Salivary Gland Disorders in Pediatric Patients: A 20 Years’ Experience

Abstract

Salivary gland disorders are uncommon in children; they show a lower prevalence when compared to adults. The literature has a relative lack of information about the management and the different treatment protocols regarding these diseases. The aim of this research is to investigate the prevalence of both benign and malignant salivary gland disorders, focusing on diagnostic and therapy. An audit of patients diagnosed with salivary gland disorders was conducted from 2000 to 2020. 99 patients’ records were selected and analyzed: 51 males’ and 48 females’, age 10 ± 4 SD. Obstructive pathologies were the most frequently diagnosed (49 patients) followed by oncologic (21 patients), inflammatory (20 patients), rheumatologic (4 patients), malformative (3 patients) and infective disorders (2 patients). The parotid was the most affected major gland in 47 cases with a prevalence of diagnosis of juvenile recurrent parotitis (JRP) (40.4%), followed by the sublingual gland in 14 cases of ranula (100%) and the submandibular gland in 11 patients suffering from sialolithiasis (84.6%). Swelling was the most common symptom (75.7% of patients). Seven different neoplasms were documented. A greater prevalence of low-grade mucoepidermoid carcinoma among the malignant group (38.1% of oncologic cases) was noted. In regards to benign tumors, pleomorphic adenoma was the most common diagnosis (47.6% of cases). The symptoms and outcomes showed statistical significance concerning gender. Although salivary gland diseases in children and adolescents are rare, it is essential to observe and monitor all of the symptoms to intervene if necessary, as painless swelling is a symptom common from both benign and malignant diseases.

1. Introduction

Salivary gland disorders are rather infrequent in children and adolescents; the literature is relatively lacking in information about the management and the different treatment protocols regarding these diseases. Laskawi et al. [1] agree with the rareness of these disorders, emphasizing only 45 cases in children over a period of 34 years; while the Orvidas et al. [2] study showed a larger sample group, describing the treatment protocol of 118 children with swelling of the major salivary glands. The authors stated that pediatric parotid masses presented a variety of pathological diagnoses, including malignancy that could be treated only through timely evaluation and treatment [2].

The literature reports that the symptoms most commonly experienced by children are pain and swelling occurring minutes to several hours after a meal and gradually receding with time [3,4]. Most commonly, children’s parents are the main source of information regarding the clinical conditions of these patients. Since the incidence of these diseases is low and Maxillofacial Surgery Units are the main referral centers for the treatment of salivary gland disorders in children and adolescents, a retrospective investigation of our data seemed reasonable.

Therefore, this study aims to collect data from our tertiary referral center database to investigate the prevalence of both benign and malignant salivary gland disorders. The study focuses on diagnostics and therapy, thus offering clinicians useful information to improve children’s and adolescents’ care.

2. Materials and Methods

An audit of patients diagnosed with salivary gland disorders attending the Maxillo-Facial Surgery Department University of Campania “Luigi Vanvitelli” from 2000 to 2020 was conducted and approved by the local ethics committee (prot. 313, 23 October 2020) in accordance with the ethical principles of the Declaration of Helsinki (2002).

Clinical records regarding the pediatric salivary gland disorders were retrieved from the hospital’s database. The following data were extracted for each patient: age and gender, affected gland (parotid, submandibular, sublingual gland or minor salivary gland), leading symptoms, diagnosis according to the obstructive, infective, inflammatory, reumatologic, malformative or oncologic origins of the disorders, treatment, long-term outcomes within the report of healed patients, reductions in episodes and relapses if any. The data were anonymized prior to analysis.

Statistical Analysis

The statistical analysis was performed using Matlab Statistics Toolbox (The Math-Works Inc., Natick, MA, USA). The variables were described as absolute values and proportions. The chi-square test was used to analyze the proportions in different groups of patients. A p-value < 0.05 was considered to be statistically significant.

3. Results

99 patients’ records were selected and analyzed; the records were for 51 males and 48 females, age 10 ± 4 SD, with a minimum age of 2 and maximum age of 19. Obstructive pathologies were the most frequently diagnosed (49 patients) followed by oncologic (21 patients) and inflammatory disorders (20 patients). A total of 9% of the diagnoses were regarding Sjogren syndrome (4 patients), lymphangioma (3 patients) and epidemic parotitis (2 patients).

The parotid was the most affected major gland in 47 cases with a prevalence of diagnosis of juvenile recurrent parotitis (JRP) (40.4%), followed by the sublingual gland in 14 cases of ranula (100%) and the submandibular gland in 11 patients suffering from sialolithiasis (84.6%). Regarding the minor salivary glands, the most affected site was the lower lip, with the diagnosis of mucocele in 23 cases out of 25 (92%).

Our findings show a greater prevalence of females suffering from mucocele (54.2%), ranula (78.6%), mucoepidermoid carcinoma (66.7%) and sialolithiasis (63.6%); a predominance of the male sex was found in JRP (84.2%).

In regard to the leading symptoms, swelling was the most common symptom (75.7% of patients) except for those patients suffering from epidemic parotitis and Sjogren syndrome, who also showed pain and fever.

A subgroup analysis (male vs. female) showed that symptoms (swelling alone, swelling + pain or swelling + pain + fever) and outcomes (healed, relapses or reduction in episodes) were the only variables showing a statistical significance among the two groups with p < 0.05. In both groups, the most frequent symptom was swelling (90% vs. 63%) and the most frequent outcome was healing (81% vs. 61%). In male and female patients, the results of outcome vs. diagnosis, outcome vs. treatment and outcome vs. lesion site analyses showed no significant statistical differences.

The demographics are summarized in

Table 1. The patients’ general demographics.

Total Patients (n)		99
Sex (n)	Male	51
	Female	48
Age (mean ± SD) (min, max)		10 ± 4 (2–19)
Diagnostic group (n)	Obstructive	49
	Infective	2
	Inflammatory	20
	Reumatologic	4
	Malformative	3
	Oncologic	21
Affected Gland (n)	Parotid	47
	Submandibular	13
	Sublingual	14
	Minor glands	25

.

3.1. Obstructive Disorders

The most common diagnosis was mucocele (11 males, 13 females, age 10 ± 3), followed by ranula (3 males, 11 females, age 10 ± 3) and sialolithiasis (4 males, 7 females, age 12 ± 4). Swelling was shown to be the only symptom in this diagnostic group and patients were mainly treated with surgical excision (89.8%) and reached complete healing in 93.9% of cases. A sialoendoscopy for intraductal calculus removal was performed only in one patient (

Table 2. The obstructive diseases.

			Mucocele	Ranula	Sialolithiasis
Total patients (n)			24	14	11
Sex (n)		Male	11	3	4
		Female	13	11	7
Age (mean ± SD)			10 ± 3	10 ± 3	12 ± 4
Affected Gland (n)		Parotid	1	/	/
		Submandibular	/	/	11
		Sublingual	/	14	/
		Minor glands	23	/	/
Symptoms (n)		Swelling	24	14	11
Treatment (n)	Semi-conservative	Sialoendoscopy	/	/	1
	Surgical	Marsupialization	/	2	/
		Surgical excision	24	12	8
		Sialoadenectomy	/	/	2
Outcome (n)		Healing	24	14	8
		Relapse	/	/	3

).

3.2. Infective Disorders

Two cases of epidemic parotitis were diagnosed: one in a 3-year-old male and one in a 9 year-old-female. Antibiotic therapy was prescribed in both cases due to purulent drainage during the glandular massage (

Table 3. The infective, inflammatory and rheumatologic diseases.

			Epidemic Parotitis	Juvenile Recurrent Parotitis	Lynphoepithelial Sialoadenitis	Sjogren Syndrome
Total patients (n)			2	19	1	4
Sex (n)		Male	1	16	1	2
		Female	1	3	/	2
Age (mean ± SD)			6 ± 4	8 ± 4	11	7 ± 4
Affected Gland (n)		Parotid	2	19	1	4
Symptoms (n)		Swelling		1	1	/
		Swelling, pain	1	8	/	3
		Swelling, pain, fever	1	10	/	1
Treatment (n)	Conservative	Antibiotics	1	10	1	2
		Fans, antibiotics	1	2	/	/
	Semi-conservative	Sialoendoscopy	/	7	/	2
Outcome (n)		Healing	2	1	1	/
		Reduction of episodes	/	18	/	4

).

3.3. Inflammatory Disorders

Out of the 20 patients included in this diagnostic group, 19 were diagnosed with JRP (16 males, 3 females, age 8 ± 4) and one with lynphoepithelial sialoadenitis (1 male, age 11).

Regarding JRP, in 52.6% of cases, swelling, pain and fever were reported. Conservative treatment was prescribed in 63% of cases and 7 sialoendoscopy procedures were performed, resulting in a reduction of episodes in 94.7% of cases.

The single case of parotid lynphoepithelial sialoadenitis was treated with antibiotics and complete healing was reached (Table 3).

3.4. Rheumatologic Disorders

Four cases of Sjogren syndrome were diagnosed and treated (2 males, 2 females, age 7 ± 4). Two patients were treated with antibiotic therapy while two patients underwent sialendoscopic treatment with intraductal dilation and lavage. A reduction in acute episodes was accomplished in every patient (Table 3).

3.5. Malformative Disorders

Three male patients (age 9 ± 7) were diagnosed with lymphangioma. One case located in the submandibular gland was followed-up and went into regression; one case rising from a minor salivary gland of the tongue was excised; and the case located in the parotid gland was treated with partial parotidectomy and relapsed afterwards (

Table 4. The malformative diseases.

			Lymphangioma
Total patients (n)			3
Sex (n)		Male	3
		Female	/
Age (mean ± SD)			9 ± 7
Affected Gland (n)		Parotid	1
		Submandibular	1
		Minor glands	1
Symptoms (n)		Swelling	3
Treatment (n)	Conservative	Observation	1
	Surgical	Surgical excision	1
		Partial parotidectomy	1
Outcome (n)		Healing	2
		Relapse	1

).

3.6. Oncologic Disorders

Seven different neoplasms were documented in 10 male and 11 female patients, with a mean age of 12 ± 5. A greater prevalence of low-grade mucoepidermoid carcinoma among the malignant group (38.1% of oncologic cases) was noted. Regarding benign tumors, pleomorphic adenoma was the most common diagnosis (47.6% of cases), 90% of which arose unilaterally in the parotid.

Swelling was the sole symptom at presentation.

The treatments varied according to the nature and origin of the disorders, the size of the masses and their benignity or malignancy.

Complete healing was reached in every patient except for one case of parotid adenoid cystic carcinoma. In this case, relapse was reported during follow-up and the patient was then referred to the oncology department (

Table 5. The oncologic diseases.

			Adenocarcinoma	Pleomorphic Adenoma	Adenoid Cystic Carcinoma	Mucoepidermoid Carcinoma	Leukemia	Schwannoma	Inflammatory Myofibroblastic Tumor
Total patients (n)			1	10	1	6	1	1	1
Sex (n)		Male	/	5	/	2	1	1	1
		Female	1	5	1	4	/	/	/
Age (mean ± SD)			18	13 ± 5	18	9 ± 5	9	17	8
Affected Gland (n)		Parotid	1	9	1	5	1	1	1
		Submandibular	/	/	/	1	/	/	/
		Minor glands	/	1	/	/	/	/	/
Symptoms (n)		Swelling	1	10	1	6	1	1	1
Treatment (n)	Conservative	Oncology	/	/	/	1	1	/	/
	Surgical	Surgical excision	/	1	1	1	/	/	/
		Extracapsular dissection	/	2	/	/	/	/	/
		Partial parotidectomy	1	3	/	/	/	1	/
		Perineural parotidectomy	/	1	/	/	/	/	1
		Superficial parotidectomy	/	3	/	1	/	/	/
		Total parotidectomy	/	/	/	3	/	/	/
Outcome (n)		Healing	1	10	/	6	1	1	1
		Relapse	/	/	1	/	/	/	/

).

4. Discussion

Since benign and malignant tumors of the salivary glands are uncommon in pediatric patients, and our hospital is a tertiary referral center, our hospital has a specialized team that has treated these disorders and the small number of patients suffering from them over the last 20 years (99 patients) [2,4,5,6,7,8]. Furthermore, even Gellrich et al. [6] underlined the rarity of salivary gland diseases, except for those that are viral-induced infections, describing 146 children and adolescents treated in 15 years.

4.1. Obstructive Disorders

Among the obstructive diseases, ranula was the most common diagnosis within the major salivary glands. These benign obstructive lesions, which present as painless mobile masses in the floor of the mouth and/or neck, can be managed with different approaches: a trans-oral surgical excision, a marsupialization or a trans-oral excision of the sublingual gland [9,10,11]. In our report analysis, 85.7% of our patients have been treated through sublingual gland removal and the remaining 14.3% through marsupialization. Despite in the literature some findings reporting a female prevalence (29%) and a 7% possibility of relapse [9], our data indicate a prevalence of 78.6% in females and a 100% success rate. In agreement with Zhi et al. [11], we believe that the main goal of pediatric ranula management is radical sublingual gland excision, since it allows for closing the mucus extravasation with low complication rates.

The second most common finding was sialolithiasis. This condition implicates the formation of stones that may be located within major salivary glands’ ducts or in the glands’ parenchyma. The obstruction can lead to inflammation caused by destructive salivary enzymes and superimposed bacterial infections causing sialadenitis or, in rare cases, abscess formation. Sialolithiasis is very uncommon in children and adolescents; the literature reports sporadic cases of calculi both in the Stensen and in the Wharton’s duct with a prevalence in males [12,13]. Our data showed impairment of the submandibular gland with a slight prevalence in the female sex (63.6%). Some authors found a positive family history among patients with sialolithiasis, highlighting the hereditary nature of salivary stones [6,14]. Sialogogues, the direct massage of distal stones out of the duct, and techniques involving interventional sialography, lithotripsy, sialoendoscopy and various surgeries were proposed as treatment choices for sialolithiasis [14]. Our patients were predominantly treated through intraoral surgical excision of the calculi (72.7%), but also through sialoendoscopy, a minimally invasive and versatile procedure that can preserve the gland with the recovery of its functions and without the risk of nerve damage [15]. When sialoendoscopy was carried out, after the dilation and the lavage of the duct, cortisone was injected; the post-operative phase was managed by administering antibiotics along with the gland massages. Some authors compared the efficacy of sialendoscopic lavage to antibiotic therapy, suggesting a faster regression of the symptoms through the lavage [16]. Regarding antibiotic therapy, the administration of antibiotics is not a causal therapy and should be limited to cases of acute bacterial superinfection. In acute episodes with no signs of bacterial superinfection, the first-line treatment should be analgesics, sialogogues and sufficient hydration.

Regarding the minor salivary gland disorders affecting the tongue and the lower lip, mucocele was the most common diagnosis made. Our findings agree with the literature [17,18,19]. In the long-term, all the patients surgically treated for mucocele presented no signs of relapse, demonstrating that correct and prompt treatment can be resolutive.

4.2. Infective Disorders

Only two cases of epidemic parotitis were referred to our department over 20 years. This low incidence can be explained by the common referral of these patients to clinical pediatrics and/or infective disease specialists rather than to maxillo-facial surgery departments. In concordance with the literature, the hallmark of infection was the swelling of the parotid gland [20].

4.3. Inflammatory Disorders

JRP is a recurrent parotid inflammation of a non-obstructive and non-suppurative nature. Congenital ductal malformations, hereditary factors, viral or bacterial infection, allergy and local manifestation of autoimmune diseases are reported as some of the etiological factors [7,8]. In our clinical records, this disorder mainly bilaterally affected the parotid glands, moreover, patients reported xerostomia and one-side symptoms. Authors stress the importance of ultrasound analysis in the diagnosis to confirm bilateral effect on the parotid gland despite unilateral swelling [6,7,8]. We agree with this approach, since we also support that it allows for a better differential diagnosis between an acute episode of JPR and acute sialadenitis. Antibiotics, sialogogues and supportive therapy (e.g., massages and application of heat) are good enough to relieve or significantly reduce the symptoms.

Regarding lymphoepithelial sialadenitis, we reported a single case, in agreement with the rarity of this disorder according to the literature [21].

4.4. Malformative Disorders

Regarding the lymphatic malformations, some authors report several treatment options, such as non-operative management, surgery, sclerotherapy, radiofrequency ablation and laser therapy [22,23,24]. In our cases, since the age range was higher (9 ± 7) than in other case studies, surgical excision and partial parotidectomy were performed.

4.5. Oncologic Disorders

Over 20 years, our team diagnosed 21 cases of neoplasms. Seven different neoplasms were documented and treated differently; collaboration with the pediatric oncology unit was established to meet the primary need.

According to the results of this audit, the most frequent benign neoplasm was the pleomorphic adenoma, in 90% of the cases arising unilaterally in the parotid. Our data are in concordance with the literature [25,26,27,28]. Fine-needle aspiration cytology, magnetic resonance imaging (MRI) and computerized tomography (CT) are useful tools for preoperative diagnosis purposes, thus, they were routinely performed. Surgical treatment was executed in every patient.

According to the literature, there is a lack of research dealing with malignant salivary tumors in children, mostly dated research or case reports [17,29,30,31]. In accordance with Cockerill et al. [25], who identified 56 patients (<18 years old) with malignant salivary gland tumors over a period of 60 years, in our findings, a greater prevalence of mucoepidermoid carcinoma was reported among the malignant group and the parotid gland was commonly involved. Furthermore, single cases of adenocarcinoma, adenoid cystic carcinoma, leukemia, inflammatory myofibroblastic tumors and classic schwannoma were diagnosed.

Regarding the outcomes, our findings showed only one case of relapse (adenoid cystic carcinoma) among all the healed patients. Although a smaller casuistry was analyzed, the overall relapse rate was lower than the previously reported ones [25]. The parotid gland is a slightly less common site for salivary tumors in children versus adults, and there is a greater chance of malignancy. For this reason, after fine-needle aspiration cytology analysis, our treatment of choice is the same as for an adult, performing wider excisions to ensure free-of-disease margins.

A single leukemia case was reported. Although it is a rare presentation, enlargement in the salivary glands with or without lacrimal gland involvement may be the sole symptom of acute lymphoblastic leukemia in children, mimicking mumps, and should be taken into consideration [32].

4.6. Rheumatologic Disorders

As described by Schiffer et al. [33], we also found the same prevalence of Sjogren syndrome in male and female patients, but in a lower age range (7 ± 4 vs. 10 ± 3). Since JPR can be considered a sentinel sign of other diseases of immunological/autoimmune etiology, it must be noted that Sjogren syndrome might overlap [34]. Indeed, ultrasound examination features may be similar, therefore, the alteration of specific and non-specific immunological parameters should be used to guide the differential diagnosis properly [34].

5. Conclusions

Although salivary gland diseases in children and adolescents are rare, it is essential to observe and monitor all symptoms. As painless swelling is a symptom common in both benign and malignant diseases, a prompt diagnostic pathway should be set to intervene properly. Due to the rarity of the oncologic disorders, exposure to known carcinogenic agents such as smoking or radiation does not, or should not, occur at this age to the same extent as with elderly patients. When a diagnosis is confirmed, a thorough anamnesis of carcinogenic exposure, Vitamin A and C deficiency and genetic study for oncogenic mutations, both of the family members and of the child, could be advocated to shed light on the origin of these diseases.