Salivary Gland Tumors
Salivary gland tumors consist of benign or malignant neoplasms of the major and minor salivary glands. Tumors may be mimicked clinically by a variety of inflammatory or infectious disorders:
- Major: Parotid, submaxillary, sublingual glands
- Minor: Intraoral, pharyngeal, and nasal glands (600–1,000 glands distributed throughout the upper aerodigestive tract)
- Adult neoplasms:
- Benign: Pleomorphic adenoma, Warthin tumor (adenolymphoma), oncocytoma, and monomorphic adenoma
- Malignant: Mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, carcinoma ex-pleomorphic adenoma, squamous cell carcinoma (SCC), adenocarcinoma
- Total distribution of salivary gland neoplasms by type:
- Pleomorphic adenoma (most common): 45% overall
- Monomorphic adenoma: 12% overall
- Mucoepidermoid carcinoma: 12% overall
- Adenoid cystic carcinoma: 6% overall
- Remaining neoplasms: 25% overall
- Distribution: Parotid (80%); submandibular (10–15%); sublingual and minor (5–10%):
- Parotid (80% benign; 20% malignant):
- Pleomorphic adenoma: 60%
- Monomorphic adenoma: 8%
- Warthin tumor: 8%
- Mucoepidermoid carcinoma: 12%
- Adenoid cystic carcinoma: 5%
- Adenocarcinoma and SCC: 5%
- Submandibular (60% benign; 40% malignant):
- Pleomorphic adenoma: 40%
- Mucoepidermoid carcinoma: 10%
- Adenoid cystic carcinoma: 20%
- Lingual and minor salivary glands (40% benign; 60% malignant):
- Pleomorphic adenoma: 40%
- Mucoepidermoid carcinoma: 25%
- Adenoid cystic carcinoma: 25%; generally, as the size of the neoplasm decreases, the incidence of malignancy increases.
- Parotid (80% benign; 20% malignant):
- Pediatric neoplasms:
- These tumors are most frequently benign, but may be malignant.
- Benign: 65% of overall cases; the most common types are hemangiomas and pleomorphic adenomas.
- Malignant: 35% of overall cases; most common type is mucoepidermoid carcinoma.
- 1.5 cases per 100,000 individuals in the US
- ~700 deaths annually
- Median age:
- Benign: 45 years
- Malignant: 60 years
- Gender predilection:
- Benign: Female > Male
- Malignant: Male = Female
Make up 6–8% of all head and neck neoplasms (1)
- Tobacco and alcohol abuse associated with Warthin tumor, but not with SCC
- Alcohol increases likelihood ratio by 2:1 (2).
- Radiation has shown a 4-fold increased dose-related response in salivary gland cancer 15–20 years after treatment. Increased risk has also been reported in atomic bomb survivors (2).
- EBV has been associated with lymphoepithelial carcinoma in Asians, but there is no evidence of causal association in other tumors (2).
- Silica dust has been associated with a 2.5-fold increase in salivary gland neoplasia (2).
- Kerosene cooking fuel exposure (2)
- Nitrosamine exposure in rubber workers (2)
- Early menarche and nulliparity (2)
Increased incidence of adenocarcinoma of parotid in Eskimos; otherwise, no known genetic pattern
Cessation of tobacco and alcohol use
Pathophysiology not fully understood; certain pathways and oncogenes have been implicated: p53, Bcl-2, PI3K/Akt, MDM2, VEGF, HGF, and ras.
- Etiology is not fully understood.
- Predominant theory: Tumors arise from either the secretory duct reserve cell or the intercalated duct reserve cell.
- Focused inquiry:
- Specific presentation of mass: Initial recognition; rate of growth; change in size with actions, especially with food consumption; laterality/focality of swelling; xerostomia (Sjögren syndrome, prior irradiation, medication)
- Intermittent, recurrent gland enlargement suggests sialolithiasis (calculi in salivary duct); rarely, can be due to malignancy.
- Pain: Type, degree, accentuating and/or alleviating factors, temporality
- Location and spread
- Effect on associated structures with relevant review of systems: Larynx (airway obstruction, hoarseness, dysphagia); nasal cavity/paranasal sinuses (nasal obstruction, sinusitis); pharyngeal wall invasion (dysphagia, muffled voice, intraoral discharge)
- Other relevant past medical history: Malnutrition; eating disorders (anorexia/bulimia); Sjögren syndrome; diabetes mellitus; sarcoidosis
- Common presentations:
- Overall: Typically, a slow-growing, painless, discrete mass
- Parotid neoplasm: Discrete mass typically in the superficial lobe of the gland
- Submandibular neoplasm: Associated with diffuse fullness of superficial lobe and possible displacement of pharyngeal tonsil
- Sublingual neoplasm: Tends to produce palpable fullness in the floor of the mouth
- Minor gland neoplasm: Depends on initial site of origin
- Indicator of malignancy:
- Facial paralysis, paresthesias, or other neurologic deficit associated with mass
- Pain suggests malignancy; may be associated with both benign and malignant neoplasms; exquisite pain is more likely due to infectious cause.
- Complete HEENT examination with emphasized focus:
- Evaluate the location (specific gland), size, mobility, tenderness and extent of the mass, and fixation to surrounding structures.
- If tenderness present, massage gland to express purulent material due to infection.
- Examine parapharyngeal area for medial displacement of ipsilateral tonsil, which may indicate deep parotid lobe involvement.
- Lymphadenopathy, especially, in neck levels I–V
- Referred pain (otalgia)
- Complete neurologic exam with focus on cranial nerves:
- Facial nerve palsy or paralysis suggests a malignant lesion with perineural invasion.
Diagnostic Tests and Interpretation
- Technetium-99m (Warthin tumor): Follow patient closely.
- Sialography (for calculi or chronic parotitis)
- Autoimmune studies (ESR, CRP, ANA)
- Fractionated amylase (inflammation)
- Drugs that may alter lab results: None known
- Disorders that may alter lab results: None known
- U/S: Inflammatory or malignant (first-line investigation of choice in the assessment of salivary gland swelling) (3)
- Sjögren syndrome
- CT scan: Provides detail of tumor invasion and temporal bone or mandibular destruction in addition to regional and distant metastases prior to planning treatment
- Provides definition of soft tissue and any evidence of perineural invasion or intracranial extension
- Discriminates tumor from mucus and bone marrow invasion
- PET scan: Useful for detecting malignancy in early stages and for detecting recurrences and differentiating soft tissue damage secondary to radiation from inflammatory changes
- Staging (2010 AJCC):
- TNM (tumor size, nodal status, and metastasis)
- Stage I–IVc
- Fine-needle aspiration:
- Concern for possible tumor seeding via needle track; however, tumor spread from tumor seeding is rare.
- Sensitivity 87%, specificity 96%, but false-negative rate up to 53% (3)
- Superficial parotidectomy with identification and preservation of facial nerve
- Metabolic causes (diabetes, vitamin deficiencies, alcohol, gout)
- Drugs (thiourea, iodine)
- Inflammatory masses
- Parotid and submandibular lymph nodes
- Mikulicz syndrome
- Salivary gland stones
- Torus palatinus (minor)
- Necrotizing sialometaplasia (minor)
- Cervical lymph nodes
- Sjögren syndrome
- HIV-associated enlargement (lymphoepithelial cyst)
- Cat-scratch disease
- Surgical excision is the primary treatment for all salivary gland tumors; wide surgical excision margins preferred (3):
- Superficial lobe parotidectomy
- Transoral or transcervical resection for deep lobe tumors
- Facial nerve is spared unless it is directly involved or highly suspicious.
- Poor general response to chemotherapy
- Adjuvant chemotherapy is currently indicated for palliation (1).
- Radiotherapy is currently used for nonresectable, extensive, large tumors (1).
- No level 1 trials have shown efficacy for postoperative radiotherapy.
Cisplatin-, fluorouracil-, or paclitaxel-based regimens for recurrent or nonoperable disease (4)
- Elevate head of bed postoperatively.
- Suction drainage for 1–2 days.
- Suture-line care with antibiotic ointment
- Examination for facial nerve function
- Monitor for signs of hematoma and drain if present.
- Usually 1–2-day hospitalization
- Postoperative irradiation (via fast neutron beam) for larger and high-grade carcinomas, perineural invasion, and incomplete excision
- Chemotherapy reserved for metastases or locally advanced and unresectable tumors
- Benign tumors: Superficial or total conservative (nerve-sparing) parotidectomy
- Malignant tumors:
- Total parotidectomy or sialadenectomy with adjuvant radiotherapy to parotid base of skull ± neck dissection
- Preservation of facial nerve unless involved by tumor
- Cervical lymphadenectomy if palpable nodes or elective neck dissection in SCC, high-grade mucoepidermoid carcinoma, or high-grade adenocarcinoma
- For malignancy: Every 6–8 weeks 1st year, every 8–12 weeks 2nd year, every 4 months 3rd year, every 6 months 4th year, and then yearly
- For benign tumors: Once a year for 5 years
Nonstimulating liquid diet
- Xerostomia treatment and mouth care
- Tobacco cessation and alcohol abstinence
- Sensorineural hearing loss
- By tumor type:
- Parotid pleomorphic adenoma: Untreated will demonstrate malignant degeneration in 2–10% over 20 years. Treated adequately, parotid pleomorphic adenoma has 1.5% recurrence rate. Extension of pseudopods of tumor beyond the tumor mass increases the risk of recurrent disease.
- Adenoid cystic:
- Parotid: 5-year survival, 73%; 15-year survival, 21%
- Submandibular: 5-year survival, 50%; 15-year survival, 0%;
- Palate: 5-year survival, 80%; 15-year survival, 38%
- Aggressive tumors with a tendency for local recurrence (38%); regional lymph node metastasis (33%); and dissemination to lungs, bone, and liver
- 5-year survival, 78%; 20-year survival, 41%
- Low-grade: 5-year survival, 81%; 15-year survival, 48%
- High-grade: 5-year survival, 46%; 15-year survival, 25%
- Rare tumor with 50% incidence of cervical lymph node metastasis and local recurrence
- 5-year survival, 18%; 15-year survival, 0%
- Rare, accounting for 1.7% of salivary neoplasms
- 5-year survival: Hodgkin-type, 90%; non-Hodgkin-type, 43%
- 5-year survival rate for stages I–IV and cause-specific survival (CSS):
- Stage I: 75% (CSS 86%)
- Stage II: 59% (CSS 66%)
- Stage III: 57% (CSS 53%)
- Stage IV: 28% (CSS 32%)
- Frey syndrome (gustatory sweating) occurs symptomatically in ~20% of patients undergoing parotidectomy.
- Hematoma with possible posterior displacement of tongue and airway obstruction
- Facial neurapraxia from surgery should resolve within 6 months, even with radiotherapy.
- Cosmetic deformity of moderate facial flattening on side of parotidectomy
- Injury to hypoglossal or lingual nerve
- If inadequately excised, pleomorphic adenoma may recur due to pseudopods in the lobe.
- Wound infection of surgical site
- Adelstein DJ, Rodriguez CP. What is new in the management of salivary gland cancers? Curr Opin Oncol. 2011;23:249–253.
- de Bree R, van der Waal I, Leemans CR. Management of Frey syndrome. Head Neck. 2007;84(8):773–778.
- 142.0 Malignant neoplasm of parotid gland
- 142.8 Malignant neoplasm of other major salivary glands
- 210.2 Benign neoplasm of major salivary glands
- 142.1 Malignant neoplasm of submandibular gland
- 142.2 Malignant neoplasm of sublingual gland
- 142.9 Malignant neoplasm of salivary gland, unspecified
- 210.4 Benign neoplasm of other and unspecified parts of mouth
- D11.9 Benign neoplasm of major salivary gland, unspecified
- C08.9 Malignant neoplasm of major salivary gland, unspecified
- C07 Malignant neoplasm of parotid gland
- C08.0 Malignant neoplasm of submandibular gland
- C08.1 Malignant neoplasm of sublingual gland
- D11.0 Benign neoplasm of parotid gland
- D11.7 Benign neoplasm of other major salivary glands
- 235132004 Tumor of salivary gland
- 92205005 Benign neoplasm of major salivary gland
- 93883004 Primary malignant neoplasm of major salivary gland
- 372004005 Primary malignant neoplasm of parotid gland
- 363380002 Malignant tumor of submandibular gland
- 94076001 Primary malignant neoplasm of sublingual gland
- Delay in diagnosis is common in rare disease, especially with diverse, nonspecific presentation of deep lobe/minor salivary gland tumors.
- To evaluate a patient with a suspected salivary gland malignancy, complete history and physical, and consider either CT scan or MRI; fine-needle aspiration likely will yield a working diagnosis.
- A neck lymphadenectomy is required with tumors ≥4 cm in size, SCC, adenocarcinoma, undifferentiated carcinoma, and high-grade mucoepidermoid carcinoma.
Richard Gacek, MD
Costa Gioules, MD
- Guzzo M, Locati LD, Prott FJ, et al. Major and minor salivary gland tumors. Crit Rev Oncol Hematol. 2010;84(2):134–148. Epub 2009 Nov 24.
- Spitz MR. Epidemiology and risk factors for head and neck cancer. Semin Oncol. 1994;21:281–288. [PMID:8209260]
- Isa AY, Hilmi OJ. An evidence based approach to the management of salivary masses. Clin Otolaryngol. 2009;34:470–473. [PMID:19793281]
- Surakanti SG, Agulnik M. Salivary gland malignancies: The role for chemotherapy and molecular targeted agents. Semin Oncol. 2008;35:309–319. [PMID:18544445]
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