Diseases of the salivary glands

The parotid, submandibular, and sublingual glands are the largest salivary glands. These glands may swell repeatedly and often bilaterally (sialadenosis), but are also subject to acute inflammation that is predominantly unilateral (sialadenitis). Diseases that commonly cause sialadenitis include: Sjögren syndrome (chronic immunologic sialadenitis), Heerfordt syndrome, and mumps (epidemic parotitis). Sialadenosis and sialadenitis primarily affect the parotid gland. However, stones in the salivary ducts (sialolithiasis) mainly form in the submandibular gland because of its ascending salivary duct.

Salivary gland tumors manifest mainly in the parotid. Painless and progressive swelling of the gland is the cardinal symptom of benign as well as malignant tumors, while facial palsy is considered a criterion for malignancy. Generally, the smaller the gland, the greater the chance that the tumor is malignant. Clinical examination and ultrasound play the biggest role in diagnosis. For all parotid tumors, the preferred treatment is parotidectomy with retention of the facial nerve. A resection of the facial nerve is indicated only if it is infiltrated by the tumor. Postoperative radiation therapy may benefit patients with malignant tumors.

• Definition: recurrent, noninflammatory swelling of the salivary glands
• Location: most often the parotid gland
• Etiology
  • Endocrine: particularly diabetes mellitus
  • Dystrophic sialadenosis: alcohol abuse, malnutrition, or eating disorders (e.g., bulimia) ^[1]
  • Medications: e.g., clonidine
• Symptoms: painless swelling (usually bilateral)
• Treatment: treatment of underlying disease

• Definition: acute inflammation of the salivary glands
• Etiology
  • Infection; : usually bacterial pathogens (commonly Staphylococcus aureus)
    • Sometimes Streptococcus viridans, Haemophilus influenzae, Streptococcus pyogenes, Escherichia coli
    • Rarely viruses such as mumps and HIV
  • Risk factors
    • Obstruction (e.g., due to salivary stones)
    • Immune disorders
    • Cachexia in intensive care patients
    • Postoperatively (due to dehydration, intubation)
    • Intensive teeth cleaning
    • Decreased salivation (due to fasting, special diet)
    • Advanced age
    • Anticholinergic drug use
    • Oral neoplasia
    • Malnutrition
• Location: most often the parotid gland
• Clinical features
  • Acute onset
  • Unilateral painful swelling and erythema overlying the salivary gland
  • Usually with purulent discharge expressed from duct orifice
  • Systemic toxicity: fever, chills
• Diagnostics
  • Mostly a clinical diagnosis
  • ↑ Serum amylase indicates parotid involvement
  • Gram stain and culture of discharge
  • Ultrasound or CT if abscess is suspected
• Treatment
  • Hydration
  • Stimulation of salivation (chewing gum, lemon drops)
  • Intravenous antibiotics: nafcillin + metronidazole OR clindamycin
    • Immunocompromised patients: vancomycin OR linezolid + one of the following:
      • Cefepime + metronidazole
      • Imipenem
      • Meropenem
      • Piperacillin-tazobactam
    • Poor response to 48 hours of antibiotics or an abscess: surgical drainage and decompression
  • Recurrent infections: parotidectomy
• Complications: deep neck infections

References:^[2][3][4]

• Definition: formation of stones in the salivary ducts
• Etiology
  • Often idiopathic
  • Dehydration
  • Trauma
• Location: may occur in any of the larger salivary glands
  • Primarily in the Wharton duct located in the submandibular gland (∼ 80% of cases; typically a large single stone)
  • Parotid gland (∼ 20% of cases)
• Clinical features
  • Recurrent, significant pain before and while eating
  • Partial swelling of the glands
• Diagnostics
  • Sonography
  • Noncontrast CT
  • Sialography (rarely)
  • Possibly x-ray of the skull (particularly the base of the mouth)
• Complications: acute or chronic sialadenitis
• Treatment
  • Mainly conservative
    • NSAIDs for pain relief
    • Stimulation of salivary flow by sucking sour candies, massaging the gland, and applying warm compresses
  • Invasive (only in severe cases): dilatation of the salivary duct or ultrasonic lithotripsy

References:^[3][4][5]

• Definition: retention cyst arising in the sublingual gland
• Epidemiology: ^[6]
  • ♂ ≈ ♀
  • Most common between 10–30 years of age
    • Has been reported in patients aged 3–61 years
  • Rare (∼ 3% of salivary cysts)
• Etiology: unclear
• Clinical features
  • Translucent blue swelling below the tongue
  • Can cause problems swallowing and speaking
• Treatment
  • Extirpation of the ranula, including the sublingual gland
  • Marsupialization

Most salivary gland tumors are benign.

Pleomorphic adenoma (benign mixed tumor)

• Epidemiology
  • Sex: ♀ > ♂
  • Peak incidence: 40–60 years
  • Most common salivary gland tumor; (accounts for 85% of benign salivary gland tumors)
• Etiology: ionizing radiation, environmental/occupational exposure (e.g., rubber manufacturing, cosmetologists, nickel compound exposure) ^[7]
• Location: usually the parotid gland (∼ 80% of cases)
• Clinical features
  • Gradual and painless unilateral swelling of the gland
  • Robust, movable tumor
• Diagnostics
  • Ultrasound: diagnostic method of choice in salivary gland tumors
  • MRI (T2-weighted image): sharply limited, lobulated hyperintense mass ^[8]
  • Histology
    • Mixed cellular constitution with myoepithelial cells and chondroid tissue
    • Cytokeratin is expressed immunohistochemically
• Complications: Malignant transformation may occur (∼ 5% of cases).
• Treatment: : Best treatment is superficial parotidectomy to prevent recurrence. ^[5]
• Prognosis
  • Very good overall prognosis
  • Recurrence (∼ 5% of cases): typically due to incomplete resection or rupture of tumor during surgery

Other types of benign salivary gland tumors (monomorphic adenomas)

These benign salivary gland tumors fall under the umbrella term "monomorphic adenoma" because they usually originate in only one type of cell – as opposed to the pleomorphic adenomas, which consist of both epithelial and myoepithelial cells.

Warthin tumor (papillary cystadenoma lymphomatosum)

• Epidemiology
  • Sex: ♂ >> ♀
  • Peak incidence: 60–80 years
  • 2^nd most common benign salivary gland tumor (accounting for 10% of benign cases) ^[9]
• Etiology
  • Ionizing radiation
  • Smoking
• Location: : most often the parotid gland (10% bilateral, 10% multifocal)
• Clinical features: gradual and painless unilateral swelling of the parotid
• Diagnostics
  • Ultrasound: diagnostic method of choice in salivary gland tumors
  • MRI
  • Histology
    • Cystic structure
    • Germinal centers
• Treatment: complete extirpation of the tumor with preservation of facial nerve
• Complications: rarely malignant transformation

WARning! Smoking makes GERMs more resilient.

Rare histologic subtypes

• Oncocytoma (∼ 2% of cases)
• Basal cell adenoma (∼ 1–2% of cases)
• Myoepithelioma (∼ 1% of cases)

Malignant salivary gland tumors are referred to collectively because of their many etiological, epidemiological, and pathological similarities.

• Location
  • Most common: parotid gland → parotid carcinoma
  • Less common locations
    • Submandibular and sublingual glands: Neoplasms in these locations are less common compared to those in the parotid gland, but they are more frequently malignant (∼ 45% of submandibular and 70–90% of sublingual tumors).
    • Minor salivary glands (gums and the base of the mouth): Most tumors are malignant.
  • Less common locations
    • Submandibular and sublingual carcinomas
    • Carcinomas of the salivary glands in the gums and the base of the mouth
• Etiology
  • Ionizing radiation
  • Viral infection (e.g., HIV or HPV may be implicated )
• Symptoms
  • Insidious onset
  • Painless submucosal swelling or mucosal ulceration (palate, buccal mucosa, lips)
  • In some cases, clinical symptoms arise if the neighboring structures are infiltrated (e.g., facial palsy caused by parotid carcinomas).
• Diagnostics
  • Ultrasound of the head and neck (to determine location and size of mass); with or without biopsy (definitive diagnosis)
  • Contrast enhanced CT/MRI of head and neck: useful as preoperative workup to determine location, size, and extension of the lesion
• Pathology
  • Subtypes
    • Mucoepidermoid carcinoma
      • Most common malignant salivary gland tumor
      • Involves squamous and mucinous cells, both of which arise from excretory stem cells ^[10]
    • Adenoid cystic carcinoma (obsolete term: cylindroma)
      • Growth along nerve sheaths
      • Cribriform or tubular growth pattern
      • Very slow but dangerous infiltrative growth
    • Acinic cell carcinoma
    • Adenocarcinoma
    • Metastases of other malignant tumors in head and neck
  • Routes of metastasis
    • Initially lymphogenic in local lymph nodes
    • Later hematogenic metastasis, particularly in the lungs
• Treatment
  • Curative
    • Parotidectomy (superficial or total), if possible, with preservation of the facial nerve
    • +/- Neck dissection and/or adjuvant radiotherapy for extensive or higher grade tumors
  • Palliative: chemotherapy
• Complications of a parotidectomy
  • Facial nerve injury (most common early complication)
  • Hematoma
  • Salivary fistula
  • Frey syndrome: gustatory sweating
  • Crocodile tears (gustatory hyperlacrimation): Regenerating parasympathetic gustatory fibers attach to the lacrimal gland.

Submandibular gland tumors are less common but more frequently malignant than parotid tumors. Generally, the smaller the gland, the higher the risk a tumor is malignant!

References:^[11][12][13]

1. Garcia Garcia B, Dean Ferrer A, Diaz Jimenez N, Alamillos Granados FJ. Bilateral parotid sialadenosis associated with long-standing bulimia: A case report and literature review. J Maxillofac Oral Surg. 2016; 17 (2): p.117-121. doi: 10.1007/s12663-016-0913-7 . | Open in Read by QxMD
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7. Lee SC. Salivary Gland Neoplasms. In: Meyers AD, Salivary Gland Neoplasms. New York, NY: WebMD. http://emedicine.medscape.com/article/852373. Updated: March 13, 2017. Accessed: March 18, 2017.
8. Smith CC, Pariser D, Dellavalle RP, Dahl MV, Ofori AO. Primary Focal Hyperhidrosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/primary-focal-hyperhidrosis.Last updated: December 30, 2015. Accessed: August 10, 2017.
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10. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education ; 2014
11. Marchese-Ragona R, De Filippis C, Marioni G, Staffieri A. Treatment of complications of parotid gland surgery. Acta Otorhinolaryngol Ital. 2005; 25 (3): p.174-178.
12. Laurie SA, Brockstein BE, Brizel DM, Fried MP, Ross ME. Salivary Gland Tumors: Epidemiology, Diagnosis, Evaluation, and Staging. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/salivary-gland-tumors-epidemiology-diagnosis-evaluation-and-staging.Last updated: November 2, 2016. Accessed: August 9, 2017.
13. Pleomorphic Parotid Adenoma Imaging. https://radiopaedia.org/articles/pleomorphic-adenoma-of-the-salivary-glands. . Accessed: May 31, 2018.
14. Warthin tumour. https://radiopaedia.org/articles/warthin-tumour. . Accessed: May 31, 2018.