Definition/General
Introduction:
Primary lymphoma of salivary glands represents 2-5% of all salivary gland malignancies and 1-3% of all lymphomas
Most common type is marginal zone lymphoma (MALT) accounting for 70-80% of cases
Strong association with Sjogren syndrome and autoimmune sialadenitis
Shows indolent behavior in most cases.
Origin:
Arises from mucosa-associated lymphoid tissue (MALT) within salivary glands
May develop from chronic inflammatory conditions like Sjogren syndrome
Autoimmune sialadenitis creates favorable microenvironment
Can arise from pre-existing lymphoepithelial lesions
Parotid gland most commonly affected.
Classification:
WHO Classification includes MALT lymphoma (most common)
Diffuse large B-cell lymphoma
Follicular lymphoma
Mantle cell lymphoma
Milan System: Category VI - Malignant
Grading follows standard lymphoma classification.
Epidemiology:
Peak incidence in 6th-7th decades
Strong female predominance (female:male = 3-4:1)
Bilateral involvement in 30-40% cases
Sjogren syndrome association in 60-70%
Indian population shows increasing incidence with improved autoimmune disease recognition.
Clinical Features
Presentation:
Slowly enlarging, painless masses
Often bilateral parotid involvement
Dry mouth and dry eyes (sicca syndrome)
May be multiple nodular lesions
Firm to rubbery consistency
Size ranges from 2-8 cm.
Symptoms:
Xerostomia (dry mouth) prominent
Xerophthalmia (dry eyes)
Swelling main complaint
Usually painless
Difficulty swallowing dry foods
Recurrent parotitis episodes
Systemic B symptoms rare.
Risk Factors:
Sjogren syndrome (strongest association)
Female gender
Advanced age
Autoimmune conditions
Chronic sialadenitis
Epstein-Barr virus (possible association)
Immunosuppression.
Screening:
Assessment for autoimmune conditions
Sjogren syndrome workup (ANA, anti-Ro, anti-La)
Bilateral examination important
Imaging: ultrasound shows multiple hypoechoic nodules
MRI/CT for staging
FNAC of dominant nodules.
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Gross Description
Appearance:
FNAC aspirate typically moderately to highly cellular
Clear to turbid appearance
Volume usually 2-4 ml
May contain lymphoid aggregates
Absence of mucoid material.
Characteristics:
Thin to moderate consistency
Contains dispersed lymphoid cells
May have tissue fragments
Absence of necrosis (typically)
Clean lymphoid appearance.
Size Location:
Usually yields abundant lymphoid cells
Multiple nodules may need separate sampling
Bilateral disease requires sampling both sides
Deep-seated nodules may need imaging guidance
Flow cytometry sample essential.
Multifocality:
Multifocal disease common
Bilateral involvement in 30-40%
May involve multiple salivary glands
Extranodal sites (stomach, lung) possible
Transformation to high-grade lymphoma possible.
Microscopic Description
Histological Features:
Monomorphic population of small to medium-sized lymphoid cells
MALT lymphoma: marginal zone cells and monocytoid B cells
Lymphoepithelial lesions
Plasma cell differentiation
Reactive follicles may be present.
Cellular Characteristics:
Small lymphocytes with round to irregular nuclei
Marginal zone cells: medium-sized with moderate cytoplasm
Monocytoid B cells: abundant clear cytoplasm
Plasma cells and plasmacytoid cells
Centrocyte-like cells
Immunoblasts scattered.
Architectural Patterns:
Diffuse infiltrate of lymphoid cells
Lymphoepithelial lesions: epithelial destruction by lymphocytes
Follicular pattern with reactive centers
Interfollicular pattern
Perivascular infiltration
Ductal infiltration.
Grading Criteria:
Low-grade MALT lymphoma: predominant small cells
High-grade transformation: large cell component >20%
Proliferation index varies
Ki-67 low in MALT (<10%)
Histologic grade affects prognosis.
Immunohistochemistry
Positive Markers:
CD20 positive (B-cell marker)
CD79a positive
PAX5 positive
bcl-2 positive
CD43 positive (aberrant)
IgM positive (surface)
Kappa or Lambda light chain restriction.
Negative Markers:
CD3 negative (T-cell marker)
CD5 negative
CD10 negative
CD23 negative
Cyclin D1 negative
CD21 negative (follicular dendritic cells absent)
bcl-6 negative.
Diagnostic Utility:
Confirms B-cell lymphoma
Light chain restriction proves clonality
Helps distinguish from reactive lymphoid proliferation
Flow cytometry essential for diagnosis
FISH studies for translocation
Molecular studies for clonality.
Molecular Subtypes:
t(11;18)(q21;q21) in 20-30% MALT lymphomas
t(14;18)(q32;q21) less common
t(3;14)(p13;q32) rare
IGH gene rearrangements
API2-MALT1 fusion
Different translocations affect prognosis and treatment response.
Molecular/Genetic
Genetic Mutations:
IGH gene rearrangements (clonal B cells)
API2-MALT1 fusion from t(11;18)
FOXP1 rearrangements
MYD88 mutations (rare in MALT)
TP53 mutations in high-grade transformation
CDKN2A deletions.
Molecular Markers:
Monoclonal immunoglobulin gene rearrangements
bcl-2 overexpression
API2-MALT1 fusion protein
NF-κB pathway activation
Low proliferation indices
Intact DNA repair mechanisms.
Prognostic Significance:
Indolent course for MALT lymphoma
10-year survival >90%
t(11;18) translocation associated with resistance to H
pylori eradication
High-grade transformation worsens prognosis
Bilateral disease may be more aggressive
Extranodal spread affects staging.
Therapeutic Targets:
Rituximab (anti-CD20)
Radiotherapy for localized disease
Chlorambucil for systemic disease
Bendamustine
Bortezomib for refractory cases
BTK inhibitors
Immunomodulatory agents.
Differential Diagnosis
Similar Entities:
Reactive lymphoid hyperplasia (polyclonal)
Chronic sialadenitis (Sjogren syndrome)
Warthin tumor (oncocytes + lymphocytes)
Lymphoepithelial carcinoma (epithelial malignancy)
Metastatic lymphoma from other sites.
Distinguishing Features:
MALT lymphoma: Monoclonal B cells
Light chain restriction
Lymphoepithelial lesions
Reactive hyperplasia: Polyclonal
Mixed cell population
Warthin tumor: Oncocytic epithelium
Bilayer architecture
Lymphoepithelial carcinoma: Malignant epithelium
EBV positive
Sialadenitis: Inflammatory infiltrate
Benign epithelial changes.
Diagnostic Challenges:
Distinction from reactive processes
Flow cytometry essential
Molecular studies for clonality
Small cell size may be overlooked
Lymphoepithelial lesions key feature
Clinical correlation with autoimmune status.
Rare Variants:
Diffuse large B-cell lymphoma (high-grade)
Follicular lymphoma
Mantle cell lymphoma
Burkitt lymphoma
T-cell lymphoma (very rare)
Hodgkin lymphoma (extremely rare)
Plasmablastic lymphoma (immunocompromised).
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 lymphoid cells
Cellular Composition
Monomorphic population of small to medium-sized lymphoid cells
Morphological Features
Small lymphocytes with marginal zone cells and monocytoid B cells
Flow Cytometry
Monoclonal B-cell population with [kappa/lambda] light chain restriction
Immunophenotype
CD20+, CD79a+, CD43+, CD5-, CD10-, CD23-, Cyclin D1-
Background
Lymphoid background with occasional plasma cells and tingible body macrophages
Milan System Category
Category VI - Malignant
Cytological Diagnosis
B-cell lymphoma, favor MALT lymphoma
Recommendation
Hematology-oncology consultation. Molecular studies for staging. Assessment for Sjogren syndrome and bilateral disease