Diseases of the Salivary Glands

Diseases of the salivary glands include sialadenosis, sialadenitis, sialolithiasis, and neoplasms. Sialadenosis is a chronic, bilateral, noninflammatory hypertrophy of the salivary glands. Sialadenitis results from inflammation or infection of the glands, and sialolithiasis is due to stone formation in the glands or ducts. Neoplasms of the salivary gland may be benign or malignant. All of these conditions manifest as salivary gland enlargement. Other clinical factors help differentiate these conditions, such as symmetry, the presence of pain, associated conditions and risk factors, and growth or stability. The diagnosis is often clinical, though imaging and biopsy may be needed. Management varies depending on the disease.

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Overview

Major salivary glands

  • Parotid glands
  • Submandibular glands
  • Sublingual glands
Location of the major salivary glands and their ducts

Diagram depicting the location of the major salivary glands and their ducts

Image: “2408 Salivary Glands” by OpenStax College. License: CC BY 3.0

Physiology

The major salivary glands produce > 95% of an individual’s saliva.

  • Secreted by acinar cells
  • Concentration of ions modified by ductal cells
  • Composition: 
    • 99.5% water 
    • Electrolytes
    • Mucus
    • Glycoproteins
    • Enzymes
    • Antibacterial compounds
  • Function:
    • Lubricates food to aid in the swallowing process
    • Starts digestion of carbohydrates and lipids
    • Immunologic defense against microbes in the oral cavity
    • Protects the oral mucosa and teeth
    • Aids in the sense of taste
Ion movement between the acinar cells and the ductal cells

Diagram displaying the differences in ion movement between the acinar cells (in charge of secretion) and the ductal cells (in charge of reabsorption)

Image by Lecturio.

Terminology for pathologic conditions

Since sialadenosis, sialadenitis, and sialithiasis are similar-appearing names, understanding the suffix may aid in differentiating the underlying process.

  • “-osis”: increase or pathologic condition
  • “-itis”: inflammation or infection
  • “-lithiasis”: stone formation

Related videos

Sialadenosis

Definition

Sialadenosis (sialosis) is a chronic, benign, noninflammatory hypertrophy of the salivary glands.

Epidemiology

  • Most common cause of salivary gland swelling
  • Incidence and prevalence are unknown
  • Men = women

Etiology

  • Drug-induced:
    • Valproic acid
    • Thiouracil
    • Antihypertensives
  • Nutritional:
    • Vitamin deficiencies and malnutrition
    • Bulimia
  • Endocrine/metabolic disorders:
    • Diabetes
    • Hypothyroidism
    • Obesity
  • Other medical conditions:
    • Sjögren syndrome
    • Cirrhosis
    • Alcoholism

Pathophysiology

  • The cause of hypertrophy is unknown.
  • Potential process: accumulation of secretory granules in acinar cells → acinar enlargement → fatty infiltration of the salivary glands

Clinical presentation

Patients will present with enlarged salivary glands with the following characteristics:

  • Usually bilateral
  • Symmetrical 
  • No fluctuation in size or progressive enlargement
  • Soft
  • Nontender
Bilateral parotid gland swelling due to sialadenosis

Bilateral parotid gland swelling due to sialadenosis (sialosis)

Image: “Buccal alterations in diabetes mellitus” by Negrato CA, Tarzia O. License: CC BY 2.0

Diagnosis

  • Suspected based on history and physical examination
  • Ultrasonography: 
    • Diffuse salivary gland enlargement
    • Other abnormalities should be ruled out

Management

No treatment is needed, other than addressing the underlying medical condition.

Sialadenitis

Definition

Sialadenitis is inflammation or infection of the salivary glands.

Epidemiology

  • The exact incidence is unknown.
  • No predilection for race or sex
  • Tends to occur in older, chronically ill, and dehydrated patients

Etiology

  • Infectious causes (most common): 
    • Viral:
      • Mumps
      • EBV
      • Parainfluenza
      • Adenovirus
      • Enterovirus
      • Parvovirus
      • HHV-6
    • Bacterial:
      • Staphylococcus aureus
      • Streptococcus viridans
      • Haemophilus influenzae
      • Streptococcus pyogenes
      • Escherichia coli
  • Iatrogenic causes:
    • Radiation treatment
    • Radioiodine or contrast exposure
  • Drug-induced:
    • Clozapine
    • Phenylbutazone
  • Juvenile recurrent parotitis

Risk factors

  • Age > 50 years
  • HIV 
  • Xerostomia
  • Dehydration
  • Anorexia or bulimia 
  • Sjögren syndrome 
  • Sialolithiasis

Pathophysiology

  • Bacterial: ductal obstruction or salivary hyposecretion → ascending bacterial contamination → secondary infection
  • Radiation or iodine-induced: inflammation or damage to gland parenchyma → acute swelling → may or may not be associated with ductal blockage

Clinical presentation

  • Acute salivary gland swelling:
    • Usually unilateral 
    • Parotid gland is most commonly involved (parotitis)
    • Pain and swelling with meals
    • Firm and diffusely tender
  • Overlying erythema and edema
  • Purulent exudate can sometimes be massaged from the duct opening.
  • Fever and chills

Diagnosis

The diagnosis is clinical. An evaluation can be done if the diagnosis is uncertain or to determine an etiology:

  • Gram stain and culture of purulent exudate from the gland (if possible)
  • PCR or serology for mumps virus
  • Imaging with CT, ultrasonography, or MRI to identify:
    • Stones in the duct
    • Abscess
    • Inflammation of the gland

Management

General measures:

  • Hydration
  • Good oral hygiene
  • Warm compresses
  • Massage of the gland
  • Sialagogues (↑ salivary flow):
    • Chewing gum
    • Lemon drops

For bacterial infection:

  • Initial antibiotics:
    • Community-acquired:
      • Ampicillin–sulbactam
      • Cefuroxime plus metronidazole
      • Nafcillin plus ceftriaxone (or levofloxacin) plus metronidazole (or clindamycin)
    • Hospital-acquired or immunocompromised: vancomycin plus any of the following:
      • Cefepime plus metronidazole
      • Carbapenem
      • Piperacillin–tazobactam
  • Abscess drainage

Sialolithiasis

Definition

Sialolithiasis is the formation of calculi within the salivary glands or ducts.

Epidemiology

  • Estimated incidence: 0.3–1 in 10,000 people
  • Men > women
  • Age range: 30–60 years
  • Approximately 80% of stones occur in submandibular glands.

Etiology

  • Stagnation of salivary flow:
    • Anatomical duct stenosis
    • Inflammation
    • Dehydration
    • Anorexia
    • Allergies
    • Medications (e.g., anticholinergics)
  • ↑ Salivary calcium

Pathophysiology

  • The pathogenesis of stone formation is not well understood.
  • Calculi can obstruct ducts → ↑ pressure within the gland → pain and swelling

Clinical presentation

  • Glandular swelling
  • May or may not have associated pain and tenderness
  • Pain is worse with eating.
  • Digital palpation may reveal the presence of calculus.
Salivary gland stone (sialolithiasis)

Salivary gland stone (sialolithiasis)

Image: “Salivary gland stone removed” by Peternickson. License: CC0 1.0

Diagnosis

  • Usually a clinical diagnosis
  • The presence of a stone may be confirmed with:
    • X-ray
    • Ultrasonography
    • CT
    • Sialography (radiopaque dye is injected into the duct for visualization on X-ray)
X-ray demonstrating a massive opacity consistent with sialolithiasis

X-ray demonstrating a massive opacity (arrow) consistent with sialolithiasis

Image: “Massive Submandibular Sialolith: Complete Radiographic Registration and Biochemical Analysis through X-Ray Diffraction” by Franco, A., et al. License: CC BY 3.0

Management

  • Conservative management:
    • Hydration
    • Hot compresses
    • Gland massage
    • Analgesia with NSAIDs
    • Sialagogues
  • Stones close to the orifice of the duct may be removed with manual expression.
  • Other methods:
    • Sialendoscopy
    • Extracorporeal shock-wave lithotripsy
    • Laser lithotripsy 
    • Basket retrieval
  • If the obstruction cannot be removed, surgical excision may be necessary.

Salivary Gland Neoplasms

Epidemiology

  • Salivary gland tumors are rare.
  • Incidence: approximately 5.5 cases per 100,000 people per year in the United States
  • Represent 6%–8% of all head and neck tumors
  • Age: 
    • Benign: > 40 years of age
    • Malignant: > 60 years of age
  • Sex:
    • Benign: women > men
    • Malignant: men = women
  • The parotid gland is the most common site (80%–85% of cases).

Classification

  • Benign neoplasms (majority):
    • Pleomorphic adenoma (most common)
    • Warthin tumor (also known as papillary cystadenoma lymphomatosum)
    • Myoepithelioma
    • Lymphadenoma
    • Sebaceous adenoma
    • Basal cell adenoma
    • Canalicular adenoma
    • Oncocytoma
    • Cystadenoma
    • Sialadenoma papilliferum
    • Ductal papilloma
  • Malignant neoplasms:
    • Mucoepidermoid carcinoma (most common)
    • Adenoid cystic carcinoma
    • Acinic cell carcinoma
    • Carcinoma ex pleomorphic adenoma (malignant transformation of pleomorphic adenoma)
    • Polymorphous low-grade adenocarcinoma
    • Salivary duct carcinoma
    • Primary squamous cell carcinoma

Risk factors

The following are risk factors for malignant salivary tumors:

  • Ionizing radiation exposure
  • Environmental exposures:
    • Rubber manufacturing
    • Nickel compounds
    • Hair salon/beauty shop personnel
  • Viral infections:
    • EBV
    • HIV

Clinical presentation

  • Presentation based on involved glands:
    • Major salivary glands: painless mass or swelling
    • Minor salivary glands:
      • Submucosal mass 
      • Mucosal ulceration
  • Malignant tumors are characterized by: 
    • Rapid growth
    • Firm
    • Nodular
    • Can be fixed to adjacent tissue
    • Facial nerve involvement: 
      • Persistent pain
      • Asymmetry of facial motion 
      • Total facial paralysis
    • Associated with cervical lymphadenopathy
  • Depending on the location, neoplasms can lead to:
    • Dysphagia or odynophagia
    • Nasal or airway obstruction
    • Vocal hoarseness

Diagnosis

  • Fine-needle aspiration biopsy establishes the diagnosis.
  • Ultrasonography:
    • Usually an initial test to distinguish characteristics of the mass
    • Useful in guiding biopsy
  • CT or MRI can be used to define the extent of the tumor:
    • Assess the location
    • Detect local invasion
    • Identify metastatic disease
CT neck soft tissue demonstrating an enhancing mass

CT of neck soft tissue demonstrates an enhancing mass (white arrow) within the left parotid gland. No enlarged lymph nodes or abnormal fluid collections are seen.

Image: “An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor” by Arcega RS, Feinstein AJ, Bhuta S, Blackwell KE, Rao NP, Pullarkat ST. License: CC BY 4.0

Management

  • Complete surgical excision:
    • Treatment of choice for all salivary gland neoplasms
    • Complications:
      • Facial nerve injury (most common early complication)
      • Frey’s syndrome: gustatory sweating and flushing due to abnormal regeneration of parasympathetic nerve fibers
  • Adjuvant radiation therapy may be used for malignant neoplasms.

Differential Diagnosis

  • Branchial cleft cyst: congenital defect resulting from incomplete obliteration of the branchial clefts during embryonic development. Branchial cleft cyst can cause a small, painless neck mass that can become infected, resulting in the cyst becoming tender and inflamed. The diagnosis is typically clinical, and excision can be considered.
  • Lymphadenopathy: palpable enlargement of the lymph nodes, which can result from a number of etiologies, including infection and malignancy. If there is concern for malignancy or worrisome physical exam findings, laboratory evaluation, peripheral blood smear, biopsy, or infectious workup should be performed. Management is directed at the underlying etiology.
  • Dental abscess: odontogenic infection that often arises because of dental caries. Patients with dental abscess can have severe tooth pain, facial erythema, and fever. The diagnosis is made with physical examination and imaging. Management includes drainage of the abscess, antibiotics, and removal of the infected tooth.
  • Cellulitis: common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. Cellulitis can occur anywhere, including the face or neck. The infection presents as an erythematous, edematous area with warmth and tenderness. Diagnosis is usually clinical, and management involves antibiotics.
  • Hodgkin lymphoma: malignancy of B lymphocytes originating in the lymph nodes. The disease presents with lymphadenopathy (most commonly involving the neck), night sweats, weight loss, fever, and potentially splenomegaly and hepatomegaly. Diagnostic testing includes lymph node histologic analysis, blood tests, and imaging. Management includes chemotherapy and radiotherapy.

References

  1. Hoffman, H. T. (2020). Salivary gland swelling: evaluation and diagnostic approach. In Kunins, L. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/salivary-gland-swelling-evaluation-and-diagnostic-approach
  2. Adhikari, R., Soni, A. (2021). Submandibular sialadenitis and sialadenosis. StatPearls. Retrieved May 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK562211/
  3. Yoskovitch, A. (2020). Submandibular sialadenitis/sialadenosis. In Meyers, A. D. (Ed.), Medscape. Retrieved May 19, 2021, from https://emedicine.medscape.com/article/882358-overview
  4. Chow, A. W. (2020). Supportive parotitis in adults. In Bloom, A. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/suppurative-parotitis-in-adults
  5. Sasaki, C. T. (2020). Sialadenitis. MSD Manual Professional Version. Retrieved May 19, 2021, from https://www.msdmanuals.com/professional/ear,-nose,-and-throat-disorders/oral-and-pharyngeal-disorders/sialadenitis
  6. Koch, M., Zenk, J., Iro, H. (2009). Algorithms for treatment of salivary gland obstructions. Otolaryngol Clin North Am 42:1173–1192. https://doi.org/10.1016/j.otc.2009.08.002
  7. Fazio, S. B., and Emerick, K. (2021). Salivary gland stones. In Kunins, L. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/salivary-gland-stones
  8. Sasaki, C. T. (2020). Salivary stones. MSD Manual Professional Version. Retrieved May 19, 2021, from https://www.msdmanuals.com/professional/ear,-nose,-and-throat-disorders/oral-and-pharyngeal-disorders/salivary-stones
  9. Hammett, J. T., Walker, C. (2020). Sialolithiasis. StatPearls. Retrieved May 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK549845/
  10. National Cancer Institute (2019). Salivary gland cancer treatment (adult) (PDQ®)-health professional version. Retrieved May 19, 2021, from https://www.cancer.gov/types/head-and-neck/hp/adult/salivary-gland-treatment-pdq
  11. Mendenhall, W. M., Werning, J. W., Pfister, D. G. (20011). Treatment of head and neck cancer. In: DeVita, V. T., Jr., Lawrence, T. S., Rosenberg, S. A. (Eds.), Cancer: Principles and Practice of Oncology, 9th ed. Philadelphia: Lippincott Williams & Wilkins, pp. 729–780.
  12. Huoh, K. C., Eisele, D. W. (2011). Etiologic factors in sialolithiasis. Otolaryngol Head Neck Surg 145:935–939. https://pubmed.ncbi.nlm.nih.gov/21753035/
  13. Lee, S. C., Johnson, J. T. (2021). Salivary gland neoplasms. In Meyers, A. D. (Ed.), Medscape. Retrieved May 19, 2021, from https://emedicine.medscape.com/article/852373-overview
  14. Young, A., Okuyemi, O. T. (2020). Benign salivary gland tumors. StatPearls. Retrieved May 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK564295/
  15. Yount, A., Okuyemi, O. T. (2020). Malignant salivary gland tumors. StatPearls. Retrieved May 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK563022/
  16. Schiff, B. A. (2021). Salivary gland tumors. MSD Manual Professional Version. Retrieved May 19, 2021, from https://www.msdmanuals.com/professional/ear,-nose,-and-throat-disorders/tumors-of-the-head-and-neck/salivary-gland-tumors
  17. Lauri, S. A. (2020). Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging. In Shah, S. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/salivary-gland-tumors-epidemiology-diagnosis-evaluation-and-staging
  18. Lydiatt, W. M., Quivey, J. M. (2021). Salivary gland tumors: treatment of locoregional disease. In Shah, S. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/salivary-gland-tumors-treatment-of-locoregional-disease
  19. Laurie, S. A., Schiff, B. (2020). Malignant salivary gland tumors: treatment of recurrent and metastatic disease. In Shah, S. (Ed.), UpToDate. Retrieved May 19, 2021, from https://www.uptodate.com/contents/malignant-salivary-gland-tumors-treatment-of-recurrent-and-metastatic-disease3

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