Description

• 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.
• 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.

Epidemiology

• 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

Prevalence
Make up 6–8% of all head and neck neoplasms (1)

Risk Factors

• 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)

Genetics
Increased incidence of adenocarcinoma of parotid in Eskimos; otherwise, no known genetic pattern

General Prevention

Cessation of tobacco and alcohol use

Pathophysiology

Pathophysiology not fully understood; certain pathways and oncogenes have been implicated: p53, Bcl-2, PI3K/Akt, MDM2, VEGF, HGF, and ras.

Etiology

• Etiology is not fully understood.
• Predominant theory: Tumors arise from either the secretory duct reserve cell or the intercalated duct reserve cell.

History

• 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.

Physical Exam

• 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)
• CXR:
  • Sjögren syndrome
  • Metastases
• CT scan: Provides detail of tumor invasion and temporal bone or mandibular destruction in addition to regional and distant metastases prior to planning treatment
• MRI:
  • 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

Differential Diagnosis

• 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
• Sarcoidosis
• HIV-associated enlargement (lymphoepithelial cyst)
• Actinomycosis
• Cat-scratch disease
• Tuberculosis

Medication (Drugs)

Cisplatin-, fluorouracil-, or paclitaxel-based regimens for recurrent or nonoperable disease (4)

Additional Treatment

Postoperative care:

• 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

Surgery/Other Procedures

• 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

In-Patient Considerations

Admission Criteria
Airway impingement

Follow-Up Recommendations

• 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

Diet

Nonstimulating liquid diet

Patient Education

• Xerostomia treatment and mouth care
• Tobacco cessation and alcohol abstinence
• Sensorineural hearing loss

Prognosis

• 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%
  • Adenocarcinoma:
    • 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%
  • Mucoepidermoid:
    • Low-grade: 5-year survival, 81%; 15-year survival, 48%
    • High-grade: 5-year survival, 46%; 15-year survival, 25%
  • SCC:
    • Rare tumor with 50% incidence of cervical lymph node metastasis and local recurrence
    • 5-year survival, 18%; 15-year survival, 0%
  • Lymphoma:
    • 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%)

Complications

• 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

See Also

Sjögren Syndrome

ICD-9

• 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

ICD-10

• 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

SNOMED

• 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