Salivary gland tumours

What are the salivary glands?

The major types of salivary glands are the parotid glands, submandibular glands and sublingual glands. There are also a large number (600-1,000) of minor salivary glands widely distributed throughout the oral mucosa, palate, uvula, floor of the mouth, posterior tongue, retromolar and peritonsillar area, pharynx, larynx and paranasal sinuses. Tumours affecting salivary glands may be benign or malignant and are diverse in their pathology. About 80% of salivary gland cancers occur in the parotid gland.¹

Malignant salivary gland tumours

The malignant tumours most commonly affecting the major salivary glands are mucoepidermoid carcinoma, acinic cell carcinoma and adenoid cystic carcinomas. Among the minor salivary glands, adenoid cystic carcinoma is the most common. Malignant tumours are designated high-grade or low-grade dependent on their histology.

High-grade salivary gland cancers

• Mucoepidermoid carcinoma (grade III): mucoepidermoid carcinoma is the most common malignancy of the parotid gland and is the second most common of the submandibular gland (after adenoid cystic carcinoma). It represents about 8% of all parotid tumours.

• Adenocarcinoma - poorly differentiated carcinoma and anaplastic carcinoma; represents 2-3% of salivary tumours.

• Squamous cell carcinoma.

• Malignant mixed tumours.

• Adenoid cystic carcinoma.

Low-grade salivary gland cancers

• Acinic cell tumours: represent 1% of all salivary gland neoplasms. 95% arise in the parotid gland.

• Mucoepidermoid carcinoma (grades I or II).

Benign salivary gland tumours

• Pleomorphic adenoma (most common) - also called benign mixed tumour: is the most common tumour of the parotid gland and causes over a third of submandibular tumours. They are slow-growing and asymptomatic.

• Warthin's tumour: second most common benign salivary gland neoplasm, representing about 6-10% of all parotid tumours. They rarely occur in other glands and 12% are bilateral. They present most often in the sixth decade in women and the seventh decade in men.³

• Rarities including oncocytomas and monomorphic adenomas.

Regional metastases from skin or mucosal malignancies may present as salivary gland lumps. 1-3% of patients with cutaneous squamous cell carcinoma of the head and neck experience metastatic spread to the parotid-area lymph nodes. Lymphomas may occasionally present in a salivary gland.⁴

• The majority of salivary neoplasms are benign (65-70%). Approximately 80% of parotid gland tumours are benign.⁵

• Malignant tumours are rare, with an age standardised incidence ranging between 0.6 and 1.4 per 100,000 people in Europe.

• Salivary gland malignancies comprise 0.5 to 1.2% of all cancers and 5% of head and neck cancers.⁵

• Malignancy typically presents after age 60, whilst benign lesions usually occur after age 40.

• Only 5% of all salivary gland cancers occur in childhood.⁶

• Certain ethnic groups (e.g. Inuit populations) have a higher rate of salivary gland cancers which is maintained even after migration to a low incidence area. The responsible environmental or genetic factors are unknown.⁷

Salivary gland tumour risk factors

• Radiation to the neck increases the risk of malignancy of salivary glands with a 15- to 20-year latency.⁸

• Radiation exposure significantly increases the risk of salivary gland malignancies. ⁵

• It remains unclear how significant smoking and tobacco use is in the development of salivary gland tumours. Compared with other head and neck cancers, the role of smoking and tobacco remains controversial.⁵Smoking appears to be a significant risk factor for the development of Warthin tumours.⁹

• Autoimmune conditions such as Sjogren syndrome may predispose an individual to develop a salivary gland malignancy such as lymphoma.⁵

• There is no evidence for any other risk factors, despite many being suggested.

In England and Wales, about 13% of patients with salivary gland cancer present with early disease, 17% with locally advanced, 7% with lymph node involvement and 28% with metastatic disease (and unknown staging in 35%).¹⁰

'Red flag' features suggesting the possibility of malignancy include:¹¹

• Facial nerve weakness.

• Rapid increase in the size of the lump.

• Ulceration or induration (or both) of the mucosa or skin overlying fixed skin.

• Paraesthesia or anaesthesia of neighbouring sensory nerves.

• Intermittent pain, increasing relentlessly.

• History of previous skin cancer, Sjögren's syndrome or previous radiation to the head and neck.

Salivary gland tumour symptoms

• Most salivary gland neoplasms are a slowly enlarging painless mass:

  • Parotid neoplasms most commonly occur in the tail of the gland as a discrete mass in an otherwise normal gland.

  • Submandibular neoplasms often appear with diffuse enlargement of the gland.

  • Sublingual tumours produce a palpable fullness in the floor of the mouth.

  • Minor salivary gland tumours vary according on the site of origin - painless masses on the palate or floor of the mouth are the most common form but laryngeal salivary gland tumours can produce airway obstruction, dysphagia, or hoarseness. In the nasal cavity or paranasal sinus they cause nasal obstruction or sinusitis.

• Facial palsy with a salivary gland mass is suggestive of malignancy and should be urgently referred.

• Pain can occur with both benign and malignant tumours. Pain may arise from suppuration or haemorrhage into a mass or from infiltration of adjacent tissue.

Salivary gland tumour signs

Use bimanual palpation of the lateral pharyngeal wall for deep lobe parotid tumours and the extent of submandibular and sublingual masses.

• Clinical features of a salivary gland mass suggestive of malignancy are:

  • Hardness.

  • Fixation.

  • Tenderness.

  • Infiltration of surrounding structures - e.g., facial nerve, local lymph nodes.

  • Overlying skin ulceration.

• Cranial nerve palsy.

See the separate Salivary gland disorders and Head and neck cancers articles.

The most common causes of salivary gland lumps are benign neoplasms, malignancy, salivary stones and stenoses and salivary swelling (adenosis) secondary to systemic diseases such as Sjögren's syndrome or HIV infection.¹¹

The National Institute for Health and Care Excellence (NICE) guidelines suggest urgent referral (for an appointment within two weeks) for patients with suspected head and neck cancer where there is a history of:¹²

• Neck lump (unexplained) in a patient aged 45 years or older.

• Neck lump (persistent and unexplained) in any patient.

Referral for imaging to define location, detect malignant features, assess local extension and invasion and detect metastases and systemic involvement:

• Ultrasound is the usual initial means to assess superficial lesions. Ultrasound is more limited at visualising the deep lobe of the parotid and some minor salivary glands depending on location.

• Ultrasound-guided fine-needle aspiration (FNA) cytology is used to obtain cytological confirmation. CT-guided biopsy can also be used.

• If deep tissue extension is suspected or malignancy confirmed on cytology, an MRI or CT scan is used to evaluate tumour bulk, local invasion and perineural spread.

• All tumours in the sublingual gland should be imaged with MRI, as the risk of malignancy is high.

• For lesions of the deep lobe of the parotid gland and the minor salivary glands, MRI and CT scanning are the imaging methods of choice.

• Sialography can be used to delineate the salivary ductal system and has a limited role in assessing tumour extent.

• Positron emission tomography is sometimes used to detect local and distant metastases.

Staging is most commonly based on the tumour, node and metastasis (TNM) classification system - based on tumour size, spread to cervical lymph node and distant metastases. It correlates with survival and assists treatment decisions. See the separate Head and neck cancers article.

NICE guidance urges specialisation at centres with sufficient expertise and volume of cases, as this improves care. At all stages, patients should have access to a multidisciplinary team with expertise in the treatment of head and neck tumours.²

• Most salivary tumours are managed via wide local excision.

• Radiotherapy may be used following surgery, usually for higher-grade tumours, or alone for non-resectable tumours. Its use improves overall survival in high-grade, advanced parotid cancer as an adjunct to surgery.¹³

• Chemotherapy is used for lymphoma but is limited for other salivary gland tumours.

Surgical treatment

• Superficial parotidectomy with careful dissection of the facial nerve is required for diagnosis and treatment of a parotid mass. Where malignant, a more radical procedure sacrificing the facial nerve may be undertaken, depending on the extent of infiltration. Complete excision of tumours in other salivary glands is required.

• Benign neoplasms of the submandibular gland require complete excision of the gland.

• Up to 60% of patients with malignant minor salivary gland tumours of the larynx will develop recurrent disease locally, regionally or at distant sites. Because of the high risk of recurrence, total laryngectomy is usually recommended.¹⁴

• Damage to the facial nerve may occur as a result of parotid tumour infiltration or surgery. Risk of damage is higher with repeat operations. Perioperative facial nerve monitoring may reduce this risk.

• Recurrence of benign or malignant tumours. Pleomorphic adenomas must be completely removed at primary surgery, as recurrent tumours are often multifocal and can occur 10-15 years later with much reduced cure rates (<25%).

• Malignant change - pleomorphic adenomas can undergo malignant change and are called carcinoma ex-pleomorphic adenoma. They represent about 2-4% of salivary gland malignancies. Sudden rapid growth of a previously stable mass is typical. They are aggressive and have a poor prognosis.

• Frey's syndrome (redness and sweating on the cheek, which can appear when eating, seeing or thinking about certain kinds of food which produce strong salivation) can occur after parotid surgery. The autonomic nerves reform inappropriately (parasympathetic impulses going to sympathetic nerves) so that a stimulus to salivation will make the face sweat.

• Xerostomia and oral mucositis may occur following radiotherapy.

Follow-up of patients who have had parotidectomy for benign or malignant disease shows hypoaesthesia as the main side effect causing long term symptoms.¹⁵

Because salivary gland cancers are rare and so diverse, there is a shortage of good clinical trials. It is hoped that a better understanding of their molecular biology will lead to improved understanding of prognosis and better treatment.

• Low grade MEC has a 5 year survival of >90%.

• High grade squamous MEC has a 5 year survival of between 30 and 41%.

• The prognosis for the other cancers is dependent on type.