Pleomorphic Adenoma: Symptoms, Types, Causes and Treatment

Pleomorphic adenoma is a unique and intriguing tumor that, despite being benign, can present a complex clinical challenge. Most commonly found in the salivary glands, this "mixed tumor" has a variable appearance and behavior, making its diagnosis and management an essential topic for both patients and clinicians. In this article, we’ll explore the symptoms, types, causes, and treatment options for pleomorphic adenoma, offering a comprehensive, evidence-based overview.

Symptoms of Pleomorphic Adenoma

When it comes to pleomorphic adenoma, the symptoms can be subtle, progressing quietly for years before they cause noticeable problems. Understanding these symptoms is critical for early detection and better outcomes.

Symptom	Description	Common Sites	Source(s)
Swelling	Slow-growing, painless lump	Parotid, palate	5 9 11
Hearing Loss	Reduced hearing or ear sensation	External ear canal	1
Obstruction	Cough, dyspnea, stridor, wheeze	Trachea	2
Facial Nerve	Rare facial nerve involvement	Parotid	5 9 11

Table 1: Key Symptoms

The Most Common Presentations

Pleomorphic adenomas usually appear as a slow-growing, painless mass. Most patients first notice a swelling—often in the parotid region—which can persist for months or years before prompting medical attention. The lump is typically well-defined, mobile, and not tender to the touch 5 11.

Location-Specific Symptoms

• Parotid and Salivary Glands: Most common site. These tumors rarely cause facial nerve dysfunction unless they are very large or recurrent 5 9 11.
• External Auditory Canal: May present as hearing loss, fullness, or ear discomfort 1.
• Trachea: Rarely, pleomorphic adenoma can arise here, leading to respiratory symptoms like chronic cough, wheezing, dyspnea (shortness of breath), and even stridor when the airway becomes obstructed 2.

Rare and Advanced Symptoms

• Facial Nerve Involvement: While uncommon, very large or recurrent tumors in the parotid can compress or involve the facial nerve, potentially causing weakness or paralysis 5 9.
• Ulceration or Rapid Growth: Sudden changes such as pain, ulceration, or rapid enlargement may signal malignant transformation and warrant urgent evaluation 3 4 7.

Types of Pleomorphic Adenoma

Pleomorphic adenomas are not just limited to one presentation or location—they have several types and subtypes, influencing both their behavior and clinical management.

Type	Description	Typical Site(s)	Source(s)
Classic PA	Benign, mixed epithelial & stromal	Parotid, minor glands	5 6 11
Carcinoma ex-PA	Malignant transformation of PA	Parotid, submandibular	3 4 7
Recurrent PA	Multinodular regrowth after surgery	Parotid, other salivary	8 10 12
Ectopic/Unusual	PA in rare/ectopic locations	Ear canal, trachea, bone	1 2 7

Table 2: Types of Pleomorphic Adenoma

Classic Pleomorphic Adenoma

The classic form is a benign, encapsulated tumor composed of a mix of epithelial, myoepithelial, and mesenchymal elements. It is most frequently found in the parotid gland, but can occur in submandibular, sublingual, and minor salivary glands 5 6 11.

Carcinoma ex Pleomorphic Adenoma

This type arises when a benign pleomorphic adenoma transforms into a malignant tumor. Carcinoma ex pleomorphic adenoma (Ca-ex-PA) is rare but aggressive, accounting for most cases of malignant change in PA. It can be difficult to diagnose early, and it carries a poorer prognosis 3 4 7.

Recurrent Pleomorphic Adenoma

Recurrence can occur if the tumor is not completely excised. Recurrent PA often presents as multiple nodules (multinodular) and may require more extensive surgery or adjuvant therapy 8 10 12. Recurrence increases the risk of malignant transformation over time 7.

Ectopic and Unusual Variants

Although rare, pleomorphic adenoma can arise in unusual locations such as the external auditory canal, trachea, mandible, and even the breast or lung. These variants often present diagnostic and therapeutic challenges due to their uncommon sites 1 2 7.

Causes of Pleomorphic Adenoma

Understanding the causes of pleomorphic adenoma remains an evolving science, blending genetics, molecular biology, and clinical observations.

Cause/Factor	Role/Mechanism	Notable Details	Source(s)
Genetic Changes	PLAG1 gene activation	Specific marker for PA	5
Epithelial–Mesenchymal Transition (EMT)	Drives cellular diversity	Involves TWIST, SLUG TFs	6
Surgical Factors	Incomplete excision leads to recurrence	Pseudopods, capsular breach	8 10 12
Age & Gender	More common in middle-aged women	4th-6th decade, F>M	5 6 11

Table 3: Causes and Risk Factors

Genetic and Molecular Mechanisms

• PLAG1 Gene Activation: The pleomorphic adenoma gene 1 (PLAG1) is a key genetic marker found in most PAs. Its activation promotes abnormal cell growth and is highly specific for this tumor 5.
• Epithelial–Mesenchymal Transition (EMT): EMT is a process where epithelial cells acquire mesenchymal (more mobile and flexible) characteristics. This drives the mixed cellular nature of PA, and factors like TWIST and SLUG transcription factors are involved in this cellular transformation 6.

Predisposing Factors

• Age and Gender: Pleomorphic adenoma most commonly affects adults aged between 30 and 60 years, with a clear female predominance 5 6 11.
• Anatomical Location: While the parotid is the most common site, minor salivary glands and rare locations can be affected depending on embryological remnants or ectopic tissue 7.

Surgical and Iatrogenic Factors

• Incomplete Excision: The most significant risk factor for recurrence is incomplete tumor removal during surgery. Microscopic extensions (“pseudopods”) and satellite nodules can be left behind if the capsule is breached or the excision is not wide enough 8 10 12.
• Enucleation: Merely scooping out the tumor (enucleation) instead of removing it with a margin of healthy tissue is associated with a high recurrence rate 8 11.

Treatment of Pleomorphic Adenoma

Effective treatment of pleomorphic adenoma aims to achieve complete removal while minimizing complications and the risk of recurrence. Treatment strategies are tailored to the tumor’s location, size, and previous treatment history.

Treatment	Approach/Details	Indication/Outcome	Source(s)
Surgical Excision	Superficial/total parotidectomy	First-line, high cure rate	9 11
Radiotherapy	Adjuvant or for unresectable cases	Recurrent/incomplete excision	9 12
Endoscopic Approach	Minimally invasive for select sites	Ear canal, small tumors	1
Observation	Select cases only	Elderly, slow-growing, high risk	10

Table 4: Main Treatment Approaches

Surgical Management

Surgery remains the gold standard.

• Superficial or Total Parotidectomy: For parotid tumors, the mainstay is superficial or total parotidectomy, aiming for complete excision with preservation of the facial nerve where possible. This approach yields local control rates of 95% or higher 9 11.
• Other Sites: For minor salivary gland or ectopic PAs, surgery is tailored to the location and size. Complete excision with a margin of healthy tissue is crucial to prevent recurrence 5 11.
• Endoscopic Resection: In rare cases like ceruminous (ear canal) pleomorphic adenoma, minimally invasive endoscopic removal has been reported 1.

Management of Recurrence

Recurrent PA is often multifocal and poses a greater surgical challenge:

• Total Parotidectomy: May be indicated in recurrent, multifocal disease 8 10.
• Adjuvant Radiotherapy: Considered in cases with positive margins, unresectable tumors, or repeated recurrences—may reduce the risk of further recurrence without significantly increasing complications 9 12.
• Nerve Integrity Monitoring: Recommended during surgery for recurrent PA to reduce morbidity 8.

Malignant Transformation

If carcinoma ex pleomorphic adenoma is diagnosed, more aggressive surgical resection and sometimes postoperative radiotherapy are indicated due to the risk of local and distant spread 3 7. Lifelong follow-up is necessary due to the risk of late recurrence or metastasis.

Observation

Observation may be considered in select patients, such as elderly individuals with small, asymptomatic, slow-growing tumors, or those at high surgical risk. However, this is the exception rather than the rule, as untreated tumors can become large, cause morbidity, or, rarely, undergo malignant change 10.

Conclusion

Pleomorphic adenoma is a common but complex benign tumor, primarily affecting the salivary glands but with the potential to arise in diverse anatomical locations. While it is usually slow-growing and painless, its tendency to recur or, in rare cases, transform into aggressive malignancies underscores the need for careful management.

Key Takeaways:

• Pleomorphic adenoma most often presents as a painless, slow-growing lump, particularly in the parotid gland, but can affect other sites 5 6 11.
• Variants include classic, recurrent, carcinoma ex pleomorphic adenoma, and rare ectopic forms 1 2 3 7.
• Causes involve genetic factors (PLAG1), EMT, and surgical factors like incomplete excision 5 6 8 10.
• Complete surgical excision is the mainstay of treatment; recurrence requires individualized management, often including surgery and sometimes radiotherapy 9 12.
• Early diagnosis and appropriate surgical technique are vital to minimize recurrence and prevent malignant transformation 5 11.

By understanding the nuances of pleomorphic adenoma, patients and clinicians can work together to achieve the best possible outcomes.