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Salivary gland diseases

We will start with new chapter today which is salivary gland diseases. We have major salivary gland and minor salivary glands. The major salivary glands are (parotid, submandibular, sublingual gland) so we have three major salivary glands, the minor salivary glands are numerous, multiple, hundreds of glands in the mucosa of the oral cavity. Location of the minor salivary gland: 1- Soft palate, lips, buccal mucosa, ventral of the tongue, lateral border of the tongue, floor of the mouth. We dont find minor salivary gland in: 1- Dorsum of the tongue (ant 2/3 only because we have von ebner gland in the post 1/3). 2- Gingiva. 3- Anterior hard palate.

The major salivary gland:

1-The parotid gland is serous acini , the cell which produce saliva is serous acini , look at picture below and notice these cells that contain blue granules .

(Parotid gland)
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The submandibular is a mixture of mucous and serous acini , but we can find more serous than mucous .look at the picture below and notice the mucous acini cytoplasm containing a lot of bale color mucous acini so they will appear as empty cell .

(Submandibular gland) The sublingual gland is mixture of mucous and serous acini. But here the mucous is more, so this will lead to produce different type of saliva. Look at picture below and notice it has more mucous cell.

(Sublingual gland) The minor salivary gland all of it is mucous acini.

(Minor salivary gland)

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Developmental Anomalies of salivary gland

1-Aplasia : the absence of one or more major SG, so Aplasia means the absence of the salivary gland from birth especially parotid gland. Aplasia of parotid gland may be associated with other anomalies. - mandibulofacial dysostosis , aplasia of lacrimal glands, hemifacial microsomia.so its associated with the decrease of the size of the cells , face, mouth , lacrimal gland . 2-Atresia: the absence of one or more major SG ducts. So aplasia for the gland itself and atresia for the duct. 3-Heterotopic salivary gland tissue : this mean normal tissue but in up normal location , we said before that the salivary gland tissue can enter the lingual surface of the mandible in concavity there especially below the IV canal and we called it Stafnes idiopathic bone cavity. 4-Accessory parotid tissue within cheek or masseter muscle is relatively common these tissues may be affected by any disease or tumor affect the parotid gland.

Infection of the salivary gland

Sialadenitis is inflammation of a salivary gland. This inflammation could be happen
by bacteria or virus or irradiation .

Bacterial infection: we have acute, chronic, recurrent Sialadenitis.

Acute Sialadenitis:
Its uncommon infection, especially affected the parotid gland, the bacteria reach the gland through ascending infection thats mean the bacteria will go up through the gland, the salivary flow may be reduced. we know that when the salivary
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secretion decrease the wash out will decrease this make the bacteria to go up to the gland . The bacteria that may cause the acute Sialadenitis are Staphylococcus aureus, Streptococcus pyogenes.

The causes:
1- Reduced salivary flow like Sjgren syndrome may reduce the salivary flow , the drug with xerostomia as a side effect, so anything reduce the salivary flow will make the patient more opportunistic to get acute bacterial Sialadenitis. 2-Used to be a common postoperative complication in debilitated, dehydrated patients following abdominal surgery. 3-Immunocompromized patients. 4- Acute exacerbation of chronic Sialadenitis, usually submandibular gland. 5- Irradiation to the area where the salivary gland locate may decrease the salivary flow and lead to acute Sialadenitis. The clinical feature: Rapid onset, swelling of involved gland, Pain, fever, malaise, Pus may be expressed from duct.look at the picture below and notice the redness in the area where the parotid gland locate.

(Acute bacterial Sialadenitis)

Now we will move to:

Chronic bacterial Sialadenitis:

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In major glands, it is usually non-specific, associated with duct obstruction (salivary calculi) & low-grade ascending infection. This infection is associated with duct obstruction so there is no complete wash out of the duct make the bacteria can ascend through the duct to affect the gland. Usually submandibular have possibility to be affected with chronic Sialadenitis more than parotidbecause saliva in the submandibular is more than the parotid according to the gravity which make the saliva more.. that make the calcium deposits..Surrounded by protein core forming the stone. So the submandibular gland most likely to have stones which obstruct the gland. 2- Disorder of secretion & decreased salivary flow may also predispose to it.

Clinical features: 1- Usually unilateral stones, sometimes it can be multiple unilateral stones. 2-Recurrent, tender swelling of affected gland related to obstruction. 3-Duct orifice may appear inflamed and red. 4-In acute exacerbations there may be purulent or salty discharge. So we can see the pus in acute Sialadenitis and acute exacerbations.

(Chronic bacterial Sialadenitis with unilateral stones)

Histopathology:
- varying degrees of ductal dilatation. - Hyperplastic ductal epithelium . - Periductal fibros : collagen bundle forming around the duct replacing the acini. - Acinar atrophy & replacement by fibrous tissue.
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- Chronic inflammatory infiltration. So when we compare with normal it will have well-defined acini mixed with fat and the fat increase with age .

(Look at the picture above and notice the dilatation, the ductal hyperplastic and the atrophy of the duct black dots is lymphocytes infiltrate in the duct ). 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) Sialography : is the injection of the salivary gland with certain material will give us a feature of ductal dilatation because the injected material will accumulate in the duct make it not straight but it will give us dilatation appearance. with dilatation we may have a features of glandular tissue obstruction and duct obstruction.

Recurrent Parotitis
This may occur in children or adult due to predisposing factor such as calculi or duct obstruction which is decrease salivary flow , up normal immune response may also play a role in recurrent parotitis and in children there is a congenital obstruction in the duct not stenosis it's congenital. Possible etiology of childhood type : *Abnormally low secretion rate. *Immaturity of immune response. *Congenital abnormalities of ductal system.

Clinical features :
1-Unilateral or bilateral. 2-Recurrent painful swelling of parotid.

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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.this is important feature because the recurrent infection may be deformed the duct and make it predisposing to duct obstruction either by itself or by allowing deposition of minerals around it , this condition may not improved in the adult life.... so the recurrent infection will change the morphology of the duct. This is all about bacterial Sialadenitis of the salivary gland.

Now we will move to

Viral Sialadenitis of the salivary gland Mumps

An acute, contagious infection which often occurs in minor epidemics Which caused by a paramyxovirus, its the most common cause of the parotid enlargement and the mump is the common of all salivary gland diseases.

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. 5- The patient may have the virus in saliva 2- 3 days before the symptoms, we dont know that the patient is infected but the virus is in saliva. 6- After healing the symptoms, the patient still have the virus for 6 days, Thats mean the patient can still contagious the virus to surrounding. 7- Sudden onset of painful swelling of one or more salivary glands, mostly the parotid gland (70%), if the patient starts with one side it will go to other side.
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8- Occasional involvement of submandibular and sublingual glands, but rarely without parotid also. 9- Enlargement gradually subsides over a week. 10- If the virus go to other organ like the testis it will induce complication like Orchitis(inflammation of the testis ) especially in 20% of affected adult males.

Child with mumps

The Diagnosis is usually clinical look at the picture above, but can be confirmed by detection of IgM antibodies after 2 weeks 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. That mean the patient will not have the virus again ... now a days we have vaccine against mumps.

Cytomegalic Inclusion Disease

In general if the healthy person infected by cytomegalic virus he will not have a clinical infection so the virus will go and latent in ductal epithelium and other organ. But it can cause severe disseminated disease in neonates and immunocompromised hosts e.g. transplant and HIV-infected patients. So the CMV will affect several organs like the kidneys, liver, lungs, brain, & other organs and cause severe infection.

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CMV is a member of the herpesvirus group and this virus have 2 stages of primary and secondary infection, Most primary infections are asymptomatic.. But when the infection get reactivated later on life if the patient have HIV or immunocompromised secondary infection will be improved.

Histopathology:
Salivary gland involvement is usually an incidental histological finding. In normal case (dont have HIV or immuncompromised ) but infected with CMV we have inclusion of the epithelium cells.. Large, doubly contoured owl-eye inclusion bodies within nucleus very big surrounding by clear area or cytoplasm of duct cells of parotid gland ,, we see the inclusion in the nucleus or cytoplasm . In disseminated case we have the same inclusion but it may involve several organ ,mean the inclusion may attack the liver, lung etc Look at the picture below and notice the owl-eye inclusion

(Cytomegalic Inclusion)

Postirradiation Sialadenitis
Direct correlation between dose of irradiation and severity of damage it could produce destruction of the acini so it will destruct everything,, some case with time we may have some improvement thats depend in the dose and acini damaged by the irradiation.. In general serous acini are more sensitive than mucous acini .here the damage is irreversible lead to fibrous replacement of damaged acini and squamous metaplasia of ducts.

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Sarcoidosis
The etiology is unknown may be bacterial or viral.. We have deposition of granulomas.. The granulomas contain microphages and multi-nucleated giant cell..If u remember the TB we have granulomas with caseating but in the sarcoidosis we have formation of granulomas that are non- caseating granulomas. 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 when we have involvement of lacrimal and salivary glands. Sarcoidosis is a separated disease may affect the gingiva and lymph node and other organ but in salivary gland the sarcoidosis is non-caseating granulomas Look at the picture and notice the granulomas with bale color but without center caseation.

(Sarcoidosis with non-caseation granulomas)

Sialadenitis of Minor Glands

Minor salivary gland is less likely to have Sialadenitis; it could be due to trauma that comes from the friction of the denture causing irritation of the minor salivary gland. Calculi through the minor salivary gland is rare the inflammation of the minor may be diagnostic of the diseases affect the major salivary gland. Because it easier for us to take biopsy from the lower labial mucosa (minor gland) than to take it from the parotid (major gland), this is advantage for us because the patient will get the biopsy from the
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minor gland not major gland, for example sarcoidosis & Sjgren syndrome will affect major gland and minor

Most frequently seen in association with:

1- Mucous extravasation cysts. 2- Nicotinic stomatitis :which mean in the smoker due to heat in the soft palate ,heat will inflame minor salivary gland ,this disease is not due to bacteria or virus its due to heat in the oral cavity, This term is used mainly in soft palatal lesions.

Histopathology: Its the same as major salivary gland Sialadenitis

- Varying degrees of ductal dilatation. - Hyperplastic ductal epithelium. - Periductal fibrosis. - Acinar atrophy & replacement by fibrous tissue, the acini will be replaced by fibrous tissue; its chronic fibrousing Sialadenitis when there is inflammation. - Chronic inflammatory infiltration.

(Sialadenitis of minor salivary gland)

Very rarely may affect labial mucosa present with multiple mucosal swellings associated with cystic dilatation of ducts and chronic suppuration (stomatitis glandularis).
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When we make eversion of the labial mucosa u will find a multiple swelling in addition the orifice of the duct will be white in color due to excreting pus this is called stomatits glandularis. Most commonly on the lips, probably as an acute exacerbation of a chronic form of Sialadenitis associated with obstruction or reduction in salivary flow (cheilitis glandularis). Cheilitis glandularis: its a rare case in lower lip (chelitis refer to lips) when we make examination we will find the minor salivary gland large and fibrouses.

Obstructive & Traumatic Lesions

1- Salivary calculi (sialoliths) : mainly in submandibular salivary gland 79-80 % of involve case ,calcium and mineral precipitate in a nidus ( core ) the core is protein or dried mucous, some time the saliva itself dried and make a core for calcium and mineral . The submandibular gland is the most affected gland followed by Parotid gland, while only 2% affect sublingual or minor glands. Usually unilateral, although may be multiple in same gland.

Salivary Calculi (Sialoliths)

Look at the picture above and notice this yellowish stone may be at the orifice of the duct or alongside the duct.

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Clinical features:
1-When symptomatic, they cause pain & sudden enlargement of affected gland, like submandibular gland, especially at meal times when secretion of saliva is stimulated; here because the gland is obstructed the saliva will accumulate in a gland and cause sudden enlargement. 2-Reduction in flow predisposes to ascending infection & chronic Sialadenitis. 3- Calculi may be detected by palpation and on radiographs.

Here we have occlusal radiograph we can detect the mineralized tissue easily because it differ from the other soft tissue.

Histopathology feature:
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. There will be chronic infection and ductal dilatation etc.

Necrotizing Sialometaplasia
A relatively uncommon disorder. The patient will have an ulcer in center of the palate and redness which start as an elevation and its take about 3 month (10-12 weeks) which make the patient think he has cancer for example sqamuous cell carcinoma. May be mistaken clinically and histologically for malignant disease. Most frequent on hard palate in middle-aged patients, especially males. 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 because it contain vasoconstrictor will decrease blood supply to the gland and cause ischemia.
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Histopathology:
1-Lobular necrosis: I can't see the boundaries of each cell it's all like one acini look at the picture below its look like a one cell and it's have the lobular pattern (lobular necrosis), this is important feature to differentiate it from Squamous cell carcinoma. 2-Squamous metaplasia of ducts & acini. Changing from columnar cells to squamous cells and sometimes its look as Epithelium Island. 3-Mucous extravasation. 4-Inflammatory cell infiltration. 5-Overlying palatal mucosa shows pseudoepitheliomatous hyperplasia, some time the surface epithelium causing something called pseudoepitheliomatous because it's have severe hyperplasia .. Nowadays pseudoepitheliomatous called Pseudocarcinomatous hyperplasis because its look like carcinoma . 6-Features may be mistaken for SCC or mucoepidermoid carcinoma.

(Necrotizing Sialometaplasia)

Sjgren Syndrome
A chronic autoimmune disease, the salivary gland are involved, mainly the parotid gland and the lacrimal gland, but it can associated with other chronic disease like Rheumatoid arthritis and its Characterized by lymphocytic infiltration and acinar destruction of lacrimal and salivary glands.
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Classified into:
1. Primary Sjgren or sicca syndrome : when the salivary gland and lacrimal gland involved only without any connective tissue disease we called it sicca or primary syndrome like dry mouth (xerostomia) and dry eyes (xerophthalmia or keratoconjunctivitis sicca) 2. Secondary Sjgren syndrome : when the salivary gland and lacrimal gland involved with another CT disease like xerostomia (dry mouth ), xerophthalmia ( decrease in the tears ) , with an autoimmune CT disease, usually rheumatoid arthritis.

Other autoimmune diseases that may be associated include: 1-Systemic lupus erythematosus. 2-Systemic sclerosis. 3-Primary biliary cirrhosis. 4-Mixed CT disease.

Clinical Features :

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The clinical features are wide spectrum, may involved glandular tissue like dryness in the skin, nasal secretion etc And non-glandular tissue like joint, skin, liver, renal we can take look in the table above.

The diagnosis of depend on mainly in six criteria :

*Ocular symptoms: the symptoms what the patient tell the doctor. *Ocular signs: the signs what the doctor notice on the patient. *Oral symptoms. *Salivary gland function: u will know how to measure the salivary gland function in ur 5th year 3la 5er wo slameh . *Labial salivary gland histology: we said that minor salivary gland diseases are helpful in the diagnoses the major gland diseases. *Ro and La autoantibodies So we need 4 to 6 criteria to diagnose Sjgren Syndrome. Predominantly affects middle-aged females (9:1 F:M ratio).

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. *The mucosa will be sticky and glaze so the patient can't talk some times.

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(Sjgren Syndrome) *Keratoconjuctivitis sicca manifests as: Dryness of eyes, conjunctivitis, gritty, burning sensation

* Salivary gland enlargement is variable, some patient will give u history of enlargement about 30% and 15% present with enlargement, so the enlargement may not be helpful in the diagnosis.

(Enlargement in salivary gland predominant in parotid gland) Look at this swelling its happen due to attack of the gland with lymphocyte mainly T cells lymphocytes, it will attack the acini and surround the duct and give enlargement of the gland.
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* Lacrimal gland enlargement is uncommon. *Although clinical involvement of minor salivary glands is uncommon, they are often involved microscopically.

Histopathological Features :

Major gland :
* Lymphocytic infiltration, initially around intralobular ducts, eventually replacing the whole affected lobules. * 20% B cells, 80% T cells, mostly T-helper: although it mostly T cells the patient more prone to have B cells lymphoma .MALT lymphoma it's not aggressive it's have better properties than other type of lymphoma . * Acinar atrophy.

(Sjgren Syndrome: Histopathological Features in major gland)

* Proliferation of duct epithelium to form epimyoepithelial islands. *The appearance is described as myoepithelial sialadenitis or benign lymphoepithelial lesion. Lympho = lymphocytes .. Epithelia = due to the epithelial islands , it's not only present in Sjgren syndrome , it's not a good indication of this syndrome. Unlike lymphoma, the infiltrate does not cross interlobular CT septa. If its lymphoma it will cross the interlobular septa.
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Minor glands:
Focal collections of lymphoid cells, initially around intralobular ducts then it will spread to the acini . The number of foci reflects the severity of the disease. The dr talked about a case in the hospital is questionable to has Sjgren syndrome, the patient had four location of more than 70 lymphocytes surrounding the intralobular duct so it was helpful to us in diagnosis the case.

(Sjgren syndrome in minor salivary gland )

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. The antibody present in the blood in case of Sjgren syndrome is anti Ro (also called SSA Sjgren syndrome A) and anti-La (also called SSb Sjgren syndrome B ) the anti-Ro are more common to present in the serum of the affected patient compared to anti-LA or SSb , and both of them are more common in primary more than secondary .

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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 auto antibodies is uncertain. Finally Risk of B cell lymphoma developing in affected gland 44 times that of general population and the percent will reach 6% to have B cell lymphoma.

Duty completed Forgive me for any mistakes Done by: Mohmmad Ahmad This work, is dedicated to the beating heart of the batch

Omar Abu-shhadeh
And to Jiana azam , Sara kazkaz ,Mohmmad rafayah ( al jineral in 2009 batch ) Fahed salman, Mo3taz al sardi,Hazim abo alzeek , Musap al Rawi ,Mohanad al rawash ,Abdullah hamdan ,Ali wattad, Anas hamid , Mohmmad tawalbeh and to all my friend ..

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