PATHOLOGY OF SALIVARY GLANDS

MAJOR SALIVARY GLANDS

 Parotid: so-called watery serous saliva rich in amylase, proline-rich proteins
Stenson s duct

 Submandibular gland: more mucinous

Wharton s duct

 Sublingual: viscous saliva

ducts of Rivinus; duct of Bartholin

MINOR SALIVARY GLANDS

 Minor salivary glands are not found within 

  

gingiva and anterior part of the hard palate Serous minor glands=von Ebner below the sulci of the circumvallate and folliate papillae of the tongue Glands of Blandin-Nuhn: ventral tongue Palatine, glossopalatine glands are pure mucus Weber glands

Embryology The major salivary glands develop from the 6th-8th weeks of gestation as outpouchings of oral ectoderm into the surrounding mesenchyme. The parotid develops first, growing posteriorly as the facial nerve advances anteriorly; eventually, the fully developed parotid surrounds VII. However, the Parotid is the last to become encapsulated, after the lymphatics develop, resulting in its unique anatomy with entrapment of lymphatics in the parenchyma of the gland

Structural elements of the salivary gland unit.

 pleomorphic adenomas originate from

the intercalated duct cells and myoepithelial cells  oncocytic tumors originate from the striated duct cells  acinous cell tumors originate from the acinar cells,  Mucoepidermoid tumors and squamous cell carcinomas develop in the excretory duct cells

 Salivary epithelial cells are often included within these lymph nodes, leading to development of Warthin s tumors and Lymphoepithelial cysts within the Parotid gland. The other major salivary glands do NOT have intraparenchymal lymph nodes.

Normal Histology

Mucous cells
 Production, storage, and secretion of proteinaceous material; smaller enzymatic component -more carbohydrates-->mucins=more prominent Golgi -less prominent (conspicuous) rough endoplasmic reticulum, mitochondria -less interdigitations

Serous cells
 Seromucus cells=secrete also polysaccharides  They have all the features of a cell specialized for

the synthesis, storage, and secretion of protein

Rough endoplasmic reticulum (ribosomal sites->cisternae) Prominent Golgi-->carbohydrate moieties are added Secretory granules-->exocytosis

Serous cells
 The secretory process is continuous but cyclic  There are complex foldings of cytoplasmic

membrane  The junctional complex consists of:

Tight junctions (zonula occludens)-->fusion of outer cell layer Intermediate junction (zonula adherens)->intercellular communication Desmosomes-->firm adhesion

Myoepithelial cells
 One, two or even three myoepithelial cells in each salivary and piece body  Four to eight processes  Desmosomes between myoepithelial cells and secretory cells  Myofilaments frequently aggregated to form dark bodies along the course of the process

Myoepithelial cells
 The myoepithelial cells of the intercalated ducts

are more spindled-shaped and fewer processes  Ultrastructurally very similar to that of smooth muscle cells  Functions of myoepithelial cells
Support secretory cells Contract and widen the diameter of the intercalated ducts Contraction may aid in the rupture of acinar cells of epithelial origin

Formation and Secretion of Saliva

 Primary saliva

Serous and mucous cells Intercalated ducts

 Modified saliva

Striated and terminal ducts End product is hypotonic

Macromolecular component
 Synthesis of proteins  RER, Golgi apparatus  Ribosomes RER posttranslational

modification (N- & O-linked glycosylation) Golgi apparatus Secretory granules  Exocytosis  Endocytosis of the granule membrane

Fluid and Electrolytes

Parasympathetic innervation Binding of acetylcholine to muscarinic receptors
 Activation of phospholipase IP3

release of Ca2+

Noepinephrine via alpha-adrenergic receptors

 Substance P activates the Ca2+

opening of channels K+, Cl- Na+ in  K+ and Cl- in  Also another electrolyte transport mechanism through HCO3-

Functions
Protection  lubricant (glycoprotein)  barrier against noxious stimuli;

microbial toxins and minor traumas  washing non-adherent and acellular debris  formation of salivary pellicle calcium-binding proteins: tooth protection; plaque

Functions
 Buffering (phosphate ions and

bicarbonate) bacteria require specific pH conditions plaque microorganisms produce acids from sugars

Functions
 Digestion

neutralizes esophageal contents dilutes gastric chyme forms food bolus brakes starch

Functions
 Tissue repair

bleeding time of oral tissues shorter than other tissues resulting clot less solid than normal remineralization

Functions
 Taste
solubilizing of food substances that can be sensed by receptors trophic effect on receptors

Function of Saliva
At least 8 major functions of saliva have been identified: 1) Moistens oral mucosa. Mucin layer is the most important nonimmune defense mechanism in the oral cavity. 2) Moistens dry food and cools hot food. 3) A medium for dissolved foods to stimulate the taste buds. 4) Buffers oral cavity contents due to high concentration of bicarbonate ions. 5) Digestion. Alpha-amylase, contained in saliva, breaks 1-4 glycoside bonds, while lingual lipase helps break down fats. 6) Controls bacterial flora of the oral cavity. 7) Mineralization of new teeth and repair of precarious enamel lesions. Saliva is high in calcium and phosphate. 8) Protects the teeth. This signifies a saliva protein coat on the teeth which contains antibacterial compounds. Thus, salivary hypofunction results in dental caries.
30

The intraoral complications of salivary hypofunction

1) Candidiasis

2) Oral Lichen Planus (usually painful) 3) Burning Mouth Syndrome (normal appearing oral mucosa with a subjective sensation of burning) 4) Recurrent aphthous ulcers 5) Dental caries. The best way to evaluate salivary function is to measure the salivary flow rate in stimulated (e.g., by using a parasympathomimetic as pilocarpine) and unstimulated states. Xerostomia is NOT a reliable indicator of salivary hypofunction. There is a hierarchy of sensory stimuli such that swallow>mastication>taste>smell>sight>thought. Stimulation results in an increase in total salivary flow from 0.3 cc/min to >1 cc/min. The salivary response is directly related to a subject s state of hunger
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The Parotid Gland

The largest salivary gland Lies wedge-shaped between the mandible and sternomastoid and over both Relations: Above: external auditory meats and temporomandibular joint Below: post belly digastric Anteriorly: mandible and masseter Medially: styloid process and its muscles
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Structures at the Angle of the Mandible Medial relations of the parotid: the styloid process and its muscles separate the gland from the internal jugular vein Internal carotid artery The last four cranial nerves Lateral wall of the pharynx

33

Relations of the Parotid

34

Parotid Bed

36

Deep relations of Parotid

37

Fascia
The parotid is enclosed in a split in the investing fascia The parotid lymph nodes lie both on and below the parotid gland Antero-inferiorly, the fascia is thickened to form the stylomandibular ligament; the only structure that separates the parotid from the submandibular glands

38

The Facial Nerve

The parotid gland is divided into superficial and deep lobes by three structures traversing the gland: The Facial Nerve The retromandibular vein (post facial) formed by the superficial temporal and maxillary The external carotid artery dividing at the neck of the mandible into the superficial temporal and maxillary
39

Relation of the Facial Nerve and Parotid The parotid develops in the crotch formed by the 2 divisions of the facial nerve As it enlarges it overlaps the nerve trunks, the superficial and deep parts fuse and the nerve becomes buried within the gland It is not a sandwich

40

Facial Nerve

41

The Facial Nerve

Emerges from the stylomastoid foramen Winds laterally to the styloid process Surgical Exposure In the inverted V between the bony external auditory meatus and the mastoid process Just beyond the point the nerve dives into the post aspect of the parotid and bifurcates almost immediately into its two main divisions

42

Branches of the Facial N

The nerve then gives rise to 2 divisions: 1) Temperofacial (upper) 2) Cervicofacial (lower) Followed by 5 terminal branches: 1) Temporal 2) Zygomatic 3) Buccal 4) Marginal Mandibular 5) Cervical
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Nerve Injury
Clinical examination of the Parotid should include examination of the Facial nerve Malignant tumors of the parotid may involve VII and cause facial palsy, while benign tumors never affect VII During Superficial Parotidectomy, the nerve is exposed posteriorly in the space bet the bony canal of external auditory meatus and the mastoid process It is then traced anteriorly into the gland to excise the gland superficial to nerve branches

44

The Parotid Duct

Stensen s duct is 5 cm long. Arises from the anterior part of the gland and runs over the masseter one finger below the zygomatic arch to pierce the buccinator and open opposite the second upper molar tooth

45

Parotid Duct orifice

Clinical examination of the parotid gland should include examination of the duct orifice opposite the upper 2nd molar for signs of inflammation, and palpated for stone Parotid Sialogram is performed by injecting a contrast through a canula placed in the orifice of the duct

46

47

Submandibular Gland
Large superficial lobe and a small deep lobe, that connect around the mylohyoid Superficial lobe lies at the angle of the Jaw, wedged bet the mandible and mylohyoid and overlapping the digastric

48

49

Superficial and Deep Relations

Superficially: The skin, the platysma, the capsule (deep fascia), the cervical branch of Facial Nerve, and the Facial Vein Deeply: the deep aspect lies against the mylohyoid for the most part. But posteriorly lies on the hyoglossus and comes in contact with the lingual and hypoglossal nerves. Both nerves lie on the hyoglossus as they pass forward to the tongue

50

The facial Artery

Posterior Arches over its superior aspect to reach inferior border of the mandible and then ascends on to the face in front of the masseter

51

52

Facial artery

The Submandibular Duct

Arises from the deep part of the gland, runs forward to open at the side of the frenulum linguae Lies beneath the mucosa of the floor of the mouth along the side of the tongue Lingual nerve loops around the duct, doublecrossing it, by passing from lateral beneath, then medial The sublingual salivary gland is also medial to the duct.

53

Clinical Applications
Submandibular LN are adherent to the gland and partly between it and the mandible Differentiating bet submandibular LN and Salivary gland: The salivary gland can be palpated bimanually as it extends into the floor of the mouth. The Lymph Nodes are only felt below the mandible. LN may be multiple and a space separates them from the mandible

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Clinical Applications
A stone in the submandibular duct can be felt bimanually in the floor of the mouth and can be seen if large The presence of LN adherent to the gland makes removal of the gland part of block neck dissection

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Autonomic Innervations
Parasympathetic Stimulation results in abundant, watery saliva with a decrease in [amylase] in saliva and an increase in [amylase] in the serum. Acetylcholine is the active neurotransmitter, binding at muscarinic receptors in the salivary glands. The parasympathetic nervous system is the primary instigator of salivary secretion. Parasympathetic Interruption to salivary glands results in atrophy, while sympathetic interruption doesn t cause a significant change. It was once thought that the sympathetic nervous system antagonizes the parasympathetic nervous system, but this is now known not to be true

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Autonomic Innervation
In the case of the parotid, parasympathetic fibers originate from CN IX In the case of the Submandibular and Sublingual glands, the parasympathetic fibers originate in CN VII

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Sympathetic Innervation
Stimulation by the sympathetic nervous system results in a scant, viscous saliva rich in solutes with an increase in [amylase] in the saliva and no change in [amylase] in the serum. For all of the salivary glands, these fibers originate in the Superior Cervical ganglion and travel with arteries to reach the glands: 1) External Carotid artery for the Parotid 2) Lingual artery for the Submandibular, and 3) Facial artery in the case of the Sublingual.

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History
Determine if solitary parotid or more generalized salivary gland involvement Progression of enlargement Inciting factors for enlargement Nature and duration of symptoms Pain: character, severity, frequency

Associated Symptoms - Head and Neck - Systemic Review of Systems Medications Past Medical History Social History (eg. alcohol use) Family History

Physical Examination
Complete Head and Neck Exam Inspection / Palpation of Salivary Glands - enlargement (unilateral/bilateral) - consistency - tenderness - mobility Differentiate diffuse gland enlargement from discrete mass or anatomic anomaly

BIMANUAL PALPATION OF SUBMANDIBULAR GLAND

Parotid gland: Inspect the pre- and infra-auricular region, observing for symmetry. Palpate the parotid gland. Lacrimal gland: Have the patient close their eyes and observe the upper and outer aspect of the upper lid. The lid is normally smooth and symmetrical. Gently retract the upper lid and have the patient gaze to the opposite side. The lacrimal gland is located under the lid near the outer angle. Submandibular gland: Observe the submandibular region. Tilt the patient's head forward and gently roll your fingers over the inner surface of the mandible.

Physical Examination
Oral Cavity -Moisture level -Dentition status -Salivary duct output amount character -Palpate for sialoliths, masses Salivary duct probing

LABORATORY
Chemical analysis of saliva
 Anti-SS-A, anti-SS-B, and rheumatoid factor

may be present in autoimmune diseases. Saliva may be cultured, which is helpful, and it may be analyzed chemically, which is rarely helpful.  Most laboratories cannot perform useful tests on saliva. Dental researchers had hopes for several decades that analysis of saliva would be of diagnostic importance. Saliva has such wide variations in composition that analysis has produced little of diagnostic value.

Laboratory Studies HIV test Angiotensin converting enzyme (Sarcoid) Autoantibodies (Sjogrens) - Rheumatoid factor - Antinuclear antibodies - Anti-SSA, Anti-SSB Antineutrophil cytoplasmic antibody;ANCA(Wegeners) Hormone levels (eg. TSH)

EXPLORATORI METHODS
 1. X-rays without preparation.  Plainfilm  The views of the salivary glands are taken full face and profile of the parotid, or the submandibular gland, depending on the pathology. A 3/4 x-ray view of the submandibular gland is preferred.  These different x-rays can show not only radio opaque stones in the salivary glands, but also old calcifications in a lymph node.

2. Regular occlusal x-rays of the floor of the mouth. These occlusal views are helpful in revealing an opaque stone in the submandibular gland, or in the duct. The procedure entails actually putting film in the mouth to obtain an x-ray image. Regular occlusal X-rays can only be made at the submandibular and sub-lingual glands levels. They either entail the positioning of an occlusal image source in an orthogonal position in relation to the mouth's floor, or scanning the ray to obtain a view of the forward sub-mandibular gland. This results in the visualisation of calcification in the glandular area. These are most frequently stones but may also be calcified lymph node

(a-d) Transverse CT scans of ductal and glandular calcifications.

SIALOGRAPHY
3. Sialography Technique A cannula is introduced into the parotid or submandibular ducts and is used to inject contrast enhancing products (eg Lipiodol) to outline the ramifications of the ductal systems of these glands, showing their patterns and calibers. This examination can be performed on everyone, including children over the age of 4. The injection should be of no more than 0.5 to 1 cc, and injected very slowly. This examination is painless if done smoothly. The only contraindication is an allergic reaction to iodine.It must be know in such cases, pre-medication with corticosterods will permit the examination. Results Basically, sialography is prescribed each time there is a suspicion of an inflammatory syndrome, especially if there is the possibility of a lithiasis, in order to visualize the exact caliber of the duct and the position of the stone, as opposed to calcification within a lymph node.

Conventional sialography.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

IMAGING

 CT scanning and MRI with gadolinium enhancement

These studies may be used to determine the size, shape, and some qualities of neoplasms or swelling within the gland. Either method reliably differentiates between solid masses, cystic lesions, and diffuse involvement of the gland.

(a-d) Transverse CT scans of ductal and glandular calcifications.

Submandibular calculi visualized at MR imaging.

Simple ranula.

(a-d) Transverse CT scans of ductal and glandular calcifications.

Glandular calcifications in a patient with sarcoidosis.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

BIOPSY
Incisional biopsy -Under local anesthesia, a biopsy of the tail of the gland
may be obtained by an experienced surgeon without injury to the facial nerve. Fine-needle aspiration biopsy frequently is diagnostic for tumors and may be helpful to identify cell types and to obtain material for cultures when the clinical picture suggests infection. Excisional biopsy of a labial minor salivary gland may be diagnostic when the clinical picture suggests Sjgren syndrome.

The Most Common Tumors

Histologically, salivary gland tumors are the most heterogenous group of tumors of any tissue in the body Of salivary gland neoplasms, >50% are benign Approximately 70% to 80% of all salivary gland neoplasms originate in the parotid The palate is the most common site of minor salivary gland tumors The frequency of malignant lesions varies by site.
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PLUNGING RANULA

RANULA

Pleomorphic Adenoma

Pleomorphic Adenoma

Submandibular pleomorphic adenoma.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

SUBMAXILLECTOMY

Warthin's Tumor
 Warthin's tumor (benign papillary cystadenoma lymphomatosum)  the second most common benign tumor of the parotid gland  It accounts for 2-10% of all parotid gland tumors  Bilateral in 10% of the cases  may contain mucoid brown fluid in FNA

Bilateral Warthin tumors.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

Monomorphic Adenoma
 Similar to Pleomorphic Adenoma except no mesenchymal stromal component Predominantly an epithelial component  More common in minor salivary glands (upper lip)  12% bilateral  Rare malignant potential  Types: Basal Cell Adenoma Canicular Adenoma Myoepithelioma Adenoma Clear Cell Adenoma Membranous Adenoma Glycogen-Rich Adenoma

Malignant Tumors
Approximately 20-25% of parotid, 35-40% of submandibular tumors, 50% of palate tumors, and > 90% of sublingual gland tumors are malignant The most common benign salivary tumor is pleomorphic adenoma, comprising 50% of all salivary tumors and 65% of parotid gland tumors The most common malignant salivary tumor is the mucoepidermoid carcinoma, comprising 10% of all salivary gland neoplasms and 35% of malignant salivary gland neoplasms, occurring most often in the parotid gland.
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Salivary Gland Tumors



PAROTID CANCER

Mucoepidermoid Carcinoma
MECs contain two major elements: mucin-producing cells and epithelial cells of the epidermoid variety (Epidermoid and Mucinous components). MEC is divided into low-grade (well differentiated). High-grade (poorly differentiated).

Acinic Cell Carcinoma

 This lesion is characterized by a

benign histomorphologic picture but by occasional malignant behavior.  These lesions are treated by surgical excision  Bilateral involvement occurs in 3% of patients, making acinic cell carcinoma the second-most common neoplasm, after Warthin s tumor, to exhibit bilateral

Adenoid Cystic Carcinoma

 Adenoid cystic carcinoma with Swiss cheese pattern.  It is the second-most common malignant tumor of the salivary glands.  ACC is the most common malignant tumor found in the submandibular, sublingual, and minor salivary glands.

Mucoepidermoid Carcinoma
 Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the parotid gland and the second-most common malignancy (adenoid cystic carcinoma is more common) of the submandibular and minor salivary glands.  Stained +ve by musicarmine.  MECs constitute approximately 35% of salivary gland malignancy, and 80% to 90% of MECs occur in the parotid gland.

Hodgkin's Lymphoma
 Hodgkin's disease

involving the parotid gland.  Note the ReedSternberg cell. (Fine needle aspiration, Pap, 630x)

PARTIAL PAROTIDECTOMY

Inflammatory Enlargement
Acute Sialadenitis Viral Bacterial Radiation Medication Chronic Sialadenitis Obstructive Granulomatous Autoimmune HIV-associated

Sialadentitis
 What is Sialadentitis?
Simply inflammation of the salivary glands Can be due to a number of factors including:
Mumps infection Coxackie Virus Parainfluenza Systemic Disease

Sialadentitis: Etiology
May be infectious:  May be caused by bacterial or viral infections May be non-infectious:  May be caused by systemic disease such as Sjogren s or Sarcoidosis or even by radiation therapy May be Post-Surgical:  Called Surgical Mumps  Pt kept without fluids and given atropine causes xerostomia predisposing to inflammation May be Pharmacological:  Drugs causing xerostomia May be architectural:  Block of the salivary gland due to a stone

SIALOLITHIASIS

Sialolithiasis
Recurrent painful parotid gland swelling Episodes of acute bacterial sialadenitis Abscess formation Chronic sialadenitis Gland atrophy

Submandibular calculi visualized at MR imaging.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

(a-d) Transverse CT scans of ductal and glandular calcifications.

Parotitis
 Definition:
Inflammation of the Parotid Gland

 May be infectious or non-infectious  Common Causes:

Mumps Sjogren s Syndrome Bacterial infection of parotid gland usually Staph. aureus Blocked salivary duct Stone in salivary duct

Parotitis
 Definition:
Inflammation of the Parotid Gland

 May be infectious or non-infectious  Common Causes:

Mumps Sjogren s Syndrome Bacterial infection of parotid gland usually Staph. aureus Blocked salivary duct Stone in salivary duct

Mumps: Clinical Features

 Transmitted via airborne droplet  Mainly effects the parotid gland  Mainly effects children between the ages of 5-

18  Has a 2-3 week incubation period  Clinically:

Will see rapid swelling of the parotids bilaterally Acute pain when salivating

Mumps (Viral endemic parotitis)

Mumps is an acute sialadenitis which caused by an RNA virus  This RNA virus is the paramxovirus  Other virus which can cause salivary infections are: Cytomegalovirus Coxsackieviruses Echovirus


Mumps (Viral endemic parotitis)

TREATMENT:  There no effective antiviral therapy available for the treatment of mumps.  Analgesics and antipyretics are given to control pain and fever  Liquid diet with vitamins should be considered  There should be complete bed rest.

Bacterial Saladenitis
 Bacterial saladinitis usually occurs after surgery

most commonly abdominal surgery.  The possible reason may be temporary lack of ductal flow which can develop while atropine sulphate is administered while delivering general anesthesia which allows ascending infections and thus pyogenic bacteria can inhibit the ducts.  Due to this there is pain and swelling .  Purulent exudate can be expressed from the orifice of the duct.

Clinical Features- continued

 When looking at the patient:
The ear lobe is elevated due to glandular enlargement

 There may be a purulent discharge from the

parotid duct but it is clear and unremarkable  Blood Work:

As the acini become infected the salivary amylase leaks into the interstitium and is absorbed in the blood stream raising the serum amylase levels

Acute right-sided parotitis.

Yousem D M et al. Radiology 2000;216:19-29

2000 by Radiological Society of North America

Overall Treatment for Parotitis

 Acute:
Antibiotics Rehydration stimulating salivary flow Possible IND

 Chronic:
Eliminate causative agent:
Get rid of salivary stone/ other blockage

Warm Compresses Sialogogues Possible surgical resection Ligation of the duct in hopes of atrophy

Radiation Sialadenitis

Inflammatory process due to radiation effect on gland parenchyma, dose-related injury Serous glands and acini most susceptible External beam radiation Radioactive iodine Painful, tender glands; swelling; xerostomia Chronic injury can result Some benefit with sialendoscopy

Chronic Sialadenitis

Non-granulomatous chronic inflammatory condition Etiology may be unclear by history - primary obstruction / secondary infection - primary infection / secondary obstruction Recurrent painful gland enlargement common - exacerbation with eating Relief of duct obstruction, sialogogues, glandular massage, warm heat Gland resection for medical therapy failure

Sjogren s Syndrome

Sjogrens Syndrome
 It is a group of autoimmune conditions with a

marked predilection for woman, it has an intense T lymphocyte mediated autoimmune process in salivary and the lacrimal glands as on of its most prominent component  Sjogren s syndrome exhibits T cells infiltration and replaces the glandular parenchyma

Sjogrens Syndrome
 Sjogren s Syndrome:
objective evidence of keratoconjunctivitis sicca characteristic pathologic features of the salivary glands 2 out of 3 of:
recurrent chronic idiopathic salivary gland swelling unexplained xerostomia connective tissue disease

Sjogren's Syndrome: Age of Onset

The frequency distributions of ages at onset of symptoms & at diagnosis of primary Sjogren's syndrome
45 40

% OF PATIENTS

35 30 25 20 15 10 5 0

Onset At diagnosis

1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90

AGE

Sjogren s Syndrome: Clinically

Subjective and Objective Findings: Subjective: Objective:
       Xerostomia  Salivary Gland Enlargement

Stomatitis Oral Ulcers Cracked, crocodile skin tongue Carious Teeth Parotid Gland Enlargement Certain Tests can be done

Crocodile Skin Teeth

Tongue, Carious

Tests and Studies: Serology

Autoantibodies
Rheumatoid factors (Igs)
Cryoglobulins (type II)

% positive
80
30

Ro/SSA La/SSB a-fodrin

60 30 95

Tests and Studies: Scintigraphy administer radioactive substance  Scintigraphy (Nuclear Medicine)
in order to show the physiology and state of the biological process:

Scintigraphy Moderate Marked Normal diagnosis involvement involvement Degree of None Mild Severe xerostomia Salivary flow 1.60 0.42 0.00 rate (ml/5min/gland)

Tests and Studies: Schirmer s Test of whether the eye has enough tears to keep moist  A test
 Procedure:

Piece of filter paper inserted for several minutes (usually 5) and moisture recorded  <5 ml in 5 minutes is characteristic of Sjogren s Syndrome

Tests and Studies: Salivary Gland Biopsy

 A lip biopsy, if positive for Sjogren s will show lymphocytes clusters and glandular destruction due to inflammation

Tests and Studies: Salivary Gland Biopsy

 A lip biopsy, if positive for Sjogren s will show lymphocytes clusters and glandular destruction due to inflammation

Pathophysiology: Continued
Multifactorial disease SS is sometimes called autoimmune epithelitis in which there is apoptosis of epithelial cells leading to degradation products and leading to antinuclear autoantigens to the immune system Molecules within the TNF family play a big role in the polyclonal activation of B Cells. This, in turn leads to autoantibodies There is known inhibition of healthy glands and/or the muscarinic receptors (via antibodies) and also abnormal function of aquaporins leading to poor function of remaining healthy glandular structure There is prolonged/permanent activation of autoreactive B cells favoring oncogenic activity and possible development of B Lymphoma

Pathological

Sjogren s Syndrome: Systemic Manifestations Systemic manifestations Frequency (%)

Arthralgia/arthritis Raynauds phenomenon Purpura/Vasculitis Lung involvement
(increased liver enzymes)

60 30 15 (1) 10 (25) 8 (25) 5 1

Kidney involvement
(Interstitial Nephritis/Glomerulonephritis)

Liver involvement Muscle involvement

Skopouli et al., Semin Arthritis Rheum. 2000, 29:296

Sjogren s Syndrome: Treatment

 To Treat Xerostomia:
Glandular Stimulation/Replacement Salivary Substitutes Dx and treatment of candidiasis Meticulous oral hygeine for prevention of caries

 To Treat Xerophthalmia:
Stimulation for tears:
Cyclosporin A Pilocarpine Cimeviline

Treatment: Continued
Treatment for Salivary Gland Enlargement:
 Local moist heat  Antibiotic Therapy  NSAIDs  Rule out a Lymphoma

Treatment for Peripheral Symptoms:

 Methotrexate  Cyclosporin A  Infliximab  Hydroxychloroquine  Corticosteroids

SARCOIDOSIS

HEERFORD SDR

Sarcoidosis
Systemic granulomatous disease, unclear etiology < 1/3 patients - painless salivary gland swelling Nontender and multinodular glands; xerostomia ACE elevation (50-80%) Most patients have pulmonary involvement CXR- hilar nodes, adenopathy, parenchymal infiltrates Noncaseating granulomas on histopathology Treatment supportive; steroids in select patients

HIV-Associated Cystic Sialadenitis

Bilateral parotid multicystic enlargement Lymphocytic (T cell) infiltration of gland Persistent, nonprogressive May be mildly painful Enlarged adenoids, cervical nodes common Diagnosis largely clinical Positive HIV test Must exclude lymphoma or other neoplasm

Non-Inflammatory Enlargement
Acute Enlargement Neoplasm Miscellaneous: Trauma Pneumoparotitis Anesthesia/ Endoscopy Chronic Enlargement Obesity Sialadenosis - Endocrine - Nutritional - Medication - Idiopathic Amyloidosis

Sialadenosis (Sialosis)
Non-inflammatory, non-neoplastic gland parenchyma enlargement Bilateral parotid enlargement most common Can be recurrent or persistent Wide variety of systemic conditions causative Unifying factor - neuropathic alteration of the autonomic innervation of salivary acini (Batsakis) Diagnosis primarily clinical, exclusion of others Complete metabolic and endocrine evaluation

Sialadenosis - Etiologies
Endocrine Disorders - Diabetes Mellitus (1/4) - Hypothyroidism Alcoholism (autonomic neuropathy) Nutritional Disorders - Bulimia (1/3) - Deficiency condition eg. protein (alcoholism) vitamin (niacin, thiamine, vit. A)

Sialadenosis - Etiologies
Medications - Direct effect on gland eg. iodine compounds - Drug side-effect (adrenergic, cholinergic) eg. antihypertensives (guanethidine) antiemetics (phenothiazine) antiepileptics (phenobarbital) bronchodilators (isoproterenol) Idiopathic - diagnosis of exclusion

SIALADENOSIS - Treatment
Correct underlying disorder Pilocarpine - Bulimia Consider parotidectomy only for unacceptable cosmetic deformity unresponsive to medical therapy