Case Series: Pleomorphic adenoma in minor salivary gland

Version Changes

Revised. Amendments from Version 1

The reviewers' comments have all been taken into account.

• The study objective was clearly stated in the introduction section, along with the epidemiological context.

• The endoscopic data of the two patients were added.

• A more detailed analysis of the pleomorphic adenoma's different histological and immunohistochemical aspects was performed.

• The references were updated and inserted into the text.

Abstract*

Pleomorphic adenomas (PA) are the most prevalent benign salivary gland neoplasms. They may occur at any age, with a peak incidence between 40 and 60 years of age. They are more commonly observed in females (60%). These tumors can arise in both the major and minor salivary glands. Approximately 80% of these tumors are diagnosed in the parotid gland, whereas 10% arise in the minor salivary glands, mainly affecting the palates, followed by the lips and cheeks.

This report describes two cases of unusual lesions that were diagnosed as (PA) in the minor salivary glands in our department via a review of the relevant literature. The first case involved an 83-year-old man who presented with a slow-growing swelling on the right side of the upper lip, and the second case involved a 45-year-old woman who presented with a slow-growing lesion on the palate. The presence of PA was confirmed histopathologically after surgical resection.

Although relatively rare, PA is a benign lesion, the diagnosis of which must be known for appropriate therapeutic management.

Introduction

Salivary gland tumors are relatively uncommon, accounting for 1-3% of head and neck cancers. Pleomorphic adenoma (PA) is a benign tumor that is most frequently diagnosed not only in the major salivary glands, namely the parotid gland (85% of cases) and submandibular gland (5% of cases), but also in the minor salivary glands (10% of cases). ¹ The most common ectopic site of PA in the minor salivary glands is the palate, followed by the upper lip and oral mucosa. ²

Salivary gland neoplasms are a heterogeneous group of tumors with variable clinical appearances and histological features.

PA, also known as “Mixed tumor, salivary gland type,” receives its name from its wide pleomorphic architectural appearance and mixed histology that consists mainly of three components: an epithelial and a myoepithelial component within a mesenchymal stroma. ³ It is equipped with a fibrous capsule whose integrity must be conserved during surgical treatment to prevent recurrence. ⁴

PA is more common in middle-aged females. ⁴

Several studies have identified risk factors associated with an increased likelihood of developing pleomorphic adenoma. These include radiation exposure, particularly in the head and neck region, potential genetic predisposition, hormonal influences, and environmental factors such as chemical or pollutant exposure. Additionally, lifestyle choices like tobacco and alcohol use may play a role. These varying risk factors can contribute to geographic differences in pleomorphic adenoma's observed frequency and characteristics. This, in turn, can influence how the disease is diagnosed and treated in different regions. ^{4 , 5}

Clinically, it is known to be a slow-developing, asymptomatic lesion, typically described as firm, well-delimited, and variable in diameter. Intraoral PAs are normally located in the submucosa with a firm or rubbery consistency. The mucosal lining remains intact, but ulcerations can be observed in some cases. ^{5 , 6}

In this context, we present two cases of PA within two different minor salivary glands to understand its etiopathogenesis, clinical and morphological findings, as well as the treatment strategies for the condition, to aid in making an accurate diagnosis.

Case 1

An 83-year-old man with no specific pathological history presented to our ENT Department with a 2-year history of painless, slow-growing swelling on the right side of the upper lip.

The patient had no medical history interfering with our case. Furthermore, a history of active smoking was reported with no alcohol consumption.

Clinical examination revealed a well-circumscribed, mobile, firm, and non-tender submucosal mass measuring 3×1.5 cm on the right side of the upper lip. The overlying mucosa appeared intact and smooth without bleeding on palpation ( Figure 1A). The lymph nodes of the head and neck were not enlarged.

Figure 1. Pleomorphic adenoma of the upper lip.

A: Preoperative view: Exposure of the mass in the palate. B: CT scan on axial section showing an oval well-defined lesion of the upper lip with homogeneous post-contrast enhancement. C: Postoperative view showing the site of the sutures. D: Excised specimen.

Nasofibroscopy did not reveal any abnormalities.

Computed tomography (CT) showed an oval well-defined lesion of the upper lip measuring 3.2×1.7 cm with homogeneous post-contrast enhancement ( Figure 1B).

A total excision of the lesion via the sublabial approach was performed ( Figure 1C). The lesion was released from the surrounding tissue, and the mass appeared to be fully encapsulated ( Figure 1D). Histopathology of the resected tumor revealed the presence of a PA, a well-encapsulated soft tissue mass consisting of epithelial, myoepithelial, and stromal components ( Figure 3). The follow-up 24 months after surgery showed no abnormalities and no evidence of recurrence.

Figure 3. Photomicrograph showing epithelial salivary gland tumor.

A: The tumor consists of three components: epithelial cells (right), myoepithelial cells (left), and myxochondroid tissue stroma (hematoxylin-eosin, 100×). B: Myoepithelial cells with epithelioid and plasmacytoid appearance (hematoxylin-eosin, 400×).

Case 2

A 45-year-old woman with no medical history or any tobacco exposure presented to our ENT department with a slow-growing painless nodular lesion in the palate that caused difficulty swallowing. Anamnesis revealed that the mass had appeared one year previously and had rapidly increased in size over the last three months.

Intraoral examination revealed a unilocular, mobile, fibrous, endophytic nodule at the junction of the soft and hard palates, measuring approximately 4 cm in diameter. The nodule was well delimited, with a regular contour, smooth surface, and normal overlying mucosa color ( Figure 2A). No lymph node involvement was observed during the physical examination. A nasofibroscopy was performed showing no abnormal lesions.

Figure 2. Pleomorphic adenoma of the palate.

A: Preoperative view: Exposure of the mass in the palate. B: T2-weighted MRI showing a hyposignal ovoid well-defined mass within the right soft palate. C: Peroperative images: the defect post excision of the mass.

Magnetic resonance imaging (MRI) revealed an ovoid well-circumscribed encapsulated mass measuring 3.7 cm in size, within the midline of the soft palate to its right para-median side. The lesion extended backward to the oropharynx and forward in the left tonsillar pillar ( Figure 2B).

The mass was completely excised with safety margins via an intraoral approach ( Figure 2C).

On final histopathological examination, the report suggested a PA ( Figure 3A & B).

An 18-month follow-up after surgery showed no abnormalities or evidence of recurrence.

Discussion

Although malignant lesions are mostly diagnosed in minor salivary glands, benign lesions have also been reported. PA are the most common benign salivary gland neoplasms, representing approximately 3–10% of all neoplasms of the head and neck region. ⁶

They represent the most prevalent histopathological benign tumors diagnosed in both the major and minor salivary glands (50% of cases). Additionally, PA mainly affects the major salivary glands, particularly the parotids. The palate is the most prevalent intraoral site (42.8-68.8%), followed by the upper lip (10.1%) and cheek (5.5%). ^{4 , 6}

It occurs in individuals of all ages ³ but tends to affect more women than men, especially middle-aged individuals. ⁴

The present cases of PA in the minor salivary glands of the palate and the upper lip corroborate literature data showing a relatively low prevalence at these sites.

Regarding the epidemiological features of PA, gender, and age in our present cases, one of our two patients agreed with the literature, which shows that PA in the minor salivary glands may occur in individuals of all ages but most frequently affects women in their fourth to fifth decade of life, with a relevant mean age of 40-60 years. ^{1 , 4}

However, in our first case, PA was diagnosed in an 83-year-old man, which does not match the relevant literature as neither the age of occurrence nor the sex of the patient was uncommon.

Etiopathogenesis of PA is known to be associated with alterations in the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), which is activated due to variable chromosomal aberrations. ^{4 , 6}

The clinicopathological features of our two cases concur with those reported in previous studies. In fact, PA generally presents as a mobile, slowly developing, painless, and firm swelling that does not cause any fixation or ulceration of the overlying mucosa with no lymph node involvement. ⁷

Histopathologically, PA is a complex mixed lesion consisting of both epithelial and myoepithelial components arranged within a mucopolysaccharide stroma, organized in various morphological patterns, predominantly in a duct-like pattern. They tend to have a fibrous capsule that separates the tumor from the surrounding tissues. The proportions of the different components can vary among individuals, parallel to changes in tumor consistency. ^{6 , 8 , 9}

These adenomas are normally classified into three main histologic subtypes: myxoid (with 80% stroma), cellular (predominantly myoepithelial cells), and mixed (classic) type. ² In minor glands, lesions tend to be more solid or cellular compared to those in major glands, with myoepithelial cells often emerging as polygonal with pale eosinophilic cytoplasm, giving an epithelioid or plasmacytoid phenotype. ^{11 , 12}

A note to mention about the importance of Immunohistochemistry (IHC) and molecular biology techniques that play a crucial role in the diagnosis management of pleomorphic adenoma since it helps to distinguish PA from other salivary gland lesions, such as adenoid cystic carcinoma or mucoepidermoid carcinoma. They may contribute as well to assessing the extent of tumor progression and to guiding the prognosis. Helpful IHC stains include calponin, cluster of differentiation 9 (CD9), p63 and S-100. ¹³

The need for complementary investigations into the management of PA in minor salivary glands depends on its localization. Indeed, a biopsy may be performed for additional oral sites.

However, if the diagnosis of PA is suspected in intraoral localizations, CT, ultrasonography, and optimal MRI are useful for studying the extent of the tumor and determining eventual bone involvement. ^{3 , 11}

Biopsy is generally avoided because of the fear of the seedling. However, fine-needle aspiration is safe and recommended. ¹²

According to recent studies, the treatment of choice is wide local excision of the tumor with adequate margins, followed by histopathological examination to establish the final diagnosis. ⁹

Our therapeutic approach was consistent with the literature, as a total excision of the lesion via a sublabial approach was performed in the case of PA of the upper lip and via an intraoral approach for the patient who presented with PA of the palate.

Minor salivary gland neoplasms require regular follow-up due to both their increased risk of recurrence (around 13%) and the rare possibility of transformation into more aggressive cancers like adenoid cystic or mucoepidermoid carcinoma. ^{14 , 15}

Conclusion

The diverse presentations of pleomorphic adenomas make diagnosis complicated and challenging. PAs of the minor salivary glands are rare neoplasms. While their occurrence in the minor salivary glands is uncommon, obtaining the correct diagnosis as early as possible is essential because early initiation of appropriate treatment allows for effective management and improves patient prognosis. Complete wide local surgical excision is the treatment of choice. Patients should be followed up for a longer period to detect late recurrences.

Ethics and consent

Written informed consent was obtained from both patients for publication and accompanying images.

Author contribution

Samia Meherzi: writing, review and editing

Rihab Omri: conceptualization, writing

Amin Khbou: conceptualization, preparation

Afifa charfi: review

Funding Statement

The author(s) declared that no grants were involved in supporting this work.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.