Definition/General
Introduction:
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in adults, representing 30-40% of all NHL cases
It is an aggressive but potentially curable B-cell neoplasm characterized by large B-lymphoid cells.
Origin:
Arises from mature B-cells at various stages of differentiation
May arise de novo or transform from indolent B-cell lymphomas (transformation from follicular lymphoma in 30% of cases).
Classification:
WHO Classification recognizes DLBCL, NOS as the main category
Molecular subtypes include Germinal Center B-cell (GCB) and Activated B-cell (ABC) types based on cell of origin.
Epidemiology:
Median age 60-70 years
Male predominance (1.4:1)
Incidence increases with age
Higher incidence in immunocompromised patients
Geographic variation with higher rates in developed countries.
Clinical Features
Presentation:
Rapidly enlarging lymph node masses (60-70%)
Extranodal involvement in 30-40% at presentation
B-symptoms in 30% of patients
Superior vena cava syndrome possible.
Symptoms:
Painless lymphadenopathy (most common)
Fever, night sweats, weight loss (B-symptoms)
Abdominal pain/distension
Dyspnea (mediastinal involvement)
Neurologic symptoms (CNS involvement).
Risk Factors:
Immunosuppression (HIV, transplant, autoimmune disorders)
EBV infection
H
pylori infection (gastric DLBCL)
Chronic inflammation
Previous chemotherapy/radiation.
Screening:
No specific screening
Diagnosed by lymph node biopsy
Staging by CT/PET scans
Bone marrow biopsy if indicated
Lumbar puncture for high-risk cases.
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Gross Description
Appearance:
Enlarged lymph nodes with effaced architecture
Cut surface shows homogeneous gray-white to tan appearance
Soft to firm consistency
Necrosis may be present.
Characteristics:
Node size typically >2 cm
Loss of normal nodal architecture
Extracapsular extension common
May form confluent masses
Necrosis in rapidly growing tumors.
Size Location:
Can involve any lymph node group
Cervical, axillary, mediastinal, abdominal nodes common
Extranodal sites: GI tract, CNS, bone, liver, kidney.
Multifocality:
Often multifocal at presentation
Tendency for contiguous spread
Extranodal spread common
CNS involvement in high-risk cases.
Microscopic Description
Histological Features:
Diffuse effacement of nodal architecture by large lymphoid cells
Cells >2x size of normal lymphocytes
High mitotic rate
Scattered apoptotic bodies.
Cellular Characteristics:
Large cells with vesicular nuclei and prominent nucleoli
Abundant basophilic cytoplasm
Nuclear size >normal macrophage nucleus
Pleomorphic nuclear features.
Architectural Patterns:
Diffuse growth pattern obliterating normal architecture
May show vague nodular areas
Sclerosis possible
Necrosis in aggressive cases.
Grading Criteria:
High-grade lymphoma by definition
Mitotic rate >10/hpf typical
Ki-67 proliferation index >40%
Starry-sky pattern may be present.
Immunohistochemistry
Positive Markers:
CD20 positive (>95%)
CD79a positive
PAX5 positive
CD10 positive (GCB type)
BCL6 positive
MUM1/IRF4 positive (ABC type).
Negative Markers:
CD3 negative
CD5 negative (except rare variants)
CD23 negative
TdT negative
CD34 negative
ALK negative.
Diagnostic Utility:
CD20 confirms B-cell origin
Cell of origin classification: GCB (CD10+ or BCL6+/MUM1-) vs ABC (CD10-/BCL6-/MUM1+)
Helps guide therapy.
Molecular Subtypes:
GCB type (40%): Better prognosis
ABC type (50%): Worse prognosis
Unclassified (10%)
Molecular profiling increasingly used.
Molecular/Genetic
Genetic Mutations:
MYC translocations (15%)
BCL2 translocations (20%)
BCL6 translocations (30%)
TP53 mutations
CREBBP/EP300 mutations
Complex karyotype common.
Molecular Markers:
Gene expression profiling distinguishes GCB vs ABC
MYC/BCL2 double-hit lymphomas (poor prognosis)
BCL2 protein expression variable.
Prognostic Significance:
Cell of origin most important: GCB better than ABC
Double/triple-hit lymphomas worse prognosis
MYC overexpression associated with poor outcome.
Therapeutic Targets:
CD20-targeted therapy (rituximab)
BTK inhibitors for ABC type
BCL2 inhibitors
CAR-T cell therapy for relapsed disease.
Differential Diagnosis
Similar Entities:
Burkitt lymphoma
Primary mediastinal B-cell lymphoma
Follicular lymphoma grade 3
Hodgkin lymphoma
Anaplastic large cell lymphoma
Reactive hyperplasia.
Distinguishing Features:
DLBCL: CD20+, Ki-67 variable
Burkitt: CD10+, Ki-67 >95%, MYC+
PMBCL: CD30+, mediastinal
HL: CD15+, CD30+, CD20-.
Diagnostic Challenges:
Distinction from Burkitt lymphoma
Recognition of transformed follicular lymphoma
Primary vs secondary CNS involvement
Double-hit lymphomas.
Rare Variants:
Primary CNS DLBCL
Primary cutaneous DLBCL
Intravascular DLBCL
Plasmablastic lymphoma
ALK-positive DLBCL.
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
[specimen type], measuring [size] cm
Diagnosis
Diffuse Large B-Cell Lymphoma, NOS
Classification
WHO Classification: DLBCL, NOS, [GCB/ABC] type
Histological Features
Shows diffuse proliferation of large B-lymphoid cells
Immunohistochemistry
CD20+, CD79a+, PAX5+, CD10 [+/-], BCL6 [+/-], MUM1 [+/-]
Cell of Origin
Cell of origin: [Germinal Center B-cell/Activated B-cell] type
Proliferation Index
Ki-67 proliferation index: [X]%
Molecular Studies
Cytogenetics: [results if performed]
Special Studies
FISH: [MYC/BCL2/BCL6 status if tested]
Flow cytometry: [if performed]
[other study]: [result]
Prognostic Factors
Prognostic factors: [cell of origin, stage, IPI score]
Final Diagnosis
Final diagnosis: Diffuse Large B-Cell Lymphoma, [GCB/ABC] type