What are the key tumor markers for different types of lymphoma?

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Key Tumor Markers for Different Types of Lymphoma

Immunophenotyping is the cornerstone of lymphoma diagnosis and classification, with specific markers essential for differentiating between various lymphoma subtypes. 1

B-Cell Lymphoma Markers

Common B-Cell Markers

  • CD20: Primary B-cell marker, expressed in most B-cell lymphomas
  • CD19: Pan B-cell marker
  • CD10: Expressed in follicular lymphoma, Burkitt lymphoma, and some DLBCL
  • BCL2: Overexpressed in follicular lymphoma (associated with t(14;18))
  • BCL6: Expressed in germinal center B-cell lymphomas

Specific B-Cell Lymphoma Subtypes

Follicular Lymphoma

  • BCL2 translocation (t(14;18)): Present in 85-90% of cases 1
  • CD10+: Typically positive
  • BCL6+: Usually positive
  • IRF4 gene abnormalities: Should be assessed when BCL2 is negative 1

Diffuse Large B-Cell Lymphoma (DLBCL)

  • CD20+: Strongly positive
  • CD10+/-: Variable (germinal center B-cell subtype)
  • BCL6+/-: Variable expression
  • MUM1/IRF4: Non-germinal center subtype marker
  • Ki-67: Usually high proliferation index

Burkitt Lymphoma

  • CD10+: Strongly positive
  • BCL6+: Positive
  • CD38: Strongly positive (higher MFI than in DLBCL) 2
  • Ki-67: Very high (nearly 100%)
  • c-MYC translocation: Characteristic genetic abnormality

Mantle Cell Lymphoma

  • CD5+: Typically positive
  • CD23-: Usually negative (helps distinguish from CLL/SLL)
  • Cyclin D1+: Overexpressed due to t(11;14)

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

  • CD5+: Positive
  • CD23+: Positive
  • Dim CD20: Characteristically dim expression
  • Dim surface immunoglobulin: Typically dim

T-Cell Lymphoma Markers

Common T-Cell Markers

  • CD3: Pan T-cell marker
  • CD2, CD5, CD7: T-cell associated antigens

Specific T-Cell Lymphoma Subtypes

Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS)

  • CD4+: Most nodal cases express CD4 and lack CD8 1
  • Variable T-cell antigen expression: May lose some T-cell antigens
  • CD30+/-: Variable expression (approximately 52% of cases) 1

Anaplastic Large Cell Lymphoma (ALCL)

  • CD30+: Strong uniform expression
  • ALK+/-: ALK status important for prognosis 1
  • DUSP22 rearrangement: In ALK-negative cases, associated with favorable prognosis 1
  • TP63 rearrangement: Should be assessed in ALK-negative cases 1

Angioimmunoblastic T-Cell Lymphoma (AITL)

  • CD4+: Typically positive
  • CXCL13+: Useful marker to distinguish from PTCL-NOS 1
  • PD1/CD279+: Marker of T-follicular helper cell origin
  • ICOS+: T-follicular helper cell marker

Adult T-Cell Leukemia/Lymphoma

  • HTLV-1+: Essential for diagnosis 1
  • CD4+: Typically positive
  • CD25+: Usually positive

Hodgkin Lymphoma Markers

Classical Hodgkin Lymphoma

  • CD30+: Expressed on Reed-Sternberg cells
  • CD15+: Typically positive
  • CD20-/+: Usually negative or weakly positive
  • PAX5+: Weakly positive

Nodular Lymphocyte-Predominant Hodgkin Lymphoma

  • CD20+: Positive on lymphocyte-predominant cells ("popcorn cells")
  • CD15-: Negative
  • CD30-: Usually negative
  • OCT2+, BOB1+: Positive (unlike classical HL)

Serum Biomarkers for Prognosis and Monitoring

  • Soluble interleukin-2 receptor (sIL-2R): Elevated in lymphomas, useful for monitoring therapeutic effect 3, 4
  • Beta-2 microglobulin (β2M): Associated with disease stage and prognosis 4
  • Lactate dehydrogenase (LDH): Correlates with disease burden and prognosis 1

Viral Markers in Specific Lymphomas

  • HTLV-1: Essential for diagnosis of adult T-cell leukemia/lymphoma 1
  • EBV (EBER-ISH): Associated with certain lymphomas, should be assessed 1
  • HHV-8/KSHV: Essential for diagnosis of primary effusion lymphoma 1

Molecular Genetic Markers

  • TCR gene rearrangements: For T-cell clonality assessment 1
  • Immunoglobulin gene rearrangements: For B-cell clonality assessment
  • Specific translocations: t(14;18) in follicular lymphoma, t(11;14) in mantle cell lymphoma, t(8;14) in Burkitt lymphoma

Practical Considerations

  1. Adequate tissue sampling is crucial - excisional biopsy preferred over FNA or core needle biopsy alone 1
  2. Comprehensive immunophenotyping panel should include both positive and negative markers 1
  3. Molecular studies should be performed when immunophenotyping is inconclusive
  4. Viral studies are essential for certain lymphoma subtypes 1

Remember that no single marker is pathognomonic for a specific lymphoma type, and interpretation should be based on the overall pattern of marker expression in conjunction with morphology and clinical features.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Research

[Tumor markers in malignant lymphoma].

Gan to kagaku ryoho. Cancer & chemotherapy, 2005

4
Research

Serum tumor markers in non-Hodgkin's lymphomas and chronic lymphocytic leukemia.

The International journal of biological markers, 1993

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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