Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study

The total number of SGT was 5,739. Of these, 65% were benign tumours (n = 3,751), and 35% (n = 1,988) were malignant (Table 1). There was a slight female predilection (54%, n = 3,093) compared to 46% male patients (n = 2,646). In both benign and malignant tumours, a higher incidence was noted in patients between the fourth to seventh decade of life accounting for 69% of the cases (Fig. 2). Most of the SGT involved the major glands 68% (n = 3,910) with 32% (n = 1,829) involving the minor glands. Parotid gland was the most common site of involvement (59%, n = 3,406). Within the minor glands, the palate was the most common location (60%, n = 1103) (Fig. 3).

The most common benign tumour was pleomorphic adenoma accounting for 70% (n = 2621) followed by Warthin tumour (17%, n = 623), basal cell adenoma (3%, n = 172), canalicular adenoma (2%, n = 96), cystadenoma (2%, n = 81), myoepithelioma (2%, n = 62) and oncocytoma (1%, n = 43). All other rare benign tumours including sebaceous adenoma, ductal papilloma, sialoadenoma papilliferum and unclassified salivary tumours comprised 1% (n = 53) of benign tumours (Table 1).

Comparison of the different geographical locations showed that pleomorphic adenoma was the most common benign tumour across all centres with a different range of incidence between centres ranging from 64% in Europe to 87% in South America. Warthin tumour was the second most common tumour for most of the centres with a range of incidence between 1% (African cohort) to 30% in the data from Europe. This was followed by basal cell adenoma accounting for 5% of the UK and 3% of both the European and African cases (Fig. 4).

For benign tumours, there was a slight female predilection (54%, n = 2035) compared to males (46%, n = 1716).

The average age for benign tumours was 52 years with a female average age of 51.7 and male average of 52.4 years. The age range was very wide (1–98 years). The most commonly affected age group was 40–59 which accounted for 38% of benign tumours (n = 1440) comprising 18% of male (n = 692) and 20% female (n = 748) patients respectively. The least affected age group was patients under 18 years of age who accounted for only 2% (n = 82) of benign tumours (Fig. 5).

Benign tumours presented in both major and minor glands with the majority of tumours involving the parotid gland (70%, n = 2582), followed by minor glands (23%, n = 899), submandibular gland (7%, n = 265) and less than 1% (n = 5) involving the sublingual gland. Within the minor glands, the palate was the most common location (58%, n = 519). followed by upper lip (20%, n = 178) and buccal mucosa (12%, n = 104). Other sites included the floor of mouth, gingiva, lower lip, tongue and labial mucosa which altogether comprised 10% (n = 98) of benign tumours (Fig. 3).

The majority of pleomorphic adenomas involved the parotid gland (67%, n = 1736), followed by minor glands (25%, n = 645) and submandibular gland (8%, n = 217). Only four cases (less than 1%) were identified in the sublingual gland. In the minor glands, (67%, n = 433) of the pleomorphic adenomas involved the palate, followed by upper lip and buccal mucosa (12%, n = 77, 11%, n = 69) respectively. Warthin tumours were exclusive to the parotid gland (n = 623). Most of the basal cell adenomas were reported in minor glands (55%, n = 95), followed by parotid gland (40%, n = 69) and submandibular gland (5%, n = 8). In the minor glands, the upper lip was the most common minor gland site for basal cell adenomas (49%, n = 47) (Fig. 6).

The most common malignant tumour was mucoepidermoid carcinoma accounting for 26% of the malignant diagnoses (n = 508) followed by adenoid cystic carcinoma (17%, n = 336), polymorphous adenocarcinoma (12%, n = 238), carcinoma ex pleomorphic adenoma (11%, n = 215), acinic cell carcinoma (9%, n = 185), adenocarcinoma NOS (7%, n = 145), salivary duct carcinoma (4%, n = 79), secretory carcinoma (3%, n = 51), epithelial myoepithelial carcinoma (2%, n = 47), myoepithelial carcinoma (2%, n = 42) and basal cell adenocarcinoma (2%, n = 41). All other rare malignant tumours including, carcinosarcoma, clear cell carcinoma, cystadenocarcinoma, intraductal carcinoma, lymphoepithelial carcinoma, neuroendocrine carcinoma, oncocytic carcinoma, poorly differentiated carcinoma, sebaceous carcinoma, sialoblastoma and squamous cell carcinoma accounted for 5% of malignant tumours collectively (n = 101) (Table 1).

Mucoepidermoid carcinoma was the most common malignant tumour in the majority of centres. The only exception was Africa, where adenoid cystic carcinoma was the most common tumour. Overall, adenoid cystic carcinoma was the second most common malignant SGT for most of the centres with a range of incidence of 10% in UK and 33% in African centres. (Fig. 4).

There was a slight female predilection for malignant SGT (53% of malignant cases, n = 1,058) compared to males (47%, n = 930).

The average age for malignant tumours was 56 years with a female average of 54.4 and male average age of 57.4 years. As for benign tumours, the age range was very wide (1 to 106 years). The average age for malignant tumours was significantly higher than benign tumours (p < 0.00001). The most affected age group was 60 to 79-year-old accounting for 36% (n = 708) of malignant tumours, comprising 17% male (n = 340) and 19% female (n = 368) patients respectively. Similar to the benign tumours, the least affected age group was patients under 18 years of age (4%, n = 69) (Fig. 7).

Minor glands were the most common site for malignant tumours (47%, n = 930), followed by parotid gland (42%, n = 828), submandibular gland (10%, n = 189) and sublingual gland (2%, n = 41). Within the minor glands, the palate was the most common location (63%, n = 584) followed by buccal mucosa (12%, n = 114), gingiva (8%, n = 78) and tongue (6%, n = 51). Other rare sites included the floor of the mouth, labial mucosa, upper and lower lip, which accounted altogether for 11% of malignant diagnoses (n = 103) (Fig. 3).

The majority of mucoepidermoid carcinomas involved the minor glands (56%, n = 285), followed by the parotid gland (34%, n = 173), submandibular glands (7%, n = 36) and sublingual glands (3%, n = 12). In the minor glands, 60% (n = 172) of the mucoepidermoid carcinomas occurred in the palate. Most of the adenoid cystic carcinomas (60%, n = 203) involved the minor glands, followed by parotid (26%, n = 87), submandibular (10%, n = 33) and sublingual (4%, n = 13) glands. Within the minor glands, 70% of adenoid cystic carcinomas presented in the palate (n = 141). Most polymorphous adenocarcinomas presented in the minor glands (98%, n = 234), with occasional cases in the parotid gland (2%, n = 4). In the minor glands, the palate was the most common site for the polymorphous denocarcinomas accounting for (72%, n = 170). The majority of carcinoma ex pleomorphic adenomas involved the minor glands (61%, n = 132), followed by the parotid gland (32%, n = 70), submandibular gland (7%, n = 13) and only one case was reported in the sublingual gland. In the minor glands, 62% (n = 82) of carcinoma ex pleomorphic adenomas occurred in the palate. Parotid gland was also the most common site for acinic cell carcinoma (65%, n = 120), followed by the minor glands (23%, n = 42), submandibular gland (9%, n = 17) and sublingual gland (3%, n = 5). The palate was the most common minor gland site for acinic cell carcinomas (50%, n = 21) (Fig. 8).

Our results show that pleomorphic adenoma was the most common benign tumour; this is consistent with prevalence rates reported in the literature [4, 5, 8, 10, 12, 14, 18, 21]. Comparison of incidence between centres showed pleomorphic adenoma to be the most common benign tumour in all geographical locations included in the study ranging from 64% in Europe to 87% in South America. Warthin tumour was the second most common benign tumour which is also similar to earlier demographical studies [8, 11, 18, 23‐25]. The present study shows that basal cell adenoma was the third most common benign tumour; however accurate comparisons between previous studies of basal cell and canalicular adenomas is difficult as older studies tended to combine these into a single group of monomorphic adenomas [7, 21, 26]. Curiously no basal cell adenomas were reported in Asia and South America, whereas they comprised 5% of benign SGT in the UK and 3% in both European and African centres. This could be related to the smaller number of cases gathered from these centres or the lower incidence as previous studies have shown that basal cell adenoma is not within the most common five benign tumours in these regions [22, 23, 27]. The possibility of variation in diagnostic criteria can also not be excluded.

In the literature, benign tumours have been reported to occur more in younger and female patients [23]. Our study shows a similar finding where benign tumours appeared to be more common in female patients; however, the average ages were quite similar (51.7 years in female compared to 52.4 in male patients).

The majority of the benign tumours were located in the parotid gland (70%), followed by minor [23%] and submandibular (7%) glands. We found only five benign cases (less than 1%) involving the sublingual gland. Similar findings were seen in other older SGT studies with some variations in distribution across different anatomical sites [4, 10, 14, 18, 21, 23].

The most common location for the pleomorphic adenoma was the parotid gland (67%), followed by minor glands and the submandibular gland (25% and 8% respectively. This observation was consistent with previous reports [4, 11, 13, 18, 23]. Warthin tumour was seen exclusively in the parotid gland (100%). This observation is similar to other studies suggesting that this tumour exclusively involves parotid gland [11, 13, 23]. Basal cell adenomas were reported in minor glands in 55% of the cases and about 40% were seen in the parotid gland. Accurate comparison with the literature was not possible due to the small number of reported studies and cases.

Mucoepidermoid carcinoma was the most common malignant salivary gland tumour accounting for 26% of diagnoses; this is in agreement with previously reported prevalence rates worldwide [4, 8, 21, 23]. We found that mucoepidermoid carcinoma was the most common tumour in all centres except Africa where adenoid cystic carcinoma (33%) was the most common malignant diagnoses. Bello et al., 2012, reported somewhat similar findings with adenoid cystic carcinoma as the most common malignant tumour in their 2012 study [18]. However, this was limited to data from two centres and did not examine the geographical differences in depth. The second most common malignant diagnosis for most of the centres in our study was adenoid cystic carcinoma accounting for 17% of all malignancies similar to other reports [5, 8, 11, 12, 21, 23] although some variations in its incidence have been reported. For mucoepidermoid carcinoma and adenoid cystic carcinoma molecular techniques such as FISH, PCR and NGS can help with the final diagnosis however, these tests are not widely available and/or affordable around the world [28]. Even in the UK, routine testing for MAML2 rearrangement in mucoepidermoid carcinoma has been the norm only since 2015–2016 with FISH the most widely available test, whereas MYB testing in adenoid cystic carcinoma is still only available in a handful of specialist centres. This is shown by the fact that within our cohort, a limited number of cases (2015 onwards) were tested (50 mucoepidermoid carcinomas and 15 adenoid cystic carcinomas). The next most common diagnoses were polymorphous adenocarcinoma and carcinoma ex pleomorphic adenoma accounting for 12 and 11% of diagnoses respectively. In fact, there is significant variability in the literature about the incidence of these two entities which is perhaps related to small and unicentric cohorts. Similarly, acinic cell carcinoma was the fifth most common diagnosis (9%) although, some studies have reported it as the third most common malignant SGT [4, 5] however these findings were also based on a small cohort size from only one centre. Adenocarcinoma NOS was the next most common diagnosis accounting for 7% of cases which may not reflect the exact incidence of this entity as development of ancillary molecular and sequencing techniques has led to more specific diagnoses and reduction in the use of this diagnosis [29].

Malignant SGT are more likely to occur in older patients [22, 23]. Our study shows similar results where the average age for malignant tumours was significantly higher than benign tumours (p < 0.00001). Malignant SGT involved the parotid gland in about 42% of cases, which aligns with known literature [11, 14]. The incidence of malignant tumours in minor salivary glands was slightly higher than the parotid gland (i.e. 47%), highlighting the importance of considering malignant SGT in differential diagnoses [14, 30]. In the present study, 42 out of 46 cases involving the sublingual gland were malignant tumours, which is similar to Tian et al.’s findings from 2010 where they reported 95% of sublingual tumours to be malignant [10].

The most common location for mucoepidermoid carcinoma was minor glands (56%), followed by parotid, submandibular and sublingual (34%, 7% and 3% respectively) glands which is in agreement with the findings of Jones et al.,2008 but in disagreement with other reports which have found parotid to be the most common site [11, 13, 23]. This could be due to the fact that a number of these cases were reported in specialist oral and maxillofacial pathology units (some of which usually only report intra-oral specimens) although many of the included centres also have expertise in head and neck (H&N) pathology.

Understanding the epidemiological landscape and distribution of histological subtypes of salivary gland tumours is crucial for a better diagnosis of this diverse and complex group of tumours. It would be useful for future studies to include more geographical locations as well as other H&N and ENT centres. It would also be useful to establish international datasets of these tumours for use by other researchers (whole slide image or research repositories) including histological reassessment and classification according to the most recent WHO criteria.