What is non-Hodgkin lymphoma?

What is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoproliferative malignancies originating from B lymphocytes (80-85% of cases), T lymphocytes (15-20%), or natural killer (NK) cells, characterized by malignant transformation of mature lymphoid cells primarily in lymph nodes. 1

Disease Classification and Origin

NHL represents a diverse collection of blood cancers that differ fundamentally from Hodgkin lymphoma in their cellular characteristics, clinical behavior, and treatment responses. 1

Cell of Origin

• B-cell lymphomas account for the vast majority (80-85%) of NHL cases in the United States 1
• T-cell lymphomas represent 15-20% of cases 1
• NK-cell lymphomas are rare 1

Common Histologic Subtypes

The most frequently encountered B-cell NHL subtypes include: 1

• Follicular lymphoma (FL): approximately 22% of newly diagnosed NHL, representing the most common indolent subtype 1
• Diffuse large B-cell lymphoma (DLBCL): accounts for 30-40% of adult NHL cases, characterized by aggressive clinical behavior 1
• Marginal zone lymphomas including mucosa-associated lymphoid tissue (MALT) lymphoma 1
• Mantle cell lymphoma 1
• Chronic lymphocytic leukemia/small lymphocytic lymphoma 1

Clinical Behavior Patterns

NHL is broadly categorized based on clinical course: 1

Indolent (Slow-Growing) Lymphomas

• Characterized by chronic disease with multiple relapses despite treatment 1
• Patients typically experience long survival but only a minority achieve cure 2
• Follicular lymphoma exemplifies this pattern with median survival that has not significantly improved over 30 years despite therapeutic advances 1

Aggressive (Fast-Growing) Lymphomas

• Up to 50% of patients with aggressive lymphomas like DLBCL are curable with standard combination chemotherapy 1
• Require immediate treatment initiation 3
• Peripheral T-cell lymphomas (PTCLs) represent aggressive disease with particularly poor prognosis 1

Epidemiology and Incidence

• Approximately 65,000-70,800 new cases are diagnosed annually in the United States 1
• NHL represents the sixth leading site of new cancer diagnoses among both men and women 1
• Accounts for 4-5% of new cancer cases and 3-4% of cancer-related deaths in the US 1
• Incidence increased 168% between 1975 and the mid-1990s, then stabilized 1, 4
• More common in men, those >65 years old, and those with autoimmune disease or family history of hematological malignancies 5

Pathophysiology

NHL arises from malignant transformation at various stages of B-cell or T-cell development, with each subtype reflecting the molecular and immunophenotypic characteristics of its cell of origin. 6 The disease involves clonal proliferation of lymphoid cells that have escaped normal regulatory mechanisms controlling cell growth, differentiation, and apoptosis. 1

Clinical Presentation

Patients typically present with: 3

• Persistent painless lymphadenopathy (most common presentation)
• Constitutional "B symptoms" (fever, night sweats, weight loss) in some cases
• Extranodal involvement affecting organs beyond the lymphoid and hematopoietic system

Diagnostic Requirements

An excisional or incisional lymph node biopsy is mandatory to establish the diagnosis—fine needle aspiration alone is insufficient for initial diagnosis. 1 The pathologic evaluation must include: 1

• Morphologic assessment
• Immunophenotyping (via flow cytometry and/or immunohistochemistry)
• Cytogenetic or molecular genetic analysis when indicated to identify characteristic chromosomal translocations

Important Clinical Caveats

• The heterogeneity of NHL subtypes means that treatment approaches, prognosis, and outcomes vary dramatically between different histologic types 6, 3
• Regional variations exist globally: Asian countries show lower incidence of follicular lymphoma and chronic lymphocytic leukemia but higher incidence of T-cell lymphomas compared to Western populations 1
• Infectious associations are important: Epstein-Barr virus with endemic Burkitt's lymphoma, HIV/HHV-8 with certain DLBCL subtypes, and HTLV-1 with T-cell lymphomas 5, 4
• Despite the dramatic increase in NHL incidence through the 1990s, HIV/AIDS, classification changes, and improved diagnostics cannot fully explain the magnitude of this rise 4