Introduction

Pleomorphic adenomas are the most common salivary gland tumour. They most commonly occur in the parotid gland. Within the parotid gland, 80% of neoplasms are benign, and of these, 80% are pleomorphic adenomas.

As pleomorphic adenomas are benign neoplasms, they do not metastasise or invade local structures. Therefore, unlike their malignant counterparts, pleomorphic adenomas do not invade the facial nerve and so facial palsy is not part of their clinical presentation.

Pleomorphic adenomas carry a significant risk of undergoing malignant transformation.

Epidemiology

  • Incidence: 3.00 cases per 100,000 person-years
  • Peak incidence: 40-50 years
  • Sex ratio: more common in females 2:1
Condition Relative
incidence
Salivary gland stones2.00
Pleomorphic adenoma1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

The aetiology of pleomorphic adenomas remains largely unknown.

  • Radiation exposure has been implicated in both benign and malignant salivary gland tumours
  • Some studies suggest an association with simian virus (SV40).
  • Some studies report female dominance (2:1)

  • Smoking has no significant association with pleomorphic adenomas.
    • Contrast this with Warthin's tumours where there is a strong association with smoking



Pathophysiology

Owing to their name, pleomorphic adenomas demonstrate varied histological appearances:

  • Microscopically, different cell types are surrounded by mucoid, myxoid or cartilaginous extracellular matrix

  • Pleomorphic adenomas contain both cells derived from epithelium (polygonal shaped) and myoepithelium (spindle-shaped) and often contain different cell types within the same tumour
    • This is why these tumours are sometimes referred to as benign mixed tumours
    • It is within these different cell types that lie the potential for malignant transformation

  • The tumour is contained within a nodular pseudo-capsule. This pseudo-capsule is an important consideration when it comes to removing the tumour; if any nodules remain, recurrence is likely.

Clinical features

A pleomorphic adenoma typically presents as a nodular lump that is:

  • Slow growing
  • Non-tender
  • Mobile
  • Of firm, rubbery consistency
  • Has no overlying ulceration

This lump occurs in the parotid gland in 85% of cases. It most commonly occurs in the superficial lobe causing visible facial swelling.

It may also affect the deep lobe of the parotid gland where it may present as a retro tonsillar or para-pharyngeal lump.

If it occurs in the tail of the parotid, eversion of the ipsilateral ear may be seen on clinical examination.

Less commonly, pleomorphic adenomas may also occur in:

  • Minor salivary glands (10%)
    • Intraoral lump or ulceration
  • Submandibular glands (5%)
    • Lump in the region of the submandibular glands



Investigations

Pleomorphic adenomas are investigated as salivary gland tumours. Although there are no NICE guidelines on the investigation of salivary gland tumours a recent review from up to date on salivary gland tumours recommends the following investigations:

  • Ultrasound guided fine needle aspiration / core needle biopsy
    • This provides a tissue diagnosis prior to definitive treatment as well as
    • Ultrasound scan may also provide high resolution imaging which is cost effective

Further imaging may be required for surgical planning to assess local invasion:

  • CT scan
  • MRI scan

Differential diagnosis

Pleomorphic adenoma is the most common reason for a persistent unexplained lump in the parotid. It is also the most common benign tumour, however, over 40 different subtypes of neoplasms are implicated in salivary gland tumours.

The following conditions may also present as head and neck lumps, and are possible differential diagnoses for pleomorphic adenomas and other salivary gland tumours:

  • Regional lymphadenopathy
    • Infection / inflammatory / malignant origin
    • Most head/neck lumps are lymph nodes
    • May be shorter time period < 3 weeks

  • Benign tumours
    • Slow growing, non-tender lumps- Similar presentation- Require histology to differentiate

  • Malignant tumours/head and neck tumour metastases
    • Suspicious features: rapid growth, pain, skin tethering, skin ulceration, cervical lymphadenopathy, facial palsy


  • Salivary cysts
    • May occur after previous trauma, stones or infection

  • Branchial cysts
    • Typically a younger patient < 20 years old
    • May present with infection or abscess formation

  • Sj√∂gren syndrome
    • Associated with dry eyes and connective tissue diseases

  • Sarcoidosis
    • Multi-system disease- lung, joint, skin involvement etc.
    • Can present bilaterally

  • Mumps
    • Fever, pain, tenderness, may be bilateral, vaccination history

  • Rarer causes
    • Chronic sclerosing sialadenitis / lymphoepithelial cysts / facial nerve schwannoma

Management

There are no NICE guidelines directly addressing salivary gland tumours. NICE clinical knowledge summaries state that:

An urgent referral (within 2 weeks) should be made for persistent unexplained lumps in the parotid or submandibular glands.

The mainstay of treatment is surgical. Pleomorphic adenomas are removed due to their risk of malignant transformation and to allow for a definitive tissue diagnosis to be made.

Surgical options include:

  • Superficial parotidectomy
    • Superficial lobe of parotid is removed
  • Extracapsular dissection
    • Less tissue is removed- this carries a lower risk of complications

Consideration of other management modalities such as radiotherapy should be discussed at MDT if invasive malignancy suspected but this is generally not indicated.

Complications

The main complication of pleomorphic adenomas is malignant transformation. This risk is 1.5% in the first 5 years but increases significantly to 9.5% after 15 years. Surgery is therefore indicated in the majority of patients to reduce the risk of 'carcinoma ex pleomorphic adenoma'. Rapid enlargement of the tumour with or without other suspicious features should prompt the clinician to consider malignant transformation.

Other complications are rare. The complications tend to stem from the surgery to remove pleomorphic adenomas. As well as the usual surgical complications of pain, bleeding and infection, specific complications of parotid surgery include:

  • Facial nerve injury
    • This is the most important complication due to the parotid gland's intimate relationship with CN VII
    • This may cause symptoms such as dribbling from the angle of the mouth or corneal drying depending on the branches affected.
  • Frey's syndrome
    • This causes 'gustatory sweating' i.e. facial sweating in response to salivary gland stimuli
  • Salivary fistula

Nerve injuries may also occur in submandibular gland surgery leading to tongue wasting or tongue numbness due to injuries of the lingual or hypoglossal nerves.

Pleomorphic adenomas, even though benign, carry a significant risk of recurrence. This is because the tumour is not contained within a 'true capsule'. The tumour has the ability to grow beyond the capsule. If any tumour cells are left behind during surgery (so-called spillage or seeding), the tumour cells have the potential to grow, causing a recurrence. To reduce this risk, at least 5mm resection margins are required during extra-capsular dissection. This must be followed up by a pathologist's report to confirm tumour-free resection margins.