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The major 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 tumours occur in the parotid gland.
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.
- 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.
- Acinic cell tumours: represent 1% of all salivary gland neoplasms. 95% arise in the parotid gland.
- Mucoepidermoid carcinoma (grades I or II).
- 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.
- Rarities including oncocytomas and monomorphic adenomas.
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. Lymphomas may occasionally present in a salivary gland.
- 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 tumours occur in childhood.
- Certain ethnic groups (eg, 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.
- Radiation to the neck increases the risk of malignancy of salivary glands with a 15- to 20-year latency.
- Smoking is an important risk factor for the development of Warthin's tumours but its relationship to malignant parotid tumours is less clear. 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 tumours.However, others have found no evidence of such a relationship.
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%).
'Red flag' features suggesting the possibility of malignancy include:
- 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.
- 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.
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:
- Infiltration of surrounding structures - eg, facial nerve, local lymph nodes.
- Overlying skin ulceration.
- Cranial nerve palsy.
The most common causes of salivary 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.
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:
- Neck lump (unexplained) in a patient aged 45 years or older.
- Neck lump (persistent and unexplained) in any patient.
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.
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 article Head and Neck Cancers.
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.
- 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.
- 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 breakthroughs.
- 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.
- 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 life.
Because salivary gland tumours 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%. 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 outcome.
- Tumours in children and adolescents are sometimes malignant but the prognosis tends to be good.
Further reading and references
Salivary Gland Cancer Treatment; National Cancer Institute
Namboodiripad PC; A review: Immunological markers for malignant salivary gland tumors. J Oral Biol Craniofac Res. 2014 May-Aug4(2):127-34. doi: 10.1016/j.jobcr.2014.05.003. Epub 2014 Aug 28.
Hatch RL, Shah S; Warthin Tumor: A Common, Benign Tumor Presenting as a Highly Suspicious Mass. JABFP July-August 2005 Vol. 18 No. 4. 320-322. [full text]
Roh JL, Huh J, Suh C; Primary non-Hodgkin's lymphomas of the major salivary glands. J Surg Oncol. 2008 Jan 197(1):35-9.
Mehanna H, McQueen A, Robinson M, et al; Salivary gland swellings. BMJ. 2012 Oct 23345:e6794. doi: 10.1136/bmj.e6794.
Iro H, Zenk J; Salivary gland diseases in children. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2014 Dec 113:Doc06. doi: 10.3205/cto000109. eCollection 2014.
Boysen T, Friborg J, Andersen A, et al; The Inuit cancer pattern--the influence of migration. Int J Cancer. 2008 Jun 1122(11):2568-72.
Schneider AB, Sarne DH; Long-term risks for thyroid cancer and other neoplasms after exposure to radiation. Nat Clin Pract Endocrinol Metab. 2005 Dec1(2):82-91.
Sadetzki S, Oberman B, Mandelzweig L, et al; Smoking and risk of parotid gland tumors: a nationwide case-control study. Cancer. 2008 May 1112(9):1974-82.
Sadetzki S, Chetrit A, Jarus-Hakak A, et al; Cellular phone use and risk of benign and malignant parotid gland tumors--a nationwide case-control study. Am J Epidemiol. 2008 Feb 15167(4):457-67. Epub 2007 Dec 6.
Schuz J, Jacobsen R, Olsen JH, et al; Cellular telephone use and cancer risk: update of a nationwide Danish cohort. J Natl Cancer Inst. 2006 Dec 698(23):1707-13.
Service guidance on improving outcomes in head and neck cancers; NICE, November 2004
Suspected cancer: recognition and referral; NICE Clinical Guideline (2015 - last updated July 2017)
Lee YY, Wong KT, King AD, et al; Imaging of salivary gland tumours. Eur J Radiol. 2008 Jun66(3):419-36. Epub 2008 Mar 11.
Jeannon JP, Calman F, Gleeson M, et al; Management of advanced parotid cancer. A systematic review. Eur J Surg Oncol. 2008 Nov 20.
Milano A, Longo F, Basile M, et al; Recent advances in the treatment of salivary gland cancers: emphasis on molecular targeted therapy. Oral Oncol. 2007 Sep43(8):729-34. Epub 2007 Mar 9.
Ganly I, Patel SG, Coleman M, et al; Malignant minor salivary gland tumors of the larynx. Arch Otolaryngol Head Neck Surg. 2006 Jul132(7):767-70.
Nitzan D, Kronenberg J, Horowitz Z, et al; Quality of life following parotidectomy for malignant and benign disease. Plast Reconstr Surg. 2004 Oct114(5):1060-7.
Laurie SA, Licitra L; Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006 Jun 1024(17):2673-8.
Agulnik M, Siu LL; An update on the systemic therapy of malignant salivary gland cancers: role of chemotherapy and molecular targeted agents. Curr Med Chem Anticancer Agents. 2004 Nov4(6):543-51.
Strick MJ, Kelly C, Soames JV, et al; Malignant tumours of the minor salivary glands - a 20 year review. Br J Plast Surg. 2004 Oct57(7):624-31.
Ellies M, Schaffranietz F, Arglebe C, et al; Tumors of the salivary glands in childhood and adolescence. J Oral Maxillofac Surg. 2006 Jul64(7):1049-58.