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General Medicine

Non-Hodgkin Lymphoma

A diverse group of blood cancers that start in lymphocytes (white blood cells), causing swollen lymph nodes and potentially spreading throughout the body.

Source: WHO / CDC / NIH Evidence Guidelines
Updated: Aug 17, 2026
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Red Flag Warning & Emergency Situations

Emergency Management: Tumor Lysis Syndrome prophylaxis and treatment: aggressive IV hydration, Allopurinol (300 mg/day) or Rasburicase (0.2 mg/kg IV) to rapidly lower uric acid levels and prevent urate nephropathy.

Core Definition:

Non-Hodgkin Lymphoma is a heterogeneous group of lymphoid malignancies originating from B-cells (85%), T-cells (15%), or NK cells. It is characterized by the uncontrolled, clonal proliferation of abnormal lymphocytes that typically accumulate in lymph nodes, leading to lymphadenopathy, but frequently involves extranodal tissues.

Detailed Overview

NHL encompasses over 60 distinct subtypes with widely varying clinical courses, from indolent (e.g., Follicular Lymphoma) to highly aggressive (e.g., Diffuse Large B-Cell Lymphoma, Burkitt Lymphoma). The pathogenesis involves specific chromosomal translocations disrupting oncogenes or tumor suppressor genes. Unlike Hodgkin lymphoma, NHL tends to spread non-contiguously and often presents with advanced-stage, extranodal disease including bone marrow, GI tract, or CNS involvement.

Epidemiology & Demographics

The most common hematologic malignancy. Incidence is roughly 19 per 100,000 annually in the US. Median age at diagnosis is 67 years. Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype (~30%).

Etiological Mechanism

Most cases are idiopathic. Specific viral infections (EBV, HTLV-1, HIV, HCV), bacterial infections (H. pylori for MALT lymphoma), and autoimmune conditions or immunosuppression strongly predispose to its development.

Primary Causes

Acquired genetic damage to lymphocytes, notably translocations linking oncogenes to immunoglobulin promoters (e.g., t(14;18) BCL2 in Follicular Lymphoma, t(8;14) MYC in Burkitt Lymphoma).

Genetic mutations halt lymphocyte differentiation or inhibit apoptosis. For instance, in Follicular Lymphoma, the t(14;18) translocation places the BCL-2 anti-apoptotic gene under the control of the active IgH promoter, leading to BCL-2 overexpression. These immortalized cells proliferate and replace normal lymph node architecture. Extranodal spread occurs via hematogenous or lymphatic routes. Aggressive subtypes have high proliferation fractions (Ki-67 >80%) rapidly expanding tumor mass.

Diagnostic Criteria & Guidelines

Requires excisional lymph node biopsy or adequate core needle biopsy demonstrating architectural effacement by malignant lymphocytes. Immunohistochemistry (IHC) or flow cytometry is mandatory to define the immunophenotype (e.g., CD20+ for B-cell).

First-Line Treatment:

Depends strictly on subtype. For DLBCL: R-CHOP chemotherapy (Rituximab 375 mg/m2 IV, Cyclophosphamide 750 mg/m2 IV, Doxorubicin 50 mg/m2 IV, Vincristine 1.4 mg/m2 IV, Prednisone 100 mg PO daily for 5 days) for 6 cycles. For Indolent Follicular Lymphoma: Observation ('watch and wait') if asymptomatic; Rituximab + Bendamustine if symptomatic.

Second-Line & Adjunctive Therapy

For relapsed/refractory DLBCL: Salvage chemotherapy (e.g., R-ICE) followed by Autologous Stem Cell Transplant if chemosensitive. CAR-T cell therapy (e.g., Axicabtagene ciloleucel) is increasingly used for early relapse or transplant-ineligible patients.

Surgical & Procedural Management

Surgery is strictly diagnostic (excisional biopsy). Seldom therapeutic except for resecting localized GI lymphomas (e.g., to prevent perforation) or splenectomy for massive symptomatic splenomegaly.

Patient Counseling & Advice

Discuss fertility preservation before starting chemo. Warn about alopecia, neuropathy (vincristine), and risk of cardiotoxicity (doxorubicin). Inform them of the risk of secondary malignancies down the line.

Follow-Up & Monitoring Schedule

Post-treatment: Clinical exam and basic labs every 3-6 months for 5 years. Routine surveillance PET/CT is generally NOT recommended due to false positives, unless clinical suspicion of relapse arises.

Preventive Strategies

No specific prevention. Treatment of underlying causes where applicable (e.g., eradicating H. pylori can cure early-stage gastric MALT lymphoma; treating HIV reduces risk).

Highly variable by subtype and IPI (International Prognostic Index) score. DLBCL is curable in ~60-70% of cases. Follicular lymphoma is considered incurable but has a median survival of >15 years.

Authoritative Sources & Evidence References
World Health Organization (WHO) & CDC Guidelines: Information compiled from current international clinical practice guidelines.

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