Definition/General
Introduction:
Primary thyroid lymphoma is a rare malignant lymphoid tumor arising in the thyroid gland, accounting for <5% of thyroid malignancies
Most common types are mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL)
On FNAC, shows monomorphic lymphoid population with loss of normal architecture.
Origin:
Arises from lymphoid tissue within thyroid, often in setting of chronic lymphocytic thyroiditis (Hashimoto)
MALT lymphoma develops from marginal zone B-cells
May transform from low-grade to high-grade lymphoma.
Classification:
WHO classification includes MALT lymphoma (60-70%), DLBCL (20-30%), follicular lymphoma (5%), and other rare types
Bethesda System may classify as Category V (Suspicious) or VI (Malignant).
Epidemiology:
Accounts for 2-5% of thyroid malignancies and 1-2% of extranodal lymphomas
Female predominance (4:1)
Peak incidence 50-70 years
Strong association with Hashimoto thyroiditis (60-80% cases).
Clinical Features
Presentation:
Rapidly enlarging thyroid mass or diffuse thyroid enlargement
May present as solitary nodule or multinodular goiter
B-symptoms (fever, night sweats, weight loss) in 10-20% cases.
Symptoms:
Painless thyroid enlargement
Compressive symptoms (dysphagia, dyspnea, hoarseness)
B-symptoms in advanced cases
Hypothyroidism common due to underlying Hashimoto.
Risk Factors:
Hashimoto thyroiditis (most important - 40-80x increased risk)
Autoimmune disorders
Female gender
Advanced age
Immunosuppression.
Screening:
Thyroid ultrasound shows hypoechoic mass with increased vascularity
LDH often elevated
Flow cytometry helpful for diagnosis
PET-CT for staging.
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Gross Description
Appearance:
Fleshy, gray-white mass with fish-flesh appearance
May be well-circumscribed or infiltrative
Soft consistency
Background of chronic thyroiditis often present.
Characteristics:
Size variable from few centimeters to massive enlargement
Homogeneous cut surface
May show areas of necrosis in high-grade lymphomas
Encapsulation uncommon.
Size Location:
Can involve one or both lobes
May extend beyond thyroid capsule
Size ranges 2-15 cm
MALT lymphomas typically smaller than DLBCL.
Multifocality:
May be multifocal within thyroid
Bilateral involvement possible (30% cases)
Regional lymph node involvement in 10-20%
Distant spread in advanced cases.
Microscopic Description
Histological Features:
Monomorphic lymphoid infiltrate effacing normal thyroid architecture
MALT lymphoma: small to medium-sized marginal zone cells
DLBCL: large atypical lymphoid cells with vesicular nuclei.
Cellular Characteristics:
MALT: small lymphocytes with irregular nuclei and moderate cytoplasm
DLBCL: large cells with vesicular nuclei and prominent nucleoli
Mitotic activity higher in DLBCL.
Architectural Patterns:
Diffuse infiltration pattern
Lymphoepithelial lesions in MALT lymphoma
Follicular pattern possible
Complete effacement of thyroid architecture.
Grading Criteria:
MALT lymphoma: low-grade with small cells, low mitotic rate
DLBCL: high-grade with large cells, high mitotic rate (>20 per 10 HPF), frequent apoptoses.
Immunohistochemistry
Positive Markers:
CD20 positive (B-cell marker)
CD79a positive
BCL-2 positive in MALT lymphoma
CD10 variable in DLBCL
Cyclin D1 negative (excludes mantle cell).
Negative Markers:
CD3 negative (excludes T-cell lymphoma)
CD5 negative in most cases
CD23 negative
Thyroglobulin negative
TTF-1 negative
Epithelial markers negative.
Diagnostic Utility:
CD20 confirms B-cell origin
Flow cytometry shows monoclonal B-cell population
Light chain restriction demonstrates clonality
Ki-67 higher in DLBCL (>40%) than MALT (<10%).
Molecular Subtypes:
MALT lymphoma: marginal zone B-cell phenotype
DLBCL: germinal center or non-germinal center subtypes
Different prognostic implications.
Molecular/Genetic
Genetic Mutations:
MALT lymphoma: t(11;18)(q21;q21) API2-MALT1 fusion in 20%
t(14;18)(q32;q21) IGH-MALT1 fusion rare
DLBCL: BCL6 rearrangements common, MYC rearrangements possible.
Molecular Markers:
Monoclonal immunoglobulin gene rearrangements
Ki-67 proliferation index: MALT <10%, DLBCL >40%
p53 mutations in transformation.
Prognostic Significance:
MALT lymphoma: excellent prognosis (>90% 5-year survival) if localized
DLBCL: intermediate prognosis (60-70% 5-year survival)
Stage most important prognostic factor.
Therapeutic Targets:
Rituximab-based therapy for CD20-positive B-cell lymphomas
Radiation therapy for localized MALT lymphoma
Chemotherapy for DLBCL
Surgery rarely indicated.
Differential Diagnosis
Similar Entities:
Hashimoto thyroiditis
Anaplastic thyroid carcinoma
Medullary thyroid carcinoma
Metastatic carcinoma
Follicular dendritic cell sarcoma
Plasmacytoma.
Distinguishing Features:
Hashimoto: polyclonal lymphoid infiltrate, residual follicles
Anaplastic carcinoma: epithelial markers positive, extreme pleomorphism
Medullary: calcitonin positive
Metastatic: site-specific markers.
Diagnostic Challenges:
Distinction from Hashimoto thyroiditis crucial
Reactive lymphoid hyperplasia may mimic low-grade lymphoma
Flow cytometry essential for clonality assessment.
Rare Variants:
Follicular lymphoma of thyroid
Mantle cell lymphoma
Hodgkin lymphoma (very rare)
T-cell lymphoma
Plasmacytoma
Primary effusion lymphoma.
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.
Site and Procedure
Site: Thyroid [right/left], Procedure: Fine needle aspiration cytology
Adequacy
Adequate for evaluation - abundant lymphoid cells
Cellularity
High cellularity with predominantly lymphoid cells
Cellular Population
Monomorphic lymphoid population with [small/large] lymphoid cells
Cellular Features
[Small irregular/Large atypical] lymphoid cells with [scant/moderate] cytoplasm
Follicular Cells
Markedly decreased or absent follicular epithelial cells
Background
Lymphoglandular bodies, [chronic thyroiditis features present/absent]
Special Features
Absence of epithelial differentiation, monomorphic population
Cytological Diagnosis
Suspicious for/Positive for lymphoma - Bethesda Category V/VI
Recommendation
Flow cytometry, hematopathology consultation, core biopsy for subtyping and staging