What Is Pleomorphic Adenoma?


Though generally overlooked, salivary gland tumours, whether benign or malign, aren’t all that rare: it is estimated that about 6 to 8% of all head and neck tumours originate in the salivary glands.¹ Pleomorphic adenoma is one example among many: also known as a benign mixed tumour (BMT), this type of tumour is the most common salivary gland tumour. Pleomorphic adenoma is characterised by having two distinctive groups of cells that proliferate, one being the epithelial cells that form the ducts of the salivary glands, and another being the myoepithelial cells that embrace the external layer of the salivary ducts.²

This type of tumour, although benign, has a potential for malignization, therefore transforming into a cancer known as a carcinoma ex pleomorphic adenoma. Pleomorphic adenoma, even as a benign tumour, has a relatively high recurrence rate, and can induce distant metastasis: therefore, it is extremely important to treat it seriously to avoid negative consequences.³ But what causes this tumour? What are common signs and symptoms one should look for? Let’s understand more about this condition.


One of the leading causes of pleomorphic adenoma is radiation exposure: patients who have received radiotherapy treatment for head and neck cancers are more at risk of developing pleomorphic adenoma over the years. Another factor that has been discussed is an infection by the oncogenic simian virus (SV40), although theories on how this virus can induce the formation of the tumour or its progression are still limited.²

What is currently known is that external factors like radiation induce mutations in the DNA of cells of the salivary glands. These mutations can lead to cell proliferation and growth.⁴ Although locally aggressive, this type of tumour is not cancerous; it has a very slow, indolent growth pattern, meaning that a person can spend years with a tumour before it grows enough to be noticeable.¹

Some known mutations associated with pleomorphic adenoma are:

  • Microfibrillar associated protein 4 (MFAP4): mediates production of collectines, a type of protein that exists in the fluid outside the cells (extracellular matrix) that is responsible for repair after inflammation; overexpression of this gene stimulates the growth of the myoepithelial cells that surround salivary ducts
  • Dystonin (DST): this protein is responsible for cell adhesion, anchoring cell groups together; it has been known to be overexpressed in other types of tumours like mammary ductal carcinoma (a type of breast cancer)
  • Solute carrier family 35 (SLC35): this protein is responsible for carrying sugar molecules inside the cells; although very little is known about it and its role in tumorigenesis (the formation of tumours), it has been linked to colon cancer
  • Potassium channel tetramerization domain containing 15 (KCTD15): this gene is associated with multiple functions, such as controlling cell adhesion, cell proliferation and cell differentiation, as well as the transition between different lineages of cells (epithelial to mesenchymal)⁴

Signs and symptoms

Pleomorphic adenoma is often characterised by a slow-growing, painless, mobile mass in the head and neck area. This mass is often solitary, and it can be seen or felt either externally (in the cheek region, or lower mandible) or inside the mouth (through the mouth roof or oral mucosa) depending on the location of the tumour. Parotid gland tumours can result in Bell’s palsy due to weakness of the facial nerve that runs through the gland. This can happen if the tumour is particularly large or if there is malignant transformation.² Submandibular gland tumours are rarer, and usually present with a mobile asymptomatic mass.⁵ Minor salivary gland tumours can present with a variety of symptoms depending on the location: dysphagia (difficulty swallowing), hoarseness,  dyspnea (difficulty breathing), difficulty in chewing, and epistaxis (nose bleeding) are a few examples of symptoms.²

There are a few indicators that can bring concern such as sudden rapid growth of the tumour, new onset of pain and or facial muscle weakness, or involvement of the nearby lymph nodes (presenting with growing mass, pain or fever) which can indicate malignant transformation.¹ Although rare, it is estimated that about 6% of pleomorphic adenomas can undergo malignant transformation and become cancerous.⁴


Clinical evaluation of the patient can reveal any hard masses or lymph node involvement that causes suspicion. Evaluating the patient’s history and risk factors is also important in determining a few diagnostic hypothesis. Complementary exams can also help eliminate other hypotheses:

  • CT scan and MRI scan can determine the overall size, location and extension of the lesion
  • Ultrasound scans are usually performed in order to guide a biopsy or fine needle aspiration for better precision
  • Fine needle aspiration is a quick method that can be done to determine the content of a lesion (if there is liquid inside it, like blood or other fluids, or if it is solid) and confirm or deny the possibility of a malignant lesion

A biopsy is essential in confirming a diagnosis; after taking a sample of the lesion, a pathologist will examine it under a microscope and evaluate its characteristics in order to determine what kind of disease it is. A pleomorphic adenoma tumour usually has three components:

  • Epithelial cells covering the inner layer of the ducts, tubules and eventual cysts (cavities) that can appear.
  • Myoepithelial cells covering the outer layer of ducts, tubules and cysts, and can be scattered across the stroma (supporting tissue layer that provides blood and nutrient supply to the tumour)
  • The abnormal stroma  can be myxoid (very loose and with few cells scattered across it), chondroid (appearing similar to cartilaginous tissue), or myxochondroid (a mixture of both types)³

Metaplasia (transformation of one cell type into another) is common in benign mixed tumours. Pleomorphic adenoma can undergo a series of transformations, in some cases more than one in a single tumour, giving it a very heterogeneous aspect. Transformation into fat tissue (adipose metaplasia), bone (osseous metaplasia), and squamous epithelial metaplasia (sometimes with keratinization) are a few examples.³

Differential diagnosis of pleomorphic adenoma include its malignant variant, carcinoma ex pleomorphic adenoma; other types of salivary gland tumours (such as adenoid cystic carcinoma and Warthin tumour), squamous cell carcinoma, and facial nerve schwannomas (nerve tumours).²,³

Management and treatment

Complete surgical removal is considered the standard procedure when dealing with pleomorphic adenoma³. Usually, this can be done by removing the entire salivary gland, while preserving the nerves that are associated with it as best as possible. Minor salivary glands can be entirely removed and, since this tumour does not invade the periosteum (nerves and vessels around the bones), there is no need to remove bone tissue surrounding it.²

Resection of the tumour while not removing much of the surrounding healthy tissue (enucleation) is not recommended due to the risk of local recurrenceof 15 to 25%. . Although recurrence can appear quickly, cases have been reported of new tumours reappearing after 50 years, which makes it a life-long mission to accompany a patient who had a pleomorphic adenoma.³

In cases in which complete removal is not possible, or when there is a recurrence, monitoring the tumour is possible, as well as radiotherapy. Recurring tumours are notoriously hard to treat and therefore, a more radical approach is preferred when dealing with a primary tumour.²

A few risk factors for malignant transformation should be observed: multiple recurrences, submandibular location, older age, a larger size of the tumour, prominent hyalinization or increased cell division rate seen during microscopic examination, and radiation exposure.³


Pleomorphic adenoma is the most common salivary gland tumour: it represents 45 to 75% of all tumours affecting the major and minor salivary glands and 70 to 80% of all benign tumours. It has a preference for the parotid glands, as well as for assigned female at birth (AFAB) individuals in a 2:1 ratio. Annually, the incidence varies between 2 to 3,5 cases for every 100.000 people.²


Pleomorphic adenoma is a type of benign tumour affecting the salivary glands. It is characterised microscopically by having two distinctive types of cells, the epithelial cells that form ducts, and the myoepithelial cells that cover these ducts externally. It is caused by genetic mutations and it is related to radiation exposure, including previous radiotherapy of the head and neck region. 

Signs and symptoms include a slow-growing, mobile and painless mass, but other symptoms might occur once it grows large enough to affect surrounding tissues; lymph node involvement (nodules, pain or fever) or sudden growth of the tumour can point to a malignant transformation into a carcinoma (cancer). 

Diagnosis is made through a combination of: clinical evaluation, previous history, image exams like CT scans and MRI, and a biopsy. As pleomorphic adenoma is a common type of salivary gland tumour without specific signs and symptoms, other possible diagnostic hypotheses can include adenoid cystic carcinoma and other salivary gland tumours, as well as oral cancer. 

Treatment consists of complete removal of the tumour along with surrounding healthy tissues, and in case there is a recurrence, follow-up surgeries or radiotherapy can be used to treat this tumour. Monitoring indefinitely is important, as this tumour can have a slow recurrence. It is the most common type of salivary gland tumour, affecting AFAB and older people the most.

  1. Middleton H, Strelow B. Pleomorphic adenoma of the parotid gland. JAAPA: official journal of the American Academy of Physician Assistants [Internet]. 2022 Sep 1 [cited 2023 Nov 10];35(9):54–6. Available from: https://pubmed.ncbi.nlm.nih.gov/36007120/
  2. Bokhari MR, Greene J. Pleomorphic Adenoma. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430829/
  3. Xu B. Pleomorphic adenoma. PathologyOutlines.com website. Available from: https://www.pathologyoutlines.com/topic/salivaryglandspleomorphicadenoma.html.
  4. Choi J-S, Cho BH, Kim H-J, Kim Y-M, Jang J-H. Identification of new genes of pleomorphic adenoma. Medicine[Internet]. 2019 [cited 2023 Nov 10];98(51).Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940165/.
  5. Khanal P. Pleomorphic Adenoma of the Submandibular Gland: A Case Report. JNMA J Nepal Med Assoc [Internet]. 2019 [cited 2023 Nov 10]; 57(215):53–5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827573/.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Isabela Araújo Rosa

Doctor of Dental Surgery - DDS, Universidade Federal de Goiás, Brazil

Isabela is a board certified dentist in Brazil, with a background in Oral and Maxillofacial Pathology, Bioethics and Oral Medicine, and previous experience with medical writing and medical communication.

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