Definition/General
Introduction:
Mucoepidermoid carcinoma is the most common primary malignant tumor of salivary glands, representing 30-35% of all salivary gland malignancies
Composed of mucin-producing cells, intermediate cells, and squamous (epidermoid) cells
Shows wide spectrum from low-grade cystic to high-grade solid tumors
FNAC demonstrates characteristic cellular triad with varying proportions.
Origin:
Arises from ductal epithelium with potential for mucous and squamous differentiation
Originates from intercalated or excretory ducts
Shows glandular and squamous differentiation patterns
Intermediate cells represent stem cell population
May arise de novo or from pre-existing benign lesions.
Classification:
WHO Classification: Mucoepidermoid carcinoma
Milan System: Category V or VI (Suspicious for malignancy/Malignant)
Grading: Low, intermediate, high grade (Healey system)
Low grade: predominantly cystic
High grade: predominantly solid
Grade affects prognosis significantly.
Epidemiology:
Accounts for 30-35% of salivary gland malignancies
Wide age range: 10-80 years
Peak incidence in 4th-6th decades
Slight female predominance
Parotid gland most common site (60%)
Minor glands affected in 20-25% cases
Indian population shows similar distribution patterns.
Clinical Features
Presentation:
Low grade: slowly growing, painless mass
High grade: rapidly enlarging, painful tumor
May cause facial nerve paralysis (high grade)
Skin fixation or ulceration in advanced cases
Regional lymphadenopathy (especially high grade)
Size varies from 2-10 cm.
Symptoms:
Pain present in 60-70% of high-grade tumors
Facial weakness (cranial nerve VII involvement)
Trismus from muscle invasion
Numbness from trigeminal nerve involvement
Bloody discharge from ductal opening
Weight loss in advanced disease.
Risk Factors:
Radiation exposure (atomic bomb survivors, medical radiation)
Prior salivary gland tumors
Genetic predisposition (familial cases rare)
Mucoepidemoid carcinoma in children associated with radiation
No association with smoking or alcohol.
Screening:
Clinical examination for salivary gland masses
Neurological assessment (facial nerve function)
Imaging: CT/MRI for extent assessment
FNAC for cytological diagnosis
Staging workup for suspected malignancy
Multidisciplinary team evaluation.
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Gross Description
Appearance:
FNAC aspirate typically moderately cellular
May be mucoid or viscous (low grade)
High grade may be less mucoid
Color ranges from clear to turbid
Volume varies 1-4 ml per aspiration.
Characteristics:
Low grade: thick, mucoid consistency
High grade: less viscous, more cellular
May contain inflammatory debris
Blood contamination common in high grade
Absence of chondromyxoid matrix (cf
pleomorphic adenoma).
Size Location:
Sample adequacy varies with tumor grade and necrosis
Multiple passes often needed for representative sampling
Superficial tumors easier to sample
Deep lobe or minor gland tumors challenging
Cystic areas may yield less cellular material.
Multifocality:
Usually unifocal tumor
Rarely shows multifocal disease
High grade may show satellites or invasion
Lymph node metastases common in high grade
Minor gland tumors may be multiple.
Microscopic Description
Histological Features:
Characteristic triad of cell types: mucin-producing cells, intermediate cells, squamous cells
Mucin cells: goblet-like with abundant cytoplasm
Intermediate cells: small, basaloid appearance
Squamous cells: polygonal with eosinophilic cytoplasm
Background contains mucin and inflammatory cells.
Cellular Characteristics:
Mucin cells: distended cytoplasm with mucin vacuoles
Eccentric nuclei pushed to periphery
Intermediate cells: high nuclear:cytoplasmic ratio
Round to oval nuclei
Squamous cells: polygonal shape with distinct borders
May show keratinization in high grade.
Architectural Patterns:
Low grade: cystic and glandular patterns predominate
High grade: solid sheets and nests
Mixed patterns with varying cell proportions
Single cells and loose clusters
May show papillary arrangements
Background mucin varies with grade.
Grading Criteria:
Healey grading system: cystic component, neural invasion, mitotic activity, anaplasia, necrosis
Low grade: predominantly cystic (>90%)
High grade: solid growth (>50%)
Intermediate grade: mixed patterns
Nuclear features correlate with histological grade.
Immunohistochemistry
Positive Markers:
Mucin cells: MUC5AC positive
PAS positive (mucin)
Alcian blue positive
Squamous cells: CK5/6 positive
p63 positive
CK14 positive
Intermediate cells: CK7 positive
CK8/18 positive
p40 positive (squamous component).
Negative Markers:
Mucin cells: p63 negative
CK5/6 negative
Squamous cells: MUC5AC negative
S-100 negative (distinguishes from adenoid cystic carcinoma)
Chromogranin negative
CD117 negative
Thyroglobulin negative.
Diagnostic Utility:
Confirms mixed differentiation
p63 highlights squamous component
Mucin stains confirm mucin production
Helps distinguish from other salivary malignancies
Ki-67 index correlates with grade (low: <15%, high: >30%)
Useful in poorly differentiated cases.
Molecular Subtypes:
t(11;19) translocation in subset (especially high grade)
Results in CRTC1-MAML2 fusion
t(11;15) translocation less common
Results in CRTC3-MAML2 fusion
Fusion-positive tumors may have better prognosis.
Molecular/Genetic
Genetic Mutations:
MAML2 rearrangements in 40-80% of cases
Most common: CRTC1-MAML2 fusion
Less common: CRTC3-MAML2 fusion
TP53 mutations in high-grade tumors
PIK3CA mutations in subset of cases
ARID1A mutations reported.
Molecular Markers:
MAML2 fusion proteins detectable by FISH or RT-PCR
Notch pathway activation
Wnt signaling alterations
p53 overexpression in high grade
EGFR overexpression in aggressive tumors
Cyclin D1 amplification.
Prognostic Significance:
MAML2 fusions associated with better prognosis
Grade most important prognostic factor
Low grade: 95% 10-year survival
High grade: 30-50% 10-year survival
Stage at presentation affects outcome
Neural invasion indicates poor prognosis.
Therapeutic Targets:
Surgical excision primary treatment
Radiation therapy for high grade or positive margins
EGFR inhibitors in recurrent disease
Immunotherapy under investigation
Targeted therapy based on molecular profiling
Clinical trials for advanced disease.
Differential Diagnosis
Similar Entities:
Adenoid cystic carcinoma (cribriform pattern, CD117+)
Acinic cell carcinoma (granular cells, PAS+)
Pleomorphic adenoma (chondromyxoid matrix)
Warthin tumor (oncocytes, lymphoid stroma)
Squamous cell carcinoma (pure squamous differentiation).
Distinguishing Features:
Mucoepidermoid: Mixed cell population
Mucin cells prominent
No chondromyxoid matrix
Adenoid cystic: Cribriform pattern
CD117 positive
Basaloid cells
Acinic cell: Granular cytoplasm
Zymogen granules
PAS positive
Warthin: Oncocytic cells
Dense lymphoid background
Pleomorphic: Matrix component
Myoepithelial cells.
Diagnostic Challenges:
Low-grade lesions may mimic benign tumors
High-grade lesions may lose mucin component
Distinction from metastatic adenocarcinoma
Crush artifacts may obscure morphology
Sampling from different tumor areas
Grading on FNAC material limited.
Rare Variants:
Clear cell variant: glycogen-rich clear cells
Sclerosing variant: prominent fibrosis
Oncocytic variant: oncocytic features
Warthin-like variant: lymphoid stroma
Mucin-poor variant: minimal mucin production.
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 tumor cells
Cellular Composition
Mixed population of mucin-producing cells, intermediate cells, and squamous cells
Morphological Features
Cellular triad with varying proportions, nuclear features suggest [grade] grade
Background
Mucoid background with inflammatory cells and cellular debris
Grade Assessment
Cytological features suggest [low/intermediate/high] grade tumor
Milan System Category
Category VI - Malignant
Cytological Diagnosis
Mucoepidermoid carcinoma, grade to be determined on histopathology
Recommendation
Urgent surgical consultation. Histopathological examination for definitive grading and staging