Salivary Gland Diseases Notes

Salivary Gland Diseases

Embryology

• Parotid glands are the first to develop, followed by submandibular, then sublingual glands.

• Development starts at day 35 via invagination of oral epithelium.

• Epithelial buds enlarge, elongate, and branch, forming solid structures initially.

• Branching creates arborization.

• Stroma (capsule and septae) originates from mesenchyme (mesodermal or neural crest origin, like pleomorphic adenoma).

Acinar Cells

• Secretory cells (acini) develop around the ductal system around the 7th-8th month in utero.

• Classified as:

  • Serous cells: produce thin, watery secretion.

  • Mucous cells: produce viscous secretion.

Salivary Gland Secretory Unit

• Composed of:

  • Terminal acini

  • Intercalated, striated, and excretory ducts

  • Myoepithelial cells

Functions of Saliva

• Mechanical cleansing of food and bacteria

• Lubrication of oral surfaces

• Protection of teeth and oro-pharyngo-esophageal mucosa

• Oral acid neutralization and dilution of detritus

• Antimicrobial activity

• Dissolution of taste compounds

• Facilitation of speech, mastication, and swallowing

• Formation of food bolus conducive for swallowing

• Initial digestion of starches and lipids

• Esophageal clearance and gastric acid buffering

Salivary Gland Physiology - Innervation

• Superior salivatory nucleus for facial nerve (CN VII).

• Inferior salivatory nucleus for glossopharyngeal nerve (CN IX).

Superior Salivatory Nucleus, Facial Nerve

• Postsynaptic fibers innervate all salivary glands except the parotid and also innervate the lacrimal gland.

• Excitation causes secretion release; action is selective (e.g., lemon juice stimulates salivation but not tearing).

• Sphenopalatine ganglion: postganglionic fibers innervate the lacrimal gland and glands of the nasal epithelium. Facial nerve excitation links crying to a runny nose.

• Submandibular ganglion: excites secretion of the sublingual and submandibular salivary glands.

Inferior Salivatory Nucleus, Glossopharyngeal Nerve

• Preganglionic parasympathetic fibers (from CN IX) arrive at the otic ganglion via the lesser petrosal nerve.

• Postganglionic parasympathetic fibers leave the otic ganglion and distribute to the parotid gland via the auriculotemporal nerve.

• Frey’s Syndrome is associated with this pathway.

Neuroreceptors in Salivary Glands

• Alpha (α) receptors:

  • Alpha 1: Acts via phospholipase C activation, forming Inositol triphosphate, increasing intracellular calcium.

• Beta (β) Receptors: Activate adenylate cyclase, raising intracellular cAMP concentration and increasing protein secretion.

• Muscarinic Cholinergic receptors: Primarily responsible for fluid and protein salivary secretion; widely distributed in the central and autonomic nervous system.

Regulation of Fluid Secretion

• Calcium-mobilizing and cAMP-generating signaling pathways linked to salivation.

• Increase in intracellular $[Ca^{2+}]$ is the primary fluid secretion signal in salivary acinar cells.

• cAMP signals regulate secretory granule discharge but produce little fluid alone.

• Multiple receptor types linked to $Ca^{2+}$ mobilization (muscarinic, α-adrenergic, substance P) are expressed on acinar cells.

Aquaporin 5

• Molecule found in the human submandibular gland.

• Molecular function: water channel activity.

• Molecular Weight (MW): $28294 Da$

Salivary Gland Physiology - Control & Production

• Physiologic control is mainly by the autonomic nervous system; parasympathetic effects predominate.

• Interruption of parasympathetic innervation causes glandular atrophy.

• Normal saliva is 99.5% water.

• Normal daily production is 1-1.5L.

Anatomy: Parotid Gland

• CN VII branches divide the parotid gland into superficial and deep lobes while coursing anteriorly from the stylomastoid foramen to the muscles of facial expression.

Anatomy: Deep Lobe

• Approximately 20% of the parotid extends medially through the stylomandibular tunnel. The tunnel is formed:

  • Ventrally by the posterior edge of the ramus.

  • Dorsally by the anterior border of the sternocleidomastoid (SCM) & posterior digastric muscle.

  • Deeply and dorsally by the stylomandibular ligament.

Parotid Duct (Stensen’s Duct)

• Small ducts coalesce at the anterosuperior aspect of the parotid gland.

• Runs anteriorly superficial to the masseter muscle.

• Follows a line from the EAM to a point just above the commissure.

  • Diameter: 1-3 mm.

  • Length: 6 cm.

• At the anterior edge of the masseter muscle, it turns sharply medial, passes through the buccinator muscle, buccal mucosa, and into the oral cavity opposite the maxillary second molar.

Great Auricular Nerve (C2, C3)

• Emerges from the posterior border of the SCM at Erb’s point.

  • Crosses the mid-portion of the SCM about 6.5 cm beneath the EAM.

• Passes parallel and superior to the external jugular vein to supply the ear and pre-auricular region.

Parotid Anatomy: Vessels

• Retromandibular Vein: Located within the substance of the gland.

• External carotid artery: Divides into the superficial temporal and internal maxillary artery at the inferior level of the gland.

Anatomy: Submandibular Gland

• Located in the submandibular triangle of the neck, inferior & lateral to the mylohyoid muscle.

• The posterior-superior portion curves around the posterior border of the mylohyoid and gives rise to Wharton’s duct.

Anatomy: Submandibular Duct (Wharton’s Duct)

• Passes forward along the superior surface of the mylohyoid adjacent to the lingual nerve.

• The nerve winds around the duct, first being lateral, then inferior, and finally medial.

  • Diameter: 2-4 mm; length: ~5 cm.

• Opens into the floor of the mouth through a punctum.

• The punctum is a constricted portion of the duct to limit retrograde flow of bacteria-laden oral fluids.

• Low flow correlates with retrograde infection (Katz et al. IJOMS).

Anatomy: Sublingual Glands

• Lie on the superior surface of the mylohyoid muscle and are separated from the oral cavity by a thin layer of mucosa.

• Ducts of the sublingual glands are called Bartholin’s ducts.

• Bartholin’s ducts usually consist of 8-20 smaller ducts of Rivinus (short and small in diameter).

• Ducts of Rivinus open:

  • Individually into the floor of the mouth (FOM) near the punctum of Wharton’s duct.

  • On a crest of sublingual mucosa called the plica sublingualis.

  • Directly into Wharton’s duct.

Minor Salivary Glands

• 600-1000 in the oral cavity.

• Simple ductal system.

• Frequently involved in pathology.

Obstructive Salivary Gland Disorders

• Sialolithiasis

• Mucous retention/extravasation

Obstructive SG Disorders: Sialolithiasis

• Results in a mechanical obstruction of the salivary duct.

• Major cause of unilateral diffuse parotid or submandibular gland swelling.

• Most frequent reason for submandibular gland resection.

Sialolithiasis - Details

• Pathogenesis remains unknown.

• Thought to form via an initial organic nidus that grows by deposition of inorganic and organic substances.

• May obstruct saliva flow from the gland to the oral cavity.

• Acute ductal obstruction may occur at mealtime, causing sudden, painful swelling.

• Swelling may gradually reduce, but recurs when flow is stimulated.

• Process can continue until complete obstruction and/or infection occurs.

Etiology of Sialolithiasis

• Water hardness: possibly increases likelihood.

• Hypercalcemia: only in rats.

• Xerostomic medications.

• Tobacco smoking: positive correlation.

• Gout: the only systemic disease known to cause salivary calculi (composed of uric acid).

Stone Composition

• Organic (often predominate in the center):

  • Glycoproteins

  • Mucopolysaccharides

  • Bacteria

  • Cellular debris

• Inorganic (often in the periphery):

  • Calcium carbonates & calcium phosphates in the form of hydroxyapatite

Parotid (PG) vs. Submandibular Gland (SMG) Sialoliths

• Mucous plugs and sialoliths are most common in the SMG because:

  • Saliva is slightly more alkaline.

  • Higher concentration of calcium and phosphate in the saliva.

  • Higher mucus content.

  • Anti-gravity flow.

• 80-90% of SMG calculi are radio-opaque. 50-80% of parotid calculi are radiolucent.

• 30% of SMG stones are multiple; 60% of Parotid stones are multiple.

Clinical Presentation of Sialolithiasis

• Painful swelling (60%)

• Painless swelling (30%)

• Pain only (10%): Described as recurrent salivary colic and spasmodic pains upon eating.

Clinical History - Questions to ask

• History of swellings/change over time

• Trismus

• Pain

• Variation with meals

• Dry mouth? Dry eyes?

• Current medications

• Radiation history

• Bilateral involvement?

• Recent exposure to sick contacts (mumps)

Exam: Inspection

• Asymmetry (glands, face, neck)

• Diffuse or focal enlargement

• Erythema extra-orally

• Trismus

• Examine external auditory canal (EAC)

• Cranial nerve testing

Exam: Palpation

• Palpate for cervical lymphadenopathy.

• Bimanual palpation of floor of mouth in a posterior to anterior direction:

  • Patient closes mouth slightly and relaxes oral musculature to aid detection.

  • Examine for duct purulence.

• Bimanual palpation of the gland (firm or spongy/elastic).

Diagnostics: Plain Occlusal Film

• Effective for intraductal stones.

• Intraglandular, radiolucent or small stones may be missed.

Diagnostic Approaches

• CT Scan: For large stones or small slices, also used for inflammatory disorders

• Ultrasound: Operator-dependent, can detect small stones (>2mm), inexpensive, non-invasive

Diagnostic Approaches: Sialography

• Opacification of ducts via retrograde injection of water-soluble dye.

• Provides image of stones and duct morphology.

• May be therapeutic, but success is not well-documented.

• Disadvantages:

  • Irradiation dose

  • Pain with procedure

  • Possible perforation

  • Infection dye reaction

  • Push stone further

  • Contraindicated in active infection.

Diagnostic Approach: Radionuclide Studies

• Useful to image the parenchyma.

• $^{99m}TcO_4$ (Technetium-99m pertechnetate) is an artificial radioactive element (atomic #43, atomic weight 99) used as a tracer in imaging studies. It decays and emits a gamma ray. Half-life of 6 hours.

• Helman et al. found Technetium-99 shares the ${Na^+K^+Cl^-}$ transport system on the basement membrane of the parotid acinar cells (JCI 1987).

Diagnostic Approach: MR Sialography

• T2 weighted fast spin echo slides in sagittal and axial planes. Volumetric reconstruction allows visualization of ducts.

• Advantages: No dye, no irradiation, no pain.

• Disadvantages: Cost, possible artifact.

Diagnostic approach: Diagnostic Sialendoscopy

• Allows complete exploration of the ductal system, direct visualization of duct pathology.

• Success rate of >95%.

• Disadvantage: Technically challenging, trauma could result in stenosis, perforation.

Sialolithiasis Treatment

• Non-invasive: Antibiotics, anti-inflammatories, hydration, saliva stimulation, hoping for spontaneous stone passage.

• Stone excision:

  • Lithotripsy

  • Interventional sialendoscopy

  • Simple removal (20% recurrence)

• Gland excision

Sialolithiasis Treatment - Deferral Considerations

• If patients defer treatment, they should know:

  • Stones will likely enlarge over time.

  • Seek treatment early if infection develops.

  • Salivary gland massage and hyper-hydration when symptoms develop.

Obstructive Salivary Gland Disorders: Mucocele

• Mucoceles, exclusive of the irritation fibroma, are most common of the benign soft tissue masses in the oral cavity.

• "Muco: mucus, coele: cavity".

• In the oral floor, they are called ranula.

• Consist of a circumscribed cavity in the connective tissue and submucosa, producing an obvious elevation in the mucosa.

• Most result from extravasation of fluid into surrounding tissue after traumatic break in the continuity of their ducts.

• Lacks a true epithelial lining.

Treatment of Mucoceles

• Excision with strict removal of any projecting peripheral salivary glands.

• Avoid injury to other glands during primary wound closure.

Ranula

• Term used for mucoceles that occur in the floor of the mouth.

• Name derived from the word rana, because the swelling may resemble the translucent underbelly of the frog.

• Source is usually the sublingual gland, but may also arise from the submandibular duct or minor salivary glands in the floor of the mouth.

Plunging or Cervical Ranula

• Occurs when spilled mucin dissects through the mylohyoid muscle and produces swelling in the neck.

• Concomitant FOM swelling may or may not be visible.

Ranula Treatment

• Marsupialization has fallen into disfavor due to the excessive recurrence rate of 60-90%.

• Sublingual gland removal via intraoral approach is the treatment of choice.

Diseases of the Salivary Glands: Viral - Mumps

• Etiology: Contagious systemic myxovirus. Incubation period of 14 to 21 days.

• Signs and symptoms:

  • Prodrome of fever, malaise, and headache may occur.

  • Painful swelling of one or both parotid glands with erythema of Stenson's duct orifice. Ingestion of sour liquids increases pain.

• Complications may occur due to involvement of other organs

  • Sensorineural deafness

  • Encephalitis

  • Orchitis or oophoritis can lead to sterility

  • Pancreatitis

• Treatment is supportive and symptomatic. No specific treatment currently available.

• Prevention by mumps vaccine

• Diagnostic Evaluation

  • Leukocytopenia, with relative lymphocytosis

  • Increased serum amylase (normal by 2-3 week of disease)

  • Viral serology essential to confirm: Complement fixing antibodies appear following exposure to the virus

Diseases of the Salivary Glands: Acute Bacterial Infection

• Etiology:

  • Stasis - secondary to obstruction, decreased flow or dehydration

  • Staphylococcus aureus is the most common pathogen in the parotid. Staph aureus and oral flora are seen in submandibular gland.

• Signs and Symptoms:

  • pain, tenderness and swelling with increased pain on eating.

  • Orifice of duct is red and swollen, and massage of the gland may express pus.

• Treatment:

  • Antibiotics (Ampicillin for SG and A+Sulbactam for PG)

  • Warm compresses

  • Promote drainage by

    • Massage

    • Sialogogues

    • Dilatation of duct

  • If condition unresponsive or progressive after above, surgical drainage is indicated.

  • In the parotid gland, care must be taken to avoid the facial nerve. A parotidectomy incision is made and skin over the gland is elevated. The gland is drained bluntly by inserting a clamp and spreading in the direction of the nerve.

  • In draining the submandibular gland, the marginal mandibular nerve must be avoided.

Diseases of the Salivary Glands: Chronic or Recurrent Infections

• Etiology:

  • Usually related to scarring and inflammation of the duct and/or parenchyma from prior infections

  • May also be due to stones

• Signs and Symptoms: as in acute infection

• Treatment:

  • Conservative treatment as for acute infection

  • In refractory disease, surgical excision is indicated

Salivary Glands Hypertrophy

• Degenerative Diseases

  • Fatty Infiltration (obesity)

  • Hypertrophy (fatty degeneration)

• Alcoholism

• Diabetes

• Metabolic diseases

Dry Mouth

• Both stimulated and unstimulated salivary flow rates decrease with an increasing number of medications taken.

• The most common cause of drug-induced xerostomia is the altering of neural pathways that stimulate salivary gland secretion.

• These are drugs that have either an anticholinergic or sympathomimetic effect.

• Stimulation of the parasympathetic nerves (cholinergic action) produces an increase in fluid volume (serous saliva).

• Stimulation by the sympathetic nerves (sympathomimetic action) produces less volume and viscous saliva.

• Drugs that have an anticholinergic action reduce the volume of serous saliva, including:

  • antihypertensives

  • antihistamines

  • antidepressants

  • antipsychotics

  • antiemetics

  • antispasmotics

  • anti-parkinsonian drugs.

• Drugs with sympathomimetic actions produce a more viscous, mucinous saliva with less volume, such as:

  • decongestants

  • bronchodilators

  • appetite suppressants

  • amphetamines.

Xerostomia

*Sjögren's syndrome is an autoimmune disease in which the body's immune system mistakenly attacks its own moisture-producing glands (salivary and lacrimal).
*Sjögren's is one of the most prevalent autoimmune disorders, striking as many as 4,000,000 Americans. Nine out of ten patients are women. The average age of onset is late 40s although Sjögren's occurs in all age groups in both women and men.

Sjögren's Syndrome - Details

• SS may affect only the eyes or mouth (primary SS, sicca complex, sicca syndrome), or generalized collagen vascular disease (secondary SS) may be present.

• Arthritis occurs in about 33% of patients and is similar in distribution to that in RA; however, joint symptoms in primary SS tend to be milder and rarely lead to destruction. Some patients with undiagnosed SS who have rheumatic symptoms may not complain of sicca complex; SS is then diagnosed by laboratory evaluation.

• Salivary and lacrimal glands become infiltrated with CD4+ T cells and with some B cells. The T cells produce inflammatory cytokines (eg, interleukin-2, -interferon). Salivary gland duct cells also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva (keratoconjunctivitis sicca). This most often produces a scratchy or irritated sensation. In advanced cases, the cornea is severely damaged, epithelial strands hang from the corneal surface (keratitis filiformis), and vision can be impaired

• One third of SS patients develop enlarged parotid glands that are usually firm, smooth, of fluctuating size, and mildly tender. Chronic salivary gland enlargement is rarely painful. Lymphocytic infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and eventual formation of compact cellular structures termed epimyoepithelial islands. When salivary glands atrophy, saliva diminishes, resulting in extreme dryness of the mouth and lips (xerostomia) that inhibits chewing and swallowing and promotes tooth decay and formation of calculi in the salivary ducts. Taste and smell may be diminished.

Sjögren's Syndrome - Details

• IV. Autoimmune Diseases - Sjogren's Syndrome

  • Etiology - collagen vascular disease

  • Signs and Symptoms -keratoconjunctivitis sicca, xerostomia, and a connective tissue disorder, such as rheumatoid arthritis. Enlargement of salivary and lacrimal glands, often with recurrent sialoadenitis

  • Diagnosis - biopsy of salivary glands, usually the lower lip, shows lymphoreticular hyperplasia

• Biopsy of SG mainly used to aid in the diagnosis

  • Single 1.5 to 2cm horizontal incision labial mucosa.

  • Not in midline, fewer glands there.

  • Include 5+ glands for identification

  • Glands assessed semi-quantitatively to determine the number of foci of lymphocytes 4/mm2/gland
    *Sialochemistry
    *Technetium salivary scan
    *Treatment
    *Treat recurrent infection
    *May develop a superimposed malignancy. Therefore, if a mass appears, surgical excision is needed.

Therapy: Salivary Stimulation & Replacement Therapies

• Salivary stimulation can be achieved mechanically by chewing sugarless gum and by chemical (gustatory) stimulation by sucking on sugarless candies or products that contain citric acid, such as vitamin C tablets, lemon drops, or lozenges. Caution must be used with citric acid due to its acidity. Sonic toothbrushing may also increase salivary flow in patients with SS.

• Artificial salivary substitutes can be recommended. They do provide short-term relief, however, compliance may be poor. Most products in this category contain sodium carboxymethylcellulose, which mimics the viscosity of natural saliva. Water-based moisturizing gels can be used intraorally as a saliva substitute and extraorally on the lips to provide 8 hours of relief from xerostomia symptoms.

Therapy: Prescription Drugs

• Two prescription drugs have been approved by the Food and Drug Administration for the treatment of xerostomia: pilocarpine and cevimeline. These drugs are cholinergic agonists that produce parasympathetic stimulation of the exocrine glands to increase serous secretions. Pilocarpine is approved for use in both head and neck radiation therapy patients and patients with SS; cevimeline is approved for SS. Because these are systemic medications, they turn on secretions from all exocrine glands-an advantage for relieving multiple symptoms of SS. However, patients may experience adverse events related to their cholinergic effects, most notably excessive sweating.

Therapy - Pilocarpine Cautions

• These drugs must be used with caution in patients with cardiovascular disease, chronic respiratory conditions, and kidney disease. Use of these medications is contraindicated in patients with narrow-angle glaucoma, uncontrolled asthma and liver disease. These are common disorders among the elderly who frequently present with xerostomia. Several clinical trials have demonstrated their efficacy in relieving xerostomia symptoms and increasing salivary flow in radiation therapy and SS patients.

Radiation Injury

• Low dose radiation (1000cGy) to a salivary gland causes an acute tender and painful swelling within 24hrs.

• Serous cells are especially sensitive and exhibit marked degranulation and disruption.

• Continued irradiation leads to complete destruction of the serous acini and subsequent atrophy of the gland7.

• Similar to the thyroid, salivary neoplasm are increased in incidence after radiation exposure.

Tissue Engineering of Functional Salivary Gland Tissue

• Primary human salivary gland cells were grown, expanded, and seeded on biodegradable polymer scaffolds. A total of 48 scaffolds with cells and 16 control polymers without cells were implanted subcutaneously in athymic mice. The implants were retrieved 2, 4, and 8 weeks after the implantation for phenotypic and functional analyses.

*Human salivary gland epithelial cells retained their phenotypic and functional characteristics at all culture stages. Histologically, formation of acinar gland-like structures was observed within the engineered tissue by 4 weeks after implantation. Immunocytochemical and Western blot analyses of the implanted tissues demonstrated the expression of human a-amylase, cytokeratins AE1/AE3, and aquaporin-5 using cell-specific antibodies. Reverse-transcription polymerase chain reaction analyses confirmed the expression of human salivary type of [alpha]-amylase ([sigma]-amylase) mRNA. The retrieved tissues demonstrated the production of human [alpha]-amylase over time using a biochemical amylase detection system.

Other therapies

• Surgical transposition of the gland to protect them from radiation

• Radioprotective drugs

• New therapies in the management of autoimmune exocrinopathies

• Excess salivary secretion, sialoceles, salivary fistulas, Frey Syndrome

• Blocking secretion of exocrine glands in the head-neck area by administration of botulinum toxin A

Granulomatous Disease

• Primary Tuberculosis of the salivary glands:

  • Uncommon, usually unilateral, parotid most common affected

  • Believed to arise from spread of a focus of infection in tonsils

• Secondary TB may also involve the salivary glands but tends to involve the SMG and is associated with active pulmonary TB.

• Sarcoidosis: a systemic disease characterized by noncaseating granulomas in multiple organ systems

• Clinically, SG involvement in 6% cases

• Heerfordts’s disease is a particular form of sarcoid characterized by uveitis, parotid enlargement and facial paralysis. Usually seen in 20-30’s. Facial paralysis transient

• Cat Scratch Disease

  • Does not involve the salivary glands directly, but involves the periparotid and submandibular triangle lymph nodes

  • May involve SG by contiguous spread.

• Bacteria is Bartonella Henselae(G-R)

• Also, toxoplasmosis and actinomycosis.

Cysts

• True cysts of the parotid account for 2-5% of all parotid lesions

• May be acquired or congenital

• Type 1 Branchial arch cysts are a duplication anomaly of the membranous external auditory canal (EAC)

• Type 2 cysts are a duplication anomaly of the membranous and cartilaginous EAC

Cysts Details

• Acquired cysts include:

  • Mucus extravasation vs. retention

  • Traumatic

  • Benign epithelial lesions

  • Association with tumors

    • Pleomorphic adenoma

    • Adenoid Cystic Carcinoma

    • Mucoepidermoid Carcinoma

    • Warthin’s Tumor

Other: Pneumoparotitis

• In the absence of gas-producing bacterial parotitis, gas in the parotid duct or gland is assumed to be due to the reflux of pressurized air from the mouth into Stensen’s duct.

• May occur with episodes of increased intrabuccal pressure - Glass blowers, trumpet players

• Aka: pneumosialadenitis, wind parotitis, pneumatocele glandulae parotis

Pneumoparotitis - Details

• Crepitation, on palpation of the gland

• Swelling may resolve in minutes to hours, in some cases, days.

• US and CT show air in the duct and gland

• Consider antibiotics to prevent superimposed infection

Other: Necrotizing Sialometaplasia

• Cryptogenic origin, possibly a reaction to ischemia or injury

• Manifests as mucosal ulceration, most commonly found on hard palate.

• May have prodrome of swelling or feeling of “fullness” in some.

• Pain is not a common complaint

• Self limiting lesion, heals by secondary intention over 6-8 weeks

• Histologically may be mistaken for SCC

Differential Diagnosis of Gland Enlargement

• Sialolithiasis

• Sialadenitis

• Lymphoma – Salivary Tumors

• Cat-scratch disease

• Sjogren’s syndrome

• Wegener’s granulomatosis

• Viral infection

Benign Tumors

• Pleomorphic Adenoma

• Warthin's Tumor (Papillary Cystadenoma Lymphomatosum)

• Oncocytoma

• Monomorphic Adenoma

Malignant Tumors

• Mucoepidermoid Carcinoma

• Adenoid Cystic Carcinoma

• Acinic Cell Carcinoma

• Squamous Cell Carcinoma

• Carcinoma ex-Pleomorphic Adenoma

• Clear Cell Carcinoma

• Polymorphous Adenocarcinoma

• Mammary Analog Secretory Carcinoma