Overview
This lecture reviews non-Hodgkin's lymphoma (NHL), focusing on its classification, pathogenesis, clinical presentation, histology, and subtypes including marginal zone B-cell, follicular, and mantle cell lymphomas.
Introduction to Non-Hodgkin's Lymphoma
- NHL and Hodgkin's disease are two primary types of malignant lymphomas from lymphoid tissue cells.
- NHL is more unpredictable and often affects extranodal sites compared to Hodgkin's lymphoma.
- Diffuse large B-cell lymphoma and follicular lymphoma are the most common NHL subtypes in developed countries.
- The World Health Organization (WHO) classification system is widely used for NHL categorization.
Classification Systems
- The REAL classification (later updated by WHO) defines lymphoma types using morphology, immunophenotype, genetics, and clinical features.
- WHO classification divides lymphomas into B-cell, T-cell/NK-cell, and Hodgkin's lymphoma.
- NHL can present at various anatomical sites, including oral cavity, pharynx, nasal cavity, paranasal sinuses, and larynx.
Pathogenesis and Risk Factors
- Key mechanisms include immunosuppression, chronic antigen stimulation, and loss of T-cell control.
- Chromosomal translocations are a hallmark, leading to oncogene activation or tumor suppressor gene inactivation.
- Risk factors: immunosuppression, UV radiation, viral infections (EBV, HTLV, HHV8), autoimmune diseases, and occupational exposures.
Clinical Presentation
- Nodal NHL usually presents as painless, multiple, mobile lymph nodes.
- Extranodal NHL commonly affects Waldeyer's ring, oral cavity, salivary glands, thyroid, larynx, nasal cavity, paranasal sinuses, and skin.
- Symptoms vary by site but may include swelling, pain, ulcers, and lytic bone destruction.
Histology and Staging
- NHL histology is described as nodular (clustered cells) or diffuse (uniform cells, loss of architecture).
- The Ann Arbor staging system stages disease I–IV based on nodal/extranodal involvement and systemic symptoms.
- The International Prognostic Index stratifies risk using age, disease stage, extranodal sites, performance status, and LDH levels.
Major NHL Subtypes
Marginal Zone B-cell Lymphoma (MALT)
- Low-grade B-cell neoplasm arising in mucosal sites, often linked to chronic inflammation or autoimmune disease.
- Histology: centrocyte-like cells, lymphoepithelial lesions.
- Immunophenotype: expresses IgM, CD19, CD20, CD22, CD79a; negative for CD5 and CD10.
Follicular Lymphoma
- Tumor of follicle center cells, mostly centrocytes and some centroblasts.
- Genetic hallmark: t(14;18) translocation involving bcl-2 gene.
- Graded by number of centroblasts/high-power field (Grades I–III).
- Immunophenotype: surface immunoglobulin+, CD10+, CD5-, CD23-/+, CD43-.
Mantle Cell Lymphoma
- Typically affects older males with advanced-stage disease.
- Presents in nodes, spleen, Waldeyer's ring, GI tract, bone marrow, and blood.
- Morphology: atypical small to medium lymphoid cells in nodular or diffuse patterns.
- Immunophenotype: CD5+, CD19+, CD20+, CD22+, CD43+, CD79a+, bcl-2+, CD10-, CD23-.
Key Terms & Definitions
- NHL (Non-Hodgkin's Lymphoma) — A diverse group of lymphoid malignancies, often with extranodal presentations.
- Extranodal — Involvement of organs/tissues outside lymph nodes.
- Immunophenotype — Marker profile of cells identified by antibodies.
- Ann Arbor Staging — A system classifying lymphoma by extent and symptoms.
- Centrocyte/Centroblast — Cell types found in follicular lymphoma.
Action Items / Next Steps
- Review WHO classification and key NHL subtypes.
- Study Ann Arbor and International Prognostic Index criteria.
- Prepare for discussion on NHL treatment modalities in future classes.