Lymphoma Overview and Classification

## Definition and Introduction Lymphoma is a neoplastic (clonal) lymphoproliferative disorder primarily involving solid lymphoid organs such as lymph nodes. Lymphoid cells can transform at any stage of maturation, leading to malignancies specific to that stage. These may present as leukaemia (bone marrow and blood involvement), lymphoma (solid organ involvement), or both (e.g., CLL/SLL). ## Major Categories | Feature | Hodgkin Lymphoma (HL) | Non-Hodgkin Lymphoma (NHL) | |---|---|---| | Frequency | ~30% | ~70% | | Spread | Orderly, contiguous | Irregular, unpredictable | | Extranodal | Uncommon | Common | | Diagnostic Cells | Reed-Sternberg (RS) cells | Absent | | Origin | B-cell (Classical HL) | 85–90% B-cell; 10-15% T/NK-cell | | Curability | Highly curable | Varies by subtype | ## Non-Hodgkin Lymphoma (NHL) ### Classification (WHO System) Modern classification integrates lineage, differentiation stage, morphology, immunophenotype, genetics, and clinical features. **1. B-cell Neoplasms (85–90%)** * **Precursor B-cell:** B-lymphoblastic leukaemia/lymphoma (B-ALL/LBL). * **Mature B-cell:** CLL/SLL, Follicular lymphoma, Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma, Burkitt lymphoma, MALT lymphoma, Hairy cell leukaemia, Plasma cell myeloma. **2. T/NK-cell Neoplasms (10–15%)** * **Precursor T-cell:** T-lymphoblastic leukaemia/lymphoma. * **Mature T/NK-cell:** Mycosis fungoides, Adult T-cell leukaemia (HTLV-1), Anaplastic large cell lymphoma (ALCL), Peripheral T-cell lymphoma. ### Grading * **Low-Grade (Indolent):** Slow-growing, good chemo response but difficult to cure (e.g., Follicular, SLL, MALT). * **High-Grade (Aggressive):** Rapidly fatal if untreated, but more often curable with intensive therapy (e.g., DLBCL, Burkitt, Lymphoblastic). ## Pathogenesis and Etiology ### Infectious Associations * **EBV:** Burkitt lymphoma, Hodgkin lymphoma, CNS lymphoma. * **HTLV-1:** Adult T-cell leukaemia/lymphoma. * **HIV-1:** DLBCL, Burkitt lymphoma. * **H. pylori:** Gastric MALT lymphoma. * **Hepatitis C:** Marginal zone lymphoma, CLL. ### Genetic Alterations Chromosomal translocations involving Immunoglobulin (Ig) genes often lead to oncogene overexpression: * **Follicular Lymphoma:** t(14;18); BCL-2 overexpression (inhibits apoptosis). * **Mantle Cell Lymphoma:** t(11;14); Cyclin D1 overexpression. * **Burkitt Lymphoma:** t(8;14); MYC overexpression. * **ALCL:** t(2;5); ALK overexpression. ## Clinical Features 1. **Lymphadenopathy:** Asymmetric, painless, superficial nodes. 2. **Constitutional (B) Symptoms:** Fever, drenching night sweats, weight loss (>10% in 6 months). 3. **Extranodal Disease:** GI tract (most common), skin, brain, testis, oropharynx (Waldeyer’s ring). 4. **Cytopenias:** Due to bone marrow infiltration or hypersplenism. ## Investigations * **Biopsy (Gold Standard):** Excisional or Tru-cut biopsy. Fine Needle Aspiration (FNA) is insufficient for primary diagnosis as architecture is required. * **Laboratory:** FBC, ESR, LDH (prognostic marker), Uric acid, LFTs, HIV screening. * **Imaging:** PET/CT scan for staging and assessing treatment response. * **Bone Marrow:** Aspirate and trephine biopsy for staging. ## Staging: Ann Arbor System * **Stage I:** Single lymph node region or single extralymphatic site. * **Stage II:** Two or more regions on the same side of the diaphragm. * **Stage III:** Regions on both sides of the diaphragm; may include the spleen. * **Stage IV:** Disseminated involvement of extralymphatic organs (e.g., bone marrow, liver). * **Suffixes:** A (asymptomatic), B (B-symptoms present), E (extranodal extension). ## Treatment Principles * **Chemotherapy:** R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) is the standard for DLBCL. * **Immunotherapy:** Rituximab (Anti-CD20) targets B-cells via ADCC and complement-mediated lysis. * **Targeted Therapy:** Ibrutinib (BTK inhibitor), Venetoclax (BCL-2 inhibitor), BRAF inhibitors for Hairy Cell Leukaemia. * **Stem Cell Transplant:** Used in relapsed or high-risk cases.