📚 Lecture Overview
This lecture covers malignant neoplasms of lymphoid tissue, divided into Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL). It details their pathophysiology, clinical presentations, key diagnostic methods, and subtype-specific treatment strategies essential for clinical hematology.
🎯 Key Concepts & Definitions
- Lymphoma: Malignant neoplasms of lymphoid tissue derived from B-cells, T-cells, or NK-cells, categorized into HL and NHL.
- Reed-Sternberg Cells: Large, multinucleated malignant cells pathognomonic for Hodgkin Lymphoma, often described as 'owl-eye' appearance.
- B Symptoms: Systemic symptoms including unexplained fever, drenching night sweats, and weight loss (>10% body weight) that confer a worse prognosis.
- Ann Arbor Staging System: The standardized staging system used to classify the extent of lymphoma spread from Stage I to IV.
- Indolent vs Aggressive: Indolent lymphomas grow slowly and are generally incurable while manageable; aggressive lymphomas grow rapidly but are often curable with intensive therapy.
📖 Main Content
Introduction and Pathogenesis
- Lymphomas arise from B-cells, T-cells, or NK-cells in lymph nodes or extranodal sites.
- Epstein-Barr virus (EBV) is implicated in Hodgkin lymphoma, Burkitt lymphoma, and NK/T-cell lymphoma.
- Helicobacter pylori infection is linked to gastric MALT lymphoma; chronic hepatitis C is linked to marginal zone lymphomas.
- Immunodeficiency states (HIV with low CD4 counts, common variable immunodeficiency) and autoimmune conditions (rheumatoid arthritis, Sjögren syndrome) elevate lymphoma risk.
- Surgical/Excisional lymph node biopsy is the gold standard for initial diagnosis; fine needle aspiration (FNA) is insufficient because it destroys histologic architecture.
- Baseline evaluation requires physical exam, CBC, comprehensive metabolic profile, lactate dehydrogenase (LDH), CT scan of chest, abdomen, and pelvis, and bone marrow biopsy.
Hodgkin Lymphoma (HL)
- Characterized by a bimodal age distribution (young adults & elderly) and painless peripheral lymphadenopathy (frequently cervical or supraclavicular).
- Alcohol-induced lymph node pain immediately after ingestion is uncommon but pathognomonic for HL.
- Classic HL Immunophenotype: CD15+, CD30+, and weak PAX5.
- Histologic Subtypes:
- Nodular Sclerosis: Most common, seen in young females, features lacunar cells and surrounding fibrosis, good prognosis.
- Mixed Cellularity: Rich in Reed-Sternberg cells and inflammatory cells, associated with EBV, intermediate prognosis.
- Lymphocyte-Rich: Rare, very favorable prognosis.
- Lymphocyte-Depleted: Elderly and HIV patients, numerous atypical cells, poor prognosis.
- Treatment: Combined-modality therapy using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) combined with radiation for early stages. Advanced stages use ABVD or BEACOPP.
Non-Hodgkin Lymphoma (NHL): B-Cell Subtypes
- Diffuse Large B-Cell Lymphoma (DLBCL):
- Most common aggressive NHL (>30% of cases).
- Presents with rapidly enlarging mass, systemic symptoms, and potential extranodal involvement (commonly GI tract).
- Standard treatment: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Curable in ~60%.
- Follicular Lymphoma (FL):
- Most common indolent B-cell NHL, derived from centrocytes and centroblasts.
- Associated with t(14;18) translocation leading to BCL-2 overexpression (anti-apoptotic).
- Can transform into aggressive DLBCL.
- Managed via watchful waiting or rituximab-based therapy (e.g., R-CHOP or R-Benda).
- Mantle Cell Lymphoma (MCL):
- Aggressive disease affecting older men, associated with t(11;14) leading to Cyclin D1 overexpression.
- Frequently presents at stage IV involving bone marrow, liver, and Waldeyer's ring.
- Burkitt Lymphoma:
- Highly aggressive with a classic starry-sky appearance on histology.
- Characterized by c-MYC translocation (t(8;14)).
- Endemic form presents with a jaw mass in Africa; sporadic form presents with an abdominal mass. High propensity for CNS involvement requiring prophylaxis.
- MALT Lymphoma:
- Indolent extranodal marginal zone lymphoma linked to chronic inflammation or infection (H. pylori).
- Gastric MALT responds to H. pylori eradication antibiotics in 50%-80% of early cases.
Non-Hodgkin Lymphoma (NHL): T-Cell and NK-Cell Subtypes
- Peripheral T-Cell Lymphoma: Heterogeneous, aggressive course with poor response to standard chemotherapy.
- Anaplastic Large Cell Lymphoma (ALCL): CD30+; ALK-positive has a better prognosis than ALK-negative.
- Adult T-Cell Leukemia/Lymphoma: Associated with HTLV-1 infection; presents with lymphadenopathy, skin lesions, and hypercalcemia.
- Extranodal NK/T-Cell Lymphoma: Associated with EBV, commonly affects the nasal cavity and upper aerodigestive tract.
📊 Visual Learning
flowchart TD
A[Lymphoma Diagnosis] --> B[Excisional Biopsy]
B --> C{Cell Type}
C -->|Reed-Sternberg Cells| D[Hodgkin Lymphoma]
C -->|Other Lymphoid Cells| E[Non-Hodgkin Lymphoma]
D --> F[ABVD Chemotherapy]
E --> G[Subtype Analysis]
G -->|Aggressive DLBCL| H[R-CHOP Regimen]
G -->|Indolent Follicular| I[Watchful Waiting or Rituximab]
mindmap
root("Lymphoma Translocations")
"Follicular Lymphoma"
"t 14 18"
"BCL 2 Overexpression"
"Mantle Cell Lymphoma"
"t 11 14"
"Cyclin D1 Overexpression"
"Burkitt Lymphoma"
"t 8 14"
"c MYC Translocation"
graph LR
A[Initial Evaluation] --> B[Physical Exam and Labs]
A --> C[CT Chest Abdomen Pelvis]
A --> D[FDG PET Imaging]
A --> E[Bone Marrow Biopsy]
B --> F[Ann Arbor Staging]
C --> F
D --> F
E --> F
💡 Important Points to Remember
- Gold Standard Diagnostic: Excisional lymph node biopsy is mandatory; FNA is inadequate because it destroys nodal architecture.
- Pathognomonic HL Symptom: Pain in involved lymph nodes immediately following alcohol consumption.
- Classic HL Markers: Positive for CD15 and CD30.
- Follicular Lymphoma Marker: t(14;18) translocation causing BCL-2 overexpression (anti-apoptotic).
- Mantle Cell Lymphoma Marker: t(11;14) translocation causing Cyclin D1 overexpression.
- Burkitt Lymphoma Marker: t(8;14) translocation causing c-MYC activation, presenting with a starry-sky histology.
- First-Line HL Regimen: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine).
- First-Line DLBCL Regimen: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).
- Gastric MALT Treatment: Antibiotic eradication of H. pylori cures a significant percentage of early cases.
- Common Trap: Confusing FNA with excisional biopsy—FNA cannot determine histological architecture or comprehensive subtype.
⚠️ Common Exam Questions
- MCQ Trick: Examiners will ask for the best initial diagnostic test and include "Fine Needle Aspiration (FNA)" as a distractor. The correct answer is always surgical or excisional lymph node biopsy.
- Matching Translocations: Questions frequently test the pairing of specific translocations to their respective lymphomas: t(14;18) for Follicular, t(11;14) for Mantle Cell, and t(8;14) for Burkitt.
- Clinical Presentation Scenarios: Questions describing a young patient with an anterior mediastinal mass and nodular sclerosis histology, or an African child with a rapidly growing jaw mass (Burkitt lymphoma driven by EBV and c-MYC).
📝 Quick Review Checklist
I can explain the difference between Hodgkin and Non-Hodgkin lymphoma
I understand the role of excisional biopsy versus fine needle aspiration
I can define Reed-Sternberg cells and their immunophenotype (CD15+, CD30+)
I know the genetic translocations for Follicular, Mantle Cell, and Burkitt lymphomas
I can recall standard treatment regimens like ABVD and R-CHOP
I recognize pathognomonic clinical features like alcohol-induced lymph node pain