Definition/General
Introduction:
Adenoid cystic carcinoma (ACC) is the second most common malignant tumor of salivary glands, representing 20-25% of all salivary malignancies
Characterized by basaloid cells arranged in cribriform, tubular, and solid patterns
Shows dual cell population: ductal and myoepithelial cells
Known for indolent growth but high propensity for neural invasion and distant metastases.
Origin:
Arises from intercalated duct cells and myoepithelial cells
Shows myoepithelial differentiation predominantly
Maintains basement membrane production (hyaline material)
Originates from ductal-myoepithelial stem cells
May arise in any salivary gland location.
Classification:
WHO Classification: Adenoid cystic carcinoma
Milan System: Category VI - Malignant
Histological patterns: cribriform, tubular, solid
Solid pattern indicates higher grade
No standard grading system but pattern affects prognosis.
Epidemiology:
Accounts for 20-25% of salivary gland malignancies
Wide age range with peak in 5th-6th decades
Slight female predominance
Minor salivary glands affected in 50% cases
Submandibular gland involvement common
Indian population shows similar distribution patterns.
Clinical Features
Presentation:
Slowly growing, firm mass
Often painful due to neural invasion
Facial nerve paralysis common in parotid tumors
Fixed to underlying structures
May cause numbness in distribution of affected nerves
Size typically 2-5 cm at presentation.
Symptoms:
Pain is characteristic feature (60-70% cases)
Neural symptoms: numbness, paresthesias
Facial weakness (cranial nerve VII)
Difficulty swallowing (cranial nerves IX, X)
Dry mouth from ductal obstruction
Trismus from pterygoid involvement.
Risk Factors:
No strong environmental associations
Gender: slight female predominance
Age: middle to older adults
Possible occupational exposures (weak evidence)
No association with smoking or alcohol
Prior radiation (minimal association).
Screening:
Clinical examination with attention to neural function
Pain assessment important clue
Imaging: MRI preferred for neural invasion
CT for bone involvement
FNAC for cytological diagnosis
Staging studies for distant metastases.
Master Adenoid Cystic Carcinoma FNAC Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
FNAC aspirate typically moderately cellular
May yield minimal material due to firm consistency
Clear to slightly turbid appearance
Volume usually 0.5-2 ml
May contain hyaline material.
Characteristics:
Firm tumor may yield scant material
Mucoid quality due to basement membrane material
May be blood-tinged due to vascularity
Absence of true mucin (unlike mucoepidermoid)
Contains proteinaceous background.
Size Location:
Sample adequacy may be challenging due to sclerotic nature
Multiple passes often needed
Deep-seated tumors require imaging guidance
Minor gland tumors may be difficult to sample
Perineural extension may be sampled inadvertently.
Multifocality:
Usually unifocal tumor
May show satellite nodules along nerves
Perineural spread extends beyond palpable mass
Skip lesions along nerve pathways
Rarely shows multicentric disease.
Microscopic Description
Histological Features:
Dual population of ductal and myoepithelial cells
Basaloid appearance with uniform small cells
Cribriform pattern: cylindromatous spaces filled with hyaline material
Tubular pattern: true glandular lumina
Solid pattern: sheets without differentiation.
Cellular Characteristics:
Small basaloid cells with scant cytoplasm
Angular nuclei with fine chromatin
Inconspicuous nucleoli
High nuclear:cytoplasmic ratio
Myoepithelial cells: spindle to stellate morphology
Ductal cells: cuboidal with central nuclei.
Architectural Patterns:
Cribriform pattern: characteristic "Swiss cheese" appearance
Cylindromatous spaces contain basement membrane material
Tubular structures lined by ductal cells
Solid areas show sheets of basaloid cells
Mixed patterns common in single aspirate.
Grading Criteria:
No standard grading but pattern-based assessment
Solid pattern indicates aggressive behavior
Cribriform pattern better prognosis
Tubular pattern intermediate prognosis
Nuclear features generally uniform
Mitotic activity variable.
Immunohistochemistry
Positive Markers:
Dual expression pattern: CK7 positive (ductal cells)
p63 positive (myoepithelial cells)
SMA positive (myoepithelial cells)
CD117 (c-kit) positive (characteristic)
SOX10 positive
S-100 positive (myoepithelial cells)
Calponin positive.
Negative Markers:
Ductal cells: p63 negative
SMA negative
Myoepithelial cells: CK7 negative
Chromogranin negative
Synaptophysin negative
TTF-1 negative
Thyroglobulin negative
PSA negative.
Diagnostic Utility:
CD117 positivity characteristic (90% cases)
Helps distinguish from other basaloid tumors
Dual immunoprofile confirms mixed differentiation
SOX10 highlights myoepithelial component
Ki-67 index varies with pattern (solid highest)
p63/CK7 highlights dual population.
Molecular Subtypes:
Two major fusion types: MYB-NFIB (most common, 40-50%)
MYBL1-NFIB (10-15%)
MYB overexpression seen in most cases
Fusion-negative cases exist
Different fusions may affect prognosis and behavior.
Molecular/Genetic
Genetic Mutations:
MYB-NFIB fusion in 40-50% of cases
MYBL1-NFIB fusion in 10-15%
t(6;9) translocation creates MYB-NFIB
MYB amplification in some cases
NOTCH1 mutations in subset
PI3K pathway alterations.
Molecular Markers:
MYB overexpression (transcription factor)
NFIB rearrangement
c-kit (CD117) overexpression
EGFR expression variable
p53 mutations rare
Rb pathway alterations.
Prognostic Significance:
MYB-NFIB fusion associated with better outcomes
Solid pattern worst prognosis
Cribriform pattern best prognosis
Perineural invasion affects local control
Distant metastases develop late (lung, bone, brain)
10-year survival 60-70%.
Therapeutic Targets:
c-kit inhibitors (imatinib) limited efficacy
EGFR inhibitors under investigation
Anti-angiogenic agents
Immune checkpoint inhibitors
Targeted therapy based on molecular profile
Radiation therapy important for local control.
Differential Diagnosis
Similar Entities:
Basal cell adenoma (benign, no neural invasion)
Pleomorphic adenoma (chondromyxoid matrix)
Basaloid squamous cell carcinoma (squamous differentiation)
Neuroendocrine carcinoma (chromogranin+)
Polymorphous adenocarcinoma (minor gland location).
Distinguishing Features:
Adenoid cystic: CD117 positive
Cribriform pattern
Perineural invasion
Basal cell adenoma: Benign morphology
No neural invasion
Pleomorphic adenoma: Chondromyxoid matrix
Mixed cell types
Basaloid SCC: Squamous differentiation
p63 diffusely positive
Neuroendocrine: Neuroendocrine markers positive.
Diagnostic Challenges:
Scant cellularity may limit diagnosis
Solid pattern may lack characteristic features
Distinction from other basaloid tumors
Crush artifacts common
Mixed patterns may be confusing
Clinical correlation essential (pain, neural symptoms).
Rare Variants:
Dedifferentiated adenoid cystic carcinoma
High-grade transformation
Clear cell variant
Oncocytic variant
Mucin-producing variant
Sarcomatoid transformation.
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
Uniform small basaloid cells with dual ductal and myoepithelial differentiation
Morphological Features
Cribriform pattern with cylindromatous spaces and hyaline material
Background
Proteinaceous background with basement membrane material
Pattern Assessment
Predominantly [cribriform/tubular/solid] pattern identified
Milan System Category
Category VI - Malignant
Cytological Diagnosis
Adenoid cystic carcinoma
Recommendation
Urgent oncological consultation. Neural assessment required. Staging studies recommended