Dent 356-11 Diseases of Salivary Glands I

Developmental Anomalies Sialadenitis Obstructive & Traumatic Lesions Sjgren Syndrome

Dr. Rima Safadi

From Dr. Huda Hammad Lectures

Salivary Glands: Major

Salivary Glands: Major

Parotid Gland

Salivary Glands: Major

Submandibular Gland

Salivary Glands: Major

Sublingual Gland

Salivary Glands: Minor

Salivary Glands: Minor

Developmental Anomalies of Salivary Glands

Rare. Aplasia of one or more major SG is rare.
Atresia of one or more major SG ducts.

Developmental Anomalies of Salivary Glands

Aplasia of parotid gland may be associated with other anomalies, e.g. - mandibulofacial dysostosis - aplasia of lacrimal glands - hemifacial microsomia.

Developmental Anomalies of Salivary Glands

Heterotopic SG tissue: e.g. Stafnes idiopathic bone cavity.
Accessory parotid tissue within cheek or masseter muscle is relatively common.

Sialadenitis
Bacterial: Acute Chronic Recurrent parotitis Viral: Mumps Cytomegalic inclusion disease Postirradiation

Sarcoidosis
Sialadenitis of minor glands

Acute Bacterial Sialadenitis

Uncommon, mostly affects parotid.
Ascending infection from mouth.

Mainly Streptococcus pyogenes & Staphylococcus aureus.

Less commonly Haemophilus species or members of the black-pigmented Bacteroides group.

Acute Bacterial Sialadenitis

Predisposing factors:
1.

Reduced salivary flow, e.g. Sjgren syndrome, drugs with xerostomic side effect.

2.

Used to be a common postoperative complication in debilitated, dehydrated patients following abdominal surgery.
Immunocompromized patients. Acute exacerbation of chronic sialadenitis, usually submandibular gland.

3. 4.

Acute Bacterial Sialadenitis

Clinical features:
1. 2. 3. 4.

Rapid onset. Swelling of involved gland. Pain, fever, malaise. Redness of overlying skin.

5.

Pus may be expressed from duct.

Chronic Bacterial Sialadenitis

In major glands, it is usually non-specific, associated with duct obstruction (salivary calculi) & low-grade ascending infection. Submandibular > parotid gland.

Disorder of secretion & decreased salivary flow may also predispose to it.

Chronic Bacterial Sialadenitis

Clinical features:
1. Usually unilateral. 2. Recurrent, tender swelling of

affected gland related to obstruction.

3. Duct orifice may appear

inflamed.
4. In acute exacerbations there

may be purulent or salty discharge.

Chronic Bacterial Sialadenitis

Histopathology: - varying degrees of ductal dilatation. - hyperplastic ductal epithelium. - periductal fibrosis. - acinar atrophy & replacement by fibrous tissue. - chronic inflammatory infiltration.

Chronic Bacterial Sialadenitis

Sialography demonstrates duct obstruction, glandular tissue destruction, & ductal dilatation. Progressive chronic inflammation of submandibular gland may result in almost complete replacement of parenchyma by fibrous tissue, which may be mistaken for a tumor (chronic sclerosing sialadenitis).

Recurrent Parotitis
Rare disorder of children or adults. Rarely, adult form may follow on from childhood type, but mostly due to persistence of predisposing factors such as calculi or duct strictures. Possible etiology of childhood type: 1. Abnormally low secretion rate. 2. Immaturity of immune response. 3. Congenital abnormalities of ductal system.

Recurrent Parotitis
Clinical features:
1. Unilateral or bilateral. 2. Recurrent painful swelling of parotid. 3. Pus may be expressed from orifice. 4. Often resolves spontaneously by early adulthood. 5. Repeated infection may cause irreversible damage to

main duct, predisposing to duct obstruction and further episodes in adult life.

Mumps (Epidemic Parotitis)

An acute, contagious infection which often occurs in minor epidemics. Caused by a paramyxovirus. Commonest cause of parotid enlargement. Commonest of all salivary gland diseases.

Mumps (Epidemic Parotitis)

Clinical features:
1. Most common in childhood.

2. Transmitted by direct contact with infected saliva and droplet spread.

3. Incubation period of 2-3 weeks. 4. Prodromal symptoms of fever & malaise.

Mumps (Epidemic Parotitis)

Clinical features, contd: 5. Sudden onset of painful swelling of one or more salivary glands, mostly parotid (70%).

Mumps (Epidemic Parotitis)

Clinical features, contd: 6. Occasional involvement of submandibular and sublingual glands, but rarely without parotid also.

7. Enlargement gradually subsides over a week.

Mumps (Epidemic Parotitis)

Clinical features, contd: 8. Virus is present in saliva 2-3 days before onset, and 6 days after. 9. Occasional involvement of other organs in adults; testes, ovaries, CNS.

10. Orchitis is the most common complication affecting 20% of affected adult males.

Mumps (Epidemic Parotitis)

Diagnosis is usually clinical, but can be confirmed by detection of IgM antibodies and by rise in serum titer to mumps virus antigens within the 1st week.
Immunity after an attack in long-lasting and recurrent infection is rare.

Cytomegalic Inclusion Disease (Salivary Gland Inclusion Disease)

CMV is a member of the herpesvirus group. Infection is common in humans worldwide. Most primary infections are asymptomatic. It can cause severe disseminated disease in neonates and immunocompromised hosts e.g. transplant and HIVinfected patients. May be associated with xerostomia in HIV infection.

Cytomegalic Inclusion Disease (Salivary Gland Inclusion Disease)

Histopathology: 1. Salivary gland involvement is usually an incidental histological finding.
2. Large, doubly contoured

owl-eye inclusion bodies within nucleus or cytoplasm of duct cells of parotid gland. similar inclusions are found in kidneys, liver, lungs, brain, & other organs.

3. In disseminated disease,

Postirradiation Sialadenitis
A common complication or radiotherapy. Direct correlation between dose of irradiation and severity of damage.

Damage is often irreversible leading to: a. fibrous replacement of damaged acini b. squamous metaplasia of ducts. In less severe cases, some degree of function may return after several months.
Serous acini are more sensitive than mucous acini.

Sarcoidosis
May affect parotid and minor salivary glands. Parotid involvement presents as persistent, often painless enlargement. May be associated with involvement of lacrimal glands in Heerfordt syndrome.

Sialadenitis of Minor Glands

Often an incidental & insignificant finding. May however be of diagnostic significance, such as in sarcoidosis & Sjgren syndrome. Most frequently seen in association with mucous extravasation cysts & nicotinic stomatitis.

Sialadenitis of Minor Glands

Histopathology: - Varying degrees of ductal dilatation. - Hyperplastic ductal epithelium.

- Periductal fibrosis.
- Acinar atrophy & replacement by fibrous tissue. - Chronic inflammatory infiltration.

Sialadenitis of Minor Glands

Very rarely may present with multiple mucosal swellings associated with cystic dilatation of ducts and chronic suppuration (stomatitis glandularis).

Most commonly on the lips, probably as an acute exacerbation of a chronic form associated with obstruction or reduction in salivary flow (cheilitis glandularis).

Obstructive & Traumatic Lesions

Salivary calculi (sialoliths)

Necrotizing sialometaplasia
Mucoceles

Salivary Calculi (Sialoliths)

Most common in middle-aged adults. May form in ducts within the gland, or in main excretory duct.

Salivary Calculi (Sialoliths)

79-90% of cases involve submandibular gland. Parotid gland is next, while only 2% affect sublingual or minor glands.

Usually unilateral, although may be multiple in same gland.

Salivary Calculi (Sialoliths)

Clinical features:
1.

When symptomatic, they cause pain & sudden enlargement of affected gland, especially at meal times when secretion is stimulated. Reduction in flow predisposes to ascending infection & chronic sialadenitis.

2.

Salivary Calculi (Sialoliths)

Clinical features, contd:

3. Calculi may be detected by palpation and on radiographs.

Salivary Calculi (Sialoliths)

Thought to form by gradual deposition of calcium salts around an initial organic nidus which may consist of altered salivary mucins with desquamated cells and microorganisms.

Necrotizing Sialometaplasia
A relatively uncommon disorder. May be mistaken clinically and histologically for malignant disease. Most frequent on hard palate in middle-aged patients, especially males.

Necrotizing Sialometaplasia
Clinical features:
1. Presents most

commonly as a deep, crater-like ulcer which may mimic a malignant ulcer.

2. May take up to 10-12

weeks to heal.
3. Ulcer may be preceded

by an indurated swelling.

Necrotizing Sialometaplasia
Histopathology:
1. Lobular necrosis. 2. Squamous metaplasia of

ducts & acini.

3. Mucous extravasation.
4. Inflammatory cell infiltration. 5. Overlying palatal mucosa

shows pseudoepitheliomatous hyperplasia.

6. Features may be mistaken for

SCC or mucoepidermoid carcinoma.

Necrotizing Sialometaplasia
Etiology unknown, but ischemia leading to infarction of salivary lobules is most widely accepted theory. In some patients there may be history of trauma, including local anesthetic injection and previous surgery.

Sjgren Syndrome
A chronic autoimmune disease. Characterized by lymphocytic infiltration and acinar destruction of lacrimal and salivary glands.

Classified into: 1. Primary Sjgren or sicca syndrome : dry mouth (xerostomia) and dry eyes (xerophthalmia or keratoconjunctivitis sicca) 2. Secondary Sjgren syndrome : xerostomia, xerophthalmia, & an autoimmune CT disease, usually rheumatoid arthritis.

Sjgren Syndrome: Clinical Features

Rheumatoid arthritis is the most common CT disease associated with 2ry SS. Other autoimmune diseases that may be associated include:* Systemic lupus erythematosus. Systemic sclerosis. Primary biliary cirrhosis. Mixed CT disease.

1. 2. 3. 4.

* Not in textbook.

Sjgren Syndrome: Clinical Features

Unless stated otherwise, the general term Sjgren syndrome (SS) is used to encompass both types. Both 1ry & 2ry SS exhibit a wide spectrum of clinical features associated with widespread involvement of other glands and other tissues.

Sjgren Syndrome: Clinical Features

Sjgren Syndrome: Clinical Features

i. ii. iii. iv. v. vi.

European criteria for diagnosis of SS relate to: Ocular symptoms. Ocular signs. Oral symptoms. Salivary gland function. Labial salivary gland histology. Ro and La autoantibodies. 4 of the 6 criteria need to be fulfilled.

Sjgren Syndrome: Clinical Features

SS predominantly affects middle-aged females (9:1 F:M ratio). The most common symptoms are related to xerostomia and xerophthalmia.

In general, ocular & oral manifestations are more severe in 1ry SS.

Sjgren Syndrome: Clinical Features

Xerostomia may be associated with:
1. 2. 3. 4.

5. 6.

difficulty in swallowing & speaking increased fluid intake disturbances of taste soreness & redness of mucosa associated with candidosis rapidly progressive caries acute bacterial sialadenitis.

Sjgren Syndrome: Clinical Features

Oral mucosa appears dry, smooth, and glazed.

Dorsum of tongue often appears red and atrophic with variable degrees of fissuring and lobulation.

Sjgren Syndrome: Clinical Features

Keratoconjuctivitis sicca manifests as: dryness of eyes conjunctivitis gritty, burning sensation.

1. 2. 3.

Sjgren Syndrome: Clinical Features

Salivary gland enlargement is variable. 30% of patients give history of enlargement. Only 15% present with enlargement. Usually bilateral. Predominantly affects parotid glands. Seldom painful.

Sjgren Syndrome: Clinical Features

Lacrimal gland enlargement is uncommon.
Although clinical involvement of minor salivary glands is uncommon, they are often involved microscopically.

Sjgren Syndrome: Histopathological Features

Major glands:
1.

Lymphocytic infiltration, initially around intralobular ducts, eventually replacing the whole affected lobules.

2.

20% B cells, 80% T cells, mostly T-helper.

Acinar atrophy.

3.

Sjgren Syndrome: Histopathological Features

Major glands: 4. Proliferation of duct epithelium to form epimyoepithelial islands. 5. The appearance is described as myoepithelial sialadenitis or benign lymphoepithelial lesion.

6. Unlike lymphoma, the infiltrate does not cross interlobular CT septa.

Sjgren Syndrome: Histopathological Features

Minor glands:
1.

Focal collections of lymphoid cells, initially around intralobular ducts.

2.

The number of foci reflects the severity of the disease.

Sjgren Syndrome: Histopathological Features

Minor glands:
3. The semi-quantitative assessment of this focal lymphocytic sialadenitis in labial minor salivay gland biopsies is an important investigation in establishing a diagnosis, and is one of the diagnostic criteria.

4. However, since the appearance is non-specific, it must be interpreted in the presence of clinical features and serological investigations.

Sjgren Syndrome: Investigations

Minor salivary gland biopsy.
Estimation of parotid salivary flow rates, usually reduced.

Sialography: shows sialectasia (snowstorm pattern, cherry tree in blossom appearance).

Serological findings: anti-Ro, anti-La.

Sjgren Syndrome: Investigations

Approximate frequencies of serological abnormalities & autoantibodies in primary & secondary Sjgren Syndrome
Serological abnormalities Elevated ESR Hypergammaglobulinemia Immune complexes Elevated 2 microglobulin (increased in exacerbations) Autoantibodies Rheumatoid factor Antinuclear antibody Anti-Ro/anti-La Gastric parietal cell 40-60 40-70 80-90 75-100 Up to 100 20-60 Primary (%) 50-100 50-90 85 30-50 Secondary (%) 50-100 50-90 Up to 50 30-50

Thyroid
Mitochondrial Smooth muscle

Variable
5-30

Variable
5-30

Sjgren Syndrome: Investigations

Although neither anti-Ro or anti-La is specific for SS, they are diagnostically helpful since they may be detected some time before clinical picture develops.

Sjgren Syndrome: Etiology & Pathogenesis

Strong evidence that it is autoimmune. Genetic factors thought to be important in increasing susceptibility to external factors which trigger the disease. Occurs with increased frequency in patients with certain HLA class II MHC genes. Several viruses, especially EBV have been suggested as potential trigger factors. Immunological mechanisms leading to destruction of glandular tissue probably involve mainly T cells and their cytokines. Pathogenic significance of the range of circulating autoantibodies is uncertain.

Sjgren Syndrome: Malignant Transformation

Risk of B cell lymphoma developing in affected gland 44 times that of general population. Risk varies from <1%-6% of SS patients. Risk may be slightly greater in 1ry SS than 2ry SS. Malignancy usually occurs late in the course of disease. May be associated with increased swelling of gland. Associated lymphomas share many similarities with MALT lymphomas; they tend to pursue indolent course & remain localized until late.

Sialadenosis (Sialosis)
Non-inflammatory, non-neoplastic, recurrent bilateral swelling of salivary glands.

Parotid glands most commonly. Probably due to abnormalities of neurosecretory control.

Sialadenosis (Sialosis)
Has been reported with:
1.Hormonal disturbances. 2.Malnutrition. 3.Liver cirrhosis. 4.Chronic alcoholism. 5.Various drugs.

Sialadenosis (Sialosis)
Histopathology:
1. Hypertrophy of serous acinar cells to

about twice their normal size.

2. Cytoplasm is densely packed with

secretory granules.

HIV-Associated Salivary Gland Disease

HIV-related parotid enlargement may be due to:
1. Persistent glandular

lymphadenopathy. 2. Multiple lymphoepithelial cysts.