disease of salivary gland

Disease of Salivary Gland Dr. Deepak K. Gupta

SYLLABUS

• Neoplastic disease of Salivary Gland – Benign Epithelial

neoplasms • Pleomorphic Adenoma, • Warthin’s tumour, • Oncocytoma

– Malignant Epithelial neoplasms • Adenoid Cystic Carcinoma • Mucoepidermoid

Carcinoma, • Acinic Cell Carcinoma • Adenocarcinomas.

• Non neoplastic Salivary Gland Diseases – Sialolithiasis, – Sialosis, – Sialadenitis, – Xerostomia – Ptyalism

• Miscelleneous Disease – Mikulicz syndrome – Sjogren’s syndrome – Mucocele – Ranula

NEOPLASTIC DISEASE

BENIGN TUMORS OF SALIVARY GLAND

•Pleomorphic Adenoma, •Warthin’s tumour, •Oncocytoma

Pleomorphic Adenoma • Mixed tumor

• A benign neoplasm consisting of cells exhibiting the ability to differentiate to epithelial cell (ductal & non ductal) and mesenchymal cell (chondroid, myxoid & osseous)

Clinical features

• Most common form of salivary gland tumor.

• Parotid gland – lower pole, superficially 90%

• Minor Salivary gland 8% - mostly palatal

• F:M = 6:4

• 4th-6th decade of life – 43 yrs mean age

• Also found in children

Clinical presentation

• Small, painless, quiscent nodule – slowly increases in size, sometimes showing intermittent growth

• Doesn’t fixes to deeper tissue – mobile on palpation

• Skin never ulcerates, although size may reach a fantastic size and of several kilograms


• PA of minor salivary gland of size >1-2 cm creates problem in mastication, talking and breathing

• Palatal PA may appear fixed to underlying bone but invasive

Histologic features - Macroscopic

– Irregular to ovoid mass

– Well defined border

– Major gland – incompletely fibrous capsulated or uncapsulated

– Minor gland – unencapsulated

– Rubbery, fleshy, mucoid or glistening with homogenous tan

– Area of infarction and haemarrage.

Encapsulation and heterogeneous pattern

Histologic features - Microscopic

• Diverse, variable structural histological patterns

• PA shows combination of glandular epithelium and mesenchyme like tissue

– Principally myxoid

– Myxoid & cellular, present in equal proportion

– Predominantly cellular

– Extremely cellular

Mixed tumor with myxoid component (right) and fibrous/epithelial

component (left).

Histologic features - Microscopic

• Epithelial component

– Forms ducts & small cysts

– Contains eosinophilic cogulaum

– Small cellular nest, sheets of cells

– Anastomosing cords and foci of keratinizing squamous or spindle cells

• Myoepithelial cell – major component • Angular, spindle

• Ecentric nuclei & hyalinized eosinophillic cytoplasm

• Responsible for mesenchyme like changes

• Mucous accumlation – myxoid appearance

• Vacoular degeneration of ME cells – cartilagenous appearance

• Foci of bone and even fat can be seen

Mixed tumor with cartilage (upper left) and bone (blue) differentiation.

Mixed tumor showing plasmacytoid myoepithelial cells

Treatment

• Surgical excision

• Intraoral lesion – treated conservatively by extracapsular excision

• Radioresistant – Radiotherapy contraindicated

Prognosis

• Malignant tumor within tumor – carcinoma ex pleomorphic adenoma

• Metastizing benign mixed tumor – histologically benign but multiple local recurrence

– Metastasizes to lungs, regional lymph node, skin & bones after several years.

Warthin’s tumour

• Adenolymphoma • Papillary cystadenoma lymphomatosum • Tumor arises in salivary gland tissue entrapped

within paraparotid or intraparotid lymph node during embryogenesis.

• Delayed hypersenstitivity disease – lymphocyte being an immune reaction with salivary duct undergoes oncocytic changes,

• Strong assoociation with smoking • Virus like EPV

Clinical features • Men predliction • 6th – 7th decade, 62

yrs mean age • Superficial lying

beneath parotid capsule

• Size 3-4 cm • Painless, firm to

palpation & clinically indistinguishable from other benign lesions of parotid

Histological features - Macroscopic

• Smooth

• Well encapsulated

• Variable number of cyst – clear fluid

• Focal hemorrhage may also be seen

Histological features - Microscopic • Two components : Epithelial & lymphoid tissue • Cyst formation with papillary projection into cystic space

and lymphoid matrix showing germinal centres • Papillary proliferation of bilayered oncocytic epithelium

– Inner layer – tall columnar with finely granular and eosinophillic cytoplasm – presence of mitochondria & hyperchromatic nucleas

– Outer layer – oncocytic triangular and occasionally fusiform basiloid cells

High magnification micrograph

http://en.wikipedia.org/wiki/Micrograph

Electron micrograph showing oncocytes in tumor cells. Note abundant mitochondria and

nucleus (upper left)

• Focal area of squamous metaplasia and mucous cell prosoplasia

• Eosinophillic cogulam – cystic space – choclate colored fluid

• Abundant lymphoid tissue may be present.

Diffrential diagnosis

• Pleomorphic adenoma

• Oncocytoma

• Enlarged parotid lymph node

• Mucoepidermoid tumor

• Lipoma

• Mucous retention cyst

• Malignant lymphoma

Investigation • Sialography : features of benign neoplasm

• Scintigram: Hot spot or hot nodule.

Treatment


• Well capsulated so recurrence is very rare

• Oncocytic adenoma

• Oxyphillic adenoma

• Acidophillic adenoma

• It’s a reare benign tumor composed of oncocytes with granular eosinophillic cytoplasm and a large number of atypical mitochondria

Oncocytoma

Clinical features

• Small benign tumor – similar to other benign lesion of salivary gland so clinically indistinguishable.

• Femal predliction.

• 5th – 8th decade,

• 3-5 cm in diameter

• Discrete, encapsulaed, sometimes nodular

• Painless

Histological features

• Large cells – eosinophillic cytoplasm & distinct cell membrane and which tend to be arranged in narrow cord or rows

• Oncocytes – sheets/nest and cords – alveolar or organoid pattern

• Cellular atypia, nuclear hyperchromatism and pleomorphism

• Mitotic figures, closely packed, little supportive stroma

Oncocytoma composed of uniform cells with pink cytoplasm and centrally

placed nuclei.

Oncocytoma, electron micrograph. Oncocytes filled with mitochondria;

nuclei in lower left and right

Oncocytoma with clear cell change.

Treatment & prognosis

• Surgical excision.

• Malignant transformation is rare

MALIGNANT TUMORS OF SALIVARY GLAND

•Adenoid Cystic Carcinoma •Mucoepidermoid Carcinoma, •Acinic Cell Carcinoma •Adenocarcinomas.

Acinic Cell Carcinoma

• Acinar cell

• Serous cell adenoma

• It’s a malignant epithelium neoplasm in which neoplastic cell expresses acinar diffrentiation.

• Low grade malignant potential

• Cytologic diffrentiation toward serous acinar cells – cytoplasmic PAS positive, zymogen type secreting granules

• 3rd most common malignant salivary gland tumor after mucoepidermoid and adenocarcinoma – 17%

Clinical features

• Closely resemble pleomorphic adenoma in gross appearance

• Chiefly in parotid – 80%

• Acessaory intraoral gland – lips & buccal mucosa

• 4th – 5th decade, 44 yrs mean age

• F:M = 3:2


• Slowly growing & mobile

• Fixed mass of various duration

• Facial muscle weakness

• Bilateral synchronous tumors


• Thin capsule – varying degree of differentiation – Well diffrentiated – normal acinar cell

– Less diffrentiation – emryonic ducts & immature acinar cells

• Four growth pattern – solid, papillary-cystic, follicular, microcystic

• Abundant basophillic cytoplasm

• Round darkly stained ecentric nucleus.

• Intercalated duct like cells – smaller, vacuolated

cells containing darkly staining zymogen granules.

Acinic cell carcinoma

Histological features • Connective tissue – fibrovascular collagenous

tissue.

• Lymphoid elements – diagnostic feature

Treatment & prognosis

• Surgical excision – preservation of facial nerve must be conserved

• Radiation therapy not good

• Poor prognosis – pain/fixation, gross invasion & m/s features of desmoplasia, atypia or increased mitotic activity

Mucoepidermoid Carcinoma

• A malignant epithelial tumor that contains both epidermoid-type and mucus secreting cells in varying proportion

• Most common malignant tumor observed in major and minor salivary gland.

• Parotid gland is the most common site of occurrence

• Palate> buccal mucosa> tongue> & retromolar area - intraorally

Clinical features • Female predilecion

• 3rd- 5th decade of life, 47 average age

• Most common malignant salivary gland of children

• Substantial exposure to ionizing radiation - predisposing risk factors

• Arise from reserve cells in the interlobular and intralobular segments of the salivary duct system

Clinical features

• Low grade malignancy : pleomorphic adenoma like features

– Slowly enlarging, painless mass

– However sizes never exceeds 5cm in diameter

– Not completely encapsulated

– Contains cysts - viscid, mucoid material – closely resembe mucocele (intraorally)

Mucoepidermoid carcinoma of the palate.

Clinical features

• High grade malignancies

– Rapidly growing, pain

– Facial nerve paralysis

– Trismus, Drainage of ear, dysphagia, numbness of adjacent areas & ulceration (minor salivary gland)

– Infiltrate surrounding tissues

– Metastasize to regional lymph nodes

– Distant metastases to lung, bone, brain & sub-cutaneous tissues are also common


• Chiefly three types of cell – together forms cystic space or solid masses or cords – Mucous secreting cells

• Various shapes

• Abundant, pale, foamy cytoplasm – positive for mucin stain

– Epidermoid type - Sqamoid features • Polygonal shape

• Intercellular bridges

• Rarely keratinization

– Intermediate or basaloid cell – highly prolific • Larger than basal cells but smaller than squamous cell

• Progenitor of epidermoid and mucus secreting cells


• Epidermoid cell and mucus cell arranged in glandular pattern

• Cyst rupture – mucus - pool in connective tissue – i/m reaction

Grading • Low Grade

– Well formed glandular structure

– Prominent mucin filled cystic spaces

– Minimal cellular atypia

– High proportion of mucous cells

Low grade: cystic spaces and mucous tumor cells

Grading • Intermediate grade

– Solid area of all the three cell

– Cyst formation but lesser than low grade

– Intermediate cell predominate

Grading

• High grade

– Solid nests or cords

– Prominent nuclear pleomorphism

– Mitotic activity

– Cystic component is very less

– Glandular component rare, necrosis & perineural invasion may be present

High grade: few tumor ducts and

mucous cells

Variant of tumor • Sclerosing mucoepidermoid carcinoma

– Sclerosing morphlogic

• Intraosseous mucoepidermoid carcinoma • Found in jaw • Central mucoepidermoid carcinoma • Epithelial lining of odontogenic cysts • Assymptomatic, radiolucent lesion & histolgically low grade

malignancy • Man>max: 3times

Treatment

• Conservative excision – preservation of facial nerve – low & intermediate grade of parotid.

• Complete – submandibular gland

• Radical neck dissection – evidences of cervical node metastasis & T3 lesion

• Postoperative radiotherapy & Chemotherapy – may be used for high grade malignancy.

• Low grade lesion – 92 %, 5 yr cure rate

• Intermediate and high grade – 49 %, 5 year cure rate

Adenoid Cystic Carcinoma • Cylindroma

• Adenocystic carcinoma

• Adenocystic basal cell carcinoma

• Pseudoadenomatous basal cell carcinoma

• Basoid mixed tumor

• It is a slow growing but aggressive neoplasm with remarkable capacity to reoccur and profound tendency to invade perineural lymphatic spaces.

Clinical features

• 5th most common malignancy of salivary gland

– Mucoepidermoid> adenocrcinoma> acinic cell carcinoma> polymorphous low grade adenocarcinoma PLGA

• Parotid, submaxillary, intraoral – palate & tongue.

• 5th-6th decade,

• Femal predliction.

Clinical presentations • Early local pain

• Facial nerve paralysis

• Fixation of deeper structure and local invasion.

• Intraoral – surface ulceration

• Clinical resemblance to pleomorphic adenoma


• Composed of myoepithelial cell and ductal cells – varied arrangement

• Three growth pattern

– Cribriform pattern

• MOST COMMON

• basaloid epitheial cell nests

• multiple cylindrical cyst like pattern – swiss cheese or honey comb

• PAS positive mucoploysaccharide secretion

Cribriform pattern

nests with retraction spaces


• Tubular pattern

– Tubular structure – lined by sratitified cuboidal epithelium

• Solid pattern • Cuboidal cells – towards duct cyst formation

• HIGH GRADE LESION

• Recurrence rate – 100 %, compared to 50-80% of earlier

Adenoid cystic carcinoma, microinvasive pattern

prominent clear cell layer surrounding inner ductal cells

perineural invasion

solid pattern

Treatment and prognosis


• X-ray radiation, radiation alone is not recommended

• Cure rate is low

• Minor gland tumor is more deadly than major gland.

Adenocarcinoma

• Rare neoplasm of salivary gland but aggressive and are common to intraoral minor salivary gland.

Clinical features

• 4O YRS OF AGE

• M=F

• 50% in parotid, intraoral minor salivary gland are next more affected site

• Enlarging mass

• Only 25 % patient complains of pain and facial weakness

Hitological features

• Firm mass with irregular borders and infilteration into sorrounding tissues

• Solid tumor w/o any cystic space

• Wide range of growth pattern – difficult to classify - degree of cellular diffrentiation

• Grades I (well formed ductal structures),

• Grade II

• Grade III – solid growth pattern with few glandular structure

Treatment and prognosis

• Aggressive tumor – aggressive t/t

• Complete local excision

– May sacrifice facial nerve

– In minor gland – portion of maxilla/mandible to be resected

• Postoperative radiation therapy useful

• Lymph node metastasis may be found.

Non neoplastic Salivary Gland Diseases

Sialolithosis

• Calcified organic matter that forms within the secretory system of the major salivary glands

• Although etiology is not clear but factors that cause pooling of saliva within the duct are known to contribute to stone formation – Inflammation

– irregularities in the duct system

– local irritants

– anticholinergic medications

Sialolithosis

• nidus of salivary organic material becomes calcified and gradually forms a sialolith.

• promoted by chronic sialadenitis and partial obstruction not related to any systemic derangement in calcium and phosphorus metabolism.

Prevalence • Submandibular (83%), parotid (10%) or sublingual (7%),

due to following factors. • Anatomic factors

– length and irregular course of Wharton’s duct. – greater size and position of the orifice. – orifice is much smaller than duct lumen.

• Physiochemical factors – High mucin content of saliva. – Great degree of alkalinity with high percentage of organic

matter. – Greater concentration of calcium and phosphate salts

phosphatase enzyme. – Low content of carbon dioxide.

Clinical Features

• Can also form within the minor salivary glands, most often in the upper lip or buccal mucosa

• any age, but they are most common in young and middle-aged adults

Clinical Features

• most frequently cause episodic pain or swelling of the affected gland, especially at mealtime

• severity of the symptoms varies, depending on the

– degree of obstruction

– amount of resultant backpressure produced within the gland

Radiographic Features

• typically appear as radiopaque masses

• not all stones are visible on standard radiographs - degree of calcification

• Stones in the terminal portion of the submandibular duct - occlusal radiograph


Sialogram of the submandibular gland demonstrating an

uncalcified sialolithiasis in Wharton’s duct


• On panoramic or periapical radiographs, the calcifi cation may appear superimposed on the mandible and care must be exercised not to confuse it with an intrabony lesion

• Multiple parotid stones radiographically can mimic calcified parotid lymph nodes, such as might occur in tuberculosis.

• Sialography, ultrasound, and CT scanning may be helpful additional imaging studies for sialoliths

HISTOPATHOLOGIC FEATURES: Macroscopic

• hard masses that are round, oval, or cylindrical

• typically yellow, although they may be a white or yellow-brown color

• Submandibular stones tend to be larger than those of the parotid or minor glands

• Usually solitary, although occasionally two or more stones may be discovered at surgery

HISTOPATHOLOGIC FEATURES: Microscopic

• Calcified mass exhibits concentric laminations that may surround a nidus of amorphous debris

• Periductal inflammation is also evident

• Ductal obstruction frequently is associated with an acute or chronic sialadenitis of the feeding gland

TREATMENT

• Small sialoliths of the major glands sometimes can be treated conservatively by gentle massage of the gland in an effort to milk the stone toward the duct orifice.

• Sialagogues, moist heat, and increased fluid intake also may promote passage of the stone

• Larger sialoliths usually need to be removed surgically

• If significant inflammatory damage has occurred within the feeding gland, then the gland may need to be removed

TREATMENT

• Minor gland sialoliths are best treated by surgical removal, including the associated gland

• Shock wave lithotripsy (extracorporeal or intracorporeal)

• Salivary gland endoscopy and radiologically guided basket retrieval are newer techniques

• These minimally invasive techniques have low morbidity and may prevent the necessity of gland removal.

Xerostomia

• Subjective clinical condition of less than normal amount of saliva.

• Mainly caused by

– Radiation

– Certain drugs

– Local factors

– Developmental

– Systemic alternations

Etiology – Radiation induced

• Ionizing radiation to head and neck region for the treatment of cancer results in pronounced changes in the salivary glands

• Degree of damage - dose-time-volume factor. • Acinar cells damage - single 100 rads dose of X-rays • Radiation sensitivity : parotid gland > submandibular>sublingual to

minor glands. • Serous aciner cells appear to be more sensitive to radiation, than

the mucus cells. • As the dose is increased, disorganization and destruction of the

acinar cells occur, resulting in their replacement by fibrous or faulty tissues

• Both, the stimulated and unstimulated salivary flow rate decreases dramatically with increasing radiotherapy

Etiology - Pharmacologically

• There are about 500 drugs which can cause xerostomia – anticonvulsants, – antiemetics, – antihistaminics, – anti-hypertensives – antispasmodics.

• Mode of action is generally related to the para-sympathetic activity, usually an antimuscarine effect

• Other actions includes – vasoconstriction of salivary glands, – changes in fluid and electrolyte balance – changes in acinar or ductal function

Etiology - Systemic alternations

• Nutritional: certain deficiency states like pernicious anemia, iron deficiency anemia and deficiency of vitamin A and hormones

• Fluid loss: associated with hemorrhage, sweating, diarrhea, vomiting.

• Diabetes mellitus

• Sjögren syndrome

• Other disease – systemic diseases, which are accompanied by high

temperature and dehydration

– HIV infection, sarcoidosis, and graft versus host resistance

Etiology

• Local Factor: decreased mastication, smoking and mouth breathing

• Developmental

– developmental abnormalities of salivary glands,

– Tumors

– Autoimmune states

– certain diseases which affect afferent or efferent portions of neural transmission reflex

Clinical Features

• increased thirst, increased uptake of fluid especially while eating

• use of means like chewing gums and consumption of sour candy

• difficulty in swallowing, speech and eating dry food

• burning and tingling sensations

• frequent oral infections,

• intolerance to dental appliances

• abnormal taste in the mouth.

• Salivary gland enlargement

Clinical Features: Systemic impact

• Hypofunction of other secretory glands

• Blurred vision and ocular dryness.

• Itching, burning and sandy sensation in eye

• also dryness of pharynx and skin

• Itching and burning sensation of vagina.

Clinical signs

• Dryness of lining oral mucosa • Oral mucosa appears thin, pale and feels dry. • Tongue blade may adhere to soft tissues • Tongue may manifest deficiency by atrophy of the papillae,

inflammation, fissuring, cracking and denudation • Increased incidence of dental caries. • Candidiasis

– pseudo membranous and hyperplastic form – absence of normal cleansing and antimicrobial activity of the

saliva.

• Residual saliva: residual saliva which remains is foamy, thick and ropey

Management

• Treatment may be divided into five main categories

– preventive therapy,

– symptomatic (palliative) treatment,

– local or topical salivary stimulation,

– systemic salivary stimulation,

– therapy directed at an underlying systemic disorder

Management: Stimulation of salivary production

• Local stimulation—chewing of gums, mints, paraffin and citric acid containing lozenges and rinses

– Disadvantages of it are:

• Effects are short lived.

• Frequent application can be inconvenient.

• Citric acid may irritate oral mucosa

• Continuous use may contribute to demineralization.

Management: Stimulation of salivary production

• Systemic stimulation – Bromhexine: mucolytic and mucokinetic agent, capable of inducing

thin copious bronchial secretions. Dose: adults (8 mg TDS), children 1-5 years (4 mg BD) and children 5-10 years (4 mg TDS).

– Anethole trithione (ANTT): directly acting cholinergic agonist which acts by neurostimulation. Dose 1 to 2 tabs (25 mg) TDS.

– Pilocarpine • Cholinergic parasympathomimetic agent, • Increases the secretion by exocrine glands and can affect the sweat, salivary,

lacrimal, gastric, pancreatic, intestinal glands and mucosal cells of the respiratory tract

• Usual dose is 5 mg, TDS. • Produces short duration of (3 hours) • without the accompanying side effects. • should not be used in patients suffering from asthma

Management: Symptomatic treatment

• Salivary substitute – most commonly contain carboxymethylcellulose or hydroxyethylcellulose as lubricants and variety of artificial sweeteners, preservative and chloride or fluoride salts

• Disadvantages – regular use is inconvenient to the patient. – Most of them are more viscous than the natural saliva. – expensive. – fail to provide antimicrobial and other protective functions of

natural saliva.

• Oral hygiene: lactoperoxidase, lysozyme, and lactoferrin. • Discontinuous of drug—drug which is causing xerostomia

should be discontinued

Management: Symptomatic treatment

• Composition of artificial saliva

– Carboxymethylcellulose—10 gm/l.

– Sorbitol—30 gm/l.

– Potassium chloride—1.2 gm/l.

– Sodium chloride—0.843 gm/l.

– Magnesium chloride—0.051 gm/l.

– Calcium chloride—0.146 gm/l.

– Dipotassium hydrogen phosphate—0.342 gm/l

Management

• Sweet and tart food - help to produce more saliva

• Sucking of sugar free candy

• popsicles or chew sugar-free gum

• Sucking ice cubes—try sucking ice cubes or ice lollies.

• Avoid dry foods such as cookies, toast and crackers, or soften them with liquids before eating.

• Avoid chocolates, peanut butter and pastry

• Avoid over salty foods.

• Drink frequently

Sialosis • Also known as Sialadenosis

• Non-neoplastic non-inflammatory enlargement of the salivary gland.

• Etiopathogenesis – Systemic disease: cirrhosis, diabetes, ovarian and

thyroid insufficiency, alcoholism, general malnutrition, anorexia nervosa, and malnutrition.

– Neurogenic medication: antihypertensive drugs, psychotropic drugs and sympathomimetic drugs

– Mechanism: result in dysregulation of the autonomic innervations of the salivary acini causing an aberrant intercellular secretory cycle.

Clinical Features

• More commonly affects the females, no age predilection

• usually bilateral and may present a course of recurrent painless enlargement of gland

• Parotid gland is more frequently affected.

Diagnosis • Sialography: leafless tree

appearance, caused by compression of finer duct by hypertrophic aciner cells

• Laboratory diagnosis – characteristic alteration in the

chemical constituents of saliva

– Significant elevation of salivary potassium

– Concomitant decrease in salivary sodium is observed

Management

• Control of underlying cause: most important management for sialosis.

• Partial parotidectomy: can be performed if swelling becomes cosmetic concern.

SIALOADENITIS

• Inflammation of a salivary gland

• May be subdivided temporally into acute, chronic and recurrent forms.

• It may be either

– Allergic -

– Viral -

– Bacterial -

ACUTE SIALOADENITIS

• Predisposing factors – Sialolithiasis – decreased flow (dehydration, post-operative, drugs) – poor oral hygiene – exacerbation of low grade chronic sialoadenitis

• Clinical features – Painful swelling – Reddened skin – Edema of the cheek, Periorbital region and neck – low grade fever – Malaise – raised ESR, CRP, leucocytosis – purulent exudate from duct punctum

CHRONIC SIALOADENITIS

• Also known as Chronic sclerosing sialadenitis

• Clinical Features – Unilateral mild pain/swelling

– common after meals

– duct orifice is reddened and flow decreases

– may or may not have visible/palpable stone.

– Parotid gland: Recurrent painful swellings

– Submandibular gland: Usually secondary to sialolithiasis or stricture

TREATMENT

• Conservative therapies – Hydration, – Analgesics (mainly NSAIDs), – Sialogogues to stimulate salivary secretion – Regular, gentle gland massage

• If infection is present – Appropriate cultures should be obtained, – Followed by empirical antibiotic therapy initially, – Ex: amoxicillin/clavulanate or clindamycin which cover oral

flora.

• If there are attacks more than approximately 3 times per year or severe attacks, surgical excision of the affected gland should be considered

Miscelleneous Disease

Mikulicz’s disease

• Previously known as benign lymphoepithelial lesion

• Characterized by symmetric lacrimal, parotid, and submandibular gland enlargement with associated lymphocytic infiltrations.

• This had at one time been included within the diagnosis of primary Sjögren’s syndrome

• But the clinical and immunologic presentations: distinct autoimmune phenomenon

ETIOLOGY

• Unknown

• speculated that autoimmune, viral, or genetic factors are involved

• predominantly affects middle-aged women

• unilateral or bilateral salivary gland swelling due to lymphoid infiltration

• reduced salivary flow makes these patients susceptible to salivary gland infections

HISTOLOGY

• Associated with prominent infiltration of igG4-positive plasmacytes into involved exocrine glands

• Mikulicz’s disease may be a systemic disease rather than a localized lacrimal and salivary gland disorder

• It has been proposed that the entity be termed an igG4-related plasmacytic exocrinopathy

DIAGNOSIS

• Diagnosis is based on – Findings of salivary gland biopsy - monoclonal lymphocytic

infiltrate

– Absence of the alterations in peripheral blood

– Autoimmune serologies seen in Sjögren’s syndrome

• Differential diagnosis: Sjögren’s syndrome, lymphoma, sarcoidosis, viral infections, and other diseases

• Important to differentiate the benign lesions of mikulicz’s disease from an indolent mucosa-associated lymphoid tissue (MALT) lymphoma (arising spontaneously or in the context of Sjögren’s syndrome)

TREATMENT

• Highly responsive to corticosteroids, which are the preferred therapy

• Methylprednisolone pulse therapy and prednisolone

• important consideration is the possibility of neoplastic transformation

Sjogren’s syndrome

• Sicca syndrome

• Gougerot-sjorgen syndrome

• Triad

– Keratonjuctivitis sicca

– Xerostomia

– Rheumatoid arthritis

• Along with SLE, polyarthritis nodosa, polymyositis or scleroderma

Primary Sjorgen’s syndrome or SICCA complex

Secondary Sjorgen’s Syndrome

Etiology

• Genetic, Hormonal, Infections or immunological factors.

• Combination of either two or more

• But mainly autoimmune disorder – antisalivary duct antibody

• HLA associated

• CMV, PMV, EPV group of viruses – but not proven

Clinical features

• 0.5-1% of population

• Female >40 yrs, F:M = 10:1

• Children or young may be affected

• Dryness of mouth and eyes – hypofunction of salivary gland and lacrimal glands

• Painful, burning sensation of oral mucosa

• Nose, larynx, pharynx, tracheobronchial tree and vagina additionally involved

Clinical presentation • Oral mucosa

– Parchment like appearance – red, dry, tendered, smooth glazed

– Difficulty in wearing dentures

• Saliva – frothy • Angular cheilitis • Disturbances of taste senation • Recurrent candidiasis –

dorsum of tongue – red & atrophic mucosa – fissuring and labulations on surface (COBBLE-STONE)

• Acute bacterial sialadenitis


• Primary Sjorgen’s syndrome (SICCA complex)

– Parotid involvement is greater than secondary

– Lymphadeopathy twice as later

– Purpura

– Raynaud’s disease

– Kidney involvement

– myositis


• Three types of histological alteration

– Intense lymphocytic infilteration of gland – replacing acinar structure but lobular preserved

– Proliferation of ductal epithelium and myoepithelium – epimyoepithelial islands

– Atrophy of gland sequential to lymphatic infilteration.

Mikulicz’s disease/ lymphoepithelial lesion

minor salivary gland expression. Note lymphocytic focus adjacent to intact

acini

minor salivary gland expression. Note confluent lymphocytic foci without

evidence of scarring.

Laboratory findings

• Polyclonal hyperglobulinemia

• Cryoglobullin

• Mulitiple organ or organ specific antibody – antisalivary, rheumatoid factor and antinuclear antibodies

• Increased ESR

• Sialochemistry: IgA, potassium and sodium – elevated with sicca complex

Radiographic features • Sialography

– Punctate – Cavitary defect – filled

with radioopaque contrast media • ‘Cherry blossom’ or

‘branchless fruit laden tree’

– Contrast media extravasates through weakened salivary gland

– Poor elimination of contrast media – over a month

• MR imaging features of the parotid glands relative to conventional sialographic grades in xerostomia patients with or without Sjögren’s syndrome.

• A–E, Axial T1-weighted MR images of the parotid glands in patients whose conventional sialographs were categorized as grade 0 (A), grade 1 (B), grade 2 (C), grade 3 (D), or grade 4 (E). Note that fat areas in the glands increase with the grades.

• F–J, Axial fat-suppressed T2-weighted MR images of the parotid glands in patients (same patients as in A–E, respectively) whose conventional sialographs were categorized as grade 0 (F), grade 1 (G), grade 2 (H), grade 3 (I), or grade 4 (J). Note that intact lobule areas in the glands decrease with the grades.

Treatment • No satisfactory t/t • SYMPTOMATICALLY treated • Keratoconjuctivitis

– Occular lubricant – artificial tears like methyl cellulose

• Xerostomia – Salivary subsitute

• Extensive dental caries • Fluoridation and oral prophylaxis is indicated

• Surgery not indicated unless the disease is cause discomfort to p/t

• Radiotherapy – not recommended

Prognosis

• Pseudolymphoma & Malignant lymphoma – non Hodgkin type

• Bening lypmphoepithelial lesion, Mikulicz disease and Sjorgen’s syndrome – close association

RANULA

• It’s a large mucocele located on the floor of the mouth

• Either a mucous extravasation phenomenon or, when the inflammatory components disappear

• Most common cause -trauma

• Other causes include an obstructed salivary gland or a ductal aneurysm

CLINICAL FEATURES

• Most common in the 2nd decade of life and in females

• Term Ranula - lesion often resembles the swollen abdomen of a frog

• Painless, slow-growing, soft, and movable mass located in the floor of the mouth

CLINICAL FEATURES

• Usually, the lesion forms to one side of the lingual frenum

• however, if the lesion extends deep into the soft tissue, it can cross the midline

CLINICAL FEATURES

• Superficial ranulas can have a typical bluish hue

• Deeply seated lesion - normal mucosa

• Size of the lesions can vary

• Larger lesions can cause deviation of the tongue

CLINICAL FEATURES

CLINICAL FEATURES

• Plunging Ranula

– deep lesion that herniates through the mylohyoid muscle

– extends along the fascial planes

– may become large, extending into the neck

DIAGNOSIS • Radiography - rule out a sialolith as a cause of

duct obstruction

• Sialography: delineating the borders and full extent of the lesion

TREATMENT • Treatment of choice -

surgical intervention

• Marsupialization - unroofs the lesion is the initial treatment, especially for smaller lesions.

• Postsurgical complications – Recurrence

– sensory deficits of the tongue

– Damage to Wharton’s duct

TREATMENT

• Frequency of recurrence is related to the surgical technique selected – Marsupialization: 67%

– Ranula excision: 58%

– Sublingual gland excision: 1%

• Due to this reason excision of the lesion and the gland should be considered

• Intralesional injections of corticosteroids have been used successfully in the treatment of ranulas

MUCOCELE

• a clinical term that describes swelling caused by the accumulation of saliva at the site of a traumatized or obstructed minor salivary gland duct.

• classified as extravasation types and retention types

• Large form of mucocele located in the floor of the mouth is known as a ranula

MUCOCELE

• Extravasation Mucocele

– Laceration of the duct results in the pooling of saliva in the adjacent submucosal tissue and consequent swelling

– more common than the retention form.

– Although often termed a cyst, does not have an epithelial cyst wall or a distinct border

MUCOCELE

• Retention mucocele – caused by obstruction of a minor salivary

gland duct

– by calculus or possibly by the contraction of scar tissue around an injured minor salivary gland duct

– blockage of salivary flow causes the accumulation of saliva and dilation of the duct

– Eventually, an aneurysm-like lesion forms, which can be lined by the epithelium of the dilated duct

Clinical Features

• Extravasation mucoceles – most frequently occur on the lower lip, where trauma

is common – buccal mucosa, tongue, floor of the mouth, and

retromolar region are other commonly traumatized areas

• Mucous retention cysts: commonly located on the palate or the floor of the mouth.

• A common clinical sequence is a history of a traumatic event, followed by the development of the lesion.

Clinical Features

Clinical Features

• Mucoceles often present as discrete, painless, smooth-surfaced swellings

• can range from a few millimeters to a few centimeters in diameter.

• Superficial lesions frequently have a characteristic blue hue

• Deeper lesions can be more diffuse, covered by normal-appearing mucosa without the distinctive blue color.

Clinical Features

• lesions vary in size over time; superficial mucoceles are frequently traumatized, allowing them to drain and deflate.

• In these circumstances, the mucocele will recur .

• Although the development of a bluish lesion after trauma is highly suggestive of a mucocele, other lesions (including salivary gland neoplasms, soft tissue neoplasms, vascular malformation, and vesiculobullous diseases) should be considered

TREATMENT

• Surgical excision is the primary treatment, particularly to prevent recurrence

TREATMENT

• Aspiration of the fluid from the mucocele will not provide long-term benefit

• Surgical management is challenging

– cause trauma to other adjacent minor salivary glands

– lead to the development of a new mucocele

• Intralesional injections of corticosteroids have been used successfully to treat mucoceles.

Refrences

• Shafers, Oral Pathology 6th edition

• Regezi: Oral Pathology: Clinical Pathologic Correlations, 5th ed

• Essential of Oral Pathology and medicine 7th ed : Cawsons & odell

• Color atlas of Oral Pathology: Nevile

• Pathology of the Head and Neck: Antonio Cardesa, Pieter J. Slootweg

• Essential of Oral Pathology : Swapan Kumar Purkait

disease of salivary gland

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