Non neoplastic disorders of salivary glands

Introduction:

A wide range of non neoplastic disorders are known to affect the salivary glands.

The common among them include:

Mumps

Acute suppurative sialadenitis

Sjogren syndrome

Drug induced xerostomia

WHO Classification of non-neoplastic salivary gland disorder:

Tumor like lesions:

1. Sialadenosis

2. Oncocytosis

3. Necrotising sialometaplasia

4. Benign lymphoepithelial lesion

5. Salivary gland cysts

6. Chronic sclerosing sialadenitis

Congenital salivary gland disease:

Agenesis of salivary glands:

Agenesis of major salivary glands is a very rare even, with only a few cases reported. This congenital anomaly may caue profound xerostomia in children. Oral cavity sequelae include dental caries, candidiasis and ascending sialadenitis. Parotid gland is more often involved. Parotid gland agenesis is usually bilateraly and may also be associated with abnormalities of head and neck region.

This condition may also be associated with ectodermal defects that include:

Hypohidrotic ectodermal dysplasia

Lacrimal-auriculo-dento-digital anomaly.

Congenital imperforate submandibular salivary gland duct:

This could cause unilateral cystic swelling in the floor of the mouth as a result of imperforate submandibular gland ducts. This is postulated to be caused by congenital failure of canalization of the terminal end of the duct. This condition responds to simple incision and decompression of the fluid filled duct.

Infections of salivary glands:

Viral and bacterial infections can frequently affect the salivary glands. It should be pointed out that fungal infections involving salivary glands are extremely rare.

Epidemic parotitis (Mumps):

This is an acute, contagious, viral disease that cause painful enlargement of the salivary gland, commonly the parotids. This condition could also lead to orchitis, meningoencephalitis and pancreatitis. Diagnosis is usually made on clinical grounds.

Laboratory diagnosis of mumps is not necessary and is indicated only in the following scenario:

1. Unilateral parotid involvement

2. Recurrent parotitis

3. When parotid gland enlargement occurs in previously immunized patients

4. When it causes prominent involvement of tissues other than the salivary glands

RT-PCR is the preferred method of diagnosis.

Spread of infection is via droplets. People with mumps are most contagious during the first 2 days before symptoms appear. Patients can also continue transmitting infections even one week after complete alleviation of symptoms.

Treatment:

This is purely supportive. The affected child should be isolated until the glandular swelling and pain subsides. Soft diet that involves minimal chewing is advisable. Acidic substances like the citrous juices that could cause worsening of the pain must be avoided.

Mumps can be prevented by vaccination. Mumps vaccine has been included in the universal immunization program.

Some of the complications of Mumps include:

1. Deafness

2. Orchitis

3. Pancreatitis

Acute suppurative sialadenitis:

This is an uncommon disorder characterized by painful swelling and purulent discharge from the duct of the affected gland. There is also associated dysgeusia and cervical adenopathy. In severe cases there could be associated pyrexia, malaise. There is always an associated risk of abscess formation, parapharyngeal space infection and Ludwig's angina.

This condition can affect both children and adults. Parotid gland is the common major salivary gland that could be involved. This condition is highly uncommon in neonates. Immunodeficiency and other concurrent illness could predispose to childhood suppurative parotitis. Long standing xerostomia caused by irradiation can cause suppurative parotitis in adults. Ductal obsturction either by sialolithiasis / malignancy / FB may also predispose to suppuration of parotid gland.

Common pathogens isolated:

Staph aureus and different anaerobic bacteria have been isolated. Gram negative pathogens have been isolated in hospitalized patients.

Diagnosis of suppurative sialadenitis is usually based on the history and clinical features. Microbial culture of pus could reveal the causative organism.

Management:

Include manitenance of hydration and administration of parenteral antibiotics. Commonly used antibiotics include penicillinase resistant antibiotis (flucloxacillin, amoxycillin clavulanic acid combination).

Surgical drainage should be considered if there is lack of improvement after 3-5 days of antibiotic therapy. Superficial parotidectomy should be performed if the disease is recurrent / chronic.

Chronic recurrent sialadenitis:

This condition commonly involves parotid gland. This is due to recurrent bacterial infection. During acute exacerbation parotid gland is enlarged and tender. Pus can be expressed from its duct. Between acute episodes the gland is firm and slightly enlarged. Culture of pus from the duct would reveal staphylococci / streptococci.

Sialadenosis:

This is a non neoplastic, non inflammatory enlargement of salivary glands. This condition involves mainly the parotid gland. The enlargement is bilateral. There may be associated recurrence or pain. This disease is due to increased weight, improper nutrition, alcoholic cirrhosis, hypothyroidism.

Classification of sialadenosis:

1. Hormonal sialadenosis

2. Sex hormonal

3. Diabetic

4. Thyroid

5. Neurohormonal sialadenosis

6. Malnutritional sialadenosis

7. Mucoviscidosis

8. Drug induced sialadenosis

Clinical features:

This condition is characterised by the presence of chronic, afebrile salivary gland enlargement usually of the parotid gland. The enlargement is slowly evolving, indolent and recurrent. There is decreased amount of salivary secretion. Analysis of saliva demonstrates increased levels of potassium and decreased levels of sodium. There is also associated hypertrophy of acinar cells which crowd and compresses the finer terminal ducts. This forms a leafless tree pattern. The acinar cells hypertrophy is so pronounced that it could be three times greater than its normal size. The nuclei of the acinar cells are found to be displaced to the cell base and the cytoplasm is engorged with zymogen granules.

In patients with long standing diabetes, there may be acinar atrophy and fatty infiltration.

Subtotal parotidectomy is the ideal management modality in these patients.

HCV related sialadenitis:

Hepatitis C viral infection frequently gives rise to a wide spectrum of extra-hepatic manifestation. This includes salivary gland disease. HCV infected individuals may have some salivary / lacrimal abnormality. HCV may present in the saliva of majority of patients.

Necrotizing sialometaplasia:

This is a benign self limiting rare inflammatory disease which mimics malignant neoplasm.

Another name to describe this condition is salivary gland infarction.  Clinical

and histopathological features could sometimes simulate squamous cell carcinoma / mucoepidermoid carcinoma.

Etiology:

1. Associated with history of trauma / RT / Surgery

2. Mostly related to vascular ischemia

3. Tobacco use has been suggested to be a risk factor

Clinical features:

These lesions are usually painless, and sometimes less frequently could cause pain and numbness. These lesions are characterized by swelling with or without ulceration in anatomic sites. Typically these lesions show crateriform ulcer of the palate that simulate malignant process.

Histopathology:

Is characterized by acinar necrosis in early lesions to be followed by associated squamous metaplasia of salivary ducts. The lobular architecture of the gland is preserved in all cases (this is a vital histologic clue).

Biopsy of the lesion is a must to rule out malignancy.

These lesions usually resolve on their own with a healing time of 5-6 weeks.

Sjogrem's syndrome:

This is the second most common auto immune disorder. This is a chronic systemic autoimmune disorder that principally involves salivary and lacrimal glands resulting in xerostomia and xeropthalmia. In the eye keratoconjunctivitis sicca is produced.

Two forms of this disease could manifest:

Primary Sjogren's syndrome:

This is sicca only syndrome

Secondary Sjorgren's syndrome:

In addition to the sicca syndrome, autoimmune diseases are seen.

HLA antigens are found with great frequency in patients with Sjogren's syndrome.

HLA -DRW52 is associated with both forms of Sjogren's syndrome.  HLA -B8 and HLA

-DR3 are seen in increased frequency in the primary form of the disease.

Pre valance:

This condition is prevalent in 0.5% of the population. Females out number males by a ratio of 9:1. Secondary Sjogren's syndrome is associated with rhematoid arthritis and systemic lupus erythematosus.

Clinical features:

Principal symptom is xerostomia (dry mouth). These patients complain of difficulty in swallowing, altered taste sensation, and difficulty in wearing dentures. The tongue becomes fissured with atrophy of the papillae. Firm enlargement of salivary glands occurs during the phase of the disease. The swelling could be unilateral / bilateral. Swelling is non painful and intermittent in nature. Sialography reveals punctate sialectasia and lack of normal arborization of ductal system showing fruit laden tree pattern.

Keratoconjunctivitis sicca, a prominent feature is not only reduced tear production by lacrimal glands but also pathological effects on the epithelial cells on the ocular surface. Schirmer test proves this condition.

Histopathology:

Lymphocytic infiltration of salivary glands with destruction of acinar units.

Management:

Dry eyes can be managed by periodic use of artificial tears. Artificial saliva / use of sugarless candy helps to keep mouth moist.

Sialogogue like pilocarpine can be used to increase salivary flow.

Mikulicz disease:

This is also known as benign lympho-epithelial lesion. This condition have bilateral painless swelling of lacrimal glands and all the salivary glands.

This condition is most common in females. It affects adult individuals.

Histology reveals infiltration of salivary gland tissue destroying / replacing the acini with the persistence of islands of epithelial cells.

Biopsy from the swollen glands is the key to diagnosis of Mikulicz disease. Treatment is purely symptomatic.

Sialolithiasis:

Also known as salivary duct stone / salivary duct calculus.

These are deposition of calcium salts around a central nidus which may consist of altered salivary mucins, desquamated epithelial cells, bacteria, foreign bodies, or products of baterial decomposition.

This is the most common disorder of salivary gland. Patients with sialolithiasis involve duct of major salivary glands. These patients complain of severe pain particularly just before and after meals owing to stimulation of salivary flow associated with swelling of salivary gland.

This condition can occur at any age, but is common in middle aged adults. Distribution of sialolithiasis is as follows:

Parotid - 20%

Submandibular gland - 64%

Sublingual gland - 16%

Microscopically calcified mass exhibits concentric laminations around a central nidus of amorphous debris. This lamellated structure of the calculus is a result of successive deposition of inorganic and organic material. Associated periductal inflammation could also be seen.

Management:

Small calculi can be removed by manipulation or increasing the salivation by sucking a lemon which causes expulsion of the stone. Inflammation and infection can be managed by intravenous administration of antibiotics. Larger stones need surgical exposure for removal. Lithotripsy has been advocated in some cases.

Drug induced salivary gland disorders:

Wide ranging drug related salivary gland disorders are possible. Salivary glands increase in size with associated xerostomia. Salivary gland pain has been rarely associated with guanethidine therapy. Other drugs that can cause these problems include Bretylium, clonidine, methyldopa and some cytotoxics.

Painless, bilateral salivary gland enlargement may be an adverse reaction of phenylbutazone, chlorhexidine, epinephrine, naproxen and clozapine. Mild acute sialadenitis (iodide mumps) can arise in patients after imaging procedures using iodine based contrast medium. These patients usually present with painless bilateral parotid / submandibular salivary gland swellings. These swellings are rapid in onset and gradually disappear during the course of one week. Radio active I 131 used in the treatment of thyroid cancers bones in on the salivary glands. Iodine is concentrated in the saliva and is secreted. This causes a certain amount of damage to the salivary gland parenchyma causing swelling and pain. This is more common in parotid gland. Symptoms may develop immediatly after its use or months later. Adequate hydration will help to mitigate this problem.

Juvenile recurrent parotitis:

This condition is defined as recurrent parotid inflammation, generally associated with non-obstructive sialectasis of parotid gland. The usual age of onset is 3-6 years. Childhood disease is more common in males, while adult onset disease normally arises in females. Number of attacks could vary between 10-20 / year. This disease is characterized by local pain, swelling that could last up to 2 weeks and could resolve spontaneously. Fever and redness are also common and occasionally a drop of pus may be expressed from the parotid duct. Sialography and ultrasound can reveal sialectasis, which is bilateral.

Pathogenesis remains unknown. These patients have a low salivary rate. Histopathology reveals periductal lymphocytic infiltration. Conservative treatment is ideal.

Pneumoparotitis:

This is another rare cause of parotid gland enlargement, caused by reflux of air through stenson's duct into the acini of the gland with subsequent dilatation. This condition could occur as a transient / recurrent phenomenon. Recurrent insufflation is not entirely benign and may predispose to sialectasis, recurrent parotitis and even subcutaneous emphysema. This condition is more common in wind instrument players, balloon and glass blowers or any individual who increase intraoral pressure by forcefully blowing up the cheeks consciously or as a habit.

There is no need for investigation as the history is often revealing. Sialography, ultrasound, CT, MRI can be used as diagnostic tools.

Management is conservative. Avoiding increase in intraoral pressure could help.

Kuttner tumor / Chronic sclerosing sialadenitis:

In 1896 Kuttner reported four cases of this condition. They presented as indurations of submandibular gland. Descriptively this condition is known as chronic sclerosing sialadenitis. This is a chronic disorder of the salivary gland.

Clinically these lesions appear as firm swelling of the glands and may be difficult to differentiate from salivary gland neoplasia. Submandibular gland is more commonly affected, sometimes parotids, sublingual and minor salivary glands can also be affected.

Histologically, these lesions are characterized by progressive periductal sclerosis, acinar atrophy and gland infiltration by lymphocytes. The pattern of distribution of these lymphocytes suggests an immunologic reaction. Sialoliths have also been found in nearly a quater of these patients.

Xanthogranulomatous sialadenitis:

This is a rare disorder manifesting as solitary swelling in a major salivary gland.

Xanthogranulomatous inflammation typically occurs as a type of pyelonephritis of

the kidney.

Histologically these lesions appear as sheets of cells with clear foamy cytoplasm and small bland nuclei admixed with neutrophils, lymphocytes, plasma cells and mast cells. It has been suggested that this condition could reflect underlying non-Hodgekin's lymphoma.