Lymphoma
Malignant lymphoproliferative disorders — from the germinal center and its translocations to staging and anti-CD20 immunotherapy.
Physiology of lymphocytes
B-cells
Humoral immunity — antibody production & antigen presentation.
T-cells
Cell-mediated immunity — direct killing (Tc) & regulation (Th). Markers: TCR, CD3, CD4, CD8.
NK cells
Innate surveillance — rapid response to viral / tumour cells.
All arise from marrow stem cells; T-cells migrate to the thymus to mature.
B-cell differentiation
CD10⁺ CD19⁺
IgD⁺ IgM⁺ CD20⁺
CD38⁺ CD138⁺
Risk factors & translocations
Risk factors
- Chronic antigenic stimulation (viral / bacterial)
- Immunodeficiency (post-transplant); autoimmune disease (SLE, RA)
- Immunosuppressant medications
Signature translocations
- t(11;14) → Cyclin D1 · Mantle cell
- t(14;18) → BCL2 · Follicular
- t(8;14) → C-Myc · Burkitt
Four families of lymphoid neoplasm
Mature B-cell
- CLL/SLL
- Follicular
- DLBCL
- Burkitt · Mantle
Mature T/NK
- Mycosis fungoides
- Peripheral T-cell
- Anaplastic large cell
Hodgkin
- Nodular sclerosis
- Mixed cellularity
Precursor
- Lymphoblastic leukemia / lymphoma
Where in the germinal center?
A lymphoma’s cell of origin maps onto the follicle. Hover or tap a zone to see what arises there.
Follicular · Burkitt · DLBCL
The germinal / follicle center gives rise to follicular lymphoma, Burkitt, and DLBCL.
Clinical presentation
B-symptoms
- Unexplained fever
- Drenching night sweats
- Weight loss > 10%
Local disease
- Painless, rubbery nodal enlargement
- GI mass / obstruction
- Rash / mycosis fungoides
Virchow’s node (left supraclavicular) is a red flag for thoraco-abdominal malignancy.
Syndromes at a distance
| Syndrome | Presentation | Association |
|---|---|---|
| Limbic encephalitis (Ophelia) | Memory loss, confusion | Hodgkin (anti-mGluR5) |
| Cerebellar degeneration | Ataxia | Hodgkin (anti-Tr) |
| Myasthenia gravis | Muscle weakness | Thymoma / lymphoma |
| Dermatomyositis | Rash + weakness | NHL |
Tumor lysis syndrome (PUCK)
Rapid cell death dumps intracellular contents into the blood.
Aggressive hydration · allopurinol · rasburicase.
Lupus, or lymphoma?
- Fatigue, weight loss, knee pain, hair loss
- Hepatosplenomegaly; no superficial nodes
- Leucopenia, normocytic anemia, high LDH, ANA⁺
The dilemma
ANA⁺ and joint pain suggest lupus — but high LDH + organomegaly raise malignancy. Two stories, one patient. Tissue will decide.
FNA vs excisional biopsy
Fine needle aspiration
Cytology only — architecture is lost. Often reads “reactive lymphoid proliferation” — a false negative.
Excisional biopsy
Gold standard. Preserves nodal architecture → accurate WHO classification.
Staging: PET/CT finds metabolic “hot spots”; CT assesses organ involvement.
Rituximab & the CD20 flag
Accurate classification unlocks targeted therapy — a monoclonal antibody that tags the malignant B-cell for destruction.
Mechanism
Anti-CD20 binds the antigen → the cell is marked for destruction.
Four pillars of treatment
- Chemotherapy (CHOP)
- Radiotherapy
- Immunotherapy (anti-CD20)
- Targeted molecular therapy
Five clinical takeaways
Definition
Malignancy of mature lymphocytes in nodes or extranodal tissue.
Pathogenesis
Driven by translocations (e.g. t(14;18)) and immune dysregulation.
Diagnosis
The great mimicker — excisional biopsy is mandatory.
Emergency
Watch for tumor lysis (hyperkalemia, hyperuricemia).
“Accurate histology guides targeted immunotherapy — the tissue is the issue.”
End of lecture.
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