SALIVARY GLAND DISORDERS
Development of the parotid gland starts between 4th-6th week, the submandibular gland at 6th week and the sublingual gland including minor salivary glands develops at 8-12 week of embryonic life. The various developmental stages are: bud formation, epithelial cord formation, branching and glandular differentiation, canalization and cyto-differentiation. The parotid is ectodermal while the submandibular and sublingual glands are endodermal in their origins.
Saliva is secreted by:
Three pairs of major(larger) salivary glands
Some minor (small) salivary glands.
- Parotid glands
- Submaxillary or submandibular glands
- Sublingual glands.
- Largest of all salivary glands.
- Situated at the side of the face just below and in front of the ear.
- Each gland weighs about 20 to 30 g in adults.
- Secretions from these glands are emptied into the oral cavity by Stensen duct.
- This duct is about 35 mm to 40 mm long and opens inside the cheek against the upper second molar tooth.
- Located in submaxillary triangle, medial to mandible.
- Each gland weighs about 8 to 10 g.
- Saliva from these glands is emptied into the oral cavity by Wharton duct (about 40 mm long).
- Duct opens at the side of frenulum of tongue, by means of a small opening on the summit of papilla called caruncula sublingualis.
- Smallest salivary glands.
- Situated in the mucosa at the floor of the mouth.
- Each gland weighs about 2 to 3 g.
- SLG has small ducts called ducts of Rivinus and a common duct, Bartholin’s duct, which connects with Wharton’s duct at the sublingual caruncula .
- It drains the anterior part of the gland and opens on caruncula sublingualis near the opening of submaxillary duct.
- Lingual Mucus Glands
Situated in posterior one third of the tongue, behind circumvallate papillae and at tip and margins of tongue.
- Lingual Serous Glands
Located near circumvallate papillae and filiform papillae.
- Buccal Glands
- Also known as molar glands.
- Present between the mucus membrane and buccinator muscle.
- Four to five of these are larger and situated outside buccinator, around the terminal part of parotid duct.
- Labial Glands
Situated beneath the mucus membrane around the orifice of mouth.
- Palatal Glands
Found beneath the mucus membrane of the soft palate.
Salivary glands are classified into three types, based on the type of secretion:
- Serous Glands
- Mainly made up of serous cells.
- Secrete thin and watery saliva.
- Parotid glands and lingual serous glands are the serous glands.
- Mucus Glands
- Mainly made up of mucus cells.
- Secrete thick, viscous saliva with high mucin content.
- Lingual mucus glands, buccal glands and palatal glands belong to this type.
- Mixed Glands
- Made up of both serous and mucus cells.
- Submandibular, sublingual and labial glands are the mixed glands.
- Volume: 1000 mL to 1500 mL of saliva is secreted per day and it is approximately about 1 mL/minute.
- Reaction: Mixed saliva from all the glands is slightly acidic with pH of 6.35 to 6.85
- Specific gravity: It ranges between 1.002 and 1.012.
- Tonicity: Saliva is hypotonic to plasma.
Mixed saliva contains
- Water – 99.5%.
- Solids – 0.5%.
- Solids consist of :
- Organic substances
- Inorganic substances
- Organic substances:
- Lingual lipase
- Carbonic anhydrase.
- Other Organic substances:
- Proline- rich proteins
- Blood group antigens
- Free aminoacids
- Non protein nitrogenous substances – urea, uric acid, creatinine, xanthine, hypoxanthine.
- Inorganic substances:
- Organic substances:
- Carbon dioxide.
Salivary function can be organized into 5 major categories that serve to maintain oral health and create an appropriate ecological balance:
- Lubrication and protection.
- Buffering action and clearance.
- Maintenance of tooth integrity.
- Antibacterial activity.
- Taste and digestion.
- 800 to 1500 ml with average volume of 1000 ml.
- Contribution by each major salivary gland is:
- Parotid glands : 30%
- Submaxillary glands : 60%
- Sublingual glands: less than 5%.
- Minor salivary glands about 7%
Whole saliva is the mixed fluid content of the mouth.
- Absorbent (swab)
Draining method is passive and requires the patient to allow saliva to flow from the mouth into a pre-weighed test tube or graduated cylinder for a timed period.
In spitting method, the patient allows saliva to accumulate in the mouth and then expectorates into a pre-weighed graduated cylinder, usually every 60 seconds for 2 to 5 minutes.
Suction method uses an aspirator or saliva ejector to draw saliva from the mouth into a test tube for a defined time period.
It uses a pre-weighed gauze sponge that is placed in the patient’s mouth for a set amount of time. After collection, the sponge is weighed again, and the volume of saliva is determined gravimetrically.
The draining and the spitting methods are more reliable and reproducible for unstimulated whole saliva collection.
- Individual parotid gland saliva collection is performed by using Carlson-Crittenden collectors.
- Collectors are placed over the Stensen duct orifices and are held in place with gentle suction.
- Collected with an aspirating device or an alginate-held collector called a segregator.
- Through suction device, gauze is placed sublingually to dry and isolate the sublingual region.
- The gauze and tongue are gently retracted away from the duct orifice; gentle suction is used to collect the saliva as it is produced. The segregator is positioned over Wharton’s ducts and is then held in place by alginate.
- As saliva is produced, it flows through tubing and is collected in a pre-weighed vessel.
- By applying a sialagogue such as citric acid to the dorsal surface of the tongue.
- Pre-weighed tubes are used for individual salivary gland collections.
- Flow rates are determined gravimetrically in milliliters per minute per gland.
- The normal salivary flow rate for unstimulated saliva from the parotid gland is 0.4 to 1.5 mL/min/gland.
- The normal flow rate for unstimulated, resting whole saliva is 0.3 to 0.5 mL/min, for stimulated saliva, 1 to 2 mL/min. Values less than 0.1 mL/min are typically considered salivary hypofunction.
- Sympathomimetic drugs like adrenaline and ephedrine.
- Parasympathomimetic drugs like acetylcholine, pilocarpine, muscarine and physostigmine.
- Sympathetic depressants like ergotamine and dibenamine.
- Parasympathetic depressants like atropine and scopolamine.
- Anesthetics such as chloroform and ether stimulate the secretion of saliva. Deep anesthesia decreases the secretion due to central inhibition.
According to Martin S. Greenberg
- Developmental Anomalies
- Abberant Salivary Glands.
- Aplasia and Hypoplasia.
- Accesory Ducts.
- Necrotizing Sialometaplasia.
- Inflammatory Disorders.
- Viral Infections
- Cytomegalovirus infections.
- HIV Associated Salivary Gland Diseases.
- Other Viral Infections.
- Bacterial Infections
- Acute Bacterial Sialedenitis.
- Chronic Bacterial Sialedenitis.
- Allergic Sialedenitis.
- Sarcoidic Sialedenitis.
- Sjogren’s Syndrome.
Also known as Agenesis.
- Any one or group of salivary glands may be absent, unilaterally or bilaterally.
- Etiology is unknown.
- May be associated with:
- Hemifacial microsomia.
- Ladd syndrome.
- Mandibulofacial dysostosis (Treacher Collins).
- Hemifacial microsomia
Scintiscanning with Radioisotope, CT Scan, Magnetic Resonance Imaging
Medication induced xerostomia, sjogrens syndrome, radiation induced xerostomia .
Treatment is supportive and directed towards relieving xerostomia.
- Salivary substitutes.
- Frequent mouth washes.
- Comprehensive dental therapy.
- Fluoride therapy.
- Successful management.
It refers to underdeveloped salivary glands
It is often seen in patients suffering with Melkersson Rosenthal Syndrome.
Unusual localized hyperplasia or hypertrophy of minor accessory salivary glands in the palate.
Etiology is unknown.
According to Giansanti et al the following conditions result in salivary gland enlargement:
- Endocrine disorders.
- Diabetes mellitus.
- Hepatic disease.
- Benign lymphoepithelial lesion.
- Sjogrens syndrome.
- Adiposity, hyperthermia, oligomenorrhea, parotid swelling syndrome.
- Aglossia-adactylia syndrome.
- Waldenstrom’s macroglobulinemia.
- Uveoparotid fever.
- Felty’s Syndrome.
- Certain drugs.
- Aging process.
- Appear as small localized swelling, measuring from several millimeters to 1 cm or more in diameter.
- Occur on the hard palate or at the junction of the hard and soft palates.
- Lesion has an intact surface and is firm, sessile, and normal in color.
- Usually asymptomatic.
- Surgical excision.
- No further treatment is necessary and the condition is not reported to recur.
- Congenital occlusion or absence of one or more of the major salivary gland ducts.
- Exceedingly rare condition.
- It may result in the formation of a retention cyst.
- Produce severe xerostomia.
An aberrant or ectopic salivary gland is salivary gland tissue that develops at a site where it is not normally found i.e . at unusual anatomic sites.
- Also called Static bone cavity or defect of mandible, lingual mandibular bone cavity, static bone cyst, stafne cyst or defect, latent bone cyst.
- First recognized by Stafne in 1942.
- Unusual form of slightly aberrant salivary gland tissue where in a developmental inclusion of glandular tissue is found within or, more commonly, adjacent to the lingual surface of the body of the mandible within a deep and well-circumscribed depression.
Appears an ovoid radiolucency located between the inferior alveolar canal and the inferior border of the mandible in the region of second or third molars.
Traumatic or hemorrhagic bone cyst lies superior to the inferior alveolar canal.
- Asymptomatic round or ovoid radiolucency may occur in the anterior segment of the mandible.
- Appear as a rather poorly circumscribed lesion somewhere between the central incisor and the first premolar area.
Development of a true central salivary gland neoplasm from the included salivary gland tissue (rare).
- A diverticulum is defined as a pouch or a sac protruding from the wall of a duct.
- Diverticuli in the ducts of the major salivary glands often leads to pooling of saliva and recurrent sialedenitis
- Diagnosis is made by sialogram.
- Regularly milking the involved salivary gland and to promote salivary flow through the duct is treatment of choice.
Sialolithiasis is a condition characterized by the obstruction of a salivary gland or its excretory duct due to the formation of calcareous concretions or sialoliths.
- Neurohumoral condition causing salivary stagnation.
- A central nidus for stone formation.
- Metabolic mechanism favouring precipitation of salivary salts into the matrix in the presence of coexisting inflammation.
- Submandibular gland (80 to 90%).
- Parotid gland (5 to 15% ).
- Sublingual or minor salivary glands (2 to 5%).
Common reasons are:
- pH of saliva: The salivary pH in submandibular gland is alkaline (6.8-7.1) favouring precipitation of calcium salts .
- Calcium content: Gland contains relatively higher concentration of calcium and phosphate salts in form of apatites.
- Viscosity: The submandibular gland expresses more viscous saliva due to higher mucous content.
- Anatomic factors: The submandibular duct drains saliva against the gravity as the gland is situated lower than the ductal orifice, contributing to stagnation.
- Ductal course is long and tortuous.
Based upon its anatomical location;
Extra glandular further classified as:
A. Anterior sialoliths – Situated anterior to the line joining mesial surfaces of mandibular second molars.
B. Posterior sialoliths – Situated in the duct posterior to this line till the extra-glandular part of the duct.
- Sialoliths are usually round or oval in shape and may have a variety of sizes.
- The obstruction can be complete or partial.
- May exhibit recurrence once removed.
- Characteristic symptom is the swelling of the salivary duct.
- Swelling occurs usually at meal times or even without any stimulating factors.
- Symptom lasts for a relatively short period, not more than 2 hours and disappears throughout the day. The swelling may be accompanied by pain,
- There is an episode of salivary colic, which is an acute, lacerating, short duration pain which disappears after 15 or 20 minutes of its initial manifestation.
- Involved gland is usually enlarged and tender.
- Stasis of the saliva may lead to infection, fibrosis, and gland atrophy.
- Fistulae, a sinus tract, or ulceration may occur over the stone (chronic cases).
Clinical Examination – Should be carried out for following:
- Presence of any swelling and palpate for eliciting possible tenderness of involved gland.
- Observe duct orifice for redness or edema.
- Secretions from the ductal orifice are observed.
- Mild turbid discharge followed by clear saliva is more indicative of inflamed gland and duct due to backpressure and stasis.
- Purulent discharge along with moderate to severe tenderness is indicative of infection
- No salivary expression in complete obstruction of the lumen.
- Plain films:
Submandibular sialoliths are 80-90% radiopaque and appear on radiographs. Three main views are:
- Mandibular occlusal view: Detect calculi in anterior two-thirds of the duct;
- 15 degrees lateral oblique view: Detect calculi in posterior one third and intra-glandular portion of the duct;
- Orthopantomogram: This is used in case of lack of expertise or availability in obtaining the required projection.
- Sialography: It may reveal radiolucent calculi in form of a “filling defect” or ductal narrowing on a sialogram.
- Computed tomography: More sensitive than plain radiographs to detect the presence of even less mineralized stones.
- Magnetic resonance imaging: It is relatively less sensitive in locating the stone but may help in detecting strictures, ductal obstructions other than sialoliths.
- Ultrasonography: Useful for gross detection of size and glandular structure. It may or may not pick sialoliths.
Calcified lymph nodes, foreign body, phlebolith, calcification in facial artery and myositis ossificans.
- Conservative approach: The gland can be milked and an effort put in to retrieve the calculus from orifice.
- Surgical approach: The anterior sialoliths can easily be retrieved under local anaesthesia and posterior sialoliths under general anaesthesia.
- Extra-corporeal shock wave lithotripsy (ESWL): Fixed stones and stones larger than 5 mm can be managed.
- Interventional sialendoscopy: Use for mobile stones and stones less than 5mm.
- Oral mucoceles (OMs) are benign soft tissue masses and are clinically characterized by single or multiple, painless, soft, smooth, spherical, translucent, fluctuant nodule, which is usually asymptomatic.
- Mucoceles (muco – mucus and coele – cavity), by definition, are cavities filled with mucus.
- It is the most common minor (accessory) salivary gland lesion.
Extravasation type: Occurs in three phases:
- I phase: spillage of mucin from salivary duct into the surrounding tissue in which some leucocytes and histiocytes are seen.
- IInd phase: In second phase, granulomas appear due to the presence of histiocytes, macrophages, and multinucleated giant cells associated with foreign body reaction.
- IIrd phase: Pseudocapsule formation.
Obstruction of salivary gland duct leads to accumulation of salivary fluid into the duct, resulting in small balloon formation and as time progresses, the balloon increases in size and bulges into the oral cavity.
- Extravasation type.
- Retention type.
- It is a pseudocyst without defined walls.
- Occurs due to mechanical trauma to the excretory duct of the gland leading to transection or rupture, with consequent extravasation of mucin into the connective tissue stroma.
- Seen frequently on lower labial mucosa, buccal mucosa and retromolar area
- Not lined by epithelial lining.
- The mucus extravasation triggers a secondary inflammatory reaction.
- Less common than extravasation.
- Usually affects older individuals.
- Seen frequently on upper lip, hard palate, floor of mouth and maxillary sinus.
- In mucous retention phenomena, mucus may be retained in the duct and/or acini as a result of duct obstruction by sialolith or strictures.
- Oral mucoceles located on the floor of mouth are termed as “ranula”.
- It usually arises in the body of the sublingual gland and occasionally in the ducts of Rivini or in the Wharton’s. Ranula name is derived from the typical swelling that resembles the air sacs of the frog – ‘Rana tigrina’.
- Manifests as a cup-shaped fluctuant bluish swelling on the floor of mouth.
- The size of the lesions can vary, and larger lesions can cause deviation of the tongue.
- A deep lesion that herniates through the mylohyoid muscle and extends along the facial planes is referred to as a “plunging ranula” and may become large, extending into the neck.
Deep blue color results from:
- Tissue cyanosis.
- Vascular congestion associated with the stretched overlying tissue.
- Translucency of the accumulated fluid beneath.
- Appear as a distinct, fluctuant, painless swelling of the mucosa.
- 75% of the lesions are smaller than 1 cm in diameter, the size can vary from few millimeters to several centimeters.
- Superficial lesions take on a bluish to translucent hue,
- Deep lesions have normal mucosal coloration and bleeding into the swelling may impart a bright red and vascular appearance.
- History of recent or past trauma to the mouth or face or habit of biting the lip.
Blandin and Nuhn mucocele, oral hemangioma, oral lymphangioma, lipoma, and soft tissue abscess.
- The history and clinical findings.
- Radiographic evaluation in cases of sialoliths.
- Ultrasonography with high-frequency transducers, demonstrates the internal structures.
- Localization and determination of the origin of the lesion can be done by CT and magnetic resonance imaging.
- Mucus retention phenomenon and inflammatory cells can be done by fine needle aspiration that reveals high amylase and protein content.
- Complete excision.
- Carbon dioxide lasers.
- Intra-lesional injection of sclerosing agent OK-432 or steroid injection.
Necrotizing sialometaplasia (NS) was first reported in 1973 by Abrams et al. as reactive necrotizing inflammatory process involving minor salivary gland of hard palate.
- Etiology is unknown.
- It may be due to ischemia of vasculature supplying the salivary gland lobules.
- Factors causing ischemia:
- Direct trauma.
- Administration of local anesthetic.
- Ill-fitting dentures.
- Cocaine use.
- Surgical procedures.
- Upper respiratory tract infections.
- Long-term use of salbutamol (causes dehydration and thinning of mucosa).
Pathogenesis can be divided into five histologic stages:
- Reparative stage.
- Healed stage.
- Age prevalence ranges from 17 to 80 years.
- Males are more affected (2:1).
- Most affected site is the minor salivary glands of the palate (80%).
- The posterior hard palate and junction of the hard and soft palate are common site.
- Two-thirds of the palatal lesions are unilateral.
- Occurs spontaneously and the initial symptoms may include fever, chills, malaise or swelling.
- Lesion could occur in the midline.
- The size may range from 0.7 to 5.0 cm (average 1.8 cm).
- Lesions initially present as a tender erythematous nodule as mucosa breaks down, a deep ulceration with a yellowish base forms.
- Lesions can be large and deep, patients often describe only a moderate degree of dull pain.
Diagnosis based on:
- Clinical history.
- Biopsy – From base of the ulcer and the edge.
- Immunohistochemistry demonstrates:
A. Focal to absent immunoreactivity for p53.
B. Low immunoreactivity for MIB1 (ki-67).
C. Presence of 4A4/p63.
D. Calponin-positive myoepithelial cells.
- Self-limiting disease.
- Lasts approximately 6 weeks.
- Heals by secondary intention.
- No specific treatment is required.
- Debridement and saline rinses increases healing process.
- Also known as Parotitis and submandibulitis.
- Bacterial sialadenitis is an acute or chronic bacterial infection of the terminal acini or parenchyma of the salivary glands.
- Bacterial infection.
- Viral infection.
Occasionally due to:
- Allergic reactions.
Also known as “surgical parotitis” because post surgery patients often experience gland enlargement from ascending bacterial infections.
- Reduction of salivary flow leads to bacterial colonization.
- Poor oral hygiene.
- Administration of iodine isotopes for treatment of thyroid carcinoma.
- Staphylococcus aureus.
- Streptococcus viridians.
- Streptococcus pneumonia.
- Escherichia coli.
- Haemophilus influenzae.
- Characterized by suddenly appearing painful preauricular swelling, either unilateral or bilateral.
- Involves the parotid and submandibular glands.
- Intense radiating pain in the affected side of the face.
- Involved gland is painful, indurated and tender on palpation.
- Overlying skin may be erythematous.
- Limited movement of mandible.
- Difficulty in swallowing.
- A purulent discharge from the duct orifice.
- Cervical lymphadenopathy.
- V. administration of antibioticis.
- Milking of gland several times throughout the day.
- Increased hydration
- Improvement of oral hygiene.
- If significant improvement is not noticed in 48 hours incision and drainage is recommended.
Sialolithiasis, Viral infections.
Chronic sialadenitis is characterized by intermittent recurrent episodes of tender swelling.
Two theories regarding the initiation of chronic sialadenitis:
- Retrograde infection by low grade opportunistic oral flora can result directly in chronic recurrent sialadenitis.
- Repeated episodes of acute infection may lead to mucous metaplasia of ductal epithelium resulting in increased mucous content of secretions, stasis and further episodes of inflammation.
- Poor oral hygiene.
- Ductal obstruction.
- Affect the adults and age between 4-5 years.
- Unilateral swelling.
- Pain is minimal.
- Salivary flow accompanied by flecks of purulent material.
- Fibrosis of glandular parenchyema.
- Decrease salivary flow.
- Culture of exudates.
- Gram staining.
- Sialography – contraindicated in acute cases as disrupted ductal epithelium may allow extravasation of contrast agent, resulting in a foreign body reaction and severe pain.
- Abscess cavities appear on CT as walled-off areas of lower attenuation within an enlarged gland.
- US may distinguish between diffuse inflammation (echo-free, light image) and suppuration (less echo-free, darker image) and may detect sialoliths greater than 2 mm in diameter.
- US examination may demonstrate abscess cavities
- Frequent gland massages.
- Antibiotics for acute exacerbations.
- Penicillinase-resistant penicillin or a first-generation cephalosporin.
- Infection with methicillin resistant S. aureus (MRSA) require vancomycin, teicoplanin or linezolid.
- Clindamycin, cefoxitin, imipenem, the combination of metronidazole and a macrolide or a penicillin (amoxicillin) plus a β-lactamase inhibitor (clavulanate) can be used.
- It is an enlargement of salivary glands associated with exposure to various pharmaceutical agents and allergens.
- The characteristic feature is acute salivary gland enlargement, often accompanied by itching over the gland.
Agents responsible for salivary gland enlargement are:
- Iodine compounds.
- Isoproterenol and heavy metals.
The diagnosis should be made judiciously especially when salivary gland enlargement is not accompanied by other signs of an allergic reaction.
- It is self limiting.
- Avoiding the allergen, maintaining hydration and monitoring for secondary infection are recommended.
- Also known as Küttner tumor.
- Described by H. Küttner in 1896.
- It is a fibro-inflammatory disease of the salivary glands, characteristically of the submandibular gland.
- WHO classified it as a tumor-like lesion of the salivary glands by the World Health Organization.
- Ascending bacterial infections of the oral cavity.
- Obstruction of salivary flow.
- Stasis of secretions.
- Immunological process triggered by intraductal epithelial agents.
Condition progress through 4 different histological stages:
- Stage 1.Focal chronic inflammation with aggregates of lymphocytes around moderately dilated salivary ducts.
- Stage 2.Diffuse lymphocytic infiltration and severe periductal fibrosis.
- Stage 3:Even more prominent lymphocytic infiltration with lymphoid follicle formation, parenchymal atrophy, periductal hyalinisation, and sclerosis as well as squamous and goblet cell metaplasia in the ductal system.
- Stage 4 (end stage):Cirrhosis-like with marked parenchymal loss and sclerosis (the “burnt-out-phase).
- Characterized by a firm, relatively painful swelling of one of the submandibular glands.
- Plasmocytic and lymphocytic periductal infiltrate eventually leading to encasement of ducts with thick fibrous tissue.
- Peak incidence in 6th to 8th decades with a slight predilection for male patients.
- Interlobular cellular fibrosis.
- Periductal inflammation.
- Lobular chronic inflammation with numerous plasma cells.
- Obliterative phlebitis.
- Florid follicular hyperplasia.
- Plasma cells are usually positive for IgG4.
- FNAC shows:
- Low-to-moderate degree of cellularity,
- Ducts surrounded by chronic inflammatory cells or collagen bundles
- Fragments of fibrous stroma.
- Immunohistochemical studies revealed abundant cytotoxic T cells especially near ducts and acini.
- Radiographic examination may demonstrate a radiopaque mass.
Surgical removal and no additional treatment has been required
- Also known as drooling or ptyalis,
- It is a debilitating symptom which occurs when there is excess saliva in the mouth beyond the lip margin.
- Common in normally developed babies but subsides between the ages 15 to 36 months with establishment of salivary continence.
- It is considered abnormal after age 4.
- Mental retardation.
- Cerebral palsy.
- Parkinson’s disease.
- Bulbar palsy*
- Inflammation (teething, dental caries, oral-cavity infection, rabies)
Medication side effects (tranquilizers, anticonvulsants)
- Gastroesophageal reflux.
- Toxin exposure (mercury vapor).
- Macroglossia (enlarged tongue)
- Oral incompetence
- Dental malocclusion
- Orthodontic problems
- Head and neck surgical defects
(*—Less common, †— Usually controlled by increased swallowing, ‡—Frequently exacerbate existing problems.)
Objective tests: done by using radioisotope scanning and collection cups strapped to the patient’s chin are used.
Subjective scales: One system rates the severity of drooling on a five-point scale and the frequency of drooling on a four-point scale.
Dry (never drools)
Mild (wet lips only)
Moderate (wet lips and chin)
Severe (clothing becomes damp)
Profuse (clothing, hands, tray, objects become wet)
Adults: Start at 0.5 mg orally, one to three times daily; titrate to effectiveness and tolerability‡ Children: 0.04 mg per kg per dose orally, two to three times daily; titrate to effectiveness and tolerability.
‡ – The maximum daily dose for adults is 8 mg.
Patch, 1.5 mg. Apply patch every day
Botulinum toxin A
Vial, 100 U per vial Under ultrasound guidance, injections of 10 to 40 units into each submandibular and parotid gland
- Also known as Sicca syndrome or Gougerat –sjogren syndrome.
- Described by Henrik Sjogren in 1933.
- Sjogren syndrome is a systemic autoimmune disorder that affects the exocrine glands. It is characterized by the development of a lympho-plasma cell infiltrate, which causes progressive loss of glandular function.
- Genetic predisposition
Genetic predisposition attributed to the alleles within the major histocompatibility complex (MHC) class II gene region, in particular HLA-DR and HLA-DQ alleles.
- Environmental Factors: Includes infectious agents like:
- Chronic Hepatitis C virus (HCV).
- Epstein – Barr virus (EBV).
- Human T-cell leukaemia virus 1 (HTLV-1).
- Hormonal Factors
- Oestrogen deficiency.
- Prolactin promotes oestrogen activity, which at high levels, inhibits estrogen production.
- Role of Epithelial Cells:
Upregulation of adhesion molecule CD54/ICAM-1 as well as CD40 and MHC-I on the epithelial cells, and presence of functional TLR2, -3, and -4 molecules on these cells allow them to act as antigen presenting cells.
- Role of Dendritic Cells and Interferon-alpha (IFN-α)
Plasmacytoid dendritic(pDC) cells are recruited from the blood to the salivary glands where they secrete increased amounts of IFN-α that cause abnormal retention of lymphocytes in the gland tissues and subsequent activation of these lymphocytes.
- Role of T-lymphocytes
CD4+ T lymphocytes comprise majority of the glandular infiltration.
These cells destroy the epithelial cells using two major pathways:
- Perforin-granzyme secretion by cytotoxic T cell population.
- Role of Cytokines
TH1 cytokines like interferon-gamma (IFN-γ) and interleukin-2 (IL-2) as well as interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour growth factor-beta (TGF-β) play major role.
- Role of B-cell activating factor (BAFF)
- B-cell activating factor (BAFF) involved in the initiation and perpetuation of B-cell dysregulation.
- Secreted by salivary epithelial cells, T cells, and also B-cells.
- Plasma BAFF levels in SS patients is associated with elevated presence of autoantibodies, including anti-SSA/SSB.
- Circulating BAFF level get elevated in SS.
- Role of Autoantibodies
- Presence of anti-SSA/Ro autoantibody is characteristic feature of
- Anti-SSA/Ro mainly targets the autoantigen Ro52.
- Ro52 negatively regulates IRF activity and hence, inhibits the production of inflammatory cytokines.
- In the presence of anti-Ro52, ubiquitination of Ro52 is inhibited by the autoantibody. This leads to increased production of pro-inflammatory cytokines regulated by IRF and hence contributes to the pathogenesis of SS.
- Primary sjogren syndrome– Occurs in the absence of other autoimmune diseases and is characterised by keratoconjunctiva sicca (dry eyes) and xerostomia (dry mouth), collectively called the sicca syndrome.
- Secondary sjogren syndrome – Consist of lacrimal and salivary involvement with an associated connective tissue disorder.
Rheumatoid arthritis, systemic lupus erythematosus (SLE), polyarteritis nodosa, polymyositis, scleroderma.
In this score, 6 different items for each patient are considered (ocular symptoms, oral symptoms, eye tests, lip biopsy, imaging or function investigation of the salivary glands and antibodies in the blood) and if 4 or more items are positive, the patient is considered to fulfil the classification criteria for SS.
Revised international classification criteria for Sjögren’s syndrome, by the American-European Consensus Group Criteria, 2002:
I – Ocular symptoms (at least one of the following symptoms)
- Daily, persistent troublesome dry eyes for more than 3 months
- Recurrent sensation of sand or gravel in the eyes
- Use of tear substitutes more than 3 times per day.
II – Oral symptoms (at least one of the following symptoms)
- Daily feeling of dry mouth for more than 3 months
- Recurrent or persistent swollen salivary glands, as an adult
- Need to drink liquids to aid swallowing dry food.
III – Ocular signs (positive result from at least one of the following tests)
- Schrimer’s I test, performed without anesthesia (< 5 mm in 5 minutes)
- Rose Bengal score or other ocular dye score (> 4, according to van Bijstervald’s scoring system).
IV – Histopathology
In minor salivary glands – biopsied from normal-appearing mucosa – focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score > 1 (defined as the number of lymphocytic foci containing more than 50 lymphocytes, adjacent to normal-appearing mucous acini, per 4 square mm of glandular tissue).
V – Salivary gland involvement (positive result from at least one of the
- Unstimulated whole salivary flow (< 1.5 ml in 15 minutes)
- Parotid sialography showing the presence of diffuse sialectasias
- Salivary scintigraphy showing delayed uptake, reduced concentration, and/or delayed excretion of tracer
VI – Autoantibodies (serum presence of the following autoantibodies)
- Antibodies to Ro (SSA) or La (SSB), or both, in the serum.
- Past head and neck radiation treatment; Hepatitis C infection; Acquired immunodeficiency syndrome; Pre-existing lymphoma or sarcoidosis; Graft versus host disease; Use of anticholinergic drugs
- Fatigue; normocytic anemia.
- Sicca complex — dry eyes and dry mouth.
- Rheumatoid arthritis or other connective tissue disease.
- Salivary gland enlargement.
- Purpura (nonthrombocytopenic); hyperglobulinemia; and vasculitis.
- Renal tubular acidosis or other tubular disorders.
- Polymyopathy and neuropathy.
- Central nervous system disease.
- Chronic liver disease.
- Chronic pulmonary disease.
- Lymphoma — local or generalized
- Cryoglobulinemia; macroglobulinemia
- Ocular signs by Schirmer’s test or rose bengal dye score, or both
- Focal sialadenitis by histopathology;
- Salivary gland involvement by salivary scintigraphy, parotid sialography, or unstimulated salivary flow.
- Autoantibodies of Ro/SSA and/or La/SSB specificity.
- Schirmer test.
- Rose Bengal or other ocular dye score (i.e., fluorescein vital staining, lissamine green, etc.)
- Break up time (BUT) test.
- Laser scanning confocal microscopy (LSCM).
- The Schirmer test for the eye quantitatively measures tear formation via placement of filter paper in the lower conjunctival sac.
- Standardized paper strips (with 5 mm width and 35 mm length) should be used and placed in the lower eyelids.
It is a well-standardized test that measures the basal tear secretion withthe conjunctival-lachrymal trigeminal reflex.
- It is performed with anaesthesia.
- Measures the basal lachrymal secretion.
- In this test the strip is placed in the lower fornix between the medial and lateral third of the eyelid of the unanaesthetised eye.
- After 5 minutes, the amount of wetting is measured from the extrafornical position ofthe strip.
- According to both the Revised International Classification Criteria for Sjögren’s syndrome and the Japanese criteria, if less than 5 mm of paper are wetted following 5 minutes of the STI test, the result of the test is considered positive.
These tests are most commonly used for the evaluation of ocular surface epithelial damage.
- The test is conducted by the application of a 1% solution of Rose Bengal, within the inferior fornix of both eyes.
- The patient should be following asked to make one or two full blinks.
- White light is used to assess the amount of staining, in the two exposed conjunctival zones (medial and lateral) and cornea.
- Each section is scored up to 3 points, according to the Van Bijsterveld:
- Score: 1 – Sparsely scattered spots.
- Score: 2 – Densely scattered spots.
- Score: 3 – Confluent spots.
- While the maximum score is 9, a score of 4 or more, or 3 or more, was considered diagnostic of SS.
- In patients with SS, Rose Bengal staining can cause the eyes to sting and the test may be painful. Scoring with lissamine green stain is less painful, but more difficult to evaluate.
- It is use to measure the quality of the tear fluid.
- It is defined as the interval between a complete blink and the appearance of the first randomly distributed dry spots.
- Usually, a 1% fluorescein solution is carefully placed in the inferior fornix of both eyes.
- The patient is then asked to blink a few times, and then, it is examined how long the tear film remains evenly distributed over the surface of the cornea.
- The tear film normally remains intact for 10 seconds or longer, being highly abnormal in SS-affected individuals.
Fast tool to quantitative assess the conjunctival inflammation and epithelial cell densities, as well as the evaluation of conjunctival morphologic alterations in patients with SS.
- Magnetic Resonance (MR) and ultrasonography (US).
- Use to measure the saliva flow function, and can be conducted with whole saliva, saliva obtained from a specific gland, both with or without stimulation.
- Salivary flow should be routinely performed, not only as part of SS diagnosis, but also as part of patient monitoring.
- Unstimulated collection is conducted by the recovery of saliva in a grading tube by a predetermined period – usually 5 or 15 minutes. Values inferior to 0.1 ml/min are considered abnormal.
- According to the Revised International Classification Criteria, the unstimulated whole saliva produced over a period of 15 minutes, without the subjects have eaten or smoked for at least 2 hours, should be measured. A result inferior to1.5 ml would transpose to a positive test result.
- Difficult in patients who do not tolerate the stimulus of salivation.
- A flow rate inferior to 10 ml/10 minutes, in the chewing gum test, is considered positive.
- 10 x 10 gauze sponge should be weighted and used for saliva collection by vigorous chewing for 2 minutes. The amount of saliva produced is determined by subtracting the original weight from the weight obtained after chewing. Value inferior to 2 g/2 minutes is considered positive.
- Stimulated parotid saliva and assessment of the flow rate can be conducted with special suction cups placed over the Stensen duct. Stimulated saliva is usually collected for 3 minutes and values inferior to 0.5 ml/min are considered abnormal.
- The lower lip mucosa is dried for 5 min expecting the small saliva drops to occur. The width of the drop less than 1mm is considered to show hypofunction.
Most systemic disease affects the composition of the saliva and the salivary gland thus they guide in the diagnosis of the disease.
Diseases showing alteration in inorganic ions in saliva:
Increased sodium, potassium ,calcium ,phosphate (po4 – ) levels.
Increased sodium, calcium ,magnesium and chlorine.
Increased sodium, chlorine,(po4–) in parotid saliva.
Increased sodium, calcium,(po4–) and ca2+ po4– concentration forms a diagnostic index.
Decreased sodium, increased potassium. Na+ /K+ ratio is of diagnostic value.
Increased calcium levels .
Increased calcium levels.
Decreased bicarbonate levels.(Hco3).
Possibly increased sodium levels.
Raised Na+ and K+ product is of diagnostic value
Diseases showing alteration in organic substances in saliva
Increased lactoferrin, kalikerin, 20 folds increase in phospholipid. Raised total protein, β2 microglobulin in parotid saliva.
Raised total protein, amylase, lysozyme in submandibular saliva. Glycoprotein in parotid saliva.
Raised total protein & amylase in parotid saliva.
Raised total protein.
Raised total protein,IgA,IgG,IgM and increased glucose levels.
Decreased amylase and lysozyme.
- Sialographs demonstrate the formation of punctuate, cavitary defects which are filled with radio opaque contrast media.
- These defects produce a “branchless fruit laden tree” or “cherry blossom” effect
- Stage 0 (Normal) – Corresponds to no contrast media collection.
- Stage 1 (Punctate) – Refers to contrast media collection≤ 1 mm in diameter.
- Stage 2 (Globular) – Refers to contrast media collection between 1 and 2 mm in diameter.
- Stage 3 (Cavitary) – Refers to contrast media collection≥ 2 mm in diameter.
- Stage 4 (Destructive) – Refers to the complete destruction of the gland parenchyma.
The scintigraphy is a non-invasive method to evaluate the function of salivary glands by addressing the uptake and secretion of a radioactive labelled substance (sodium pertechnate of 99mTc).
- Normally, a rapid uptake and increased concentration of the radioactive probe is attained in the salivary glands (it can normally be seen within 10 minutes following intravenous administration).
- After 20 – 30 minutes, the substance is rapidly secreted into the mouth. Salivary flow may be stimulated with the use of a sialogogue (e.g., diluted lemon juice) administered on the dorsum of the tongue.
- Time-activity curves are calculated using manually drawn oval regions-of-interest around both the parotid and the submandibular glands. In Sjögren’s syndrome, lower concentration and less secretion into the mouth are seen.
- The test reports a high sensitivity but a low specificity in SS diagnosis.
- In SS, MRI reveals an inhomogeneous internal pattern on both T1 and T2 sequences, with multiple hypo- and hyper-intense nodules of different sizes.
- MRI quantitative analysis for the standard deviation of the signal intensity was found to be useful in SS diagnosis.
- The signal intensity in T1-weighted parotid MR images was found to increase proportionally to the severity of the disease.
- On MRI this has a “salt and pepper” or “honeycomb” appearance on T2 weighted images.
Inhomogeneous structure of the gland (early stages), with scattered multiple small, oval, hypoechoic or anechoic areas of lymphocytic infiltrates (intermediate stages), and the presence of echogenic lines.
Patients affected by SS usually present a wide range of serologic and laboratory findings:
- Cytopenias (e.g., anaemia, leukopenia, thrombocytopenia),
- Hypergammaglobulinemias (usually of the IgG class, and more rarely of the IgA and IgM classes),
- High erythrocyte sedimentation rate, C-protein levels and auto-antibodies.
- Antinuclear antibodies (ANAs) are most frequently detected, while anti-Ro/SS-A is most specific. Cryoglobulins and hypocomplementemia is main prognostic markers.
Treatments for sicca symptoms in patients with primary Sjögren’s syndrome.
Therapeutic measure (grade of recommendation)
· Tear substitutes (A)
· Secretagogues: pilocarpine, cevimeline (A)
· Cyclosporine A eye drops 0.1% (B)
· Short-term topical corticosteroids (C)
· Punctal plugs (C)
· Patient education
· Avoid drugs that promote xerostomia (A)
· Topical fluorides for caries prevention (A) Secretagogues: pilocarpine, cevimeline (A)
· Saliva substitutes, sugar-free chewing gum and electrostimulation of salivary glands (C)
Systemic traditional treatment in patients with primary Sjögren’s syndrome.
Short-term oral corticosteroids (D)
Antibiotic treatment, if required (D)
Short-term oral/intraarticular corticosteroids (C)
Other DMARDs as with rheumatoid arthritis (C)
Interstitial lung disease
Corticosteroids, oral or intravenous (C)
Cyclophosphamide for active alveolitis (C)
Pirfenidone, nintedanib (C)
Potassium and bicarbonate replacement (D)
Corticosteroids, oral or intravenous (C)
Mycofenolate mofetil (according to specific nephrologic guidelines)
Corticosteroids, plasmapheresis (C)
Grades of Recommendation according to Centre for Evidence-based Medicine in Oxford:
(A) Evidence obtained from meta-analyses or at least one randomized controlled trial.
(B) Evidence from at least one well designed experimental study.
(C) Evidence from at least one well designed descriptive study or case–control studies.
(D) Evidence from expert opinion.
DMARD: Disease-modifying antirheumatic drug; IVIg: Intravenous immunoglobulins; NSAID: nonsteroidal antiinflammatory drug.
Allergic conjunctivitis, blepharitis, xerostomia, sarcoidosis
Johann Mikulicz first presented Mikulicz Disease (MD) in 1888.
- Infectious (syphilis).
- Inflammatory diseases (gout).
- Parotid enlargement (Bilateral or unilateral).
- Dry eyes.
- Lacrimal gland enlargement( Bilateral or unilateral).
- MRI demonstrated diffuse enlargement of parotid gland without nodularity or focal lesion.
- Sialography demonstrate abnormal ductal architecture with deficient secondary and tertiary ducts and dye pooling in ectatic terminal ducts.
- Corticosteroid therapy (acute phase).
- Surgical excision of the affected gland.
- Irradiation therapy.
Sjogren’s syndrome, Sialadenitis, HIV-SGD
Xerostomia or dry mouth, is the abnormal reduction of saliva and can be a symptom of certain diseases or be an adverse effect of certain medications.
- Local radiation.
- Chronic graft-versus-host disease.
- Diseases of the salivary glands
- Sjogren’s syndrome.
- HIV disease.
- Hepatitis C virus infection.
- Primary biliary cirrhosis.
- Cystic fibrosis.
- Diabetes mellitus.
- Rare causes
- Wegener’s disease.
- Salivary gland agenesis (with or without ectodermal dysplasia).
- Triple A syndrome.
- Drugs with anticholinergic effects
- Atropine and analogs (antimuscarinics).
- Tricyclic antidepressants.
- Serotonin reuptake inhibitors.
- Drugs with sympathomimetic actions
- Appetite suppressants.
- Other drugs
- Protease inhibitors.
- Increased frequency of caries (particularly cervical caries).
- Proclivity toward acute gingivitis.
- Proclivity toward candidal infection (eg, acute pseudomembranous candidiasis, median rhomboid glossitis, denture-associated stomatitis, angular cheilitis).
- Burning tongue/depapillation of tongue.
- Oral mucosal soreness.
- Dry, sore, cracked lips.
- Salivary gland enlargement (various causes).
- Diagnosis made by assessment of salivary gland function by sialometry, or salivary flow measurement. The collection devices are placed over the opening of parotid gland or the submandibular gland.
- Hyposalivation is considered to appear when salivary flow rates are under 0.1–0.2 mL/min (unstimulated) or 0.7 mL/min (stimulated).
- Sialography is an imaging technique that may be useful in identifying salivary gland stones and masses.
- Salivary scintigraphy can be useful in assessing salivary gland function.
- Symptoms of xerostomia are often worse between meals, at night and in the morning.
Clinical signs proposed by Osailan et al:
- Sticking of an intraoral mirror to the buccal mucosa or tongue;
- Frothy saliva.
- No saliva pooling in floor of mouth.
- Loss of papillae of the tongue dorsum.
- Altered/smooth gingival architecture.
- Glassy appearance to the oral mucosa (especially the palate).
- Lobulated/deeply fissured tongue.
- Cervical caries (more than two teeth).
- Mucosal debris on palate (except under dentures).
A. Management of symptoms
- Diet and habit modifications
- Frequent and regular sips of water.
- Avoidance of dry, hard, sticky, acidic foods.
- Avoidance of excess caffeine and alcohol.
- Salivary substitutes and lubricants
- Artificial saliva.
- Use of bedside humidifier during sleeping hours. B. Preventive measures
- Increased frequency of oral/dental evaluation.
- Topical fluoride application.
- Varnish (0.5% NaF).
- Daily use of fluoridated dentifrice.
- Topical: over-the-counter (0.05% NaF); prescription (1.0% NaF, 0.4% SnF). C. Treatment of oral conditions
- Dental caries
Restorative therapy, topical fluoride.
- Oral candidiasis
- Chlorhexidine (CHX) 0.12%: rinse, swish, and spit 10 ml twice daily.
- Nystatin/triamcinolone ointment for angular cheilitis: apply topically 4 times daily.
- Clotrimazole troche: 10 mg dissolved orally 4–5 times daily for 10 days.
- Systemic therapy for immunocompromised patients.
- Denture antifungal treatment: soaking of denture for 30 min daily in CHX or 1% sodium hypochlorite
- Bacterial infections
- Systemic antibiotics for 7–10 days
- Ill or poor fitting prostheses
- Denture adjustment.
- Hard and soft reliner.
- Use of denture adhesives.
- Implant-borne prostheses.
- Increased salivary flow
- Sugar-free, xylitol-containing mints, candies, and gum.
- Pilocarpine: 5–10 mg orally 3 times daily.
- Cevimeline: 30 mg orally 3 times daily.
Manage underlying systemic conditions
Multidisciplinary management with other health-care providers
First described in 1879 by Kussmaul as pain and diffuse swelling of the parotid and/or submandibular glands caused by the obstruction of the salivary ducts by mucofibrinous plugs.
Etiology remains unknown although the most accepted hypothesis is that it is an allergic process.
- Recurring episodes of parotid/submandibular gland swelling,
- Discharge of mucofibrinous plugs with a high content of eosinophils.
- Elevated levels of IgE and/or eosinophils in blood.
- Presence of concomitant allergic processes such as asthma or allergic rhinitis.
- Irregular dilation of the main salivary ducts as seen by imaging studies (sialography or MRI).
- Glandular biopsy shows lymphocytic infiltrates and abundant eosinophils within the interstium surrounding the salivary ducts.
- Rehydration with gentle massage to help expel the thick mucous and plugs may reduce swelling and pain.
- Enlarging the duct orifice to enable plug expulsion and irrigation of the gland with a saline or steroid solution.
- Sialogogues may improve salivary flow and aid in plug expulsion.
- Antihistamines and/or steroids considering the allergic underpinnings associated with the disease.
- Parotidectomy in parotid gland enlargement.
Defined as a noninflammatory disease causing recurrent, bilateral swelling of the salivary glands, particularly the parotids, which may or may not be associated with pain.
- Diabetes insipidus.
- Diabetes mellitus.
- Adrenal disorders.
- Anorexia nervosa.
- Antihypertensive drugs (e.g. guanethidine).
- Psychotropic drugs (e.g. thioridazine).
- Sympathomimetic drugs (e.g. isoprenaline).
- Characterized by diffuse, usually bilateral swelling of the salivary glands.
- No particular sex predominance.
- Begins between the ages of 20 and 60 years, may persist for more than 20 years.
- Affect the parotid glands most commonly.
- May or may not be associated with pain.
- Swelling is unrelated to meals.
- Blood analysis (for systemic diseases).
- Biopsy of the affected gland
- Specific vitamin levels.
- Fine needle aspiration cytology.
- Sialography shows characteristic appearances of a thin, hairline salivary duct system.
- Scintigraphy shows increased uptake and retention of Technetium (Tc99 m) in the salivary tissues.
- Initially, simple glandular enlargement.
- Later, density of the gland is reduced (due to fatty degeneration).
- Prominent septa of soft tissue density.
- Electron microscopy shows degenerative changes
- Identify the etiology of the metabolic or secretory disorder.
- Conservative treatment: local massage, increased fluid intake and use of oral sialogogues (sour citrus fruit wedges or salivary stimulants).
Sialadenitis, obstruction due to salivary calculi, sarcoidosis, autoimmune connective tissue diseases
Mumps is caused by a paramyxovirus, which is a single-strand RNA virus in the Rubulavirus genus in the family Paramyxoviridae, order Mononegavirales.
- Transmitted either through droplet spread or direct contact with the saliva of an infected person.
- The incubation period is 15 to 24 days.
- Patient considered being contagious from two days before to five days after the onset of parotitis.
- Occur in children between the ages of 4 and 6 years.
- Characterized by painful, unilateral, or bilateral swelling of the salivary glands, in particular, parotid glands.
- The most common form of parotitis is called “epidemic parotitis” and is more
commonly referred to as “mumps.”
2 Distinct phases:
A. Prodromal phase:
Presents with initial onset of mild systemic symptoms such as:
- Low-grade fever.
- Neck pain.
- Poor appetite.
- Fever usually resolves after 4 days. B. Swelling phase:
- Occur 24 hours after prodromal phase
- Classic sign is parotitis.
- Parotitis typically starts as unilateral and then later develops into bilateral parotitis.
- The edema peaks within 3 days and subsides over a 7-day period.
- Edema develops below the ear, pushing the ear up and out; the jawbone is no longer visible and often no longer palpable.
- Stimulating the salivary gland by having the client eat something sour can elicit pain, known as the “pickle sign.”
Diagnosis based on:
- Careful history of present illness and immunization verifi
- Demonstration of antibodies to the mumps S and V antigens and to the hemagglutination antigen.
- Serum amylase levels may be elevated.
- Buccal swab specimen and a blood specimen for viral detection via reverse transcription polymerase chain reaction.
- Consists mainly of antipyretics and pain relief.
- Warm salt-water gargles.
- Intermittent application of heat or ice to affected areas.
- Soft foods and avoidance of sour or highly acidic food and liquids.
- Increasing fluids and maintaining electrolyte balance.
- Vaccination is important for prevention.
- HIV salivary gland disease (HIV-SGD) is the preferred term. HIV-SGD describes xerostomia and benign (unilateral or bilateral) salivary gland enlargement in HIV positive patients.
- HIV-SGD is associated with a cluster designation 8 (CD8) cell lymphocytosis of the salivary glands and with the diffuse infiltrative lymphocytosis syndrome (DILS).
This entity is characterized by a CD8 lymphocytosis, bilateral parotid swelling, a diffuse visceral CD8 lymphocytic infiltration (usually involving the lung), and cervical lymphadenopathy.
- Salivary gland swelling may or may not be associated with xerostomia.
- Parotid glands most commonly involved.
- Parotid gland usually presents as painless bilateral parotid enlargement but unilateral swelling may also occur.
- Diffuse cervical lymphadenopathy.
- Parotid gland enlargement is commonly due to the development of benign lymphoepithelial cysts (BLEC) within the parotid gland.
- Reduced salivary flow rates.
- Elevated salivary immunoglobulin A (IgA).
- Minor salivary gland biopsy.
- Immunohistochemical staining shows a preponderance of CD8-positive (+) cells in HIV-SGD.
- Major salivary glands, can be imaged with ultrasonography, CT or MRI.
- Multiple cystic masses are characteristic of HIV-associated benign lymphoepithelial hypertrophy.
- HIV-SGD–involved major gland demonstrates hyperplastic lymph nodes, lymphocytic infiltrates and cystic cavities.
- Treatment for HIV-SGD is symptomatic.
- Xerostomia may be relieved by sipping water, using saliva substitutes, chewing sugar-free gum or sucking sugar-free candy.
- Topical fluoride application.
- Management includes a conservative approach:
- Serial follow-up and observation of lesions.
- Aspiration of lesions.
- Sclerosing therapy (tetracycline sclerosis).
- Highly active antiretroviral therapy (HAART).
- Radiation therapy (24 Gy delivered in 1.5 Gy doses).
It is an enveloped, single-stranded positive-sense RNA virus, having a diameter of about 50 nm and classified as a separate genus (Hepacivirus) within the Flaviviridae family.
- HCV patients had patterns of salivary gland disease similar to those seen in primary SS patients.
- Cross-reactivity between the HCV envelope and host salivary tissue or HCV envelope-mediated immune stimulation against salivary glands.
Clinical features are:
- Greater tendency for sialadenitis.
- Increased caries rate.
- Mucosal dryness.
- Increased infections (both fungal and bacterial).
- Altered properties of saliva (thicker, opaque, or viscous secretions).
- Enlargement of the salivary glands.
Clinical, serological, histological, genetic differences between sialadenitis in Sjogren’s syndrome and hepatitis C virus +ve patients are:
Hepatitis C virus
Sicca symptoms(Dry eyes/dry mouth)
Usually absent or modest
Moderate to severe
Mild to moderate
Mainly pulmonary, gastrointestinal, renal, and neurologic involvement
Mainly gastrointestinal and musculo-skeletal involvement
Periductal lymphocytic infiltration
Pericapillary lymphocytic infiltration
Infiltrating lymphocytic phenotype
Predominantly CD4+ T cells
Mixed CD4+/CD8+ T cells
High-frequency RF, ANA, anti-Ro/SSA and anti-La/SSB, alpha-fodrin antibodies
High frequency of RF, ANA, alpha-fodrin, low prevalence of anti-Ro/SSA and anti-La/SSB antibodies, high frequency of cryoglobulins
B8, DR2 and DR3
Preferentially affecting salivary glands
Affecting both liver and salivary glands
ANA: Antinuclear antibodies; RF: Rheumatoid factor; HLA: Human leukocyte antigen.
- Tuberculous involvement of the salivary glands is seen secondary to systemic dissemination of pulmonary tuberculosis.
- Salivary gland swelling with granuloma or cyst formation within the affected glands.
- Parotid gland is involved 70% of the time.
- Involvement of the parotid gland may develop in two ways:
- Focus of mycobacterial infection in the oral cavity liberates the mycobacterium that ascends into the salivary gland via its duct or pass to its associated lymph nodes via lymphatic drainage.
- Haematogenous or lymphatic spread from a distant primary lung focus.
- Present as a unilateral swelling or abscess involving the parenchyma of the gland.
- Parotid gland TB mostly presents as a localized and progressive chronic swelling.
- Depends on the identification of Mycobacterium.
- Complete blood count, ESR.
- FNAC should be performed in the evaluation of a parotid mass
- Sonographically parotid tuberculosis can be of two types:
- Parenchymal – Appears as a diffusely enlarged, comparatively hypoechoic gland, with or without focal intra-parotid nearly anechoic zones, which might have a cavity or cavities within it.
- Peri-parotid type – Appears as hypoechoic nodules located in the peripheral zone of the hyperechoic parotid gland, consistent with enlarged periglandular lymph nodes.
On MRI, the lesions usually appear hypointense on T1 and hyperintense on T2 weighted images with homogenous contrast enhancement which is a nonspecific finding.
Four drug regimen (rifampicin, isoniazid, ethambutol and pyrazinamide) in the intensive phase followed by two drugs (rifampicin and isoniazid) in continuation phase is a recommended treatment regimen.
- Sarcoidosis is a chronic condition in which T lymphocytes, mononuclear phagocytes, and granulomas cause destruction of involved tissue.
- Etiology of the disease is unknown.
- Occurs in the third or fourth decades of life.
- Women are affected more often than men.
- African Americans are affected more often than Caucasians.
- Present with bilateral, painless, and firm salivary gland enlargement.
- Uveo parotid fever or Heerfordt’s syndrome.
- Unilateral salivary gland enlargement.
- Decreased salivary function.
- Histological evidence of non caseating granulomas in the absence of infection and malignancy.
- Elevated ACE levels in combination with a positive 67Gallium scintigraphy.
- Chloroquine alone or in combination with corticosteroids.
- Immunosuppressive and immunomodulatory drugs.
- Tumor Necrosis Factorinhibitors (in refractory cases).
- Heerfordt’s syndrome is an atypical manifestation of acute sarcoidosis presenting with fever, uveitisand swelling of the parotid glands and, most often, unilateral facial nerve palsy.
- Other potential indications of the syndrome include:
- Sensori-neural hearing loss.
- Labyrinthine involvement with vestibular dysfunction.
- Nasal pain or obstruction.
- Low-grade non-specific fever.
- Night sweats and visual disturbances.
- Plain radiography.
- Sialography (conventional, CT, MRI).
- High‑resolution ultrasonography (HRUS).
- Computed tomography (CT).
- Magnetic resonance imaging (MRI).
- Radionuclide scintigraphy.
Useful in detecting ductal calculi, calcifications (as in hemangioma and lymph nodes) and adjacent osseous lesions.
Limitations: 20% of the sialoliths of the submandibular gland and 40% of parotid gland are not well calcified and therefore are radiolucent and not visible in plain films.
- Dental panoramic tomography.
- Oblique lateral
- Rotated PA or AP
- Intraoral view of cheek.
- Dental panoramic tomography.
- Oblique lateral
- Lower 900 occlusal (for duct)
- Lower oblique occlusal (for gland)
- True lateral skull with tongue depressed.
Sialography can be defined as the radio-graphical demonstration of the major salivary gland by introducing a radiopaque contrast medium into their ductal system.
- To determine the presence and or position of calculi or other blockage and their radiodensities.
- To assess the extent of ductal and glandular destruction secondary to an obstruction.
- To determine the extent of glandular breakdown and as a crude assessment of function in cases of dry mouth
- To determine the location size nature and origin of swelling or mass.
- Allergy to compound containing iodine.
- Period of acute infection/inflammation, when there is discharge of pus from the duct opening.
- When clinical examination or routine radiograph have shown a calculus close to the duct opening.
Procedure is divided into three phase
- The preoperative phase
- The filling phase
- The emptying phase
This involves taking preoperative radiographs if not already taken before the introduction of the contrast medium for the following reasons:
- To note the position and or presence of any radiopaque obstruction.
- To assess the position of shadows cast by normal anatomical structures that may overlie the gland, such as the hyoid bone.
- To assess the exposure factors.
Having obtained the scout films, the relevant duct orifice needs to be found, probed and dilated and then cannulated, the contrast medium can then be introduced. This is called the filling phase.
- The cannula is removed and the patient is allowed to rinse out.
- Use lemon juice to aid excretion of the contrast medium.
- After 1 and 5 minutes the emptying phase radiographs are taken.
- Simple Injection Technique:
Oil-based or aqueous contrast medium is introduced using gentle hand pressure until the patient experience tightness or discomfort in the gland.
Quantity: About 0.7ml for the parotid gland 0.5 ml for the submandibular gland.
- The arbitrary pressure which is applied may cause damage to the gland.
- Reliance on patient’s response may lead to under filling or overfilling of the gland.
- Hydrostatic Technique:
Aqueous contrast media is allowed to flow freely into the gland under the force of gravity until the patient experience discomfort
- The controlled introduction of contrast medium is less likely cause damage or gives an artifactual picture.
- Reliant on the patient responses.
- Patient has to lie down during procedure so they need to be positioned in advance for the filling phase radiograph.
- Continue Infusion Pressure Monitored Technique
Using aqueous contrast medium, a constant flow rate is adopted and the ductal pressure monitored throughout the procedure
- The controlled introduction of contrast media at known pressure is not likely to cause damage.
- Does not cause overfilling of the gland.
- Does not rely on the patient’s response.
- Complex equipment is required.
- Time consuming.
Contrast media suitable for saliography are all iodine -based and include:
- Ionic aqueous solution:
- Non-Toxic Aqueous Solution
- Oil Based Solution:
- Iodized oil
- Water-insoluble organic iodine compound e.g pantopaque
- Densely radiopaque thus show good contrast.
- High viscosity, thus slow excretion from gland.
- Extravasated contrast may remain in the soft tissues for long time. May produce foreign body reaction.
- Considerable pressure needed to introduce the contrast, calculi may be forced down in main duct.
- Low viscosity thus easily introduced.
- Easily and rapidly removed from gland.
- Easily absorbed and excreted if extravasated.
- Less radiopaque thus shows reduced contrast.
- Excretion from gland is very rapid unless used in closed system.
- The main duct is of even diameter (1-2 mm wide) and should be filled completely and uniformly.
- The duct structure within the gland branches regularly and tapers gradually toward the periphery of the gland the so called “Tree in winter appearance.”
- The main duct is of even diameter (3-4mm wide) and should be filled completely and uniformly.
- The gland is smaller than the parotid, but the overall appearance is similar with the branching duct structure tapering gradually towards the periphery- having a “Bush in winter appearance.”
Pathological changes can be divided in to:
- Ductal Changes Associated With
- Sialdochitis (ductal Inflammation/infection)
- Glandular changes associated with
- Sialadenitis (Glandular Inflammation /Infection)
- Sjogren syndrome
- Intrinsic tumor
- Filling defect (s) in the main duct.
- Ductal dilatation proximal to the calculus.
- Emptying film usually show contrast medium retained behind the stone.
- Segmented sacculation or dilatation and stricture of the main duct the so called “sausage link appearance.”
- Associated calculi or ductal stenosis.
- Dots or blobs of contrast medium within the gland, an appearance known as sialectasis caused by the inflammation of the glandular tissue producing saccular dilatation of acini
- The main duct in usually normal.
- An area of under filling within the gland, owing to ductal compression by the tumour.
- Ductal displacement- Ducts adjacent to the tumor get usually stretched around it giving an appearance known as “ball in hand”.
- Retention of contrast medium in displaced ducts during the emptying phase.
- Recent advancement with non-invasive 3D imaging technique.
- Performed using a heavily T2-weighted sequence that allows the imaging of the salivary ducts because the containing saliva appears hyperintense and the surrounding tissue appears hypointense.
- It does not require cannulation of the duct nor does it use a contrast media.
- It is neither painful nor does it require ionizing radiation.
- CT images obtained by using continuous fine cuts through the involved gland.
- Osseous erosions and sclerosis are better visualized by CT (especially cone‑beam CT).
- Provides definition of cystic walls, making it possible to distinguish fluid-filled masses (ie, cyst) from abscess.
- Non-enhanced and enhanced CT images are routinely obtained.
- Initial non-enhanced scans reviewed for sialoliths, masses, glandular enlargement and/or asymmetry, nodal involvement, and loss of tissue planes.
- Contrast-enhanced images are more defined and accentuate pathology.
- Tumors, abscesses, and inflamed lymph nodes have abnormal enhancement compared to that of normal structures.
- Provides accurate localization of masses especially in the deep lobe of the parotid
- The nature of the lesion can often be determined.
- Image can be enhanced by using contrast media either in the ductal system or intravenously.
- Provides no indication of salivary gland function.
- Risks associated with intravenous contrast media if used.
- Fine duct details are not well imaged.
- Has multiplanar capability and higher soft tissue resolution.
- Demonstrates the extent of lesion and their perineural/meningeal spread.
- Diffusion‑weighted (DW) images and gadolinium‑enhanced dynamic MR (Gd‑MRI) imaging useful in differentiating benign from malignant tumors.
- DW images can be used to calculate apparent diffusion coefficient (ADC) values, which are different for different salivary gland tumors.
- Gd‑MR with dynamic imaging using 120 s as cut‑off for time to peak enhancement and 30 % wash‑out ratio can differentiate benign and malignant tumors as the latter take less time for peak enhancement and show rapid wash‑out.
- Ionizing radiation is not used.
- Provides excellent soft tissue details.
- Provides accurate localization of masses.
- Facial nerve may be identifiable.
- Images in all planes are available.
- Co-localization possible with PET scan.
- MR sialography may be performed.
- Provides no information on salivary gland function.
- Limited information on surrounding hard tissues.
- May not distinguish benign lesion with high water content from cysts.
- Quick and noninvasive method of evaluating parotid and submandibular glands.
- Both glands appear homogeneously hyperechoic on HRUS (high resolution ultra-sonography)
- Retromandibular vein can be noted within the parotid gland.
- It is performed by a high‑frequency linear (7-10 MHz) transducer.
- It helps in differentiating cystic from solid lesions.
- Aids in guiding the exact site of Fine Needle Aspiration Cytology (FNAC) in suspected salivary gland lesions.
- When combined with color Doppler imaging, it helps in assessing the vascularity and nature of the lesion
- Discrete and generalized swelling both intrinsic and extrinsic to the salivary gland.
- Salivary obstruction.
- Ionizing radiation is not used.
- Provide good imaging of superficial masses.
- Useful for differentiating between solid and cystic masses and for identifying nature and location of the margin of a lesion.
- Different echo signals are obtained from different tumor.
- Identification of radiolucent stones.
- Lithotripsy of salivary stones.
- Ultrasound –guided fine needle aspiration (FNA) biopsy is
- Intraoral ultrasound possible with small probes.
- The sound waves used are blocked by bone so limiting the areas available for investigation.
- Provides no information on fine ductal architecture.
- Provides information on the functional capabilities of the glands.
- Technetium (Tc-99m) radionuclide is taken up by the salivary glands (following intravenous injection), transported through the glands, and then secreted into the oral cavity.
- Uptake and secretion phases can be recognized on the scans.
- Uptake of Tc 99m by a salivary gland indicates that there is functional epithelial tissue present.
- Performed following the injection of 10 to 20 mCi of Tc 99m pertechnetate.
- The uptake, concentration, and excretion of the pertechnetate anion by the major salivary glands and other organs is imaged with a gamma detector that records both the number and the location of gamma particles released in a given field during a period of time.
- This information can be stored in a computer for later analysis or recorded directly on film from the gamma detector, to give static images.
- Sodium pertechnetate (Tc) is actively concentrated and secreted by salivary gland cells while it is not taken up by majority of neoplastic lesions, hence the latter appear as “cold spots”.
- Warthin’s tumor is an exception to the rule and appears as a “hot spot”.
- Actively dividing cells take up Gallium‑67; hence it is useful in detecting diffuse inflammatory/neoplastic processes like sarcoidosis and lymphoma.
- Positron emission tomography (PET) imaging using 2‑deoxy‑2‑[18F] fluoro‑d ‑glucose (FDG) can be used to differentiate benign from malignant tumors of the salivary glands as the former appear as cold spots with the exception of Warthin’s tumor and oncocytoma.
- Provide an indication of salivary gland function.
- Allow bilateral comparison and images all four major salivary gland at the same time.
- Computer analysis of result is possible.
- Can be performed in case of acute infection.
- Co-localization of PET with CT or MRI scan.
- Provide no indication of salivary gland anatomy or ductal architecture.
- Relatively high radiation dose to the whole body.
- The final images are not disease –specific.
Classification of salivary gland tumors (WHO 1991)
- Pleomorphic adenoma.
- Myoepithelioma (myoepithelial adenoma).
- Basal cell adenoma.
- Warthin’s tumor (adenolymphoma).
- Oncocytoma (oncocytic adenoma).
- Canalicular adenoma.
- Sebaceous adenoma.
- Ductal papilloma:
a. Inverted ductal papilloma.
b. Intraductal papilloma.
c. Sialadenoma papilliferum.
a. Papillary cystadenoma
b. Mucinous cystadenoma
• Acinic cell carcinoma.
• Mucoepidermoid carcinoma.
• Adenoid cystic carcinoma.
• Polymorphous low grade adenocarcinoma (terminal duct adenocarcinoma).
• Epithelial-myoepithelial carcinoma.
• Basal cell adenocarcinoma.
• Sebaceous carcinoma.
• Papillary cystadenocarcinoma.
• Mucinous adenocarcinoma.
• Oncocytic carcinoma.
• Salivary duct carcinoma.
• Malignant myoepithelioma (myoepithelial carcinoma).
• Carcinoma in pleomorphic adenoma (malignant mixed tumor).
• Squamous cell carcinoma.
• Small cell carcinoma.
• Undifferentiated carcinoma.
• Other carcinomas.
3. Nonepithelial tumors
4. Malignant lymphomas
5. Secondary tumors
6. Unclassified tumors
7. Tumor like lesions
• Necrotizing sialometaplasia (salivary gland infarction)
• Benign lymphoepithelial lesion
• Salivary gland cysts
• Chronic sclerosing sialadenitis of submandibular gland (Küttner tumor)
- Cystic lymphoid hyperplasia in AIDS.
According to American Joint Committee on Cancer staging system for salivary gland malignancies
Primary tumor (T)
Tx Primary tumor cannot be assessed.
T0 No evidence of primary tumor.
T1 Tumor 2 cm or less in greatest dimension without extra parenchymal extension.
T2 Tumor more than 2 cm but no more than 4 cm in greatest dimension without extra parenchymal extension.
T3 Tumor more than 4 cm and/or tumor having extra parenchymal extension.
T4a Moderately advanced disease: Tumor invades skin, mandible, ear canal, and/or facial nerve.
T4b Very advanced disease: Tumor invades skull base and/ or pterygoid plates and/or encases carotid artery.
Regional lymph nodes (N)
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in the greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but no more than 6 cm in greatest dimension
N2b Metastasis to multiple ipsilateral lymph nodes, more than 3 cm but no
more than 6 cm in greatest dimension.
N2c Metastasis in bilateral lymph nodes, none more than 6 cm in greatest
N3 Metastasis in a lymph node, more than 6 cm in greatest dimension
Distant metastasis (M)
M0 No distant metastasis
M1 Distant metastasis
- Also known as benign mixed tumor.
- The “pleomorphic” nature of the tumor can be explained on the basis of its epithelial and connective tissue origin.
- World Health Organization (1972) defined PA as a well-defined tumor characterized by its pleomorphic or mixed appearance.
- There is intermixing of the clearly recognizable epithelial component with mucoid, myxoid and chondroid component.
Mixed tumor, enclavoma, branchioma, endothelioma, enchondroma.
- Simian virus 40 (SV 40)
- Neoplastically altered epithelial cells leads to multidirectional differentiation.
- Cytogenetic abnormalities of chromosome 12q 13-15.
- Occur at any age, but most common in young and middle aged adults, between 30 to 60 years.
- A slight female predilection.
- PA is located in the parotid glands (85%), minor salivary glands (10%), and the submandibular glands (5%)
- Tumors originate in the superficial lobe.
- Occasionally involve the deep lobe of the parotid gland, parapharyngeal space.
- Minor salivary gland tumors are encountered on the palate, followed by the lip, cheek, tongue and floor of the mouth.
- Manifests as a mobile, slow progressing, asymptomatic firm swelling that does not cause ulceration of the overlying mucosa.
- Oral retrotonsillar mass/ parapharyngeal space tumor seen in cases of deep lobe involvement.
CT images show:
- Well-defined margin, a smooth border, an inhomogeneous aspect, a low or high contrast, and intermediate or high signal intensity.
- After contrast medium administration, it shows a slightly high enhancement and either an inhomogeneous or a periphery enhancement on the contrast enhanced (CECT) images.
MR images show:
- T2-weighted images on MRI with increased signal intensity and proton density is highly suggestive of Pleomorhic adenoma
- Well-defined margin, a lobulate border, an inhomogeneous aspect, a high contrast, and intermediate or high signal intensity.
- After contrast medium administration, pleomorphic adenoma tended to show a high enhancement and either an inhomogeneous or a periphery enhancement on MR images.
A benign mixed tumor does not usually concentrate 99mTc-pertechnetate so tumor appears as a cold spot when examined by scintigraphy. Solid tumors
larger than 5 mm are usually well visualized.
- Also known as myoepithelial adenoma.
- Term used by Sheldon 1943.
- It is a benign tumor arising from neoplastic myoepithelial or basket cells which are found between the basement membrane and the basal plasma membrane of acinar cells.
Classified by cell morphology:
- Spindle – Interlacing fascicles with a stroma-like appearance.
- Plasmacytoid/hyaline – Polygonal cells with eccentric nuclei and dense, nongranular or hyaline, abundant eosinophilic cytoplasm.
- Epithelioid – Nests or cords of round to polygonal cells, with centrally located nuclei and a variable amount of eosinophilic cytoplasm.
- Clear – Polygonal cells with abundant optically clear cytoplasm, containing large amounts of glycogen but missing mucin or fat.
- Average age 44 years, with a range of 9–85 years.
- Both genders are affected equally.
- On inspection, they have a solid, tan or yellow-tan, glistening cut surface.
- Appear as slow growing, painless mass.
- Grow locally without invading surrounding structures.
- Based on radiologic imaging and tissue histology.
- CT scans, showed well circumscribed, smooth or lobulated, homogenous enhancing lesions.
- Typical MRI showed a well-defined homogenous isointense and hyperintense mass on T1- and T2-weighted imaging, respectively.
Mucocele, schwannoma, neurofibroma, leiomyoma, benign fibrous histiocytoma, extramedullary plasmacytoma, rhabdomyosarcoma, smooth muscle neoplasms, pleomorphic adenoma.
- First reported by Kleinsasser and Klein in 1967.
- According to WHO it is a distinctive benign neoplasm composed of basaloid cells organized with a prominent basal cell layer and distinct basement membrane-like structure and no myxochondroid stromal component as seen in pleomorphic adenomas.
Non-membranous: Trisomy 8 and chromosome 13 alterations.
Membranous: Alterations at the CYLD1 gene locus at chromosome 16q12–13.
- Accounts for 1–2 % of all salivary gland tumours.
- Slow-growing encapsulated tumour.
- Do not exceed 3-cm of major diameter.
- It is a firm mobile painless mass.
- Usually superficial within the glandular body, and a brownish appearance is usually observed.
- Most commonly involved parotid gland, although upper lip, buccal mucosa, lower lip, palate and nasal septum also involved.
- Affect patients between 5th and 7th
- Cytopathological diagnosis is accurate in over 90–95 %.
- In computed tomography (CT) tumor appeared as a round or oval, sharply marginated mass.
- Well-enhanced, solid tumor or mixed solid and cystic hemorrhagic tumor with low signal intensity rim on the T2-weighted image.
- Surgical excision with superficial or total parotidectomy.
- Extracapsular excision if there is affectation of minor salivary glands.
Adenoid cystic carcinoma, basal cell adenocarcinoma, and pleomorphic adenoma.
It is a synchronous basal cell adenoma of the salivary gland with multiple cutaneous adnexal tumors.
- Also known as Papillary cystadenoma lymphomatosum (PCL).
- It was first reported by Hildebrad in 1895.
- Albrechet and Artz, in 1910, termed this tumour as papillary cystadenoma.
- In 1929, Aldred Scott Warthin’s called it as Papillary cystadenoma lymphomatosum (PCL).
- Warthin’s tumour’ was first applied in 1944 by Martin and Ehrlich in respect to Warthin’s.
- Develops from heterotopic salivary gland tissues or through the attraction of a heavy lymphoid reaction.
- Later Albrech and Artz who proposed its heterotropic origin from neoplastic proliferation of salivary gland ducts present within intra-/para-parotid nodes.
- Smoking habit.
- Second most frequent benign salivary gland neoplasm.
- Highest incidence in the early 60’s.
- Occasionally occurs in young patients.
- In men, the peak incidence is in the 7th
- In women the peak incidence is 6th
- Male-to-female ratio up to 10:1.
- Mainly arises in parotid salivary glands but also occurs in upper lip, palates, nasopharynx.
- Presents as a nodular painless, slow growing, firm to fluctuant at palpation.
- It can be unilateral, bilateral or multicentric and is asymptomatic.
- History and clinical examination
- Fine-needle aspiration cytology.
- On CT, tumor may be of either soft tissue or cystic density.
- On MRI, it is heterogeneous and may demonstrate hemorrhagic foci.
- Warthin tumor is characteristically ‘intensely hot on 99mTc-pertechnetate scans.
Benign and malignant tumours, Sarcoidosis, Sialolithiasis, Sialoadenosis, Wegener’s granulomatosis, Tuberculosis.
- Surgical removal performed due to the superficial location of the tumour.
- Local resection with surrounding tissue.
- Superficial parotidectomy in order to avoid the rupture of tumour capsule.
These are benign papillary neoplasms derived from the neoplastic proliferation of any epithelial layer of the ductal system.
- Etiology is unknown.
- Lesions originate from the salivary gland duct epithelium, most likely the excretory duct.
According to the cell type, morphology, and location ductal papillomas are characterized by 3 patterns:
- Sialadenomapapilliferum – Is a papillomatousexophytic lesion that extends above the adjacent mucosal surface.
- Inverted ductal papilloma – Is submucosal and expands or pushes into the surrounding tissue.
- Intraductal papilloma – Arise in the duct system more distant from the mucosal surface and present as well-defined unicystic lesions.
- Minor salivary gland is more frequently involved.
- Common sites of involvement are the lip, palate, buccal mucosa, parotid gland, and submandibular glands.
- Presents as a painless, solitary, small mass.
- Affects patients aged 50 to 70 years.
- Sex distribution is equal on an average.
- Histological pathological examination.
- CT and MRI for the assessment of the lesion’s location and extension.
- Ultrasonography cannot provide useful information.
- Immunohistochemical staining of tumor cells reveals strong positivity for the expression of cytokeratin (CK), an epithelial membrane antigen; partial positivity for the expression of S-100, and negative expression of SMA, P63, or CK14.
Warthin’s tumor, papillary cystadenocarcinoma, papillary cystadenoma, and polymorphous low-grade carcinoma.
- Oncocytomas were first described by Jaffé in 1932.
- Oncocytomas are benign epithelial tumors characterized by oncocytes with eosinophilic granular cytoplasm rich in mitochondria.
- Mitochondrial functional defects may lead to the progressive degeneration of the salivary epithelial cells.
- Certain viruses, such as EBV, HIV, HHV-8, HTLV-1 and HPV
- Occurs between 6th to 8th decades of life.
- Females are more affected.
- Present as solitary slow growing painless mass, which is firm, multilobulated and mobile entity upon clinical examination.
- Seen in any of the major salivary glands.
- Lesions found in the superficial lobe of the parotid gland.
- Can occur bilaterally.
- Fine needle aspiration cytology.
- Histologically there are three distinct types: oncocytosis, oncocytoma and oncocytic carcinoma.
- CT – Well-defined homogeneous parotid mass.
- MRI – Hypodense on T1 and T2 sequences.
- Increased uptake of technetium-99m pertechnetate by oncocytoma.
- Accumulation in cystic spaces due to the absence of intralobular duct.
- Cells cannot excrete so much technetium-99m pertechnetate, meaning that the uptake is prolonged.
- Complete surgical excision.
- Superficial parotidectomy.
- Systemic chemotherapy.
Intraductal papilloma, Warthin tumor, papillary cystadenocarcinoma, papillary cystadenoma.
- Mucoepidermoid carcinoma is a malignant tumor of epidermoid, intermediate, and mucous cells of the salivary glands.
- First reported by Massao and Berger in 1942 and by Stewart et al. in 1945
Arise from pluripotent reserve cells of excretory ducts that are capable of differentiating into squamous, columnar, and mucous cells.
- 50–60% of these tumours arise in the major salivary glands:
- Parotid gland (80%).
- Submandibular gland(8–13%).
- Sublingual gland (2–4%).
- Rest in minor salivary glands (palate).
- Slight female preponderance.
- More common in adults (4th to 6th decades), high during the 5th decade of life.
- Low-grade malignancy is characterized by a slow-growing painless swelling which rarely exceeds 5
- Pain or facial nerve palsy may develop, usually in association with high-grade tumours.
- Minor salivary gland tumours are asymptomatic, fluctuant and red/blue in appearance.
- Classified into three grades.
- Histopathological grades are based on degree of cytological atypia, amount of cyst formation, and relative numbers of mucous, epidermoid and intermediate cells
- Low-grade tumours: macroscopically is small and partially encapsulated and microscopically characterized by the presence of more mucous-producing cells.
- Intermediate-grade tumours: comprises solid rather than cystic architecture with more intermediate cells.
- High-grade tumours: Have a smaller proportion of mucous cells and are considered to be a more malignant tumour with poorer prognosis.
- Histopathological examination.
- Low-grade carcinomas are typically not apparent on plain films.
- CT section shows:
- Irregular homogeneous mass, not much more dense than the parenchyma.
- CT with intravenous contrast enhancement shows sharply defined homogeneous mass that is considerably more opaque than on the CT images without contrast.
- Tl-weighted images have lower intensity (are darker) than the surrounding structures and are relatively homogeneous.
- T2-weighted images of the tumor are more heterogeneous and intense (brighter) than Tl-weighted images and are just slightly darker than the surrounding tissues.
- Regardless of clinical presentation and margins, low signal intensity is suggestive of a high-grade malignancy.
- Surgery, the extent of which depends on location, size and histopathological grading.
- Local resection for less aggressive low-grade tumours, while high-grade tumours require wide resection with involvement of adjacent structures.
- For MEC in minor salivary glands is primarily surgical.
- Radiotherapy should be used.
- Prognosis is dependent on clinical stage, site, grading, and adequacy of surgery.
- Adenoid cystic carcinoma (ADCC) is a malignant salivary gland tumor.
- First described by Billroth in 1859.
- Term “adenoid cystic carcinoma” was introduced by Ewing (Foote and Frazell) in 1954.
- Alterations in chromosomes 6q, 9p and 17p12-13.
- Hypermethylation of the promoter region of the p16.
- Genomic deletions of chromosome 6.
- Palate is the most commonly involved site, tongue being the second most common; other sites are floor of mouth, and lip
- Peak incidence occurs between the 5th and 6thdecades of life.
- Predominantly occurs among women.
- Present as a firm unilobular mass in the gland.
- Occasionally, the tumor is painful, and parotid tumors may cause facial nerve paralysis in a small number of patients.
- Tumor has a propensity for perineural invasion; thus, tumor tissue often can extend far beyond the obvious tumor margin.
- Tumor’s slow growth may delay diagnosis.
- Tumors of minor salivary glands usually have the tendency to infiltrate extra glandular soft tissues and bone thereby allowing increased dissemination of the tumor.
- The lesion is uncapsulated and infiltrative; invasion of underlying bone is common.
- Distant metastasis occurs through blood stream to lungs and bones.
- Pain occurs early in the course of the disease before there is a noticeable swelling.
- Neoplastic cell neurotropism causes pain.
Cribriform, tubular and solid
- Cribriform pattern: Epithelial cells are arranged in multiple cylindrical spaces, having a pseudo cystic appearance, and many of these pseudo cysts contain a hyaline material.
- Tubular type: made up of ducts that can be formed by one or two layers of cells similar to the myoepithelial cells.
- Solid variant: composed of solid epithelial islands with central areas of necrosis; the cells are small, basophilic and hyperchromatic with a densely granulated nucleus and scarce mitotic figures.
Most common is mucoepidermoid carcinoma (21.8%) followed by polymorphous low grade adenocarcinoma (PLGA) (7.1%) and ADCC was the third most common (6.3%).
- Progressive nasal stenosis.
- Dysfunction of the Eustachian tube.
- Disorders of ocular motility.
- Facial pain.
- Dysfunction of IX, X, XI and XII pairs of cranial nerves.
Polymorphous low-grade adenocarcinoma, Basal cell adenoma (BCA), mixed tumor and basaloid squamous cell carcinoma (BSC).
- Histopathological examination.
- Low-grade tumours tend to be well-defined.
- High-grade tumours, appear infiltrative.
- Both subtypes are usually homogeneously enhancing after contrast administration.
- Pseudocysts are positive for periodic acid schiff reagent (PAS) and Alcianblue and contain basement membrane components such as type IV collagen, heparin sulfate and laminin isoforms.
- Epithelial cells are positive for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Duct lining cells are positive for C-kit (CD117).
- Myoepithelial cells are positive for S-100 protein, calponin, p63, smooth muscle actin and myosin.
- Microarrays and comparative genomic hybridization have been used to identify candidate genes for ADCC.
- Surgery, radiotherapy, chemotherapy and combined therapy.
- Neutron therapy: Involves larger particles of greater energy can achieve reasonable local control as a primary therapeutic modality.
- Adoptive immunotherapy along with chemoradiotherapy.
- E-cadherin expression can be used as prognostic marker.
It is a malignant epithelial neoplasm of the salivary glands in which the neoplastic cells show acinar cell differentiation.
- Familial predisposition: Cytogenetic alterations like 6q rearrangement, loss of Y chromosome and gain of chromosome 7 and 8 are related to occurrence of familial AcCC .
- Previous radiation exposure.
- Occur in the parotid gland (80%) followed by minor intraoral salivary glands (13-17%).
- Female to male ratio is approximately 1.5:1.
- Occur in 2nd to 7th decades of life, with a slight peak in the 5thand 6th
- Appear as a slowly growing, mobile or fixed mass of various durations.
- Frequently surrounded by a thin capsule, may be composed of cells of varying degrees of differentiation.
- Usually asymptomatic but sometimes pain or tenderness is seen.
- Facial muscle weakness may be seen.
- Histopathological examination:
- Described as solid, microcystic, follicular and papillary cystic tumors.
- Composed of diverse cell types and include acinic cells, vacuolated cells, intercalated cells, nonspecific glandular cells and clear cells. Large lobules or nests of tumor cells with little intervening stroma are characteristic.
- Useful in evaluating tumor size, location, and nature.
- Used to perform ultrasound-guided fine needle aspiration biopsies.
- CT scan:
- Demonstrates a slight contrast enhancement.
- Appropriate for the evaluation of tumor size, involvement, and relationship to facial nerves, other structures and distant metastasis.
4. MRI: Demonstrate nonspecific signal intensity pattern and low T1 and T2 signals can be detected on some images.
- Complete surgical excision of the tumor by intraoral or extraoral approach.
- Radiation therapy in cases of:
- Poor prognosis.
- Positive surgical margins.
- Stage T3 or T4 tumors, high histologic grade, multiple positive lymph node involvement and vascular or perineural invasion.
Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant epithelial tumor arising from pre-existing pleomorphic adenoma.
Classify Carcinoma ex pleomorphic adenoma (CXPA)?
- Noninvasive: treated with surgical resection and radiation, and carry a fair prognosis.
- Minimally invasive: treated with surgical resection and radiation, and carry a fair prognosis.
- Widely invasive: extremely aggressive and has a high recurrence rate despite localized treatment.
- It follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p.
- Malignant transformation of a PA to Ca ex PA can be attributed to the 12q genes, HMGIC, HMGA2 and MDM2.
- Mutation of p53.
- Gene commonly dysregulated in cancer is COX-2, increased COX-2 expression may be an important early stage event in the pathogenesis.
- Originates in parotid gland.
- In minor salivary glands of palate.
- Occurs more commonly in women.
- Patients become aware when they experience rapid enlargement of the mass, pain.
- Rare patients with Ca ex PA may carry a slow growing mass
- Facial paralysis.
- Regional metastasis is common and mortality is high.
- Skin ulceration.
- Tumour fungation.
- Skin fixation.
- Palpable lymphadenopathy.
- Swollen jaw (due to bone invasion),
- Dental pain.
- Sudden loss of vitality.
- Fine needle aspiration cytology (FNAC).
- Computed tomography (CT) scan, and magnetic resonance imaging (MRI) scan.
- CT imaging:
- Ring or rim enhancement in contrast enhanced CT.
- Enlarged mass with central low density area and irregular rim enhancement.
- Aggressive area in CAexPA shows “a necrotic center, thick, irregular walls and infiltrating margins.
- If affects the parotid gland, the ablative surgery often involves parotidectomy.
- Superficial parotidectomy for intracapsular or minimally invasive Ca ex PA.
- Total or radical parotidectomy is indicated for frankly invasive Ca ex PA.
- Post-operative radiotherapy is used for high grade disease.
- Also known as Oncocytic adenocarcinoma
- Bauer first described OC in 1953.
- Extremely rare malignancy in salivary glands.
- Characterized by epithelial cells with abundant eosinophilic and granular cytoplasm, filled with numerous mitochondria.
- Mostly occur in the parotid gland but the submandibular gland, minor glands of the palate, nasal cavity, and ethmoid and maxillary sinuses are also involved.
- 13:3 (male:female).
- The average age of onset is 62.4 years
- Patients usually develop parotid masses that cause pain or paralysis.
- The skin overlying the gland is occasionally discolored or wrinkled.
- Infiltrative growth of the neoplasm is represented by perineural, vascular or lymphatic invasion, destruction of adjacent structures and local lymph node metastasis.
- Diagnostic indicators of OC arising in the salivary gland include a lack of encapsulation, regional nodal or distant metastasis, intravascular, lymphatic or perineural invasion, and mitoses or cellular pleomorphism.
Diagnosis of OC includes:
- Hematoxylin-eosin staining,
- Electron microscopy.
- Fine-needle aspiration (FNA).
Light microscopy and hematoxylin-eosin staining can indicate whether the cytoplasm is filled with eosinophilic granules.
PTAH staining and electron microscopy be used to examine the mitochondria. PTAH staining can indicate profuse dark-blue cytoplasmic granules and mitochondrial immunostaining may indicate positive, finely granular immunoreactivity in the cytoplasm of oncocytes.
FNA can be used to aid the diagnosis of OC when the tumor is highly atypical.
Immunohistochemical positivity for mithochondrial antigen, keratin, alpha-1-antichymotrypsin.
- Combination of complete surgical resection and metastatic area is the widely accepted treatment.
- Adjuvant radiotherapy may be useful for local control of OC.
- Carlson GW. The salivary glands: Embryology, anatomy, and surgical applications. Surgical Clinics of North America. 2000;80:261–273.
- Johns ME. Salivary-glands – anatomy and embryology. Otolaryngol Clin N Am. 1977;10:261–271.
- Torres-Lagares, D., et al., Parotid sialolithiasis in Stensen’s duct. Med Oral Patol Oral Cir Bucal, 2006. 11(1): p. E80-4.
- Feinberg SE (1992) Diagnosis and surgical management of salivary gland disorders. In Peterson LJ (Ed.), Principles of Oral and Maxillofacial Surgery, Volume 2. JB Lippincott, Philadelphia, USA, p. 841.
- Marx RE, Stern D (2003) Non neoplastic salivary gland diseases. In Oral and Maxillofacial Pathology: A rationale for diagnosis and management. Quintessence Publishing co, Illinois, USA, p. 519.
- Huoh KC, Eisele DW Etiologic factors in Sialolithiasis. Otolaryngol Head Neck Surg 2011;145: 935-939.
- Tandler B. Electron microscopical observations on early sialoliths in a human submaxillary gland. Arch Oral Biol 1965;10:509-22.
- Epker BN. Obstruction and inflammatory diseases of the major salivary glands. Oral Surg Oral Med Oral Pathol 1972;33:2-27.
- Katz P, Fritsch MH Salivary stones: Innovative techniques in diagnosis and treatment. Curr Opin Otolaryngol Head Neck Surg 2003;11:173-178.
- Dalley RW (1994) Sialography-present status: Does it still have a role to play in light of computed tomography, magnetic resonance imaging and ultrasound? In Worthington P, Evans JR (Eds.), Controversies in Oral and Maxillofacial surgery. WB Saunders, Philadelphia, USA, p. 41.
- Van den Akker HP Diagnostic imaging in salivary gland disease. Oral Surg Oral Med Oral Pathol1988; 66: 625-637.
- Capaccio, P., M. Gaffuri, and L. Pignataro, Sialendoscopy-assisted transfacial surgical removal of parotid stones. J Craniomaxillofac Surg, 2014;42:1964-9.
- Daniels J, Mohammed I. Mucocele of lingual glands of Blandin and Nuhn: A report of 5 cases. Saudi Dent J. 2005;17:154–61.
- Ata-Ali J, Carrillo C, Bonet C, Balaguer J. Oral mucocele: Review of literature. J Clin Exp Dent. 2010;2:e18–21.
- Re Cecconi D, Achilli A, Tarozzi M, Lodi G. Mucoceles of the oral cavity: A large case series (1994-2008) and a literature review. Med Oral Pathol Oral Cir Bucal. 2010;15:e551–6.
- Sugerman PB, Savage NW, Young WG. Mucocele of the anterior salivary glands: Report of 8 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:478–82.
- More C. B., Bhavsar K., Varma S., Tailor M. Oral mucocele: a clinical and histopathological study. Journal of Oral and Maxillofacial Pathology.2014;18:72–76. doi: 10.4103/0973-029x.141370.
- Sagari S. K., Vamsi K., Shah D., Singh V., Patil G. B., Saawarn S. Micro-marsupialization: a minimally invasive technique for mucocele in children and adolescents. Journal of Indian Society of Pedodontics and Preventive Dentistry. 2012;30:188–191. doi: 10.4103/0970-4388.105008.
- Rao P. K., Hegde D., Shetty S. R., Chatra L., Shenai P. Oral mucocele—diagnosis and management. Journal of Dentistry, Medicine and Medical Sciences. 2012;2(2):26–30.
- Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease simulating malignancy. Cancer 1973;32:130-5.
- Daudia A, Murty GE. First case of full-thickness palatal necrotizing sialometaplasia. J Laryngol Otol 2002;116:219-20.
- Nah KS, Cho BH, Jung YH. Necrotizing sialometaplasia: Report of 2 cases. Korean J Oral Maxillofac Radiol 2006;36:207-9.
- Carlson DL. Necrotizing sialometaplasia: A practical approach to the diagnosis. Arch Pathol Lab Med 2009;133:692-8.
- Shreve M et al Mumps: A Call for Vigilance available from: npjournal.org/article/S1555-4155(17)30945-5/fulltext
- Wiggers, J. B., Chan, T., Gold, W. L., MacFadden, D. R. Mumps in a 27-year-old man. CMAJ 2017;189:69-71.
- Rakhi Chandak R, Degwekar S, Chandak M, Shivlal Rawlani S Acute Submandibular Sialadenitis—A Case Report Case Reports in DentistryVolume 2012, Article ID 615375, 3 pages doi:10.1155/2012/615375
- Available from: https://bestpractice.bmj.com/topics/en-us/1038.
- Itzhak brook. Aerobic and anaerobic microbiology of suppurative sialadenitis. J. Med. Microbiol. 2002; 51: 526-529.
- Bijai LK, Jayaraman V, Austin RD Chronic Bacterial Sialadenitis-A Case Report Oral Surgery, Oral Medicine, Oral Radiology, 2013;1:1-3
- Geyer JT, Ferry JA, Harris NL, Stone JH, Zukerberg LR, Lauwers GY, Pilch BZ, Deshpande V. Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease. Am J Surg Pathol.2010;34:202-10
- Güçlü Kaan Beriat, Sefik Halit Akmansu, Sinan Kocatürk, and Ömür Ataoğlu Chronic Sclerosing Sialadenitis (Küttner’s tumour) of the Parotid Gland. Malays J Med Sci. 2010;17: 57–61.
- Marino E. Leon,Neetha Santosh, Amit Agarwal, Theodoros N. Teknos, Enver Ozer, and Hans Iwenofu Diagnostic Challenges in the Fine Needle Aspiration Biopsy of Chronic Sclerosing Sialadenitis (Küttner’s Tumor) in the Context of Head and Neck Malignancy: A Series of 4 Cases Head Neck Pathol. 2016;10: 389–393.
- Lakraj AA, Moghimi N, Jabbari B Sialorrhea: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins Toxins 2013, 5, 1010-1031; doi:10.3390/toxins5051010
- Hockstein NG, Samadi DS, Gendron K, Handler SD. Sialorrhea: a management challenge. Am Fam Physician.2004;69:2628-34.
- Harley J, Scofield R, Reichlin M. Anti-Ro in Sjogren’s syndrome and systemic lupus erythematosus. Rheumatic diseases clinics of North America. 1992;18:337–58.
- Shearn MA. Sjögren’s syndrome in association with scleroderma. Annals of internal medicine. 1960;52:1352–62.
- Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D. Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjogren’s syndrome. J Immunol. 1993;150:3615–23.
- Ramos-Casals M, Loustaud-Ratti V, De Vita S, Zeher M, Bosch J A, Toussirot E. Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases. 2005;84:81–9.
- Pflugfelder SC, Crouse CA, Monroy D, Yen M, Rowe M, Atherton SS. Epstein-Barr virus and the lacrimal gland pathology of Sjogren’s syndrome. Am J Pathol. 1993;143:49–64.
- Green JE, Hinrichs SH, Vogel J, Jay G. Exocrinopathy resembling Sjogren’s syndrome in HTLV-1 tax transgenic mice. 1989;341:72–4.
- Jisha J. Nairand Tejas P. Singh Sjogren’s syndrome: Review of the aetiology, Pathophysiology & Potential therapeutic interventions J Clin Exp Dent. 2017; 9:e584–e589.
- Fox RI, Stern M, Michelson P. Update in Sjo¨gren syndrome. Curr Opin Rheumatol 2000;12:391-8.
- Bowman SJ. Collaborative research into outcome measures in Sjo¨gren’s syndrome. Update on disease assessment. Scand J Rheumatol Suppl 2002;116:23-7.
- Vitali C. Classification criteria for Sjo¨gren’s syndrome. Ann Rheum Dis 2003;62:94-5.
- Jonsson R, Moen K, Vestrheim D, Szodoray P. Current issues in Sjo¨gren’s syndrome. Oral Dis 2002;8:130-40.
- Mandel ID: The functions of saliva. J Den Res:1987; 66:623-27.
- Elliaz Kaufman, Ira B Lamster: Diagnostic applications of saliva. Crit Rev Oral Biol Med 2002;13:197-212.
- Mandel ID: The diagnostic uses of Saliva. J Oral Pathol Med,1990; 19:119-25.
- Sanjeev Mittal, Vikram Bansal, Sushant Garg , Gaurav Atreja , Sanjay Bansal . The diagnostic role of Saliva — A Review. J Clin Exp Dent.2011;3:e314-20.
- Groschl M. Current status of salivary hormone analysis. Ann Biol Clin (Paris); 2009;67:493-504.
- Paschides CA, Kitsios G, Karakostas KX, Psillas C, Moutsopoulos HM. Evaluation of tear break-up time, Schirmer’s-I test and rose bengal staining as confirmatory tests for keratoconjunctivitis sicca. Clin Exp Rheumatol. 1989;7:155-7.
- Cho P, Yap M. Schirmer test. I. A review. Optom Vis Sci. 1993;70:152-6. Review.
- Cho P, Yap M. Schirmer test. II. A clinical study of its repeatability. Optom Vis Sci. 1993;70:157-9.
- Vitali C, Moutsopoulos HM, Bombardieri S. The European Community Study Group on diagnostic criteria for Sjögren’s syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sjögren’s syndrome. Ann Rheum Dis. 1994;53:637-47.
- Rubin P, Holt J. Secretory sialography in diseases of the major salivary glands. Am J Roentgenol Radium Ther Nucl Med. 1957;77:575-98.
- Vinagre F, Santos MJ, Prata A, da Silva JC, Santos AI. Assessment of salivary gland function in Sjögren’s syndrome: the role of salivary gland scintigraphy. Autoimmun Rev. 2009;8:672-6.
- Niemelä RK, Takalo R, Pääkkö E, Suramo I, Päivänsalo M, Salo T, Hakala M. Ultrasonography of salivary glands in primary Sjogren’s syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands. Rheumatology (Oxford). 2004;43:875-9.
- Gannot G, Lancaster HE, Fox PC. Clinical course of primary Sjögren’s syndrome: salivary, oral, and serologic aspects. J Rheumatol. 2000;27:1905-9.
- Ramos-Casals M, Font J, Garcia-Carrasco M, Brito MP, Rosas J, Calvo-Alen J, Pallares L, Cervera R, Ingelmo M. Primary Sjögren syndrome: hematologic patterns of disease expression. Medicine (Baltimore). 2002;81:281-92.
- Ramos-Casals M, Font J. Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005;44:1354-67.
- Nicoletta Del Papaand Claudio Vitali Management of primary Sjögren’s syndrome: recent developments and new classification criteria. Ther Adv Musculoskelet Dis. 2018;10:39–54.
- Thursfield H. Bilateral salivary swellings (Mikulicz’s disease): A clinical review. 1914;7:237–249. Available at: http://www. worldcat . org/title/quarterly-journal-of-medicine/oclc/1763235.
- da Mata AD, da Silva Marques DN, Silveira JM, Marques JR, de Melo Campos Felino ET, Guilherme NF. Effects of gustatory stimulants of salivary secretion on salivary pH and flow: a randomized controlled trial. Oral Dis 2009; 15: 220-8.
- Greenspan D. Xerostomia: Diagnosis and management. Oncology 1996;10:7-11.
- Sreebny LM, Valdini A. Xerostomia: A neglected symptom. Arch Intern Med 1987; 147:1333-1337. 52. McDonald E, Marino C. Dry mouth: Diagnosing and treating its multiple causes. Geriatrics 1991; 46: 61- 63.
- Dyke S. Clinical management and review of Sjögren’s syndrome. Int J Pharm Compound 2000; 4: 338-341.
- Bryan Josue Flores Robles et al Sialodochitis fibrinosa (kussmaul disease) report of 3 cases and literature review Medicine (Baltimore). 2016;95: e5132. Published online 2016 Oct 21. doi: 1097/MD.0000000000005132.
- Amrita Ray, M.P.H., Sarah J. Burgin, and Matthew E. Spector, A rare case of Kussmaul Disease (Sialodochitis Fibrinosa) J Case Rep Med. 2015; 4(1+3): 235894. Published online 2015 Jan 31. doi: 4303/jcrm/235894
- A. Pape, R. I. MacLeodt, N. R. McLean and J. V. Soames Sialadenosis of the salivary glands British Journal of Plastic Surgery1995;48: 419-22
- White SC, Pharaoh MJ Salivary Gland Radiology. Oral Radiology Principles and Interpretation 5th edition published by Mosby page:658-70.
- Shanti RM, Aziz SR. HIV-associated Salivary Gland Disease. Oral and Maxillofacial Surgery Clinics of North America. 2009;21:339-43
- Naidoo M, Singh B, Ramdial P, Moodley J, Allopi L, Lester B. Lymphoepithelial lesions of the parotid gland in the HIV era-a South African experience. South African Journal of Surgery. 2009;45:136-41
- DiGiuseppe JA,Corio RL,Westra WH.Lymphoid infiltrates of the salivary glands: pathology, biology, and clinical signifi cance. Curr Opin Oncol 1996;8:232–7.
- Schiodt M, Greenspan D, Levy JA, et al. Does HIV cause salivary gland disease? AIDS 1989;3:819–22.
- Pol S, Vallet-Pichard A, Corouge M, Mallet VO. Hepatitis C: Epidemiology, diagnosis, natural history and therapy. Contrib Nephrol. 2012;176:1–9.
- Lodi G, Porter SR, Scully C. Hepatitis C virus infection: Review and implications for the dentist. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;86:8–22
- Marco Carrozzoand Kara Scally Oral manifestations of hepatitis C virus infection. World J Gastroenterol. 2014;20: 7534–7543.
- Seyed-Moayed Alavian, Nastaran Mahboobi,Nima Mahboobi, and Peter Karayiannis Oral Conditions Associated with Hepatitis C Virus Infection Saudi J Gastroenterol. 2013;19:245–251.
- Myer C, Cotton RT. Salivary gland disease in children: a review—part 1. Acquired non-neoplastic disease. Clinical Pediatrics. 1986;25:314–323.
- Som PM, Curtin HD. Head and Neck Imaging.3rd edition. St Louis, Mo, USA: Mosby-Year Book; 1996.
- Majeed FA. Parotid gland tuberculosis an unusual presentation. Pakistan Armed Forces Medical Journal.2008;58:346–347
- Chou YH, Tiu CM, Liu CY, Hong TM, Lin CZ, Chiou HJ, et al. Tuberculosis of the parotid gland: Sonographic manifestations and sonographically guided aspiration. J Ultrasound Med. 2004;23:1275–81.
- He Y, Zhang ZY, Tian Z. The diagnostic value of fine-needle aspiration cytology (FNAC) for lesions in the parotid gland. Shanghai Kou Qiang Yi Xue. 2003;12:410–3.
- WHO/CDS/TB/2003.313.Geneva: WHO; 2003. World Health Organization. Treatment of tuberculosis: Guidelines for national programs.
- Sagowski C, Ussmüller J. Clinical diagnosis of salivary gland sarcoidosis (Heerfordt syndrome)]2000;48:613-5.
- Rao V, Curran J, Blair EA, Sweiss NJ Salivary glands sarcoidosis Operative Techniques in Otolaryngology-Head and Neck Surgery. 2008;19:234-236
- Harvey J,Catoggio L, Gallagher PJ,Maddison PJ. Salivary gland biopsy in sarcoidosis. Sarcoidosis 1989;6:47–50.
- McGee J, Minagar A. Heerfordt’s Syndrome An interesting and under-recognised manifestation of sarcoidosis Sultan Qaboos Univ Med J. 2015; 15: e7–e8.
- Sujatha S Reddy, N Rakesh, Namita Raghav, D Devaraju, Shridevi G Bijjal Sialography: Report of 3 cases. IJDR 2009;20:499-502.
- Rajul Rastogi, Sumeet Bhargava , Govindarajan Janardan Mallarajapatna , Sudhir Kumar Singh Pictorial essay: Salivary gland imaging ndian Journal of Radiology and Imaging. 2012;22:325-33.
- Natalya Chernichenko Critical Update on Malignant Salivary Gland Neoplasms International Journal of Head and Neck Surgery 2017;8:71-75.
- S Jain, S Hasan, N Vyas, N Shah, and S Dalal Pleomorphic Adenoma of the Parotid Gland: Report of a Case With Review of Literature Ethiop J Health Sci. 2015;25:189–194.
- Sunil & Devi Gopakumar Pleomorphic Adenoma. A Case Report and Review of Literature Int. J. Odontostomat. 2013;7:171-174.
- Kakimoto N, Gamoh S, Tamaki J, Kishino M, Murakami S, Furukawa S. CT and MR images of pleomorphic adenoma in major and minor salivary glands.Eur J Radiol.2009;69:464-72.
- Rahnama M, Koszel UQ, Czupkałło L, Michał Łobacz M Pleomorphic adenoma of the palate: a case report and review of the literature Contemp Oncol (Pozn). 2013;17:103–106
- Mark Weitzel,Jason E. Cohn, Harvey Spector Myoepithelioma of the Parotid Gland: A Case Report with Review of the Literature and Classic Histopathology Case Rep Otolaryngol 2017 published online 2017 Aug 16. doi: 1155/2017/6036179
- Luna MA, Batsakis JG, Tortoledo ME, et al. Carcinomas ex monomorphic adenoma of salivary glands. J Laryngol Otol. 1989;103:756–759.
- Demir MG, Aydin S and Basak K Basal Cell Adenoma of the Parotid Gland: Case Report SAJ Case Rep 2015;2:1-4
- Kanaujia SK, Singh A, Nautiyal S, Ashutosh K Basal Cell Adenoma of Parotid Gland: Case Report and Review of Literature .Indian J Otolaryngol Head Neck Surg. 2015;67:430–433.
- Chawla AJ, Tan TY, Tan GJ. Basal cell adenomas of the parotid gland: CT scan features. Eur J Radiol.2006;58:260-5.
- Quintyne KI, Wallis F, Healy V, Shine Unilateral Warthin’s tumour in a patient of Afro-Caribbean descent BMJ Case Rep. 2014; 2014: bcr2014204813. Published online 2014 Jun 2. doi: 10.1136/bcr-2014-204813
- Pereira J, Machado S, Lima F, Lima M, Miguel M. Warthin tumor in an unusual site: a case report. Minerva Stomatol.2013;62:189-92
- Raghu A R, Shweta Rehani, Kundendu Arya Bishen, and Shitalkumar Sagari Warthin’s Tumour: A Case Report and Review on Pathogenesis and its Histological Subtypes J Clin Diagn Res. 2014;8: ZD37–ZD40.Published online 2014 Sep 20. doi: 7860/JCDR/2014/8503.4908
- Mukherji S,Sheth S Warthin’s Tumor of Bilateral Parotid Glands: A Case Report J Maxillofac Oral Surg. 2012;11:483–486.
- Sun S, Panpan Wang P, Yufan Wang, Wen Su, Feng Wang, Hongyu Yang, Intraductal papilloma arising from the accessory parotid gland A case report and literature review Medicine (Baltimore). 2018;97:e10761. Published online 2018 May 18. doi: 1097/MD.0000000000010761
- Ramaswamy,Tanya Khaitan,A. Anuradha, B. Praveen Kumar, and S. Sudhakar Intraductal Papilloma: Atypical Presentation Case Rep Dent. 2013; 2013: 652728. Published online 2013 May 23. doi: 10.1155/2013/652728
- Efthimia Vlachaki, Apostolos Tsapas, Konstantinos Dimitrakopoulos, George Kontzoglou, and Ioannis Klonizakis Parotid gland oncocytoma: a case report Cases J. 2009; 2: 6423. Published online 2009 Mar 10. doi: 1186/1757-1626-2-6423
- Ilson Sepúlveda,Enrique Platín, Loreto Spencer, Pablo Mucientes, Michael Frelinghuysen, Pablo Ortega, and David Ulloa Oncocytoma of the Parotid Gland: A Case Report and Review of the Literature Case Rep Oncol. 2014;7: 109–116.
- Devaraju R, Gantala R, Aitha H, Gotoor SG Mucoepidermoid carcinoma BMJ Case Rep. 2014; 2014: bcr2013202776. Published online 2014 Aug 1. doi: 1136/bcr-2013-202776
- Jarde SJ, Das S, Narayanswamy SA, Chatterjee A, Babu Mucoepidermoid carcinoma of the palate: A rare case report J Indian Soc Periodontol. 2016; 20: 203–206. doi: 10.4103/0972-124X.170828
- Chundru NSV, Rajesh Amudala R, Thankappan P, Nagaraju Adenoid cystic carcinoma of palate: A case report and review of literature Dent Res J (Isfahan). 2013;10: 274–278.
- Yaga US, Gollamudi N, Mengji AK, Besta R, Panta P, Prakash B, Rajashekar E Adenoid cystic carcinoma of the palate: case report and review of literature Pan Afr Med J. 2016; 24: 106. Published online 2016 May 31. doi: 11604/pamj.2016.24.106.8596
- Pushpanjali M, Sujata DN, Subramanyam SB, Jyothsna M Adenoid cystic carcinoma: An unusual presentation J Oral Maxillofac Pathol. 2014;18:286–290.
- Song JY Adenoid cystic carcinoma of the sublingual gland: A case report
Imaging Sci Dent. 2016;46:291–296.
115. Maxime St-Amant et al. Adenoid cystic carcinoma of the salivary glands available from:https://radiopaedia.org/articles/adenoid-cystic-carcinoma-of-the-salivary-glands-2.
116. Sepúlveda I, Frelinghuysen M, Platin E, Spencer ML, Urra A, Pablo Ortega P Acinic Cell Carcinoma of the Parotid Gland: A Case Report and Review of the Literature Case Rep Oncol. 2015;8:1–8.
117. Rosero DS, Alvarez R, Gambó P, Alastuey M, Valero A, Torrecilla N, Roche AB, Simón S Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features Iran J Pathol. 2016;11:181–185.
118. Khelfa Y, Mansour M, Abdel-Aziz Y, Raufi A, Denning K, Yehuda Lebowicz Y, Relapsed Acinic Cell Carcinoma of the Parotid Gland With Diffuse Distant Metastasis Case Report With Literature Review J Investig Med High Impact Case Rep. 2016 Oct-Dec; 4(4): 2324709616674742. Published online 2016 Nov 4. doi: 10.1177/2324709616674742.
119. Buva KB, Deshmukh AA, Deshmukh AA A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description J Clin Diagn Res. 2017;11:ZD15–ZD17.
120. Chooback N, Shen Y, Jones M, Kasaian K, Martin M, T. Thomson T, Marra M, Laskin J, Ho C, Curr Oncol. 2017;24:e251–e254.
121. Antony J, Gopalan V, Smith RA, Lam AKY Carcinoma ex Pleomorphic Adenoma: A Comprehensive Review of Clinical, Pathological and Molecular Data Head Neck Pathol. 2012;6:1–9.
122. Keerthi R, Raut RP, Vaibhav N, Ghosh A Carcinoma ex pleomorphic adenoma: Diagnostic dilemma and treatment protocol Indian J Dent. 2014; 5: 157–160.
123. Sano K, Fujita S, Sekine J, Uehara M, Sakihama N, Hayashi T, Yoshimura H, Tobita T. Metachronous manifestation of carcinoma ex pleomorphic adenoma in a buccal minor salivary gland and the contralateral parotid gland: a case report and review of the literature. J Oral Maxillofac Surg. 2012 ;70:2701-12.
124. Som PM, Brandwein-Gensler MS. Anatomy and pathology of the salivary gland, in Som PM, Curtin HD (eds): Head and Neck Imaging (ed5). St Louis, MO, Elsevier, 2011; p: 2525-35.
125. Giordano G, Gabrielli M, Gnetti L, Ferri T Oncocytic carcinoma of parotid gland: a case report with clinical, immunohistochemical and ultrastructural features. World J Surg Oncol. 2006; 4: 54.
126. Xiao H, Wen T, BS, Liu X, Submandibular oncocytic carcinoma A case report and literature review Medicine (Baltimore). 2016;95:e4897. Published online 2016 Sep 16. doi: 10.1097/MD.0000000000004897