Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma - OMPATH
## Overview & Epidemiology
Non-Hodgkin Lymphoma (NHL) is a diverse group of clonal lymphoid tumors. Approximately 85% are of B-cell origin, while 15% arise from T or NK cells. It is the fifth most common malignancy in developed countries, with a rising incidence over the last 50 years. Unlike Hodgkin lymphoma, NHL is characterized by irregular spread, variable natural history, and significant extranodal involvement.
## WHO Classification
Classification is based on histology, immunophenotype, genotype, age, and site of origin.
### B-cell Subtypes (85%)
- Diffuse large B-cell lymphoma (DLBCL): 37%
- Follicular lymphoma: 29%
- CLL/SLL: 12%
- MALT lymphoma: 9%
- Mantle cell lymphoma (MCL): 7%
- Burkitt lymphoma, Lymphoplasmacytic lymphoma, Hairy cell leukaemia.
### T/NK-cell Subtypes (15%)
- Adult T-cell lymphoma/leukaemia (HTLV-1 associated)
- Mycosis fungoides / Sézary syndrome
- Anaplastic large cell lymphoma (ALK+)
- Peripheral T-cell lymphoma
## Grading: Low-Grade vs. High-Grade
| Feature | Low-Grade (Indolent) | High-Grade (Aggressive) |
|---|---|---|
| Course | Slow-growing | Rapidly progressive |
| Examples | Follicular, MALT, SLL | DLBCL, Burkitt, Lymphoblastic |
| Curability | Difficult to cure | More often curable |
| Urgency | Watch and wait often acceptable | Urgent treatment required |
## Pathogenesis & Etiology
- **Chromosomal Translocations**: Often involve Immunoglobulin (Ig) genes on chromosomes 2, 14, or 22, leading to oncogene overexpression (e.g., BCL-2, MYC).
- **Infectious Associations**:
- EBV: Burkitt lymphoma, PTLD.
- HTLV-1: Adult T-cell leukaemia/lymphoma.
- HHV-8: Primary effusion lymphoma.
- H. pylori: Gastric MALT lymphoma.
- Hepatitis C: Marginal zone lymphoma.
- HIV-1: High-grade B-cell and CNS lymphomas.
## Clinical Features
1. **Lymphadenopathy**: Asymmetric, painless, superficial nodes (most common).
2. **B Symptoms**: Fever, night sweats, weight loss (indicates disseminated disease).
3. **Extranodal Disease**: GI tract (most common site after bone marrow), Waldeyer’s ring (oropharyngeal), skin, brain, and testis.
4. **Cytopenias**: Due to bone marrow involvement or splenic sequestration.
## Investigations
- **Biopsy (Gold Standard)**: Trucut or whole lymph node biopsy. Fine needle aspiration (FNA) is insufficient for architecture.
- **Immunophenotyping**: Confirms clonality via light chain restriction (kappa/lambda).
- **Laboratory**: FBC, LDH (prognostic marker for tumor burden), Uric acid, HIV status.
- **Imaging**: PET/CT for staging (Ann Arbor System) and monitoring response.
## Key Cytogenetics
- **Follicular**: t(14;18); BCL-2 overexpression.
- **Mantle Cell**: t(11;14); Cyclin D1 overexpression.
- **Burkitt**: t(8;14); MYC overexpression.
- **Anaplastic Large Cell (ALCL)**: t(2;5); ALK overexpression.
## Treatment Principles
- **Chemotherapy**: R-CHOP is the standard for DLBCL.
- **Monoclonal Antibodies**: Anti-CD20 (Rituximab) for B-cell NHL; Anti-CD30 (Brentuximab) for ALCL.
- **Targeted Therapy**: Ibrutinib (BTK inhibitor), Venetoclax (BCL-2 inhibitor), Idelalisib (PI3K inhibitor).
- **Specific Management**:
- **Gastric MALT**: H. pylori eradication (antibiotics).
- **Burkitt**: Intensive regimens (e.g., CODOX-M/IVAC) + CNS prophylaxis.
- **Waldenström’s**: Plasmapheresis for acute hyperviscosity.