 536 | P a g e than the submandibular gland in our study as well as in previous studies [1,12,13]. However, in other series [14,15] the sequence of involvement of the tumors was parotid gland followed by submandibular gland and minor salivary glands. Palate was the commonest site involved, among the minor salivary glands, which is similar to the study reported in literature [4].
Pleomorphic adenoma was the most common tumor accounting for 40 (83.33%) of benign tumors and 61.54% of all tumors. This is similar to the results of other studies [5,12,13,18]. The peak age incidence of pleomorphic adenoma was 40-49 years with a female preponderance. These findings are similar to De Oliveria FP et al [19].
No case was recorded in the sublingual gland. Five cases showed squamous metaplasia of the ducts with epithelial pearl formation and in one case, adenoid cystic-like areas was seen. Similar observations have been recorded by Ellis et al [6].
Three cases showed fatty change and one case was of a recurrent pleomorphic adenoma. Calcification and ossification were not observed in the present study. Chondromyxoid areas showed strong metachromatic reaction with toluidine blue and stained strongly with alcian blue.
Peak age distribution was between 50 and 59 years which correlates with other studies [14] where as Ito et a [13] showed an higher age incidence. A male predominance in all studies is similar to the present study, probably related to the environmental factor. Parotid gland was the only gland involved which was similar with the results obtained by other studies [12,17]. No case was seen in minor salivary gland.  [13]. The present study showed an higher incidence of mucoepidermoid tumors which was similar to the findings ofIto et al [13]. Other studies [1,9,12,19] showed a lower incidence as compared to the present study. The peak incidence was 50-59 years which was similar to study of De Oliveria FP et al [19].
Our study showed male predominance as compared to study done by De Oliveria FP et al [19] which showed a female predominance. Parotid gland was frequently involved which correlates with other studies [2,12] Adenoid cystic carcinoma constituted 4 (6.15 %) of all tumors of salivary glands and 23.53% of malignant tumors. Our study showed a male predominance whereas the other studies [19] showed a female predominance. Minor salivary glands was commonly involved which was similar to other studies [12,19].
One case of clear cell carcinoma, NOS was observed in a 52 year male, accounting for 1.54% of all salivary gland tumorswhich was located in the minor salivary gland which correlates with the study by Yang S et al [20].
One case of salivary duct carcinoma was seen in a 60 year male, comprising 1.54% of all tumours involving the parotid gland, which correlates with the study of Gonzalvez-Alva P etal [21].
One case of adenocarcinoma, NOS was seen in a 58year male, accounting for 1.54% of all tumors located in minor salivary gland which was similar to the study observed by Ashkavandi ZJ [22].
A single case of acinic cell carcinoma was seen in 45 year female, accounting for 1.54% of all tumor slocated in parotid gland which was similar to the findings reported in literature [1,12].
The present study revealed a peculiar case of squamous cell carcinoma arising in warth in'stumorin a 65-year old male, involving the parotid gland which accounted for 1.54% of all salivary gland tumors and 5.88% of malignant tumors. Until now only 32 cases are reported in the literature [23].

Conclusion
It is evident from the present study that the histopathological examination of salivary gland lesions is the most important method to differentiate between benign as well asmalignant tumors and also in predicting the incidence. It is also useful in typing, staging and grading of malignant lesions.

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 537 | P a g e

What is new in this study?
Our distribution of histomorphological spectrum of epithelial tumors salivary gland is similar to most of the otherstudies worldwide as stated in discussion. However, in our study, minor salivary glands (23.08%) was more likely to be involved as compare to the submandibular glands (4.62%.).
A rare case of squamous cell carcinoma arising in Warthin's tumor was seen in a 65 yearold male patient, located in parotid gland was noted in our study.

Contribution by different authors
• Dr. Cryslesaldanha contributed toliterature review, data acquisition and analysis, statistical analysis, manuscript preparation and editing.
• Dr. ParasappaYaranal contributed to study designing, manuscript preparation and editing.
• Dr. Krishnaraj Upadhyaya contributed to study designing, data analysis.