Explore Non-Hodgkin Lymphoma (NHL) including its classification, epidemiology, clinical features, diagnostic methods, and current treatment principles for vario
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.