ANATOMY

There are two categories of salivary glands.

Minor: Around 600 milimetric structures disseminated throughout the oral mucosa.

Major: The parotid, submandibular and sublingual glands, as briefly described below.

PAROTID

It is the biggest salivary gland, located behind the mandibular ramus, below the outer ear, anterior to the mastoid and styloid process and overlying the upper quarter of the sternocleidomastoid muscle. It is divided into two lobes by the facial nerve.

The parotid duct (Stensen’s duct) exits the anterior border of the parotid, 1.5 cm below the zygomatic arch and runs for approximately 5 cm in length, superficial to the masseter muscle. It turns medially and pierces the buccinator muscle at the level of the second maxillary molar where it opens onto the oral cavity.



SUBMANDIBULAR

It is located between the inner surface of mandible and the floor of mouth. Its medial face lies at digastric, mylohyoid, hyoglossus muscles and pharynx lateral wall.

The submandibular duct (Wharton’s duct) arises from the medial surface of the gland and runs approximately 5cm medial to the mylohyoid muscle until it empties into the intraoral cavity, lateral to the lingual frenulum on the anterior floor of mouth.

SUBLINGUAL

It is located beneath the floor of the mouth, superior to the mylohyoid muscle and anterior to the submandibular gland. The saliva drains by 15 to 30 secretory ducts, one of which tends to be more prominent and therefore called the major submandibular duct, which opens close to the Wharton’s duct orifice.

SALIVARY GLAND SWELLINGS- AN OVERVIEW

The wide variety of pathology concerning the salivary glands can be grouped into the following categories:

  • Infection (viral, bacterial)
  • Neoplastic
  • Non-infectious, non-neoplastic (sialolithiasis, chronic recurrent parotitis, sialoadenosis, autoimmune and granulomatous disease)

Note:

Hereby, sialolithiasis has been classified as a noninfectious and nonneoplastic condition to emphasis its mechanical obstructive pathogenesis, but it should be noted that saliva obstruction allows bacterial ascent into the main ducts and is a predisposing factor for salivary gland infection.

Chronic recurrent parotitis in children and adults does not have a fully elucidated pathogenesis, but recent opinions suggest an autoimmune etiology. It presents with similar clinical signs and symptoms as infectious salivary gland swellings.

SIGNS AND SYMPTOMS

The following table summarises the usual presentation of each aforementioned clinical condition.



SIMPLIFIED DIAGNOSTIC AND TREATMENT STRATEGY

According to the clinical findings a simplified diagnosis and treatment strategy can be outlined.

 

 

INFECTION



LUMPS (NEOPLASTIC)



NON-INFECTIOUS, NON-NEOPLASTIC



INVESTIGATION

 

IMAGING METHODS

Ultrasound(US) is a primary imaging tool that acts as a guide to the need and choice for further imaging and can be used harmlessly on children and pregnant woman. Its disadvantages include the unreliability for evaluating deep masses or directly visualising the facial nerve.

Magnetic resonance (MR) is the most proficient imaging modality when it comes to spatial resolution and capability of contrast. Therefore it is considered the best option when there is clinical suspicion of neoplastic mass, particularly in the parotid gland, because of its fatty hyperintense background on T1-weighted images allowing adequate delineation of the tumor interface. It helps to visualise the facial nerve and assess perineural, bone and meningeal invasion. However it is expensive, with limited availability and is incompatible in patients with magnetic devices.

Computer tomography (CT) is cheaper, less time-consuming and more available compared to MRI. It is very informative in obstructive and inflammatory lesions.

Sialography is only adequate for assessing chronic sialadenitis thats etiology has been not been elucidated by other imaging methods. Is it contraindicated in acute inflammation because the retrograde injection can force inflammatory products into more peripheral parenchyma.

 

IMAGING FEATURES

           NEOPLASTIC DISEASE



           SIALOADENITIS (EITHER FROM INFECTIOUS OR NON-INFECTIOUS ORIGIN)

In acute inflammation, US and CT are the best imaging choices. The salivary gland is diffusely or focally enlarged, enhancing avidly in contrast enhanced CT which is the modality of choice when there is suspicion of abscess.

In a chronic setting, the gland may appear atrophic with focal calcifications, strictures and ductal stenosis or dilations, hyperdense in CT scan, with increase contrast enhancement.

If a sialolith is present it appears as a hyperechoic mass with posterior shadowing in US and hyperdense in CT scan.

 

OTHER INVESTIGATION METHODS

Fine needle cytologyhas a reasonable specificity and sensitivity for histological assessment of salivary gland lumps and is regularly performed for surgical planning. Core biopsies are usually avoided in parotid lumps sampling due to the delicate position of the facial nerve.

Sialometry is used to assess xerostomy. Normal basal flow is around 0.25ml/min. When lower than 0.16 ml ⁄min it can be classified as hyposalivation.

Serum salivary isoamylase is a unspecific marker of salivary gland damage. It can occur even in asymptomatic cases of sialoadenosis secondary to chronic alcoholism, anorexia nervosa or bulimia, or other conditions without evidence of salivary gland involvement such as postoperative states, lactic acidosis, malignant neoplasms that secrete amylase. Therefore, the levels of this isoenzyme should be interpreted along with clinical systemic signs, pancreatic isoamylase, lipase or trypsin and renal function.

In case of sialoadenitis, blood tests may show systemic signs of inflammation with leukocytosis and elevated C-reactive protein.

Curiously, owing to the easiness of saliva sampling, there has been growing interest into the possibility of indentifying biomarkers of systemic conditions, using different methods (eg: sialochemistry, immunological tests), aiming for the detection of HIV antibodies, hormones, alcohol and illicit drugs.

 

KNOW MORE ABOUT:

INFECTION

 

VIRAL INFECTIONS

Viruses are the commonest cause of salivary gland infection. Mumps and Cytomegalovirus are the most frequent viruses. For the sake of brevity, only mumps will be depicted here.

          MUMPS

          GENERAL INFORMATION

    It was classically an infantile disease but recently there have been outbreaks in young adults (18-24 years old) most of them college students, already under two-dose vaccine coverage.

    Mumps is an enveloped RNA virus restricted to human beings that is transmitted by airborne saliva droplets and acquired through inoculation and replication of the virus in the nasal or upper respiratory tract mucosa.

    The incubation period is about 15 to 24 days. Infected patients are most contagious 1 to 2 days before the onset of clinical symptoms and for several days afterwards.

             CLINICAL AND LABORATORY ASSESSMENT

      Around 65% of patients will be symptomatic. 95% of those will have parotitis which usually starts unilaterally, but in 90% of cases will progress into a bilateral enlargement. Nuchal rigidity, Brudzinski’s and Kernig’s sign should be part of the examination in order to assess for possible meningism. Kernig’s sign is positive when the patient is lying supine with leg bent at the hip and knee at 90 degree angles and subsequent extension in the knee is painful. Brudzinski’s sign is positive when the patient is lying supine and passive flexion of the neck causes involuntary flexion of the legs.

      Under non-outbreak conditions the following laboratory tests are advisable:

      - White blood cell count: tend to remain at normal values.

      - Serum amylase: concentrations are raised in most cases.

      - A definite diagnosis can be made through a serological test based on detection of virus-specific IgM antibody measured by direct or indirect ELISA.

      - Virus isolation from saliva, urine, seminal fluid or cerebral fluid is limited to the viral replication period (7 days before and until the first week after the onset of clinical symptoms).

                COMPLICATIONS

        Epididymo-orchitis/oophoritis, abortion, pancreatitis, meningitis/encephalitis, deafness

                  TREATMENT

        Being a self limiting disease, treatment is mainly supportive with analgesics and anti-inflammatory drugs (eg: acetaminophen, ibuprofen).

        STEROIDS SHOULD BE AVOIDED because they may boost testicular atrophy in cases of orchitis.

        Intravenous immunoglobulin may be used to treat autoimmune complications such as post-infectious encephalitis, Guillain-Barré syndrome or idiopathic thrombocytopenic purpura.

                  VACCINE AND IMMUNITY

          Natural infection confers lifelong immunity, meanwhile vaccination induced immunity may wane. It should be noted that serological tests used for diagnosis do NOT inform on immunity protection.

          Despite developed countries already have a high two-dose childhood vaccination coverage, there have been recent outbreaks in young adults as aforementioned.

           

           

          BACTERIAL INFECTIONS

                    ACUTE SUPPURATIVE PAROTIDITIS

                    GENERAL INFORMATION

          It is usually a unilateral condition but affects both parotid glands in 20% of cases. The other salivary glands are rarely involved.

          Dehydration is the main cause, leading to reduced flow and thickening of the saliva which in turn promotes ascending ductal infection. Newborns and elderly are therefore the most prone. Blood borne infection may also occur in infants and immunocompromised patients.

          The most common microorganisms are Staphylococcus aureus, Steptococcus viridians, Streptococcus hemolyticus and Streptococcus Pneumonia.

                    TREATMENT

            Therapy includes:

            - Antibiotics (co-amoxiclav is an adequate empiric choice. In complicated cases, it should be upgraded to a triple antibiotic coverage adding metronidazole and an aminoglycoside, if renal function allows to).

            - Hydration and electrolyte replacement

            - Adequate oral hygiene

            - Extraoral manual milking (massage to promote ductal system flushing).

             

            Surgery may be necessary when there is:

            - No response to antibiotic therapy

            - Abscess

            - Concurrent risk factors (e.g. diabetes)

             

             

            22 year-old female with right acute parotitis. There is a clear facial asymmetry (photo on the left side) and severe restriction to mouth opening - trismus (photo on the right side). 

             

            CT scan reveals an enlarged right parotid gland with a hypodense area corresponding to an abscess (red arrow). The masseter and internal pterygoid muscle show inflammatory stranding, accounting for the aforementioned trismus. The trachea is slightly deviated to the patient's left side.

            NEOPLASTIC DISEASE

              Salivary gland neoplasms account for less than 3% of all tumors. They are more common in men and those over the age of 40, but can also be seen in children. Regardless of age, the parotid glands are the commonest site involved. The main risk factors are  tobacco, alcohol misuse, irradiation, previous history of cancer and HIV infection. Rapidly growing mass, pain, facial nerve involvement and cervical lymphadenopathy are suspicious symptoms and signs of malignancy. The usual metastatic sites from salivary gland carcinomas are lymph nodes, lungs, liver and bone. In adults, benign tumors of the parotid (pleomorphic adenoma and Warthin's tumor) are the most frequent. The probability of malignancy rises in the submandibular gland (50%), minor salivary glands (up to 80%) and sublingual gland (up to 90%). In children up to 50% of salivary gland tumors are malignant. 90% of the malignant cases are made up by mucoepidermoid carcinomas, adenoid-cystic carcinomas and acinic cell carcinomas (the corresponding figure in adults is only 45%). The most frequent benign conditions in children are: pleomorphic adenomas, haemangiomas and lymphangiomas.

               

              SPECIFIC CONDITIONS

              For the sake of brevity, there is a short description of the most frequent salivary gland neoplasms, which are both benign conditions.

               

                        PLEOMORPHIC ADENOMA

                It is the most common neoplasm of the salivary glands, accounting for 70% of cases and the majority (90%) in the superficial lobe of parotid gland.

                A pleomorphic adenoma is not completely encapsulated, therefore enucleation carries a risk of tumor cell transfer with high probability of tumor recurrence.

                Partial or complete parotidectomy is the mainstain therapy and should not be deferred due to the risk of malignant degeneration.

                 

                Left: clinical aspect of pleomorphic adenoma.

                Right: macroscopical features of the lesion after its surgical excision (right, top), including a transverse cut to show its inner aspect (right, bottom).

                MR of a left parotid pleomorphic adenoma in a 35 year-old woman. The mass is round, well-defined hypointense in T1 weighted images, hyperintense in T2 weigheted images, and with discrete heterogeneity in constrast enhanced images.

                Top (left to right): axial T1 weighted image; axial T2 weighted image; coronal STIR T2 weighted image

                Bottom (left to right): coronal and axial images with contrast.

                           WARTHIN'S TUMOR

                  It occurs almost exclusively in parotid where is the second most common neoplasm. It has strong association with cigarette smoking which explains the recent demographic shift from male predominance to equal sex incidence.

                  Contrary to pleomorphic adenoma, Warthin's tumor may be treated expectantly.

                   

                  NON-INFECTIOUS, NON-NEOPLASTIC

                  SIALADENOSIS

                    It is a painless bilateral parotid swelling which may involve the submandibular glands at times. There is no size fluctuation with meals and salivary ducts are patent with a free and fluid salivary flow.

                    It is caused by systemic conditions such as alcohol misuse, endocrine disorders (diabetes mellitus in particular), malnutrition (anorexia/bulimia), liver disease and drugs (e.g. antipsychotic drugs containing phenothiazine).

                     

                    CHRONIC RECURRENT PAROTITIS

                      There are two forms; infantile and adult. In children, it is the second most common cause of parotid enlargement after mumps.

                      The etiology is not fully understood although autoimmunity seems to be involved. Some cases of recurrent parotitis in adults may represent an early sign of Sjögren’s syndrome.

                      Regardless of age, the clinical presentation is similar between the forms, characterized by an alternating unilateral or bilateral gland enlargement that may last for 2 weeks and spontaneous remission and recurrence.

                       

                      Therapy is mainly supportive:

                      - massage for ductal flush

                      - ductal probing

                      - ductal dilation of strictures from chronic inflammation

                      - antibiotics (in some cases)

                      Parotidectomy is only advisable when conservative strategies fail. In children all attempts should be made to avoid it as after puberty symptoms tend to wane and there is a high probability of spontaneous healing.

                       

                        AUTOIMMUNE DISEASES

                                  SJÖGREN'S SYNDROME

                        It is a chronic autoimmune disease affecting multiple organs and can be associated with other systemic autoimmune disorders such as rheumatoid arthritis, lupus erythematosus and scleroderma. Middle-aged women are the most susceptible.

                        The salivary gland is infiltrated by mononuclear cells, responsible for inflammatory duct obstructions and decrease of salivary flow leading to xerostomy. Besides, decreased salivation allows bacterial ascent into the salivary glands.

                        Clinically it presents as an intermittent swelling which lasts for weeks to months, is moderately painful and exacerbated by eating.

                        Diagnostic investigation includes lip or parotid biopsy showing a mononuclear infiltration, serum autoantibodies (rheumatoid factor, antinuclear antibody, anti- SS-A and anti-SS-B antibodies) and eventually a sialometry. Ophthalmological investigation to assess lacrimal gland function is helpful.

                        Sjögren’s disease increases the risk of parotid lymphoma therefore any mass must be investigated.

                         

                        GRANULOMATOUS DISEASES

                                     SARCOIDOSIS

                          It is a multiple organ chronic granulomatous inflammation with a predilection for the lungs and hilar lymph nodes, with bilateral parotid enlargement in up to 30% of patients and can also affect the other major and minor salivary glands.

                           

                                     WEGENER'S GRANULOMATOSIS

                          It is a multiple organ necrotizing granulomatous inflammation, characterized by vasculitis of the small and medium sized arteries with a predilection for the kidneys and respiratory tract. Salivary gland involvement is rare. Diagnosis is supported by ANCA positivity and definite diagnosis is revealed by a biopsy.

                           

                          PNEUMOPAROTID

                            Pneumoparotid is a consequence of air reflux through the parotid ducts. It occurs by constant forceful intraoral inflation increasing intraoral pressure. Wind instrument players and glass blowers are the most prone. Superimposed infection is likely.

                            There are reports of pneumoparotid following general anesthesia. Its mechanism is not fully understood but difficult intubation with increased intraoral pressure and decreased muscle tone of Stensen's duct orifice may allow air reflux. It is a transient condition with rapid recovery.

                             

                            ENLARGEMENT SECONDARY TO IODIDE

                              Salivary glands are able to partly clear iodide from plasma. High concentrations of iodide (following iodide contrasting dyes or kidney impairment) lead to increased concentration in the salivary gland, which in turn causes inflammation and glandular swelling. With adequate supportive therapy it tends to subside quickly.

                               

                              MASSETERIC HYPERTROPHY (FALSE POSITIVE)

                                The masseter muscles rest closely to the parotid glands and their hypertrophy may lead to a misdiagnosis. The muscle hypertrophy is a consequence of its continuous exertion by constant clenching, bruxism or gum chewing. There are some occasional congenital varieties.

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