Definition/General
Introduction:
Pleomorphic adenoma is the most common benign tumor of salivary glands, representing 80% of parotid and 60% of submandibular gland tumors
Also known as mixed tumor due to epithelial and mesenchymal components
Shows characteristic biphasic pattern with epithelial cells and chondromyxoid matrix
FNAC demonstrates pathognomonic features allowing confident diagnosis in most cases.
Origin:
Arises from intercalated duct cells and myoepithelial cells of salivary gland parenchyma
Shows dual differentiation toward ductal and myoepithelial lineages
Myoepithelial cells undergo metaplastic transformation producing chondromyxoid matrix
Epithelial component maintains glandular architecture
Represents true mixed epithelial-stromal tumor.
Classification:
Classified under Milan System Category IV - Neoplasm: Benign
Subtypes based on predominant component: epithelial-rich, myoepithelial-rich, stroma-rich variants
Cellular pleomorphic adenoma: increased cellularity with minimal matrix
Matrix-rich variant: abundant chondromyxoid material
Grading not applicable for benign tumor.
Epidemiology:
Accounts for 70-80% of all salivary gland tumors
Peak incidence in 4th-5th decades
Slight female predominance (female:male = 1.5:1)
Parotid gland involvement in 85% cases
Submandibular gland in 10% cases
Minor salivary glands in 5% cases
Indian population shows similar demographic patterns.
Clinical Features
Presentation:
Slow-growing, painless mass typically in parotid gland
Well-circumscribed, mobile tumor
Size ranges from 2-10 cm at presentation
May show lobulated surface
Facial nerve paralysis is rare (suggests malignancy)
Long history of gradual enlargement.
Symptoms:
Usually asymptomatic except for cosmetic concerns
Mild discomfort or pressure sensation
No functional impairment of salivary secretion
Rarely causes trismus if large
No associated lymphadenopathy
Patients may report slow growth over months to years.
Risk Factors:
Age: peak incidence in middle age
Gender: slight female predominance
No definite environmental factors
Possible genetic predisposition
Radiation exposure (weak association)
No association with smoking or alcohol.
Screening:
Clinical examination for palpable masses
Imaging: ultrasound first-line
MRI for detailed characterization
FNAC for cytological diagnosis
Core biopsy if FNAC inconclusive
Multidisciplinary approach with head-neck surgeons.
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Gross Description
Appearance:
FNAC aspirate typically moderately cellular
May be mucoid or viscous due to matrix material
Color varies from clear to slightly turbid
Volume usually 1-3 ml per aspiration
May contain tissue fragments visible grossly.
Characteristics:
Viscous consistency due to mucoid matrix
Clear to slightly opalescent appearance
May show stringy quality when expressed
Tissue fragments may be rubbery in consistency
Absence of blood or necrotic material.
Size Location:
Sample adequacy depends on tumor vascularity and matrix content
Multiple passes often needed for representative sample
Parotid tumors yield more cellular material
Deep lobe tumors may be difficult to sample
Minor gland tumors provide smaller specimens.
Multifocality:
Typically unifocal tumor
Rarely shows multifocal growth
May have satellite nodules in parotid gland
Bilateral occurrence is extremely rare
No associated lymph node involvement.
Microscopic Description
Histological Features:
Dual population of epithelial and myoepithelial cells embedded in chondromyxoid matrix
Epithelial cells form ductal structures and sheets
Myoepithelial cells show spindle, stellate, or plasmacytoid morphology
Matrix varies from myxoid to chondroid
Background contains metachromatic material.
Cellular Characteristics:
Epithelial cells: cuboidal to columnar with round nuclei
Fine chromatin and small nucleoli
Myoepithelial cells: spindle-shaped with elongated nuclei
Plasmacytoid cells with eccentric nuclei and eosinophilic cytoplasm
Matrix-producing cells with vacuolated cytoplasm.
Architectural Patterns:
Mixed patterns: ductal, solid, and myxoid areas
Epithelial cells in cohesive clusters
Myoepithelial cells as single cells or loose aggregates
Chondromyxoid matrix as amorphous material
Fibrillary matrix between cells.
Grading Criteria:
No grading system for benign tumor
Cellularity varies from moderate to high
Nuclear pleomorphism is mild to moderate
Mitotic activity is minimal or absent
Matrix component varies quantitatively
Overall morphology is bland and uniform.
Immunohistochemistry
Positive Markers:
Epithelial component: CK7 positive
CK8/18
EMA positive
Myoepithelial cells: p63 positive
SMA positive
Calponin positive
S-100 positive
GFAP positive
Matrix: Alcian blue positive (mucin).
Negative Markers:
Myoepithelial cells: CK7 negative
Epithelial cells: SMA negative
p63 negative in ductal cells
Chromogranin negative
Synaptophysin negative
CD117 negative (distinguishes from adenoid cystic carcinoma).
Diagnostic Utility:
IHC confirms dual cell population
p63/SMA highlights myoepithelial component
Helps distinguish from other salivary tumors
Useful in matrix-poor cases
Ki-67 index typically low (<5%)
Support morphological diagnosis.
Molecular Subtypes:
No specific molecular subtypes recognized
PLAG1 gene rearrangements in subset of cases
HMGA2 rearrangements less common
These alterations not routinely tested
Molecular studies mainly for research purposes.
Molecular/Genetic
Genetic Mutations:
PLAG1 gene rearrangements in 60-70% of cases
Common partners: CTNNB1, LIFR, CHCHD7
HMGA2 rearrangements in 20-30% of cases
Usually involves 12q13-15 region
These alterations are mutually exclusive
Some cases show no detectable rearrangements.
Molecular Markers:
PLAG1 protein overexpression due to gene rearrangement
HMGA2 overexpression in subset of cases
Normal p53 expression pattern
Low proliferation index
Intact DNA repair mechanisms
Normal apoptotic pathways.
Prognostic Significance:
Molecular alterations have no prognostic impact in benign tumors
PLAG1 rearrangements may be associated with recurrence risk
Complete surgical excision is curative
Risk of malignant transformation to carcinoma ex pleomorphic adenoma (<5%)
Long-term follow-up recommended.
Therapeutic Targets:
No targeted therapy needed for benign tumor
Surgical excision is treatment of choice
Complete excision prevents recurrence
Molecular markers not used for treatment decisions
Research into targeted prevention of malignant transformation.
Differential Diagnosis
Similar Entities:
Warthin tumor (oncocytic cells, lymphoid background)
Basal cell adenoma (basaloid cells, less matrix)
Adenoid cystic carcinoma (cribriform pattern, CD117+)
Mucoepidermoid carcinoma (mucin cells, epidermoid cells)
Myoepithelioma (pure myoepithelial cells).
Distinguishing Features:
Pleomorphic adenoma: Chondromyxoid matrix
Dual cell population
Bland nuclear morphology
Warthin tumor: Oncocytic cells
Lymphoid background
Papillary architecture
Adenoid cystic: Cribriform pattern
CD117 positive
Uniform basaloid cells
Mucoepidermoid: Mucin-producing cells
Squamoid cells
No matrix.
Diagnostic Challenges:
Matrix-poor variants may be difficult to diagnose
Cellular variants may mimic malignancy
Crush artifacts can obscure morphological details
Sampling from different tumor areas may show variable features
Distinction from carcinoma ex pleomorphic adenoma.
Rare Variants:
Lipomatous pleomorphic adenoma: mature adipose tissue
Ossifying pleomorphic adenoma: bone formation
Sebaceous pleomorphic adenoma: sebaceous differentiation
Respiratory epithelium metaplasia
Squamous metaplasia (must exclude malignancy).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Fine needle aspiration from [location] salivary gland mass
Specimen Adequacy
Adequate for evaluation - contains representative epithelial and stromal components
Cellular Composition
Dual population of epithelial and myoepithelial cells with chondromyxoid matrix
Morphological Features
Bland epithelial cells in ductal arrangements and spindle-shaped myoepithelial cells
Matrix Component
Abundant chondromyxoid matrix with fibrillary and myxoid areas
Background
Clean background with metachromatic matrix material
Milan System Category
Category IV - Neoplasm: Benign (favor pleomorphic adenoma)
Cytological Diagnosis
Pleomorphic adenoma (mixed tumor)
Recommendation
Surgical excision recommended. Histopathological correlation advised for definitive diagnosis