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 gland¹ .

Salivary gland cancer classification

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 men² .

• 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 gland³ .

Who gets salivary gland cancer? (Epidemiology)⁴

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

• Based on data from Nottingham in the UK, the annual incidence of benign tumours in the UK is between 6.2 and 7.2 per 100 000 people.

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

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

• Only 5% of all salivary gland cancers occur in childhood⁵ .

• Certain ethnic groups (eg, 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 unknown⁶ .

Salivary gland cancer risk factors

• Radiation to the neck increases the risk of malignancy of salivary glands with a 15- to 20-year latency⁷ .

• Smoking is an important risk factor for the development of Warthin's tumours but its relationship to malignant parotid tumours is less clear⁸ . Warthin's tumours are eight times more common in smokers compared with non-smokers.

• Some studies have suggested an association between high use of mobile phones and an increased risk of benign and malignant parotid tumours⁹ . However, others have found no evidence of such a relationship¹⁰ .
  

Salivary gland cancer presentation

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%)¹¹ .

'Red flag' features suggesting the possibility of malignancy include⁴ :

• 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 cancer 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 indicates malignancy.

• 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 cancer 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 - eg, facial nerve, local lymph nodes.

  • Overlying skin ulceration.

• Cranial nerve palsy.

Differential diagnosis

See the separate Salivary Gland Disorders and Head and Neck Cancers articles.

Referral

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 infection⁴ .

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 of¹² :

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

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

Investigating salivary gland tumours¹³

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 metastases¹⁴ .

Staging

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.

Salivary gland cancer treatment and management

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 tumours¹¹ .

• Most current treatment depends on local ablation.

• 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 surgery¹⁵ .

• Response of malignant tumours to single-agent chemotherapy is generally poor and tends to be reserved for the palliative management of advanced disease that is not amenable to local therapies such as surgery and/or radiation.

• Polychemotherapy is likely to induce a higher response rate but has not been shown to improve survival.

• Targeted molecular therapy is hoped to bring breakthroughs¹⁵ .

Surgical

• 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 recommended¹⁶ .

Complications

• 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 remarkably little adverse effect on the quality of life¹⁷ .

Salivary gland cancer prognosis¹⁴

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.

• The mean five-year survival for advanced high-grade parotid cancer is 35%¹⁸ . Where there is facial nerve involvement, this falls to 9%. Earlier-stage disease has a better prognosis - ten-year survival for stage 1 parotid tumours (tumour <2 cm with no local or metastatic spread) is 83%.

• Malignancies of the minor glands are rare but tend to have a better outcome¹⁹ .

• Tumours in children and adolescents are sometimes malignant but the prognosis tends to be good²⁰ .