What are the different types of lymphoma?

Types of Lymphoma

Lymphomas are primarily classified into two major categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), with NHL having over 90 subtypes according to the World Health Organization (WHO) classification system. 1, 2

Major Classification Systems

The classification of lymphomas has evolved significantly over time:

1. IWF Classification (older system)

   • Classified NHL as low-, intermediate-, or high-grade based on morphology and natural history
   • Limited by lack of immunophenotyping and poor reproducibility 1

2. REAL Classification (1994)

   • Developed by the International Lymphoma Study Group
   • Classified lymphomas based on cell of origin (B, T, or NK)
   • Incorporated morphology, immunophenotype, genetic, and clinical features 1

3. WHO Classification (current standard)

   • Updated in 2001 and again in 2008
   • First international consensus on hematologic malignancy classification
   • Subdivides lymphomas by:
     • Cell of origin (B, T, or NK cells)
     • Precursor vs. mature lymphocytes
     • Immunophenotype, genetic, and clinical features 1

Hodgkin Lymphoma (HL)

Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells, which typically represent only 0.1-1% of the cell population within a heterogeneous background of inflammatory cells 1.

Types of Hodgkin Lymphoma:

1. Lymphocyte Predominant HL (LPHL) - 5% of cases

   • Immunophenotype: CD15-/CD30-/CD20+

2. Classical Hodgkin Lymphoma (cHL) - 95% of cases

   • Immunophenotype: CD15+/CD30+/CD20-
   • Subtypes:
     • Nodular sclerosing
     • Mixed cellularity
     • Lymphocyte rich
     • Lymphocyte depleted
     • Unclassifiable 1

Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin lymphomas comprise approximately 90% of all lymphomas and are much more diverse than HL. According to the International Lymphoma Classification Project, the most common NHL subtypes in the United States are:

B-cell Lymphomas (most common):

1. Diffuse Large B-cell Lymphoma (DLBCL) - 31% of NHL cases

   • Further subdivided into:
     • Germinal Center B-cell (GCB) subtype
     • Activated B-cell (ABC) subtype
     • Double-hit lymphomas (with MYC and BCL2/BCL6 rearrangements)
     • Double-expressor lymphomas (overexpressing MYC and BCL2 proteins) 1, 3

2. Follicular Lymphoma (FL) - 22% of NHL cases

   • Graded 1-3 based on number of centroblasts per high-power field 1

3. Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL) - 6% of NHL cases

4. Mantle Cell Lymphoma (MCL) - 6% of NHL cases

5. Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma - 5% of NHL cases

6. Other B-cell lymphomas:

   • Burkitt's lymphoma
   • Lymphoplasmacytic lymphoma
   • Hairy cell leukemia
   • Splenic marginal zone lymphoma
   • Nodal marginal zone lymphoma 1

T-cell and NK-cell Lymphomas:

1. Peripheral T-cell Lymphoma Not Otherwise Specified (PTCL-NOS) - 25.9% of T-cell lymphomas

2. Angioimmunoblastic Lymphoma - 18.5% of T-cell lymphomas

3. NK/T-cell Lymphoma - 10.4% of T-cell lymphomas

4. Adult T-cell Leukemia/Lymphoma - 9.6% of T-cell lymphomas

5. Anaplastic Large Cell Lymphoma (ALCL):

   • ALK-positive - 6.6% of T-cell lymphomas
   • ALK-negative - 5.5% of T-cell lymphomas 1

6. Other T-cell lymphomas:

   • Mycosis fungoides/Sézary syndrome
   • Enteropathy-type T-cell lymphoma
   • Hepatosplenic T-cell lymphoma
   • Subcutaneous panniculitis-like T-cell lymphoma 1

Clinical Relevance of Classification

The classification of lymphomas is not merely academic but has direct implications for treatment and prognosis:

• Treatment selection: Different subtypes respond differently to therapy. For example:

  • NHL is typically treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) 4, 2
  • HL is treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) 1, 2

• Prognosis: Subtypes have varying outcomes:

  • ABC DLBCL has worse outcomes than GCB DLBCL with standard chemoimmunotherapy
  • Double-hit lymphomas have poor prognosis despite aggressive treatment 3

Diagnostic Approach

Accurate diagnosis requires:

• Lymph node biopsy (preferably an open biopsy)
• Immunophenotyping (CD markers)
• Genetic studies when appropriate
• PET-CT for staging and response assessment in FDG-avid lymphomas 1

Key Points for Clinicians

• Over 50% of lymphoma cases in the United States are either DLBCL or FL 1
• While HL primarily involves lymph nodes (only 5% arise in extranodal sites), approximately 30% of NHLs present in extranodal sites 5
• Imaging studies cannot reliably distinguish between HL and NHL or their subtypes; pathologic diagnosis is essential 5
• The WHO classification is the current gold standard for lymphoma classification and guides treatment decisions 1