Salivary Gland Pathology

Chapter 11

NON-NEOPLASTIC DISEASES
Mucocele
- Most common salivary gland lesion
- Rapid onset, fluctuates in size, appear dome-shaped with bluish hue
- Results from damage to minor salivary gland duct
– Mucus escapes from duct
– Mucus pools in connective tissue
- Not a true cyst (i.e., not lined by epithelium)
- Clinical features
– Fluctuant, fluid-filled, bluish, compressible dome-shaped swelling
– Fluctuates in size (pt may report history of rupture and drainage).
– Most common location is lower lip
- Microscopic features
– Spilled mucin surrounded by granulation tissue, foamy histiocytes, inflammatory cells
- Treatment and prognosis
– Many are self-healing
– Local surgical excision (must include the adjacent salivary tissue to prevent recurrence)
– Excellent prognosis

Ranula
- “Frog belly”
- A less common variant of mucocele
- Found in the floor of the mouth (FOM)
- Main source is sublingual gland (constant mucous secretion), also from submandibular gland
- Clinical features
– Blue, dome-shaped mass of the FOM
– May elevate tongue
– Usually lateral to the midline (how to differentiate from dermoid cyst)
– Plunging ranula
• Dissects through mylohyoid muscle
• Produces swelling in neck without intraoral findings
- Treatment and prognosis
– Removal of lesion and offending gland; may try marsupialization.
– Prognosis good, but likely to recur if gland is not removed
Salivary duct cyst
- Epithelium-lined cavity “true cyst”
- Cause: Possibly dilation of duct from obstruction. Some might be true developmental cysts separate from
normal ducts.
- Parotid gland is most common location
- Clinical features
– Usually in adults
– Intraoral lesions most common in FOM, buccal mucosa, or lips
– Bluish, dome-shaped
– Clinically resembles a mucocele
- Microscopic features
– Lined by ductal epithelium: cuboidal, columnar, or squamous
– May be papillary and oncocytic (large, pink cells)
- Treatment (intraoral lesions): Conservative excision.

Sialolithiasis (Salivary Stones)

- Sialolith--calcified deposit in salivary gland or duct
- Possibly caused by deposition of calcium salts around debris in the duct lumen
- Decreased salivary flow or increased viscosity (as from infection, xerostomia) can lead to sialolith
- May or may not cause duct obstruction
- Clinical features
– Most common with submandibular gland (Wharton’s duct: has a more twisted pathway)
– More common with mucus secreting glands
– Can also form within minor salivary glands (generally asymptomatic)
– Episodic pain and swelling of gland, especially at mealtime (salivation)
– Hard, palpable mass may be evident
- Radiographic appearance
– Usually radiopaque if visible
– May be superimposed on mandible
– May also be seen by sialography, CT, sonogram
- Treatment and prognosis
– Some can be removed by gentle massage
– Sialogogues (e.g., pilocarpine) to increase flow
– Increased fluid intake
– Surgical removal
– May need to remove gland
– Shock wave lithotripsy
– Good prognosis
Sialadenitis
- Inflammation of salivary glands
- Non-infectious causes:
– Blockage of duct (congenital stricture, compression by adjacent tumor, sialolithiasis)
– Decreased salivary flow (dehydration, medications)
-- Sjogren syndrome, sarcoidosis, radiation tx, allergens
- Infectious causes:
– Viral - mumps
– Bacterial--Via retrograde spread
• Acute bacterial sialadenitis
– Most common in parotid gland
– Often bilateral
– Swollen, painful glands; low-grade fever
– Edematous tissue, trismus, purulent discharge from ducts
• Chronic bacterial sialadenitis
– Caused by recurrent or persistent ductal obstruction
– Get periodic swelling and pain, usually at mealtime
– May get fibrosis of the gland
• Subacute necrotizing sialadenitis
– Most commonly in teenagers and young adults
– Minor salivary glands, hard or soft palate
– Painful nodule/swelling, but does not ulcerate
– Perhaps infectious or allergic
– Self-limiting; resolves within 2 weeks

Necrotizing sialometaplasia
- Caused by ischemic necrosis of minor salivary glands
- Predisposing factors: trauma, dental injections, ill-fitting dentures, etc.
- 75% of cases occur on palate; 2/3 are unilateral
- Starts as a tender swelling; necrosis and sloughing of tissue within 2-3 weeks, leaving a crater-like ulceration
(“part of my palate fell out”). Compare to cancer, which has a raised, rolled border.
- It mimics a malignant process, so unless bilateral and symmetrical, biopsy may be needed to rule out cancer.
- Otherwise, no treatment. Resolves within 5-6 weeks.
Xerostomia
- Subjective dry mouth
- Usually associated with salivary gland hypofunction
- Reported in 25% of older adults, most cases probably medication-induced
- Causes:
- Developmental: salivary gland aplasia
- Systemic diseases: Sjogren syndrome, diabetes, sarcoidosis
- Medications: diuretics, antihistamines, decongestants, antidepressants
- Clinical features
– Reduction in salivary secretions
– Residual saliva is foamy or thick and “ropey”
– Mucosa appears dry
– Complains of difficulty chewing and swallowing
– Increased prevalence of candidiasis
– Increased dental decay, especially cervical/root decay
– May see fissured tongue
- Treatment and prognosis
– Artificial salivas (Salivart®), sipping water
– Biotene® toothpastes/mouth rinses
– Have physician alter medications
– Pilocarpine (Salagen®) 5-10 mg tab, tid or qid
• Side effects: Sweating, increased heart rate, increased BP, hypersalivation (Note: Use with caution with
certain heart medications)
• Can also try 4 gtt (drops) ophthalmic solution on sugarless gum, tid. The tablets cost 10x the solution.
– Fluoride rinses, frequent dental visits
Sjögren syndrome
• Chronic, systemic autoimmune disease of exocrine glands
• Cause unknown
• Not hereditary, but there is a genetic influence
– Increased frequency in relatives
– Greater frequency with certain HLA types
• Patients form antibodies to salivary and lacrimal glands and other exocrine glands
• Results in xerostomia and xerophthalmia
• Primary Sjögren syndrome (sicca “dry” syndrome): xerostomia + xerophthalmia
• Secondary Sjögren syndrome: xerostomia + xerophthalmia + a connective tissue disease (rheumatoid
arthritis, lupus “SLE”)
• Clinical features
– Female predominance (10:1), middle age adults
– Xerostomia
– Diffuse, benign enlargement of major salivary gland (with increased risk for bacterial sialadenitis).
– Xerophthalmia: Keratoconjunctivitis sicca, reduced tear production. Scratchy, gritty sensation, blurred
vision. May be painful.
– Schirmer test <5 mm in 5 minutes (filter paper on lower eyelid)
• Radiographic features--Sialography
– “Fruit-laden, branchless tree”
– Punctate sialectasia, lack of normal branching of ducts
• Laboratory abnormalities
– None is specific for Sjögren syndrome
– Increased erythrocyte sedimentation rate (ESR)--common in many inflammatory conditions
– Rheumatoid factor presents in 75% of cases
– Antinuclear antibodies (ANA) may be present
• Anti-SSA (anti- Rho), Anti-SSB (anti-La)
• Treatment and prognosis
– Chronic, but not usually life-threatening
– Incurable disease: Artificial tears, artificial saliva, topical fluoride, OHI, frequent recalls
– Up to 20x increased risk for lymphoma
Sialadenosis
• Non-inflammatory salivary gland enlargement
• Usually in parotids
• Underlying systemic problem (alcoholism, diabetes, bulimia, etc.)
• Clinical features
– Slowly evolving swelling
– May or may not be painful
– Sialography shows “leafless tree”
• Microscopic features: Hypertrophy of acinar cells, no inflammation
• Treatment and prognosis
– Treat underlying cause
– Cosmetic—parotidectomy
NEOPLASTIC SALIVARY GLAND DISEASE

Overview of Salivary Gland Neoplasms:

- The majority of salivary gland tumors occur in the parotid and the majority are benign (parotid > minor
salivary glands > submandibular gland > sublingual gland).
- The most frequent intraoral sites are the palate, lips (esp. upper), and the buccal mucosa.
- Although less frequently involved, the retromolar area, the floor of the mouth, and the tongue are associated
with more aggressive lesions.
- In minor salivary glands, almost half of all tumors are malignant; in the submandibular gland, 37-45% are
malignant; in the sublingual gland, 70-90% are malignant.
- The most common salivary gland tumor overall is the pleomorphic adenoma.
- The most common malignant salivary gland tumor is the mucoepidermoid carcinoma.

Pleomorphic Adenoma (Benign Mixed Tumor):

- Most common salivary gland neoplasm in both children and adults
- Benign tumor composed of a mixture of epithelial and mesenchymal elements.
- Typically presents as a painless, slow-growing mass in the superficial lobe of the parotid.
- Intraorally, the palate is the most common site, where it presents as a smooth-surfaced, dome-shaped lesion.
- Histological findings: Well-circumscribed or encapsulated tumor composed of a varying mixture of glandular
structures (including double-layered ducts), myoepithelial cells, and mesenchymal stromal tissue ranging from
hyalinized to myxoid to myxochondroid.
- Treatment: Surgical excision (do not enucleate).
- Overall, very good prognosis; up to 5% risk of malignant transformation.
-Malignant mixed tumors: Carcinoma ex pleomorphic adenoma, carcinosarcoma, metastasizing mixed tumor.
Warthin's Tumor (Papillary Cystadenoma Lymphomatosum):
- Benign tumor characterized by a papillary proliferation of oncocytic cells and lymphoid tissue.
- Occurs almost exclusively in the parotid.
- Smokers are 8X more likely to develop a Warthin's tumor.
- Tendency to occur bilaterally, metachronously (5-14%).
- Typically presents as a slow-growing, painless, nodular mass in the tail of the parotid.
- Histological findings: Thinly encapsulated, papillary cystic tumor composed of a bilayer of columnar and
basaloid oncocytes with a surrounding lymphoid stroma.
- Treatment/prognosis: Surgical removal (6-12% recurrence rate).

Monomorphic Adenomas (Canalicular adenoma; basal cell adenoma)

Canalicular Adenoma:
- Benign salivary gland tumor which occurs almost exclusively in minor glands, with a striking
predilection for the upper lip (75%).
- 2nd most common salivary gland tumor of the upper lip.
- Almost always occurs in adults over 50.
- Painless, slow-growing, firm or fluctuant, bluish mass. Similar to Mucoceles.
- Histological findings: Cords of dark, short columnar cells which form "canaliculi" when the cords are
parallel.
- Treatment/prognosis: Local excision; recurrence is uncommon.

Mucoepidermoid Carcinoma:
- Most common malignant salivary gland tumor in the U.S.
- Wide age distribution (most common salivary gland tumor in children).
- 45% parotid (major salivary gland); 21% palate (minor salivary gland); 19% buccal mucosa.
- Lower lip > upper lip (unlike other salivary gland tumors).
- May also develop in the jawbone (see below).
- Most often asymptomatic, but may be associated with pain or palsy.
- Usually appears as a bluish mass or swelling (but may be normal in color), and may mimic a mucocele.
- Histologic grading: Low grade (mimics benign neoplasm), Intermediate grade (fewer and smaller
cysts), High grade (highly aggressive)
- Histological findings: Islands and cysts containing a variable mixture of epidermoid cells, mucous
cells, and "intermediate" cells.
- Treatment: - Depends on the grade and location of the tumor.
- Surgical excision, +/- neck dissection, +/- radiation therapy.
- Prognosis: Low grade lesions- 90-95% cure rate; high grade lesions- 30-54% survival rate.

Intraosseous (Central) Mucoepidermoid Carcinoma:

- Most common salivary gland tumor in bone.
- May arise from ectopic salivary gland tissue (trapped in bone during development), sinus glandular
tissue, or odontogenic epithelium.
 - 3X more common in the mandible (posterior molar region).
- Patients will often have a cortical swelling, with or without pain, trismus, and/or paresthesia (in the
mandible often called “numb chin syndrome”).
- Radiographically: Uni- or multilocular radiolucency with well-defined or irregular borders; may be
associated with an unerupted tooth.
- Histological findings: Same as extraosseous ME.
- Treatment: Radical surgical excision, +/- radiation therapy.
- Prognosis: Fairly good--13% recurrence with radical excision, 12% metastasize, 10% of patients die.

Acinic Cell Carcinoma

- Characterized by serous acinar differentiation
- Wide age range
- Most common malignant salivary neoplasm to arise bilaterally
- Second most common salivary malignancy in children
- Usually an asymptomatic swelling, slow growing
- Major salivary gland: parotid
- Treatment: surgical excision, 10-20% recurrence rate, 8% metastasis rate, minor salivary lesions have better
prognosis
- Histologic Features: serous features

Adenoid Cystic Carcinoma “ACC”

- One of the more common salivary gland tumors.
- Half occur in minor salivary glands (palate is the most common intraoral site).
- Most common salivary gland tumor of the submandibular gland.
- Affects middle-aged adults.
- Slow-growing, painful mass (pain may be present before the lesion is clinically obvious, tumor invades nerve)
- Major salivary gland: parotid gland
- Minor salivary gland: palate
- Histological findings: Myoepithelial and ductal cells arranged in a cribriform (“Swiss cheese” appearance of
minor salivary glands), tubular, and/or solid pattern with a tendency for perineural invasion.
- Treatment: Surgical excision +/- radiation therapy.
- Prognosis: Relentless (regardless of treatment); likely to recur and metastasize (high recurrence rate at 5yrs)
Polymorphous Low-Grade Adenocarcinoma (PLGA)
- First described in 1983.
- Found almost exclusively in minor salivary glands.
- Relatively common malignancy of minor glands.
- Painless, slow-growing mass which may infiltrate the underlying bone.
- Posterior lateral palate is most common location
- Histological findings: Tumor composed of round, ovoid or spindled cells arranged in single-file, nests, cords,
or ducts; may be cystic or cribiform in areas; architecturally polymorphous; stroma may be mucoid or
hyalinized; perineural invasion is common.
- Treatment: Wide surgical excision.
- Prognosis: Good (9-17% recur; 10% metastasize to lymph nodes; death from tumor is rare)

Mammary Secretory Analogue Secretory Carcinoma (MASC)

- Malignancy with histiopathologic and molecular features similary to secretory carcinoma of the breast
- Slowly growing, painless mass
- Many minor salivary gland lesions preciously called zymogen granule poor acinic cell carcinomas are
probably better classified as this entity
- Major gland: Parotid
- Minor gland: lifts, soft palate, buccal mucosa