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Special pathology of salivary glands

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Aetiological classification of salivary gland disorders

Aetiology Examples
Deformities Aplasia (rare), hypoplasia, ectopic salivary gland tissue, ductal atresia
Inflammation (sialadenitis)
(Seifert 1995)
Bacterial sialadenitis Acute bacterial sialadenitis (ascending, suppurative, abscess-forming, and post-operative sialadenitis)
Viral sialadenitis Mumps (epidemic parotitis), CMV, coxsackie virus, HIV-associated salivary gland changes)
Chronic recurrent parotitis
Chronic sclerosing sialadenitis of the submandibular glands (Küttner's tumour)
Obstructive (traumatic) sialadenitis Papillary obstruction, sialolithiasis, mucocoele (mucous cyst), ranula (sublingual cyst)
Radiation sialadenitis Following radiotherapy
Immune sialadenitis Acute allergic sialadenitis,
Chronic epitheloid-cell sialadenitis (Heerfordt's syndrome, Boeck's disease, sarcoidosis),
Chronic myoepithelial autoimmune sialadenitis (Sjögren's syndrome)
Other granulomatous forms of sialadenitis Giant-cell sialadenitis,
Sialadenitis following sialography
Sialadenitis of the minor salivary glands
Necrotising sialometaplasia Salivary gland infarction
Other rare forms of sialadenitis Tuberculosis, actinomycosis, syphilis
Neoplasia
Benign tumours Pleomorphic adenoma
Warthin's tumour (cystadenoma lymphomatosum), etc.
Malignant tumours Mucoepidermoid carcinoma
Adenoidcystic carcinoma
Acinic cell carcinoma
Adenocarcinoma NOS
Squamous cell carcinoma, etc.
Other Sialadenosis (sialosis)

Deformities

Aplasia and hypoplasia of the salivary glands are rare. They may be associated with deformity syndromes of the face combined with other deformities. Aplasia of all salivary glands is rare; resulting xerostomia is associated with increased susceptibility to infection and premature tooth loss. Hypoplasia of a salivary gland, though, is functionally compensated for by the other salivary glands.

Ectopic salivary glands (dislocated, but regularly structured salivary gland tissue), accessory salivary glands (perfectly functioning additional glands with a duct system), and aberrant salivary glands (heterotopic, do not function, do not have ducts, for instance, in regional lymph nodes) are frequently only detected as a result of complications (mucocoele, inflammation, salivary fistulas or salivary gland tumours).

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Salivary gland inflammation (sialadenitis)

The most frequent salivary gland disorders are acute bacterial and viral inflammations (sialadenitis, sialangitis). Infection is due to ascending spread via the ducts, haematogenous or lymphogenous spread. The acute suppurative and often abscess-forming sialadenitis is usually caused by streptococci and/or staphylococci. Post-operative parotitis, secondary to changes in fluid and electrolyte balance, is a special, and often bilateral, form of the disease. Small salivary glands are also often affected by stomatitis.

Chronic or recurrent inflammation leads to atrophy and fibrosis of the parenchyma. Küttner's tumour of the submandibular gland, or sclerosing sialadenitis, is a special form. This is a lymphocytic, and later sclerosing, sialadenitis associated with swelling and tumour-like firmness and flap changes (cirrhosis of the salivary glands). The scarring inflammation spreads to the surrounding tissues of the salivary gland so that malignant tumours must be excluded in differential diagnosis. This disorder accounts for approx. 30% of all cases of chronic sialadenitis, occurring in men more frequently than in women.
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Another special form is radiation sialadenitis which may lead to atrophy and fibrosis, depending on the dose.

Epidemic parotitis (mumps) and cytomegalovirus (CMV) infection are examples of viral sialadenitis. Mumps is an endemic disorder transferred by droplet infection and occurring almost commonly in school age. It usually manifests as a bilateral painful swelling of the parotid glands. In adults, bilateral orchitis is a serious late complication of mumps which may result in testicular atrophy and infertility. Unilateral or bilateral deafness may also develop if the nervous system is affected. Histologically, acinic cell necrosis, alteration of the ductal epithelium and a pronounced interstitial lymphocytic and plasmacellular infiltrate with concomitant oedema may be seen.

Cytomegaly affects small children and recurs in adults in people who are immune-compromised. Cells affected by virus replication are swollen and contain viral nuclei; the pathognomonic owl's eye cells develop.

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Immune-mediated diseases

Salivary glands are affected by various granulomatous disorders, auto-immune disorders and collagen diseases (inflammatory connective tissue disorders).

Sjögren's syndrome (Sicca syndrome, lymphoepithelial sialadenitis) is characterised by increasingly dry mouth and eyes, occasionally also affecting the vagina and the skin. It is due to chronic lymphocytic inflammation of exocrine glands with destruction of the glandular parenchyma. It often occurs sporadically and mostly in pre-climacteric women.

Based on scientific knowledge, the disorder is nowadays classified in two groups: Primary Sjögren's syndrome consists of salivary gland and eye symptoms (xerostomia, dry keratoconjunctivitis), while secondary Sjögren's syndrome is characterised by its association with other connective-tissue disorders (e.g. rheumatoid arthritis).

Diagnosis can be histologically proved by biopsy of the small salivary glands in the lips. Mason and Chisholm histologically determined the stages depending on the extent of: gland atrophy, lymphocytic infiltrate and myoepithelial proliferates (the latter may be absent in the small glands; in this case the severity is determined according to Cummings et al.). In rare cases, salivary glands affected by Sjögren's syndrome produce a small-cell lymphoma of mucosa-associated lymphatic tissue (MALT lymphoma).
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Sjögren's syndrome may also occur as a symmetric bilateral disease of the lacrimal and salivary glands and is then referred to as Mikulicz's disease (myoepithelial autoimmune sialadenitis). However, Mikulicz's disease is not yet clearly defined in literature since some authors also refer to symmetric infiltrates of leukaemia and lymphoma as Mikulicz's disease.

Heerfordt's syndrome (uveoparotid fever) is characterised by fever, uveitis and usually symmetrical and painful swelling of the parotid gland; it is considered an extra-pulmonary manifestation of sarcoidosis with epitheloid-cell granulomas of the sarcoidosis type in salivary gland parenchyma and periglandular and intraglandular lymph nodes.
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Sialolithiasis

The development of salivary stones (analogous to urolithiasis and cholecystolithiasis) impairs the drainage of saliva and favours a secondary inflammation (sialadenitis). Stones occur most frequently in the submandibular gland (approx. 83%), and more rarely in the parotid (10%) and sublingual glands (7%). The exact origin remains unclear; factors favouring the condition are metabolic disorders (hypercalcaemia, diabetes mellitus, gout), duct obstruction with secretion build-up, and the occurrence of particular crystallisation foci secondary to inflammation.

Clinically, the stones cause swellings which are often related to mealtimes and sometimes moderate to severe pain. In the long term, they lead to chronic sialadenitis and atrophy. Further complications are ascending suppurative sialadenitis and abscesses with the formation of internal or external fistulas.
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Cysts of the salivary glands

Non-neoplastic cysts account for 6% of all salivary gland disorders, 75% of which are mucoceles, often the result of trauma due to accidental biting of the lips or cheeks. Real mucoceles (retention mucoceles) possess an epithelial lining while extravasation mucoceles are limited by an inflammatory product with many foam-cell macrophages (muciphages). Salivary gland cysts will be discussed in more detail together with other soft-tissue cysts

Cystic lymphoid hyperplasia associated with AIDS

Cystic lymphoid hyperplasia of the parotid gland is an early sign of HIV infection. It typically manifests before the actual onset of AIDS as a painless unilateral or bilateral swelling of the parotid gland with concomitant cervical lymphadenopathy and affects 5% of all HIV-positive patients. The cystic cavities in the parotids, of variable lumen size, can be detected via imaging techniques (ultrasound, MRI) and macroscopically. Under the microscope, the cysts are lined with squamous cells between which there is lymphatic tissue with hyperplastic lymph follicles.

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Sialadenosis

Sialadenosis is a non-inflammatory, non-neoplastic parenchymatous disease affecting, above all, the parotid gland. It is associated with endocrine disturbances (especially hypophyseal and thyroid gland disease), dystrophy (liver disease, starvation), neurogenic disturbances, or may occur as an adverse response to medication (e.g. long-term treatment with antihypertensives). Pathogenetically, there is a peripheral autonomous neuropathy associated with a disorder of secondary salivary secretion. Males and females are equally affected, with a peak age incidence between 40 and 70.

Clinically, a chronic recurrent, painless, usually bilateral and afebrile enlargement of the gland, not associated with meal times, is seen, most commonly, in the lower pole of the parotid. The earlobes are displaced laterally. The histological picture is characterised by swollen acini filled with granules of secretion resulting in a two- to three-fold increase in diameter. As a result, the duct system seems compressed.

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Necrotising sialometaplasia

It is the result of an ischaemic insult (salivary gland infarction), usually of the palate. Men are more frequently affected than women (8:1). Most patients are heavy smokers, so that necrotising sialometaplasia is considered a late stage of smoker's palate. Clinically, initial small painful swellings that occur in the palate may ulcerate later. The histological picture is characterised by squamous cell metaplasia of the duct epithelium with a surrounding inflammatory reaction.

An inexperienced examiner may easily mistake the histological picture for squamous cell carcinoma!!!


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