Introduction
Only 3% to5% of all salivary gland neoplasms occur in children and adolescents [
1,
2]. Two types of neoplasms are found in the salivary glands of pediatric age group patients: neoplasms of epithelial or parenchymal origin and neoplasms of mesenchymal or interstitial origin. The vast majority of the mesenchymal neoplasms occurring in the parotid gland are vasoformative, that is, hemangiomas [
1], while the most common types of salivary gland neoplasms of epithelial (parenchymal) origin are pleomorphic adenomas and mucoepidermoid carcinomas.
Most of these epithelial neoplasms are found in the parotid gland; only a limited number of cases occurring in the minor glands of children and adolescents have been well-documented [
2]. In fact, a review of the literature revealed only 40 well-documented cases of benign minor salivary gland tumors in this age group [
3‐
28]. Therefore, the purpose of this retrospective analysis was to investigate the clinical features and biologic behavior of a series of benign epithelial minor salivary gland neoplasms occurring in children and adolescents, aged 19 months to 18 years.
Discussion
We attempted to outline the clinical features and biologic behavior of benign neoplasms arising from minor salivary glands in children and adolescents. It is acknowledged that there are limitations to the interpretation of data from a retrospective study such as this. For example, the clinical findings and other pertinent information recorded on submitted pathology request forms are unfortunately highly variable and often lack complete information and the same is true for reported cases.
While more pediatric cases have been reported cumulatively in other published salivary gland series, any correlation between patient-specific details and the clinical lesion cannot be made. The approach of our study limits the number of accepted cases, but yields more clinically relevant information. The patients in the LSUSD series were only from the state of Louisiana, thus representing patients from a single geographic area and a single institution experience. The cases accepted from the literature review represent a more global pediatric population, including Hispanic and Asian children, who were not represented in our LSUSD series. Since the socioeconomic status of the children was not known in our study, the association of socioeconomic status to the incidence as well as prognosis of the lesions could not be explored.
Epithelial neoplasms originating in the minor salivary glands account for approximately 15% of all salivary gland neoplasms [
29,
30]. In the current LSUSD series, 2.3% of the benign epithelial minor salivary gland neoplasms occurred in patients below 19 years of age, which is in close agreement with the series of Waldron
et al. and Kusama
et al. who found an incidence of 3.1% and 4.6%, respectively [
30,
31].
A PA is composed of a wide spectrum of epithelial and mesenchymal tissue derived from cells with ductal and myoepithelial features and it is by far the most common salivary gland neoplasm in children [
1,
32]. Although it is commonly stated that neoplasms of minor salivary glands rarely occur prior to the second decade [
33], we found that, when combining the well-documented literature cases with our LSUSD cases, 28.6% of PAs arising from minor salivary glands in children occurred during the first decade of life. Cumulative data assessment revealed a female gender predilection of 2.8:1 and a predilection for the hard and/or soft palate (69.1%).
Information regarding the biologic behavior of minor salivary gland PAs in children and adolescents is, in general, underprovided. The risk of recurrence of PAs has been speculated to be lower if arising from the minor salivary glands rather than the major glands [
34]. In fact, Chau and Radden reported follow-up on 27 intra-oral PAs in patients over a wide age range (second to eighth decade) treated by excisional biopsy and found no recurrences (mean follow-up period 5.3 years), including in two neoplasms which were incompletely excised and two where the tumor extended to the surgical margins [
35]. Additionally, Budnick reported a PA in the upper lip of a 17-year-old black woman which was incompletely excised and had no evidence of recurrence on 3 years of follow-up [
7]. The recurrence rate of PAs in minor salivary glands of children in our study was 13.0%, which is of clinical significance. This recurrence rate was recorded from 24 well-documented pediatric and adolescent PAs with an average follow-up duration of 9.2 years. The three recurrent PAs involved the hard palate, with one causing bone resorption, one with no bone involvement [
19] and one case did not state if there was bone involvement [
3]. The assessment for possible causes of recurrence in the three cases varied. The size of the lesion was recorded in two of the three recurrent cases; both were 2.0cm or less in diameter. With regards the surgical margins of these recurrent cases, Byars
et al. [
3] did not comment on the state of the surgical margins, Shaaban
et al. [
19] reported the surgical margins in the definitive excision were free of tumor and, in the LSUSD case, the margins could not be definitively determined as treatment consisted of tumor excision with curettage of the involved palatal bone, making assessment difficult to evaluate with certainty.
In the cases with no recurrence, the surgical margins were not described with any degree of certainty, making it impossible to adequately explore margin involvement as an absolute predictor of recurrence. However, in four of the newly reported LSUSD cases with follow-up of 8 months, 5 years, 8 years and 24 years, the surgical margins were free of tumor. Of those, the case that was followed for 5 years had a focus of tumor in the capsule, but did not recur.
A myoepithelioma is a benign tumor composed of various proportions of plasmacytoid, spindle, epithelioid, and clear cells that exhibit myoepithelial differentiation and generally lack ductal differentiation [
36]. While some investigators consider it to be a distinct entity, others believe that it represents one end of the spectrum of the PA and is therefore a variant of PA [
27,
36]. Regardless of its specific classification, it possesses a similar if not identical biologic behavior to a PA [
36]. There are too few cases reported to define its characteristics in the first and second decade of life. However, based on four cases, it does appear to possess similar clinical characteristics and biologic behavior to a PA ( Additional file
1: Table S2).
Minor salivary gland cystadenomas are rare benign well-circumscribed tumors composed of cystic and papillary structures lined with cuboidal or columnar ductal epithelium that appears benign on histology [
30]. The average age of incidence is 57 years; they are exceedingly rare below the age of 20 years. The youngest patient reported to have a cystadenoma was 12 years old [
7]. Lastly, a sialadenoma papilliferum is a benign exophytic papillary tumor arising from the salivary gland duct. It too is rare below the age of 20 years with only one case reported, in the upper lip of an 18-year-old man [
24].
Although minor salivary gland tumors are decidedly uncommon in the first two decades of life, they should be considered in the clinical differential diagnosis for any submucosal nodule or mass in a salivary gland-bearing area. In this study, the average duration of 16 PAs with reliable historical information was 2.1 years before definitive diagnosis. As with any benign or malignant tumor, early definitive diagnosis and appropriate treatment afford a better chance for a cure. This is especially important for minor salivary gland tumors because a high percentage are malignant [
1,
2].
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
PR and RBB reviewed the clinical and histopatholgic data from the selected cases and the literature, and analyzed the data. RBB reviewed histopathologic microslides and confirmed the diagnosis for the cases from the LSUSD series. Both authors read and approved the final manuscript.