Definition/General
Introduction:
Primary pulmonary lymphoma is rare malignancy of lung
Represents 0.4% of all lung malignancies
3-4% of extranodal lymphomas
MALT lymphoma most common type
B-cell origin predominantly.
Origin:
Arises from bronchus-associated lymphoid tissue (BALT)
Acquired MALT in response to chronic inflammation
Clonal B-cell proliferation
Autoimmune associations.
Classification:
WHO 2017: MALT lymphoma (most common)
Diffuse large B-cell lymphoma
Lymphomatoid granulomatosis
Primary effusion lymphoma
NK/T-cell lymphoma (rare).
Epidemiology:
Peak incidence 5th-6th decades
Female predominance
Associated with autoimmune diseases
Sjögren syndrome
Immunosuppressed patients.
Clinical Features
Presentation:
Chronic cough
Dyspnea
Chest pain
Weight loss
Low-grade fever
Recurrent pneumonia
Hemoptysis rare.
Symptoms:
Persistent cough
Shortness of breath
Constitutional symptoms
Chest discomfort
Fatigue
Night sweats
Recurrent infections.
Risk Factors:
Autoimmune diseases (Sjögren)
Immunosuppression
EBV infection
HIV infection
Organ transplantation
Chronic inflammation.
Screening:
Chest CT
Multiple nodules/masses
Ground-glass opacities
Hilar lymphadenopathy
Pleural effusion
Tissue biopsy essential.
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Gross Description
Appearance:
Multiple nodules
Gray-white, firm
Well-circumscribed
Homogeneous cut surface
No necrosis (MALT)
Consolidation pattern.
Characteristics:
Fleshy consistency
Tan-gray color
Nodular appearance
Smooth surface
Infiltrative growth
Pleural involvement.
Size Location:
Multiple bilateral nodules
Lower lobe predilection
Peripheral distribution
Variable size (0.5-10 cm)
Diffuse infiltration.
Multifocality:
Multifocal disease common
Bilateral involvement
Synchronous lesions
Hilar lymphadenopathy
Pleural spread.
Microscopic Description
Histological Features:
MALT lymphoma: Small lymphocytes, marginal zone cells
DLBCL: Large B-cells, sheets
Lymphoepithelial lesions
Reactive germinal centers
Plasma cell differentiation.
Cellular Characteristics:
Small to medium B-cells (MALT)
Centrocyte-like cells
Monocytoid B-cells
Large transformed cells (DLBCL)
Plasma cells.
Architectural Patterns:
Marginal zone pattern
Peribronchial infiltration
Lymphoepithelial lesions
Sheet-like growth (DLBCL)
Follicular colonization.
Grading Criteria:
Low-grade (MALT lymphoma)
High-grade (DLBCL)
Transformation assessment
Large cell component
Proliferation index.
Immunohistochemistry
Positive Markers:
CD20 - positive (B-cells)
CD79a - positive
PAX5 - positive
BCL2 - positive
CD43 - positive (MALT)
CD21 - positive (follicular dendritic cells).
Negative Markers:
CD3 - negative
CD5 - negative
CD10 - negative
BCL6 - negative (MALT)
Cyclin D1 - negative.
Diagnostic Utility:
CD20 positivity confirms B-cell origin
CD43 helps identify MALT lymphoma
Ki-67 distinguishes low from high-grade
Light chain restriction proves clonality.
Molecular Subtypes:
MALT lymphoma: CD20+, CD43+, BCL6-
DLBCL: CD20+, BCL6+, high Ki-67
Follicular lymphoma: CD10+, BCL2+
All B-cell: CD20+, PAX5+.
Molecular/Genetic
Genetic Mutations:
t(11;18)(q21;q21) - API2-MALT1
t(14;18)(q32;q21) - IGH-MALT1
t(3;14)(p14;q32) - FOXP1-IGH
MYD88 mutations
TNFAIP3 deletions.
Molecular Markers:
NF-κB pathway activation
API2-MALT1 fusion
BCL6 rearrangements
MYC translocations (transformation)
p53 mutations.
Prognostic Significance:
Stage most important
Histologic grade
t(11;18): Better prognosis
Transformation to DLBCL
Extrapulmonary involvement.
Therapeutic Targets:
Rituximab (anti-CD20)
Chemotherapy (CHOP, CVP)
Radiation therapy
Targeted agents (BTK inhibitors)
Immunomodulators.
Differential Diagnosis
Similar Entities:
Reactive lymphoid hyperplasia
Lung adenocarcinoma
Inflammatory pseudotumor
Organizing pneumonia
Metastatic lymphoma.
Distinguishing Features:
Lymphoma: Monoclonal B-cells, CD20+
Reactive: Polyclonal, mixed cells
Adenocarcinoma: TTF1+, Napsin A+
IPT: ALK+, younger age
OP: Masson bodies.
Diagnostic Challenges:
Small biopsies
Crush artifact
Reactive vs neoplastic
Flow cytometry helpful
Molecular studies.
Rare Variants:
Lymphomatoid granulomatosis
Primary effusion lymphoma
NK/T-cell lymphoma
Hodgkin 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.
Specimen Information
[Biopsy/lobectomy] specimen with multiple nodules
Tumor Description
Multiple gray-white nodules with lymphomatous infiltration
Microscopic Features
[Small B-cell lymphoma with marginal zone pattern / Large B-cell lymphoma with sheet-like growth]
Cell Type
[Small centrocyte-like cells / Large transformed B-cells] with [lymphoepithelial lesions present/absent]
Grade
[Low-grade MALT lymphoma / High-grade DLBCL]
Immunohistochemistry
CD20: Positive, CD79a: Positive, CD3: Negative, CD43: [Positive/Negative], Ki-67: [%]
Flow Cytometry
Monoclonal B-cell population with [kappa/lambda] light chain restriction
Molecular Studies
[FISH/PCR results if performed: t(11;18), t(14;18), etc.]
Stage
Primary pulmonary lymphoma, [Stage IE/IIE/etc.]
Final Diagnosis
Primary pulmonary [MALT lymphoma/DLBCL], [low-grade/high-grade]