Definition/General
Introduction:
Acinic cell carcinoma is a malignant epithelial tumor composed of cells resembling serous acinar cells of salivary glands
Represents 10-15% of all salivary gland malignancies
Characterized by granular, basophilic cytoplasm containing zymogen-like granules
Shows variable morphological patterns and generally indolent behavior.
Origin:
Arises from acinar cells or intercalated duct cells with acinar differentiation
Maintains serous acinar phenotype
Secretory granules contain amylase and other enzymes
May arise from pre-existing pleomorphic adenoma
Shows acinar cell differentiation markers.
Classification:
WHO Classification: Acinic cell carcinoma
Milan System: Category V or VI (Suspicious/Malignant)
Histological patterns: solid, microcystic, papillary-cystic, follicular
No standard grading system
High-grade transformation can occur.
Epidemiology:
Accounts for 10-15% of salivary gland malignancies
Wide age range with peak in 4th-5th decades
Slight female predominance
Parotid gland most common site (90%)
Bilateral occurrence in 5% cases
Indian population shows similar demographic patterns.
Clinical Features
Presentation:
Slowly growing, painless mass
Usually well-circumscribed
Size typically 2-6 cm
May be multinodular
Rarely causes facial nerve paralysis
Mobile on palpation initially.
Symptoms:
Usually asymptomatic in early stages
Mild pain (20-30% cases)
Swelling main complaint
Rarely causes facial weakness
No functional salivary impairment
Regional lymphadenopathy uncommon.
Risk Factors:
Female gender (slight predominance)
Middle age
Prior radiation exposure (weak association)
No association with smoking or alcohol
Genetic predisposition not established
Autoimmune conditions (minimal association).
Screening:
Clinical examination for parotid masses
Bilateral palpation important
Imaging: ultrasound first-line
MRI/CT for detailed assessment
FNAC for cytological diagnosis
Functional assessment of facial nerve.
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Gross Description
Appearance:
FNAC aspirate typically moderately to highly cellular
Clear to slightly turbid appearance
Volume usually 1-3 ml
May be slightly viscous
Contains cellular aggregates.
Characteristics:
Fluid consistency thin to moderate
May contain tissue fragments
Absence of mucoid material
May be blood-tinged
Contains abundant cellular material.
Size Location:
Usually yields adequate cellular material
Multiple passes may show different patterns
Superficial tumors easily sampled
Deep lobe tumors may need imaging guidance
Sample quality generally good.
Multifocality:
Usually unifocal tumor
Bilateral occurrence possible (5%)
May be multinodular within gland
Rarely shows lymph node metastases
Local recurrence if incompletely excised.
Microscopic Description
Histological Features:
Cells resembling normal acinar cells with granular cytoplasm
Basophilic, granular cytoplasm containing zymogen-like granules
Round to oval nuclei with fine chromatin
Variable architectural patterns
PAS-positive granules (diastase resistant).
Cellular Characteristics:
Large cells with abundant cytoplasm
Cytoplasm is finely granular and basophilic
Eccentric nuclei with fine chromatin
Small, inconspicuous nucleoli
May show clear cell change
Vacuolated cytoplasm in some cells.
Architectural Patterns:
Solid pattern: sheets and clusters of cells
Microcystic pattern: small cystic spaces
Papillary-cystic pattern: papillary projections
Follicular pattern: thyroid-like appearance
Mixed patterns common in single specimen.
Grading Criteria:
No standard grading system
Nuclear morphology generally bland
Mitotic activity low to moderate
High-grade transformation shows pleomorphism
Necrosis uncommon
Overall architecture maintained.
Immunohistochemistry
Positive Markers:
Amylase positive (characteristic)
PAS positive (diastase resistant)
CK7 positive
EMA positive
GCDFP-15 positive
Lysozyme positive
Lactoferrin positive
DOG-1 positive (subset).
Negative Markers:
S-100 negative
Chromogranin negative
Synaptophysin negative
Thyroglobulin negative
CD117 negative
p63 negative
SMA negative
TTF-1 negative.
Diagnostic Utility:
Amylase positivity characteristic feature
PAS stain highlights zymogen granules
Helps distinguish from other granular cell tumors
CK7 confirms epithelial nature
Ki-67 index typically low (<10%)
DOG-1 positive in subset of cases.
Molecular Subtypes:
No specific molecular subtypes recognized
NR4A3 rearrangements in subset of high-grade cases
HTN3-MSANTD3 fusion rarely described
Most cases show no specific alterations
Copy number changes in aggressive variants.
Molecular/Genetic
Genetic Mutations:
Generally genetically stable tumors
NR4A3 rearrangements in high-grade transformation
TP53 mutations in aggressive variants
HRAS mutations occasionally
PIK3CA mutations rare
Chromosomal gains/losses in some cases.
Molecular Markers:
NR4A3 (NOR1) rearrangements detectable by FISH
Amylase gene expression maintained
Acinar differentiation markers preserved
Low proliferation indices
Intact DNA repair mechanisms
Normal apoptotic pathways.
Prognostic Significance:
Generally good prognosis with complete excision
10-year survival 80-90%
Local recurrence if incomplete excision
Distant metastases rare (5-10%)
High-grade transformation worsens prognosis
Late recurrences possible (>10 years).
Therapeutic Targets:
Surgical excision primary treatment
Radiation therapy for high-grade or recurrent tumors
Targeted therapy limited options
Immunotherapy under investigation
Clinical trials for recurrent disease
Long-term follow-up essential.
Differential Diagnosis
Similar Entities:
Normal acinar cells (reactive/hyperplastic)
Oncocytoma (mitochondrial granules)
Pleomorphic adenoma (chondromyxoid matrix)
Clear cell carcinoma (clear cytoplasm)
Granular cell tumor (S-100 positive)
Metastatic renal cell carcinoma.
Distinguishing Features:
Acinic cell: Amylase positive
PAS-positive granules
Basophilic cytoplasm
Oncocytoma: Mitochondrial stains
Eosinophilic cytoplasm
Normal acinar: Benign morphology
Context-dependent
Pleomorphic adenoma: Matrix component
Mixed cell types
Granular cell tumor: S-100 positive
Different location.
Diagnostic Challenges:
Clear cell variant may be difficult
Distinction from normal acinar tissue
Oncocytic change may be confusing
Microcystic pattern mimics other tumors
Follicular pattern resembles thyroid
High-grade areas may lose typical features.
Rare Variants:
Clear cell variant: glycogen-rich cells
Oncocytic variant: mitochondrial-rich cells
Lymphoepithelial variant: prominent lymphoid infiltrate
Papillary-cystic variant
Dedifferentiated acinic cell carcinoma
High-grade 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 parotid gland mass
Specimen Adequacy
Adequate for evaluation - contains representative tumor cells
Cellular Composition
Uniform population of cells with granular, basophilic cytoplasm
Morphological Features
Acinar-type cells with abundant granular cytoplasm and round nuclei
Cytoplasmic Granules
Basophilic, zymogen-like granules throughout cytoplasm
Architectural Pattern
Predominantly [solid/microcystic/papillary-cystic] pattern
Background
Clean cellular background with scattered single cells
Milan System Category
Category VI - Malignant
Cytological Diagnosis
Acinic cell carcinoma
Recommendation
Histopathological correlation recommended. PAS/amylase stains suggested