Definition/General
Introduction:
Warthin tumor (papillary cystadenoma lymphomatosum) is the second most common benign salivary gland tumor after pleomorphic adenoma
Represents 10-15% of all parotid gland tumors
Characterized by oncocytic epithelial cells and dense lymphoid stroma
FNAC shows distinctive dual population of oncocytes and lymphoid cells
Also known as adenolymphoma.
Origin:
Arises from ductal epithelium entrapped within intraparotid lymph nodes
Epithelial component shows oncocytic metaplasia
Lymphoid component represents reactive lymphoid tissue
Develops from heterotopic salivary tissue within lymph nodes
Shows papillary architecture with cystic spaces.
Classification:
Classified under Milan System Category IV - Neoplasm: Benign
Subtype of oncocytic tumor
No grading system for benign lesion
Variants include stroma-poor and stroma-rich types
Rarely shows malignant transformation (<1%).
Epidemiology:
Strong male predominance (male:female = 7-10:1)
Peak incidence in 6th-7th decades
Almost exclusively involves parotid gland (95% cases)
Strong association with smoking (80-90% patients)
Bilateral occurrence in 10-20% cases
Indian population shows similar patterns with increasing smoking prevalence.
Clinical Features
Presentation:
Painless, slowly enlarging mass in parotid gland
Often multilobulated on palpation
May be bilateral (more common than other salivary tumors)
Size typically 2-6 cm
Well-circumscribed and mobile
May show rapid growth during infection.
Symptoms:
Usually asymptomatic except for visible swelling
Occasional mild tenderness
May have fluctuant consistency due to cystic areas
No functional impairment of salivation
Rarely causes facial asymmetry
Patients often have smoking history.
Risk Factors:
Male gender (strongest risk factor)
Advanced age (>50 years)
Smoking history (most significant modifiable risk)
Possible viral infections (EBV, CMV)
Autoimmune conditions (weak association)
No hereditary predisposition.
Screening:
Clinical examination for parotid masses
Bilateral palpation important
Imaging: ultrasound first-line
CT/MRI for detailed assessment
FNAC for definitive cytological diagnosis
Consider smoking cessation counseling.
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Gross Description
Appearance:
FNAC aspirate typically moderately to highly cellular
Often blood-tinged due to vascularity
May contain cystic fluid component
Color ranges from clear to turbid
Volume usually 2-5 ml per aspiration.
Characteristics:
Fluid may be slightly viscous
Contains both cellular and fluid components
Brownish tinge from hemosiderin
May show foamy appearance
Absence of mucoid material (unlike pleomorphic adenoma).
Size Location:
Usually yields abundant material due to cystic nature
Multiple passes may provide different components
Superficial lobe tumors easier to sample
Deep lobe involvement less common
Bilateral sampling may be needed.
Multifocality:
Bilateral occurrence more common than other salivary tumors
May be multifocal within gland
Usually unifocal per gland
No associated lymph node enlargement
Rarely involves minor salivary glands.
Microscopic Description
Histological Features:
Dual population of oncocytic epithelial cells and mature lymphoid cells
Oncocytes show abundant granular cytoplasm and round nuclei
Lymphoid cells include small mature lymphocytes and plasma cells
Background may contain proteinaceous material
Absence of chondromyxoid matrix.
Cellular Characteristics:
Oncocytic cells: large polygonal cells with abundant eosinophilic cytoplasm
Cytoplasm is finely granular (mitochondrial)
Nuclei are round to oval with prominent nucleoli
Lymphoid cells: predominantly small mature lymphocytes
Plasma cells and tingible body macrophages may be present.
Architectural Patterns:
Oncocytic cells in cohesive sheets and clusters
May show papillary arrangements
Lymphoid cells in dense aggregates
Mixed pattern of epithelial and lymphoid elements
Cystic spaces lined by oncocytic epithelium
Germinal centers may be present.
Grading Criteria:
No grading system for benign tumor
Cellularity is typically high
Nuclear morphology is uniform
Mitotic activity is minimal
Lymphoid component shows mature morphology
Overall architecture is orderly.
Immunohistochemistry
Positive Markers:
Oncocytic cells: Mitochondrial antibody positive
CK7 positive
EMA positive
GCDFP-15 positive
Lysozyme positive
Lymphoid cells: CD20 positive (B cells)
CD3 positive (T cells)
CD68 positive (macrophages).
Negative Markers:
Oncocytic cells: S-100 negative
Chromogranin negative
Synaptophysin negative
Thyroglobulin negative
Lymphoid cells: CD10 negative
bcl-2 negative in germinal centers
Cyclin D1 negative.
Diagnostic Utility:
IHC confirms oncocytic nature of epithelial cells
Lymphoid markers confirm polyclonal B cell population
Helps distinguish from lymphoepithelial carcinoma
Useful in cases with predominant lymphoid component
Ki-67 index low in epithelial component.
Molecular Subtypes:
No specific molecular subtypes
Polyclonal lymphoid population (not monoclonal)
Normal immunoglobulin gene rearrangements
Absence of oncogenic mutations
Mitochondrial DNA may show alterations (smoking-related).
Molecular/Genetic
Genetic Mutations:
Generally diploid tumor without significant mutations
Possible mitochondrial DNA alterations (smoking-related)
p53 mutations rare
No consistent chromosomal aberrations
Oncogene activation not detected
Normal tumor suppressor gene expression.
Molecular Markers:
High mitochondrial enzyme expression
Normal cell cycle regulators
Low proliferation markers
Polyclonal immunoglobulin patterns
Normal apoptosis regulators
Cytochrome C oxidase overexpression.
Prognostic Significance:
Excellent prognosis with complete surgical excision
Very low recurrence rate (<2%)
Malignant transformation extremely rare
Bilateral tumors do not affect prognosis
Long-term survival is near 100%
No molecular markers for progression prediction.
Therapeutic Targets:
No targeted therapy required for benign tumor
Surgical excision is curative
Smoking cessation may prevent new tumors
No molecular targets identified
Focus on complete surgical removal.
Differential Diagnosis
Similar Entities:
Oncocytoma (pure oncocytic cells, no lymphoid component)
Acinic cell carcinoma (granular cells, different architecture)
Lymphoepithelial carcinoma (malignant features, EBV+)
Pleomorphic adenoma (chondromyxoid matrix)
Chronic sialadenitis (inflammatory, no oncocytes).
Distinguishing Features:
Warthin tumor: Dense lymphoid background
Oncocytic epithelium
Bilayer epithelium
Oncocytoma: No lymphoid component
Pure oncocytic cells
Acinic cell: Granular cytoplasm
Different nuclear features
Lymphoepithelial: Malignant morphology
EBV positive
Pleomorphic adenoma: Chondromyxoid matrix
Myoepithelial cells.
Diagnostic Challenges:
Lymphoid-rich cases may mimic lymphoma
Oncocyte-poor cases difficult to diagnose
Crush artifacts may obscure morphology
Distinction from metastatic renal cell carcinoma
Infected cases show reactive changes
Sampling adequacy issues.
Rare Variants:
Stroma-poor Warthin tumor: minimal lymphoid component
Metaplastic variant: squamous or sebaceous differentiation
Oncocytic hyperplasia: reactive changes
Malignant transformation: carcinoma arising in Warthin tumor
Infected Warthin tumor: acute inflammatory changes.
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 epithelial and lymphoid cells
Cellular Composition
Dual population of oncocytic epithelial cells and mature lymphoid cells
Morphological Features
Oncocytic cells with abundant granular cytoplasm in sheets and clusters
Lymphoid Component
Dense background of mature lymphocytes with plasma cells and tingible body macrophages
Background
Mixed cellular and proteinaceous background, no chondromyxoid matrix
Milan System Category
Category IV - Neoplasm: Benign (favor Warthin tumor)
Cytological Diagnosis
Warthin tumor (papillary cystadenoma lymphomatosum)
Recommendation
Surgical excision recommended. Examine contralateral parotid for bilateral disease