Sialolithiasis

Etiology

The etiology of salivary stone formation remains elusive, and research into etiologic factors is still limited due to the relatively rare incidence of the disease, which makes extensive studies difficult. Factors that are believed to affect salivary stone formation are divided into two major groups: anatomical, affecting saliva formation or flow (ie, duct stenosis or inflammation), and compositional (ie, increased calcium content or altered enzyme function).

Research examining the geographic distribution of hard water and salivary calculi formation demonstrated no correlation with an increased incidence of salivary stones in areas of increased water hardness.[5] Studies examining the effects of hypercalcemia using animal models demonstrated no evidence of increased salivary stones with hypercalcemia.[3] Additional factors, such as decreased fluid intake and pharmacologic side effects resulting in decreased salivary production (ie, diuretic use), remain under study. In recent years tobacco smoking has been discussed as a potential risk factor for the formation of salivary stones. Tobacco may induce inflammation within the salivary ducts and decrease the production of salivary amylase.[1][3]

Epidemiology

The incidence of sialolithiasis is estimated at 1 in 10,000 to 1 in 30,000 individuals.[1] The primary age of diagnosis is between 30 and 60, with a higher incidence in men. Approximately 85% of sialoliths occur within the submandibular gland, making it the most common location for sialolithiasis. One of the reasons is that the submandibular duct ascends towards its opening in the oral cavity, resulting in a stagnant flow of saliva. Additionally, the submandibular gland produces predominately mucinous saliva, which is more viscous than the secretions created by the parotid gland, resulting in a more stagnant flow of secretions. The submandibular gland also produces more alkaline saliva, which predisposes to the precipitation of inorganic salts (eg, calcium and phosphate), further leading to salivary stone formation. Approximately 15% of salivary stones occur within the parotid gland, and less than 5% occur within the sublingual and minor salivary glands.[2][6]

Pathophysiology

The exact pathogenesis of sialolithiasis is not well understood, but two dominant theories were suggested. One of them proposes that there are multiple internal microcalculi within salivary gland secretory granules. When these microcalculi get secreted into the salivary ducts, they may act as a nidus for the formation of larger calculi, ultimately forming a sialolith.[7] The second hypothesis suggests bacteria or food debris within the oral cavity enter the distal submandibular or parotid ducts. Over time, this organic substrate may act as a nidus for the formation of larger calculi.[8]

Histopathology

Histologically, sialoliths are composed of varying ratios of organic and inorganic materials within an inner core. The inner core is considered the initial sialolith, which subsequently enlarges from the deposition of additional organic and inorganic material, forming the outer lamellae (layers). Inorganic materials include hydroxyapatite, whitlockite, and octacalcium phosphate, with hydroxyapatite being the most prevalent. The exact ratios of inorganic material found within a sialolith depend on the chemical environment in which it forms. Organic materials found within sialoliths include glycoproteins, cellular debris, bacteria, and mucopolysaccharides.[3][7] Studies utilizing scanning electron microscopy and polymerase chain reaction have demonstrated bacteria within sialoliths, predominantly the Streptococcus genus.[9][10] Bacteria are not present in all sialoliths suggesting they are not necessary for their formation.

History and Physical

Clinical diagnosis of sialolithiasis can be challenging as patients may not be symptomatic unless the stone obstructs the salivary ducts, termed sialadenitis. Patients with obstructing stones will commonly present a history of unilateral salivary gland swelling and acute onset of pain that worsens with meals.[4] The physical exam will demonstrate asymmetric swelling of the affected salivary gland. Approximately 60% of parotid stones and 30% of submandibular stones will be located distally in their respective ducts. If large enough, these stones may be visually apparent on examination of the oral cavity (see Image. Submandibular Stone). Salivary stones typically demonstrate an oval or round shape and a white or yellow color on visual inspection. If not visually apparent, the stones are usually palpable along the anatomic course of the affected salivary duct or gland.[11][12][13] Salivary stones’ size and weight vary. Sialoliths’ diameter ranges between 2.1 and 10 mm, and only 7.6% exceeds 15 mm in diameter.[14] Submandibular stones are usually larger than parotid ones.[15] Sialoliths weigh 300 mg on average, ranging between 1 mg to 5 g.[14]

Evaluation

Conventional radiographs using occlusal views were the initial diagnostic choice in the past. These can detect large radiopaque ductal stones relatively well, but they miss smaller and parenchymal stones. Additionally, only around 80% of stones are radioopaque, which leads to many stones not being diagnosed. While conventional radiography can still be useful in the initial workup of salivary stones, modern imaging techniques using ultrasound or CT scans can accurately diagnose the sialoliths and provide their exact location.[3] Sialography is traditionally regarded as the gold standard for diagnosing sialolithiasis as it allows excellent visualization of the salivary ducts and underlying ductal pathology. In this technique, contrast is injected via a small needle, enabling radiographic visualization, acting as a sialogogue, and allowing passage of smaller stones. Disadvantages include radiation exposure and risk of contrast reaction.[3][16]

Non-contrast computed tomography (NCCT) is a widely used modality for the evaluation of sialolithiasis. It is a valid tool for diagnosing sialolithiasis when it is big enough or when the radiographic slices are done every millimeter.[3] Advantages include excellent sensitivity and specificity for calcified stones, fast acquisition time, and widespread availability. Disadvantages include radiation exposure and limited evaluation of the ductal system or underlying pathology (ie, obstructing masses). The administration of intravenous contrast has been used only as an adjunct to NCCT due to concerns small vessels may simulate calcifications resulting in false-positive results. A recent study in the American Journal of Neuroradiology comparing contrast-enhanced CT (CECT) and NCCT demonstrated excellent sensitivity and specificity with no false-positive results. Benefits of initial contrast-enhanced CT include better evaluation of the ductal system, improved soft-tissue contrast in assessing salivary masses, and decreased radiation dose (compared to dual-phase NCCT with CECT).[17]

MR sialography demonstrates similar sensitivity and specificity to NCCT for the evaluation of sialolithiasis. Benefits of MR include excellent visualization of the salivary ducts without the need for contrast and no radiation exposure. Disadvantages include cost, image acquisition time, and limited availability compared to NCCT and Ultrasonography.[3][16] Sialendoscopy allows for direct visualization of salivary stones and the salivary ducts, thus providing excellent sensitivity and specificity. In addition to aiding in the diagnosis of sialolithiasis, clinicians increasingly use sialoendoscopy for therapy and stone removal, given the advancements in endoscopic technology.[3] Research has shown sialoendoscopy to be a safe and effective alternative to conventional open surgical techniques with a more favorable complication profile.[18] Additionally, sialoendoscopy is performable in the outpatient setting utilizing local anesthesia. 

Ultrasonography provides a non-invasive method of imaging sialolithiasis. The usual appearance of sialoliths on ultrasound is a hyperechoic focus with posterior shadowing. The benefits of ultrasonography include no radiation exposure, real-time image interpretation, and widespread availability. Ultrasound is often available at the point of care and can provide rapid diagnostic information. Ultrasound is highly operator-dependent, revealing a wide range of reported sensitivity and specificity. Reported sensitivities are best for stones greater than 2 to 3 mm in size. Recent research has demonstrated sensitivity and specificity for stones greater than 3 mm in size comparable to conventional NCCT and sialoendoscopy.[19]

Treatment / Management

Management of sialolithiasis should begin with conservative measures, including massaging the salivary gland, nonsteroidal anti-inflammatory drugs, and sialogogues. Signs of infection, including cervical adenopathy, purulent discharge from the salivary ducts, or erythema surrounding the salivary ducts, indicate the need for antibiotic therapy.[4][11] Further treatment is dictated based on the sialolith's size, number, and location if conservative management is unsuccessful. Mobile submandibular stones measuring less than 5 mm located within the distal duct should initially undergo management with endoscopy. Impacted submandibular stones within the distal duct and stones larger than 5 mm should have treatment with transoral duct slitting. Stones of 5 to 7 mm within the proximal duct or hilar region should receive initial treatment endoscopically. If this is unsuccessful or the stone becomes impacted, the next step is a transoral surgical approach.

External shockwave lithotripsy (ESWL) is an option for not palpable stones or visualized under endoscopy. Intraparenchymal stones can be extracted endoscopically if they are 5 to 7 mm and visualized. Larger stones require treatment with transoral slitting. ESWL is indicated for smaller stones that are not palpable and not visualized endoscopically. ESWL is generally unsuccessful for stones larger than 7 to 10 mm. Surgical excision of the submandibular gland should be a last resort.[11][20][21][22] Salivary stones within the parotid duct that measure less than 7 mm and are mobile require endoscopic removal. If endoscopic management is unsuccessful or the stones have become impacted, external shockwave lithotripsy is considered the most appropriate second-line therapy with subsequent endoscopic removal of fragmented stones. Treatment of salivary stones that do not respond to external shockwave lithotripsy is with a combined transcutaneous and endoscopic approach (assuming the stone is visible under endoscopy). Surgical excision of the parotid gland should be a last resort.[11][21][22](B2)

Differential Diagnosis

The differential diagnosis for salivary gland swelling includes:

• Sialolithiasis
• Sialadenitis (inflammatory or infectious)
• Neoplasm 

However, the clinical presentation can vary, and the differential diagnosis for the pathology of the oral cavity and face can be extensive and relies heavily on physical exam findings and clinical history. Conditions that can have a similar presentation include: 

• Cellulitis
• Poor dentition and dental abscess formation
• Infection of the buccal or masticator space
• Herpes zoster
• Neoplasm

Prognosis

Sialolithiasis has an excellent prognosis, and the majority of patients can be managed conservatively with sialogogues and nonsteroidal anti-inflammatory drugs. The minimally invasive procedures discussed above have excellent success rates with minimal morbidity compared to traditional surgical techniques. Sialadenectomy for the treatment of sialolithiasis is rarely necessary with modern treatment techniques.[21]

Complications

The primary complications of sialolithiasis are the development of sialadenitis, acute or chronic, and atrophy of the affected salivary gland. Obstruction of the salivary glands by a sialolith blocks the flow of saliva resulting in swelling and pain. Additionally, this blockage of flow prevents the removal of bacteria and debris from the salivary duct, resulting in bacterial infection. If the obstruction is chronic, the blocked flow of saliva will damage the salivary glands' acinar cells, resulting in local inflammation. Without proper treatment, it can result in permanent fibrosis of the gland and atrophy.[7]