CHAPTER 18. Neoplastic and non-neoplastic diseases of salivary glands
Normal function and health of the mouth depend on normal secretion of saliva by the major and minor glands. Failure of salivary secretion causes a dry mouth which is both distressing and promotes oral infections.
A stone can form in a salivary gland or duct. At least 80% of calculi form in the submandibular gland, about 6% in the parotid and about 2% in the sublingual and minor salivary glands.
Adults are mainly affected – males twice as often as females. Calculi are usually unilateral. The classical symptom is pain when the smell or taste of food stimulates salivary secretion. Alternatively, duct obstruction can lead to infection, pain and swelling of the gland.
Occasionally there are no symptoms until the stone passes forward and can be palpated in the duct or seen at the duct orifice (Fig. 18.1). Alternatively, the stone may be seen in a radiograph. However, about 40% of parotid and 20% of submandibular stones are not radiopaque and sialography may be needed to locate them.
Calculi are not a cause of dry mouth.
Salivary calculi usually form by deposition of calcium salts around a nidus of organic material and have a layered structure. The roughness of their surface may cause the duct lining to undergo squamous metaplasia (Fig. 18.2). An adherent layer of microbial flora often grows on stones and this, together with obstruction, usually triggers inflammation and fibrosis around the duct.
The stone should be identified by plain radiography and the degree of damage to the gland from ascending infection and sialadenitis assessed by sialography.
If sufficiently far forward in the duct, a stone may sometimes be milked forward and manipulated out of the orifice without difficulty. If this fails, or the stone is distally placed, treatment should start with the least invasive method likely to succeed. Lithotripsy uses an ultrasonic shock wave applied extraorally and focused on the stone. A series of repeated treatments may be enough to fracture the stone into small pieces that will pass out of the duct orifice. If this fails, stones in the duct but outside the gland can be removed using a ‘basket’ of fine wire manipulated down the duct and around the stone. Alternatively, microendoscopy can be combined with laser disruption of the stone. These conservative techniques are often successful and, perhaps surprisingly, the gland will often recover normal function despite repeated attacks of chronic sialadenitis.
If conservative measures fail and the stone is within the duct, the duct has to be opened. An incision, usually under local anaesthesia, is made along the line of the duct just long enough to release the mass. A temporary suture should be put around the duct behind the calculus to prevent it from slipping backwards. The papilla should be left unsutured or the margins of the opening are sutured to the mucosa on either side to prevent subsequent scarring and fibrous obstruction.
When stones are within the gland or a sialogram reveals that the gland is severely damaged by recurrent infection and fibrosis, it will probably have to be excised.
Key features of salivary calculi are summarised in Box 18.1.
• Adult males mainly affected
• Usually (80%) in submandibular gland
• Usually form by accretion of calcium salts round organic nidus
• Typically cause pain by obstructing food-related surge of salivary secretion
• Occasionally asymptomatic until palpable in the mouth or seen in routine radiograph
• Do not cause dry mouth
• Should be removed by manipulation or incision of duct
Parotid papilla and duct strictures → Summary p. 314
The usual cause of strictures at the papilla is chronic trauma (from such causes as projecting clasps, faulty restorations or sharp edges of broken teeth) leading to fibrosis. Fibrosis makes the duct papilla difficult to find and may prevent insertion of a probe.
Strictures of the duct are almost always caused by fibrosis resulting from ulceration and inflammation round a calculus or scarring following inadequate surgery.
Sialography should show the degree of narrowing of the duct or papilla and dilatation behind. Once the cause has been removed, treatment depends on the site of the obstruction. The papilla may have to be excised and the duct lining sutured to the oral mucosa on either side. Alternatively, the duct may be dilated with bougies.
Salivary fistula, a communication between the duct system or gland with the skin or mucous membrane, is uncommon. Internal fistulae drain into the oral cavity and cause no symptoms. By contrast, parotid fistula on the skin is troublesome and often persistent. It may be the result of an injury to the cheek or a complication of surgery. Infection often becomes superimposed and persistent leakage of saliva prevents healing. The treatment is primarily by surgical repair but is difficult, especially because of the risk of damage to branches to the facial nerve.
Mucoceles and cysts
The most common type of salivary and soft-tissue cyst is the extravasation mucocele of minor glands. It is not a true cyst as it has no epithelial lining. Retention cysts are far less common. Mucoceles mainly affect the minor salivary glands, particularly of the lip. The cause is usually damage to the duct of a mucous gland. This may be caused by a blow on the lip, as might happen to a football referee holding a whistle in his mouth.
Mucoceles most often form in the lower lip but, occasionally, on the buccal mucosa or floor of the mouth (ranula). They are usually superficial and rarely larger than 1 cm in diameter. In the early stages, they appear as rounded fleshy swellings. Later, they are obviously cystic, hemispherical, fluctuant and bluish due to the thin wall (Fig. 18.3). A mucocele cannot be distinguished from a retention cyst clinically, but this is of little practical importance. A similar mass in the upper lip is much more likely to be a salivary neoplasm.
Preceding the formation of a mucocele, saliva leaking from a damaged duct into the superficial surrounding tissues excites an inflammatory reaction (Figs 18.4 and 18.5). The pools of saliva gradually coalesce to form a rounded collection of fluid, surrounded by compressed connective tissue without an epithelial lining.
Less frequently, the duct may become obstructed but less severely damaged so that saliva does not escape into the surrounding tissues. A retention cyst thus forms with a lining of compressed duct epithelium (Fig. 18.6).
A small superficial mucocele should be excised with the underlying gland. The latter is usually found to have been removed with the cyst but if not, recurrence is likely.
Key features are summarised in Box 18.2.
• Most common soft tissue cyst
• Most frequently on lower lip
• Usually caused by damage to duct and extravasation of saliva
• Saliva leaking into surrounding tissues causes mild inflammation
• Saliva eventually pools up to form a mucocele with connective tissue lining
• Rarely due to duct obstruction and dilatation forming a retention cyst with epithelial lining
A ranula is an uncommon type of salivary cyst arising from the sublingual or submandibular salivary glands.
The structure is usually the same as other salivary retention cysts. Ranulae are usually unilateral and 2 or 3 cm in diameter (Fig. 18.7). Occasionally, they extend across the whole of the floor of the mouth. They are soft, fluctuant and bluish. They are typically painless but may interfere with speech or mastication. Treatment is preferably by marsupialisation with removal of the related gland. A simple incision leads to recurrence. Enucleation is difficult because of the very thin wall.
Mumps → Summary p. 316
Mumps is due to a paramyxovirus (the mumps virus) and causes painful swelling of the parotids and sometimes other glands. It is highly infectious and is the most common cause of acute parotid swelling.
Children are mainly affected. An incubation period of about 21 days is followed by headache, malaise, fever and tense, painful and tender swelling of the parotids. Permanent nerve deafness or, rarely, meningitis are possible complications. Adults who contract mumps may develop orchitis or oophoritis and may have severe and prolonged malaise. After an attack immunity is long-lasting.
The diagnosis is usually obvious from the history and clinical findings, especially in a child. However, mumps may be mistaken for a dental infection or bacterial sialadenitis, if unilateral. Rarely, when the submaxillary or sublingual glands are affected, mumps may have to be differentiated from lymphadenitis. In cases of doubt, a history of mumps earlier in life usually excludes this diagnosis. If necessary, the diagnosis can be confirmed by a rise in titre of complement-fixing antibodies. Afterwards, antibodies to the S antigen disappear relatively quickly, and their presence indicates recent mumps. The V antibody is persistent and indicates infection at some time previously.
Mumps vaccination is provided as the measles-mumps-rubella (MMR) vaccination, introduced in 1988. Before this there were epidemics every three years. Recent patient concern about the MMR has reduced uptake to below the level required to prevent epidemics and there have been recent outbreaks, notably in 2005 among university students who had not been immunised. Immunisation is not completely effective in preventing the disease, but the acute episode is milder and, particularly in adults, may take atypical forms.
MMR vaccination is given at around 1 and 4 years of age. It is a live virus and a small minority of recipients develop a mild presentation of mumps with salivary gland swelling 3 weeks after the first dose.
Suppurative parotitis traditionally affected debilitated patients, particularly postoperatively, as a result of xerostomia secondary to dehydration. Currently, suppurative parotitis is more commonly seen in ambulant patients with severe xerostomia, particularly Sjögren’s syndrome, and as an uncommon complication of tricyclic antidepressant treatment. Important bacterial causes include Staphylococcus aureus, streptococci and anaerobes. Typical clinical features are pain in one or both parotids with swelling, redness and tenderness and often increasing malaise and fever. The regional lymph nodes are enlarged and tender, and pus exudes or can be expressed from the parotid duct (Fig. 18.8). The progress of the infection depends largely on the patient’s underlying physical state.
An intense acute inflammatory infiltrate extends along and dilates the ducts. Inflammation also extends into the periductal tissues and to a varying degree into acini. If neglected, abscesses form and there are varying degrees of acinar destruction.
Treatment can be started with flucloxacillin, but only after pus has been obtained for culture and sensitivity testing. The antibiotic can be changed if the bacteriological findings dictate and drainage is rarely necessary.
Mycobacterial parotitis is frequently a feature of advanced AIDS but, occasionally, also develops in immunocompetent adults. The chronic inflammatory swelling typically resembles a tumour and the diagnosis is only made after histological detection of non-caseating granulomas and identification of M. tuberculosis by PCR.
Chronic sialadenitis → Summary p. 314
Chronic sialadenitis is usually a complication of duct obstruction. It is usually unilateral and asymptomatic or with intermittent painful swelling of the gland. Sialography may show dilatation of ducts behind the obstruction.
There are varying degrees of destruction of acini, duct dilatation and a scattered chronic inflammatory cellular infiltrate, predominantly lymphoplasmacytic (Fig. 18.9). Extensive interstitial fibrosis and, sometimes, squamous metaplasia in the duct epithelium follow. Calculus formation may be seen in the dilated ducts.
If possible, the obstruction should be removed but, more often, the gland has to be excised and the mass examined histologically to exclude a neoplasm.
DRY MOUTH (XEROSTOMIA)
Many patients with severe xerostomia make no complaint of dry mouth, though they may, for instance, admit that they have difficulty in eating dry food. Some complain of an unpleasant taste in the mouth. Conversely, some who complain of dry mouth have normal salivary flow rates on objective testing and the problem is neurotic in nature. Salivary flow studies are valuable when patients complain of dry mouth. Important causes are summarised in Box 18.3. Patients may suffer xerostomia, calculi and ascending infection and the relationships between these conditions are shown in Fig. 18.10.
• Sjögren’s syndrome
• Mumps (transient)
• HIV infection
• HCV infection
• Iron deposition (haemochromatosis, thalassaemia)
• Fluid deprivation or loss
• Persistent diarrhoea and/or vomiting
• Diuretic overdosage
• Drugs with antimuscarinic effects
Atropine, ipratropium, hyoscine and other analogues
Tricyclic and some other antidepressants
Antiemetics (including antihistamines and phenothiazines)
Neuroleptics, particularly phenothiazines
• Some older antihypertensives (ganglion blockers and clonidine)
• Drugs with sympathomimetic actions
‘Cold cures’ containing ephedrine, etc.
Appetite supressants, particularly amphetamines
SJÖGREN’S SYNDROME → Summary p. 316
In 1933, Sjögren noticed the association of dryness of the mouth and dryness of the eyes. Later, he found that there was a significant association with rheumatoid arthritis. These combinations of complaints are caused by two closely related but distinct diseases.
Primary Sjögren’s syndrome (sicca syndrome) comprises dry mouth and dry eyes not associated with any connective tissue disease. ‘Sicca syndrome’ is also sometimes used for organic causes of dry mouth that lack the immunological anomalies of Sjögren’s syndrome.
Secondary Sjögren’s syndrome comprises dry mouth and dry eyes associated with rheumatoid arthritis or other connective tissue disease.
Females are affected nearly 10 times as frequently as males. Sjögren’s syndrome affects 10–15% of patients with rheumatoid arthritis, possibly 30% of patients with lupus erythematosus and a variable proportion of patients with or without other connective tissue diseases. Sjögren’s syndromes are therefore relatively common. In the absence of drug treatment or radiotherapy, they are the main cause of dry mouth, but their most serious consequence is damage to the eyes and the risk of lymphoma. Primary Sjögren’s syndrome tends to cause more severe oral and ocular changes and has a higher risk of lymphomatous change than secondary.
Major oral effects of Sjögren’s syndrome are summarised in Box 18.4.
• Difficulties with eating or swallowing
• Disturbed taste sensation
• Disturbed quality of speech
• Predisposition to infection
In the early stages, the mucosa may appear moist, but salivary flow measurement shows diminished secretion. In established cases, the oral mucosa is obviously dry, often red, shiny and parchment-like (Fig. 18.11). The tongue is typically red, the papillae characteristically atrophy and the dorsum becomes lobulated with a cobblestone appearance (Fig. 18.12). With diminished salivary secretion, the oral flora changes and candidal infections are common. The latter are the main cause of soreness of the mouth in Sjögren’s syndrome and cause generalised erythema of the mucosa, often with angular stomatitis. Plaque accumulates and there may be rapidly progressive dental caries (Fig. 18.13). The most severe infective complication is suppurative parotitis.
Swelling of the parotids is not common, but a history of swelling at some stage may be obtained in about 30% of patients. Swelling due to the syndrome itself shows no inflammation and is rarely painful (Fig. 18.14). A hot, tender parotid swelling with red, shiny overlying skin indicates suppurative parotitis. Parotid swelling appearing years after the onset strongly suggests lymphomatous change (below).
Drug allergies may be a feature. In particular, a curious feature is allergy to trimethoprim which can cause a syndrome of fever, headache, backache and meningeal irritation.
The association of dry mouth, which can destroy appetite, together with the pain of rheumatoid arthritis persisting over many years is a deeply distressing condition. Depression is a common consequence. These patients need support and reassurance as well as efforts to overcome the symptoms.
Sjögren’s syndrome can have serious ocular effects (Box 18.5).
• Failure of tear secretion
• Failure of clearance of foreign particles from the cornea and conjunctiva (keratoconjunctivitis sicca)
• Gritty sensation in the eyes and inflammation
• Risk of impairment or loss of sight
Aetiology and pathology
Sjögren’s syndrome is an autoimmune (connective tissue) disease which shows a corresponding variety of immunological abnormalities (Table 18.1). A retrovirus or other virus is as yet unconfirmed as a cause. The disease is systemic and affects all exocrine glands including those of the skin, vagina, lung and pancreas, though these rarely cause significant problems.
|Autoantibodies||Primary SS||Secondary SS|
|Salivary duct antibody||10–36%||67–70%|
|SS-A (Ro) antibodies||5–10%||50–80%|
|SS-B (La) antibodies||50–75%||2–5%|
|Rheumatoid arthritis precipitin||5%±||75%±|
Histological changes are shown in Box 18.6. Lymphocytes infiltrate the glands and cluster around ducts, replacing acinar cells (Fig. 18.15). The mechanisms of acinar cell destruction are unclear; they do not appear to be the target of direct lymphocyte killing. Over a period of years, the lymphocytic infiltrates enlarge and replace more of the gland. The ductal cells proliferate, possibly in response to cytokines released by the lymphocytes to form islands and sheets of cells around the ducts. Although myoepithelial cells are not a feature, the islands are often called myoepithelial islands (Fig. 18.16) and the overall appearance is sometimes called myoepithelial sialadenitis.
• Polyclonal infiltration mainly by CD4 lymphocytes
• Infiltrate initially periductal
• Progressive spread of infiltrate through the glandular tissue
• Progressive destruction of secretory acini
• Proliferation of some duct tissue as epimyoepithelial islands