Salivary Gland Tumours

The major salivary glands are paired:

1. The parotid glands
2. The submandibular glands
3. The sublingual glands

There are also a large number (600-1000) 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 may affect any of these glands, may be benign or malignant and are diverse in their pathology.

• Of salivary gland neoplasms, 80% arise in the parotid glands, 10-15% arise in the submandibular glands and the remainder arise in the sublingual and minor salivary glands.¹
• About 80% of parotid neoplasms are benign but the relative proportion of malignancy increases in smaller glands - about 50% of submandibular gland neoplasms and the majority of sublingual and minor salivary gland tumours are malignant.

Malignant tumours are designated high or low grade dependent on their histology.

• High grade:
  • Mucoepidermoid carcinoma (grade III)
  • Adenocarcinoma - poorly differentiated carcinoma and anaplastic carcinoma
  • Squamous cell carcinoma
  • Malignant mixed tumours
  • Adenoid cystic carcinoma
• Low grade:
  • Acinic cell tumors
  • Mucoepidermoid carcinoma (grades I or II)

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.

Benign tumours:

• Pleomorphic adenoma (most common)
• Warthin tumour
• Rarities including onococytomas and monomorphic adenomas

• Neoplasms of salivary glands have an incidence of about 1 to 2 per 100,000 per annum in England and Wales, with about 470 new cases diagnosed every year.³
• They are fewer than 1% of all cancers and 3-6% of all tumours of the head and neck.
• Tumours and are most common in the sixth decade of life.
• Malignancy typically presents after age 60, whilst benign lesions usually occur after 40.
• Benign tumours are more common in women, but malignant tumours have an equal sex distribution.
• Certain ethnic groups, e.g. Inuit populations, have a higher rate of salivary gland tumours which is maintained even after migration to a low incidence area. The responsible environmental or genetic factors are unknown.⁴

Risk factors

• Radiation to the neck increases the risk of malignancy of salivary glands with a 15 to 20 year latency.⁵
• Smoking is an important risk factor for the development of Warthin tumours but its relationship to malignant parotid tumours is less clear.⁶ Warthin tumours are 8 times more common in smokers compared to non-smokers.
• Some studies have suggested an association between high use of mobile phones and an increased risk of benign and malignant parotid tumours⁷ although others have found no evidence of such a relationship.⁸

Symptoms

• Ask about:
  • Duration and nature of symptoms
  • Growth rate
  • Changes
  • Symptoms associated with eating
  • Facial weakness or asymmetry
  • Pain
  The history may suggest possible inflammatory, infectious, or autoimmune causes.
• 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 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.

Signs

Check:

• The size and mobility of the mass
• Fixation to local structures
• Tenderness
• Skin and mucosa in sites which drain to the parotid and submandibular lymphatics
• Cranial nerve palsy

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

• Pleomorphic adenoma, also called benign mixed tumour, is the commonest tumour of the parotid gland and causes over a third of submandibular tumours. They are slow-growing and asymptomatic.
• Mucoepidermoid carcinoma is the commonest malignancy of the parotid gland and is the second commonest of the submandibular gland (after adenoid cystic carcinoma). It represents about 8% of all parotid tumours.
• Adenocarcinoma represents 2-3% of salivary tumours.
• Acinic cell carcinoma is a low-grade neoplasm that represents 1% of all salivary gland neoplasms. 95% arise in the parotid gland.
• Warthin tumours are the second commonest 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 6th decade in women and the 7th decade in men.⁹
• Regional metastases from skin or mucosal malignancies may present as salivary gland masses. 1-3% of patients with cutaneous squamous cell carcinoma of the head and neck experience metastatic spread to the parotid-area lymph nodes.
• Lymphoma can occasionally present in a salivary gland.¹⁰
• In children, most parotid tumours are benign and are haemangiomas.¹¹

• Imaging's role in the assessment of a salivary gland tumour is to:
  • Define location
  • Detect malignant features
  • Assess local extension and invasion
  • 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 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 parotid gland and the minor salivary glands, MRI and CT 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.

Staging is most commonly based on the TNM system - based on tumour size, spread to cervical lymph node and distant metastases. It correlates with survival and assists treatment decisions.
In England and Wales, about 13% 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%).³

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 surgery.¹⁴

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 break-throughs.¹⁵

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 multi-disciplinary team with expertise in the treatment of head and neck tumours, including surgeons, clinical oncologists, dentists, pathologists, radiologists, specialist nurses, palliative care, speech and language therapists and dieticians.³

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 tumors 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.¹⁶

• Damage to the facial nerve may occur as a result of parotid tumour infiltration or surgery. Risk of damage is higher with repeat operations. Peri-operative 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 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 (or gustatory sweating) 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 life.¹⁷

• The mean 5 year survival for advanced high-grade parotid cancer is 35%.¹⁴ Where there is facial nerve involvement, this falls to 9%. Earlier stage disease has a better prognosis - 10-year survival for Stage 1 parotid tumours (tumour <2cm with no local or metastatic spread) is 83%.
• Malignancies of the minor glands are rare but tend to have a better outcome.¹⁸
• Tumours in children and adolescents are sometimes malignant but the prognosis tends to be good.¹⁹

Because salivary gland tumours are rare and so diverse, there is a shortage of good clinical trials.²⁰ It is hoped that a better understanding of their molecular biology will lead to improved understanding of prognosis and better treatment.²¹