Dent 356-11 Diseases of Salivary Glands I Developmental

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Dent 356-11Diseases of Salivary Glands I

• Developmental Anomalies
• Sialadenitis
• Obstructive Traumatic Lesions
• Sjögren Syndrome
• Dr. Rima Safadi
• From Dr. Huda Hammad Lectures

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Salivary Glands Major
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Salivary Glands MajorParotid Gland
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Salivary Glands MajorSubmandibular Gland
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Salivary Glands MajorSublingual Gland
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Salivary Glands Minor
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Salivary Glands Minor
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Developmental Anomalies of Salivary Glands

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

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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.

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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.

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Sialadenitis

• Bacterial
• Acute
• Chronic
• Recurrent parotitis
• Viral
• Mumps
• Cytomegalic inclusion disease
• Postirradiation
• Sarcoidosis
• Sialadenitis of minor glands

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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.

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Acute Bacterial Sialadenitis

• Predisposing factors
• Reduced salivary flow, e.g. Sjögren syndrome,
  drugs with xerostomic side effect.
• Used to be a common postoperative complication in
  debilitated, dehydrated patients following
  abdominal surgery.
• Immunocompromized patients.
• Acute exacerbation of chronic sialadenitis,
  usually submandibular gland.

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Acute Bacterial Sialadenitis

• Clinical features
• Rapid onset.
• Swelling of involved gland.
• Pain, fever, malaise.
• Redness of overlying skin.
• Pus may be expressed from duct.

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Chronic Bacterial Sialadenitis

• In major glands, it is usually non-specific,
  associated with duct obstruction (salivary
  calculi) low-grade ascending infection.
• Submandibular gt parotid gland.
• Disorder of secretion decreased salivary flow
  may also predispose to it.

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Chronic Bacterial Sialadenitis

• Clinical features
• Usually unilateral.
• Recurrent, tender swelling of affected gland
  related to obstruction.
• Duct orifice may appear inflamed.
• In acute exacerbations there may be purulent or
  salty discharge.

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Chronic Bacterial Sialadenitis

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

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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).

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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
• Abnormally low secretion rate.
• Immaturity of immune response.
• Congenital abnormalities of ductal system.

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Recurrent Parotitis

• Clinical features
• Unilateral or bilateral.
• Recurrent painful swelling of parotid.
• Pus may be expressed from orifice.
• Often resolves spontaneously by early adulthood.
• Repeated infection may cause irreversible damage
  to main duct, predisposing to duct obstruction
  and further episodes in adult life.

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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.

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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.

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Mumps (Epidemic Parotitis)

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

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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.

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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.

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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.

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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 HIV-infected patients.
• May be associated with xerostomia in HIV
  infection.

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Cytomegalic Inclusion Disease(Salivary Gland
Inclusion Disease)

• Histopathology
• Salivary gland involvement is usually an
  incidental histological finding.
• Large, doubly contoured owl-eye inclusion
  bodies within nucleus or cytoplasm of duct cells
  of parotid gland.
• In disseminated disease, similar inclusions are
  found in kidneys, liver, lungs, brain, other
  organs.

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Postirradiation Sialadenitis

• A common complication or radiotherapy.
• Direct correlation between dose of irradiation
  and severity of damage.
• Damage is often irreversible leading to
• fibrous replacement of damaged acini
• 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.

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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.

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Sialadenitis of Minor Glands

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

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Sialadenitis of Minor Glands

• Histopathology
• - Varying degrees of ductal dilatation.
• - Hyperplastic ductal epithelium.
• - Periductal fibrosis.
• - Acinar atrophy replacement by fibrous tissue.
• - Chronic inflammatory infiltration.

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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).

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Obstructive Traumatic Lesions

• Salivary calculi (sialoliths)
• Necrotizing sialometaplasia
• Mucoceles

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Salivary Calculi (Sialoliths)

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

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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.

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Salivary Calculi (Sialoliths)

• Clinical features
• 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.

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Salivary Calculi (Sialoliths)

• Clinical features, contd
• 3. Calculi may be detected by palpation and on
  radiographs.

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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.

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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.

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Necrotizing Sialometaplasia

• Clinical features
• Presents most commonly as a deep, crater-like
  ulcer which may mimic a malignant ulcer.
• May take up to 10-12 weeks to heal.
• Ulcer may be preceded by an indurated swelling.

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Necrotizing Sialometaplasia

• Histopathology
• Lobular necrosis.
• Squamous metaplasia of ducts acini.
• Mucous extravasation.
• Inflammatory cell infiltration.
• Overlying palatal mucosa shows pseudoepitheliomato
  us hyperplasia.
• Features may be mistaken for SCC or
  mucoepidermoid carcinoma.

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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.

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Sjögren Syndrome

• A chronic autoimmune disease.
• Characterized by lymphocytic infiltration and
  acinar destruction of lacrimal and salivary
  glands.
• Classified into
• 1. Primary Sjögren or sicca syndrome dry mouth
  (xerostomia) and dry eyes (xerophthalmia or
  keratoconjunctivitis sicca)
• 2. Secondary Sjögren syndrome xerostomia,
  xerophthalmia, an autoimmune CT disease,
  usually rheumatoid arthritis.

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Sjögren 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.
• Not in textbook.

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Sjögren Syndrome Clinical Features

• Unless stated otherwise, the general term Sjögren
  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.

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Sjögren Syndrome Clinical Features
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Sjögren Syndrome Clinical Features

• 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.

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Sjögren Syndrome Clinical Features

• SS predominantly affects middle-aged females (91
  FM ratio).
• The most common symptoms are related to
  xerostomia and xerophthalmia.
• In general, ocular oral manifestations are more
  severe in 1ry SS.

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Sjögren Syndrome Clinical Features

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

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Sjögren 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.

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Sjögren Syndrome Clinical Features

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

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Sjögren 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.

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Sjögren Syndrome Clinical Features

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

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Sjögren Syndrome Histopathological Features

• Major glands
• Lymphocytic infiltration, initially around
  intralobular ducts, eventually replacing the
  whole affected lobules.
• 20 B cells, 80 T cells, mostly T-helper.
• Acinar atrophy.

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Sjögren 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.

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Sjögren Syndrome Histopathological Features

• Minor glands
• Focal collections of lymphoid cells, initially
  around intralobular ducts.
• The number of foci reflects the severity of the
  disease.

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Sjögren 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.

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Sjögren Syndrome Investigations

• Minor salivary gland biopsy.
• Estimation of parotid salivary flow rates,
  usually reduced.
• Sialography shows sialectasia (snowstorm
  pattern, cherry tree in blossom appearance).
• Salivary scintiscanning with 99Tcm shows
  reduced uptake.
• Serological findings anti-Ro, anti-La.

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Sjögren Syndrome Investigations

• Approximate frequencies of serological
  abnormalities autoantibodies in primary
  secondary Sjögren Syndrome

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Sjögren 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.

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Sjögren 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.

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Sjögren Syndrome Malignant Transformation

• Risk of B cell lymphoma developing in affected
  gland 44 times that of general population.
• Risk varies from lt1-6 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.

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Sialadenosis (Sialosis)

• Non-inflammatory, non-neoplastic, recurrent
  bilateral swelling of salivary glands.
• Parotid glands most commonly.
• Probably due to abnormalities of neurosecretory
  control.

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Sialadenosis (Sialosis)

• Has been reported with
• Hormonal disturbances.
• Malnutrition.
• Liver cirrhosis.
• Chronic alcoholism.
• Various drugs.

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Sialadenosis (Sialosis)

• Histopathology
• Hypertrophy of serous acinar cells to about twice
  their normal size.
• Cytoplasm is densely packed with secretory
  granules.

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HIV-Associated Salivary Gland Disease

• HIV-related parotid enlargement may be due to
• Persistent glandular lymphadenopathy.
• Multiple lymphoepithelial cysts.