Salivary Gland Pathology

H. Stan McGuff, D.D.S.

Functions of Saliva
• Protection
• Lubrication
• Buffering
• Digestion
• Taste
• Antimicrobial
• Tooth integrity
Diseases of Salivary Glands
• Developmental
• Infectious
• Inflammatory
• Autoimmune
• Hemodynamic
• Ischemic
• Metabolic
• Neoplastic
 Salivary Gland Pathology

Mucocele
(Mucous Extravasation Phenomenon)
 Mucocele
• Rupture of salivary duct – mucin spillage
• Incidence: common
• Age: children and young adults
• Site: Lower lip (60%)
• Duration of symptoms: days – years
• May rupture, drain then recur
 Mucocele
• Submucosal cavitation
• Spilled mucin
• Granulation tissue
• Inflammation
• Foamy macrophages
• Ruptured duct
• Sialadenitis
 Mucocele
• Treatment:
- spontaneous resolution
- surgical excision
- remove associated salivary lobules
- marsupialization
• Prognosis:
- excellent
- recurrence
• Differential diagnosis: salivary gland tumor
Salivary Gland Pathology

Ranula
 Ranula
• Mucous extravastaion reaction
• Floor of mouth
• Origin:
- sublingual gland
- submandibular duct
- minor salivary glands
 Ranula
• Blue
• Fluctuant swelling
• Lateral floor of mouth
• Large
• Elevates tongue
• Rupture and re-form
 Ranula

• Spilled mucin
• Granulation tissue
• Foamy histiocytes
• Inflamed salivary
glands
Plunging Ranula
• Dissection through
mylohyoid
• Extension in cervical
soft tissue
• May have limited
intra-oral component
 Ranula
• Treatment:
- marsupialization
- remove offending gland
- complete dissection is unnecessary
• Prognosis:
- good
- recurrence
Salivary Gland Pathology

Salivary Duct Cyst

(Mucous Retention Phenomenon)
 Salivary Duct Cyst
• True epithelial lined cyst
• Ductal dilatation
• Obstruction – mucus plug
• Developmental duct cyst
• Adults
• Major glands
– parotid
• Minor glands
– floor of mouth, buccal/labial mucosa
Salivary Duct Cyst
• Asymptomatic
• Slow growing
• Swelling
• Soft fluctuant
• Bluish - amber
Salivary Duct Cyst
• Submucosal
• Epithelial lined cyst
• Cuboidal, columnar or
squamous epithelium
• Mucoid secretions
• Chronic saliadenitis
 Salivary Duct Cyst
• Treatment:
- conservative excision
- removal of associated gland
• Prognosis:
- good
- recurrence rare
- multifocal lesions
Salivary Gland Pathology

Sialolithiasis
 Sialolithiasis
• Calcification within salivary duct system
• Calcium salt deposition
• Nidus – mucin, bacteria, epithelial cells
• Promoted by sialadenitis – obstruction
• Unrelated to calcium/phosphorus metabolism
 Sialolithiasis
• Submandibular Gland
- most commonly involved
- long tortuous dependant duct
- thick mucoid secretions
• Parotid Gland
- Less frequently involved
• Minor Glands
- upper lip, buccal mucosa
 Sialolithiasis
• Age: young to middle aged adults
• Episodic pain and swelling
• Symptoms related to meals – obstruction
• Solitary – anywhere in duct system
• Palpable hard submucosal mass
• Radiopaque mass – imaging studies
• Round, ovoid or cylindrical yellowish mass
 Sialolithiasis
• Calcified mass
• Laminated
• Nidus
• Ductal metaplasia
• Sialodochitis
• Sialadenitis
 Sialolithiasis
• Gentle masssage – pass stone
• Sialogogues
• Fluid intake
• Moist heat
• Surgical removal
• Excision of salivary gland
• Lithotripsy, endoscopy
Salivary Gland Pathology

Xerostomia
 Xerostomia
• Subjective sensation of dry mouth
• Salivary hypofunction
• Incidence: common
• 25% of older adults
• Numerous causative factors
• Oral complications
 Causes of Xerostomia
• Medications • Graft vs host disease
• Aging • Diabetes incipidus
• Radiation therapy • Smoking
• Sjogren’s syndrome • Mouthbreathing
• Diabetes mellitus • Fluid/electrolyte
• Sarcoidosis imbalance
• HIV infection • Salivary gland aplasia
 Drug Induced Xerostomia
• Over 500 drugs are known to produce
xerostomia
• 63% of 200 most frequently prescribed
medications
• Prevalence of xerostomia increases with
total number of drugs taken
Drugs Causing Xerostomia

• Antihistamines
• Decongestants
• Antihypertensives
• Anticholinergics
• Antidepressants
• Antipsychotics
 Clinical Findings
• Reduced salivary pool
• Thick ropey or foamy saliva
• Dry sticky mucosa
• Fissured tongue
• Atrophy of filiform papillae
• “Cracker” sign
 Complications
• Mucositis - discomfort
• Candidiasis
• Dental caries
• Difficulty with mastication
• Dysphagia
• Difficulty with speech
• Altered taste
• Difficulty wearing dentures/prostheses
 Management
• Symptomatic relief
• Water – artificial saliva
• Sugarless candy or gum
• Discontinue contributing factors
• Parasympathomimetic drugs
• Antifungal medication
• Dental maintenance care
Salivary Gland Pathology

Myoepithelial Sialadenitis
(Benign Lymphoepithelial Lesion)
 Myoepithelial Sialadenitis
• Firm diffuse swelling of salivary glands
• Lymphoid infiltrate
• Sjogren’s syndrome
• Age: mean age – 50 years old
• Gender: female – 60-80%
• Site: parotid gland – 85%
• Asymptomatic – mild discomfort
Myoepithelial Sialadenitis
• Diffuse lymphoid
infiltrate
• Acinar destruction
• Germinal centers
• Epimyoepithelial
islands
 Myoepithelial Sialadenitis
• Treatment:
- surgical removal
• Low grade marginal zone lymphoma of
mucosa associated lymphoid tissue
(MALT lymphoma)
• Prognosis:
- good
Salivary Gland Pathology

Lymphoepithelial Carcinoma
 Lymphoepithelial Carcinoma
• Rare
• High grade/poorly differentiated carcinoma
• Lymphoid stroma
• Inuits, Asians, Greenlanders
• Epstein-Barr virus
• Prognosis - guarded
Salivary Gland Pathology

Sjogren’s Syndrome
 Sjogren’s Syndrome
• Autoimmune disease
• Salivary and lacrimal glands
• Xerostomia
• Keratoconjunctivitis sicca
• Primary
• Secondary
 Sjogren’s Syndrome
• Etiology – unknown
• Genetic
- HLA-DRw52, HLA-B8, HLA-DR3
• Viruses
- Epstein-Barr virus
- Human T-cell lymphotropic virus
 Sjogren’s Syndrome
• Incidence: 0.2-3.0% of the population
• Female gender predilection (80-90%)
• Middle aged adults
• Associated autoimmune disease
- rheumatoid arthritis
- systemic lupus erythematosus
 Sjogren’s Syndrome
• Reduced salivary pool • Candidiasis
• Mucositis • Angular cheilitis
• Fissured atrophic • Dental caries
tongue • Difficulty wearing
• Dysphagia prostheses
• Altered taste • Enlargement of
• Speech difficulties salivary glands
• Sialadenitis
 Diagnosis
• Ocular dryness
- Schirmer’s test, Rose Bengal staining
• Xerostomia
- reduced salivary flow rate, + focus score
• Serologic evidence of autoimmunity
– rheumatoid factor, ANA, SS-A, SS-B
• Associated systemic autoimmune disease
 Labial Minor Salivary Gland
Biopsy
• Focal lymphocytic sialadenitis
• Focus = greater than fifty lymphocytes
• Greater than one focus per 4mm squared
• Focus score = # foci x 4/area
• Focus score greater than one supports
diagnosis
• No regressive changes
 Clinical Laboratory Values
• Elevated erythrocyte sedimentation rate
• Hypergammaglobulinemia
• Rheumatoid factor (75%)
• Antinuclear antibodies (ANA)
• Anti-SS-A (Ro)
• Anti-SS-B (La)
• Salivary duct autoantibodies
 Keratoconjunctivitis Sicca
• Reduced tear production
• Mucoid secretions
• Blurred vision
• Pain
• Gritty foreign body sensation
• Corneal erosion
• Lacrimal enlargement
 Extra-Glandular Manifestations
• Nephritis • Raynaud’s
• Interstitial phenomenon
pneumonitis • Fatigue
• Vasculitis • Depression
• Neuropathy • Lymphadenopathy
• Primary biliary • Malignant lymphoma
cirrhosis
 Management
• Rheumatologist
• Ophthalmologist
• Supportive care
- saliva substitutes
- sialogogues
- antifungal therapy
- preventive dental care
• Risk of lymphoma (40X normal)
Salivary Gland Pathology

Necrotizing Sialometaplasia
 Necrotizing Sialometaplasia
• Necrotizing ulcerative process
• Ischemia – local infarction
• Trauma – predisposing factors
• Incidence: uncommon
• Palatal salivary glands (75%)
• Adults (mean age 46 years)
• Male gender predilection (2:1)
• Mimics a malignant process
 Necrotizing Sialometaplasia
• Begins as a painful swelling
• Necrotic tissue sloughs
• “Part of the roof of my mouth fell out!”
• Pain subsides
• Craterlike ulceration (1 to 5 cm)
• Bone destruction is rare
• May have alarming clinical appearance
Necrotizing Sialometaplasia
• Ulceration
• Acinar necrosis
• Lobular architecture
• Squamous metaplasia
• Inflammation
• Mucin release
• Pseudoepitheliomatous
epithelial hyperplasia
 Management
• Biopsy to establish diagnosis
• No specific treatment
• Supportive care
• Spontaneous healing – 5 to 6 weeks
• Avoid misdiagnosis
• Prevent inappropriate therapy
Salivary Gland Tumors

General Considerations
 Salivary Gland Tumors
Classification
• Benign epithelial tumors
- pleomorphic adenoma
- monomorphic adenomas
• Malignant epithelial tumors
• Mesenchymal tumors
• Lymphomas
• Metastatic tumors
 Salivary Gland Tumors
• Incidence:
- 0.4 - 6.5 cases per 100,000
- 2.0 - 6.5 % of head & neck neoplasms
• Age: 6 – 7th decades - peak incidence
• Gender: female predilection
• Site:
- parotid: 64 - 80%
- minor glands (palate): 9 -23%
- submandibular gland: 8 - 11%
- sublingual gland: < 1%
 Salivary Gland Tumors
Etiologic Factors
• Radiation exposure
• Genetic predisposition
• Tobacco
• Chemical carcinogens
• Viruses
 Salivary Gland Tumors
• Benign tumors: 54 -79%
• Malignant tumors: 21 - 46%
• Malignancy by site:
- sublingual gland: 70 - 90%
- minor glands: 50%
- submandibular gland: 37 - 45%
- parotid: 15 - 32%
Salivary Gland Pathology

Benign Tumors
Salivary Gland Tumors

Pleomorphic Adenoma
(Mixed Tumor)
 Pleomorphic Adenoma
• Benign glandular neoplasm
• Incidence: common
• 70% of salivary tumors
• Gender: female > male
• Age: 3-6th decades
• Site: parotid, palate, upper lip, buccal mucosa
• Symptoms: slow growing painless mass
 Pleomorphic Adenoma
• Gross Pathology:
- well circumscribed firm tan white solid or
partially cystic mass
• Histology:
- ductal epithelial cells
- myoepithelial cells
- stroma: myxoid, chondroid, fibrohyaline
 Pleomorphic Adenoma
• Treatment:
- surgical excision
- superficial parotidectomy
• Prognosis: excellent
• Complications:
- recurrence – multifocal
- malignant transformation (5%)
Benign Tumors

Oncocytoma
 Oncocytoma
• Benign salivary gland neoplasm
• Incidence: rare (1% of salivary tumors)
• Site: parotid gland (85-90%)
• Age: 6-8th decades
• No gender predilection
• Symptoms: painless mass (<4 cm)
• Multifocal/bilateral
 Oncocytoma
• Encapsulated
• Trabecular-organoid
• Oncocytic epithelial
cells
• Fibrous septae
• Clear cells
 Oncocytoma
• Treatment
- surgical excision
• Prognosis
- excellent
- recurrence uncommon
• Oncocytic Adenocarcinoma - sinonasal tract
 Salivary Gland Tumors

Warthin’s Tumor
(Papillary Cystadenoma Lymphomatosum)
 Warthin’s Tumor
• Benign salivary gland tumor
• Incidence: common
• Gender: male > female
• Age: 5-7th decades
• Symptoms: painless mass
• Site: parotid, multi-focal/bilateral (14%)
• Etiology: smoking (8 fold risk)
 Warthin’s Tumor
• Gross Pathology:
- well circumscribed cystic mass
- papillations
- “machine oil fluid”
• Histology:
- encapsulated cystic lesion
- papillary fronds
- oncocytic columnar cells
- lymphoid stroma
 Warthin’s Tumor
• Treatment:
- surgical excision
- superficial parotidectomy
• Prognosis: excellent
• Complications:
- recurrence – 6-12% (multicentric)
- association with other salivary tumors
- malignant transformation – extremely rare
 Benign Tumors

Canalicular Adenoma
 Canalicular Adenoma
• Benign salivary gland neoplasm
• Monomorphic adenoma
• Site: upper lip (75%)
• Age: 7th decade
• Gender: female predilection
• Symptoms: slow growing mass
• Multifocal
 Canalicular Adenoma
• Treatment
- conservative surgical excision
- enucleation not recommended
• Prognosis
- excellent
- rare recurrence
• Can be misdiagnosed as a malignancy
 Benign Tumors

Basal Cell Adenoma

 Basal Cell Adenoma
• Benign salivary gland neoplasm
• Monomorphic adenoma
• Incidence: 2% of salivary gland tumors
• Site: parotid gland (75%)
• Age: 4-9th decades
• Gender: female predilection (2:1)
• Symptoms: slow growing mass (< 3cm)
Basal Cell Adenoma
• Basaloid cells
• Peripheral palisading
• Circumscribed
• Multi-nodular
• Intact basement
membrane – stroma
• Variable histologic
patterns
 Basal Cell Adenoma
• Treatment
- complete surgical excision
• Prognosis
- excellent
- recurrences may occur
• Malignant transformation
- rare
- hybrid tumor
Salivary Gland Tumors

Malignant Tumors
 Malignant Epithelial Tumors
• Mucoepidermoid • Basal cell
carcinoma – 29% adenocarcinoma
• Adenocarcinoma, – 2.9%
NOS – 27% • Epithelial
• Acinic cell carcinoma myoepithelial
– 17% carcinoma – 1%
• Polymorphous low
grade carcinoma – • Clear cell carcinoma
19.6% – 1%
• Adenoid cystic • Salivary duct
carcinoma – 7.5% carcinoma – 0.5%
 Malignant Epithelial Tumors
• Squamous cell • Lymphoepithelial
carcinoma carcinoma
• Cystadenocarcinoma • Adenosquamous
• Oncocytic carcinoma carcinoma
• Sebaceous carcinoma • Undifferentiated
• Mucinous carcinoma carcinoma
• Myoepithelial • Sarcomas/lymphomas
carcinoma • Metastatic tumors
 Salivary Gland Tumors
• Benign tumors: 54 -79%
• Malignant tumors: 21 - 46%
• Malignancy by site:
- sublingual gland: 70 - 90%
- minor glands: 50%
- submandibular gland: 41 - 45%
- parotid: 15 - 32%
Intraoral Minor Salivary Gland
Malignant Tumors By Site :
• Retromolar trigone: 93%
• Floor of mouth: 93%
• Tongue: 80%
• Lower lip: 66%
• Palate: 50%
• Upper lip: 31%
 Salivary Gland Tumor Staging
• T1: tumor < 2 cm
• T2: tumor 2 - 4cm
• T3: tumor > 4 cm or extraparenchymal
• T4a: invades skin, mandible, ear canal or
facial nerve
• T4b: tumor invades skull base, pterygoid
plates or encases carotid artery
Salivary Gland Tumors

Mucoepidermoid
Carcinoma
 Mucoepidermoid Carcinoma
Clinical:
• Malignant epithelial salivary gland tumor
• 2nd most common salivary gland tumor
• 30% of malignant salivary gland tumors
• Age: 2nd – 7th decades
• Gender: slight female predilection
• Site: parotid gland, palate
• Etiology: radiation exposure
• Asymptomatic swelling
Mucoepidermoid Carcinoma,
Histology:
• Unencapsulated
• Cystic or solid growth
patterns
• Epidermoid cells
• Mucous cells
• Intermediate cells
• Clear cells
• Low, intermediate and
high grades
Mucoepidermoid Carcinoma
Treatment:
• Surgical resection
• Neck dissection
• Radiation therapy
 Mucoepidermoid Carcinoma
Prognosis:
• Recurrence
• Metastasis – lymph nodes, lung, bone, skin
• Low to intermediate grades
– good prognosis ( 90% 5 year survival )
• High grade
– poor prognosis (40% 5 year survival)
• Site: submandibular, floor of mouth, tongue
Salivary Gland Tumors

Central Mucoepidermoid
Carcinoma
 Intraosseous Salivary Tumors
• Mucoepidermoid carcinoma
• Adenoid cystic carcinoma
• Pleomorphic adenoma
• Adenocarcinoma
• Acinic cell carcinoma
• Monomorphic adenoma
Central Mucoepidermoid Carcinoma
• Primary intra-osseous carcinoma
• Origin from odontogenic epithelium
• 4% of mucoepidermoid carcinomas
• Mandible > Maxilla (4:1)
• Middle age females
• Third molar region - impacted tooth
• Multilocular radiolucency
• Swelling, pain, paresthesia
Central Mucoepidermoid Carcinoma
• Treatment:
- enucleation/curettage
- resection
• Prognosis:
- good
- 13 – 40% recurrence rate
- 12% metastatic rate
- 10% mortality
 Salivary Gland Tumors

Acinic Cell Adenocarcinoma

 Acinic Cell Adeoncarcinoma
• Malignant epithelial salivary gland tumor
• Serous acinar differentiation
• Incidence:
- 6.5 % of salivary gland tumors
- 18% malignant salivary gland tumors
• Site: parotid (85%), minor glands (9%)
• Age: 2nd - 7th decades
• Female gender predilection
• Symptoms: slow growing mass, pain
Acinic Cell Adenocarcinoma
Gross Pathology:
• Well demarcated
• Lobulated
• Size: 3-13 cm
• Solid
• Cystic
• 3% - bilateral
Acinic Cell Adenocarcinoma
Histopathology:
• Circumscribed
• Variable growth
patterns
• Variable cytology
• Low grade tumor
• Scant stroma
• Lymphoid infiltrate
 Acinic Cell Adenocarcinoma
• Treatment:
- surgical excision
• Prognosis:
- low-grade malignancy
- 12% recur
- 8% metastasize
- 6% mortality
- prognosis is better for minor gland tumors
• Undifferentiated carcinoma component (rare)
• Difficult diagnosis for pathologist
 Salivary Gland Tumors

Adenoid Cystic Carcinoma

(Cylindroma)
 Adenoid Cystic Carcinoma
• Malignant epithelial neoplasm
• Incidence: relatively common
(12% of salivary gland tumors)
• Gender: slight female predilection
• Age: 5-7th decades
• 50% occur in minor salivary glands
• Site: palate, submandibular gland, parotid
• Symptoms: painful mass, facial paralysis
 Adenoid Cystic Carcinoma
• Gross Pathology:
- unencapsulated firm solid tan mass
• Histology:
- highly infiltrative
- small hyperchromatic cells
- cribriform (“Swiss cheese”), tubular, solid
- mucohyaline stroma
- perineural invasion
 Adenoid Cystic Carcinoma
• Treatment:
- radical surgical excision
- radiation therapy
• Prognosis:
- protracted relentless clinical course
- multiple local recurrences
- 75% 5 year survival
- 13% 20 year survival
- late distant metastasis (nodes, lung, bone)
- worse prognosis for submandibular tumors
 Salivary Gland Tumors

Polymorphous Low Grade

Adenocarcinoma
 Polymorphous Low Grade Carcinoma

• Malignant epithelial neoplasm

• Oral cavity - minor glands
• Age: wide range – 6-8th decades
• Female gender predilection
• Site: palate (65%), lip, buccal mucosa
• Symptoms: painless swelling
• Duration: weeks to years
Polymorphous Low Grade Carcinoma
• Unencapsulated
• Bland uniform
cytology
• Cuboidal epithelial
cells
• Multiple growth
patterns
• Perineural invasion
 Polymorphous Low Grade Carcinoma

• Treatment:
- complete surgical excision
• Prognosis:
- good
- slow growing indolent tumor
- recurrences (9-17%)
- metastasis to cervical lymph nodes (10%)
- mortality is rare
The End