CD2 Marker: Clinical Applications in Hematologic Malignancies
Primary Clinical Use
CD2 is a T-cell surface marker used primarily for immunophenotyping to diagnose and classify T-cell and NK-cell lymphomas and leukemias. 1
Diagnostic Immunophenotyping
Essential Role in T-Cell Neoplasm Diagnosis
CD2 is one of the core T-cell antigens (CD2, CD3, CD5, CD7) used to establish T-cell lineage in mature T-cell and NK-cell neoplasms. 1
The NCCN guidelines recommend CD2 as part of the essential paraffin panel (CD45, CD20, CD79a, CD3, CD2, CD5, TdT, CD1a, CD10, cyclin D1) for initial lymphoma diagnosis. 1
For flow cytometry evaluation, CD2 is included in the standard cell surface marker panel to differentiate T-cell from B-cell malignancies. 1
Specific T-Cell Lymphoma Subtypes
CD2 expression patterns help distinguish specific T-cell lymphoma entities:
Mycosis fungoides/Sézary syndrome typically shows CD2+, CD5+, CD7-, CD8- phenotype with βF1+ expression. 1
Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL) characteristically demonstrates CD2+, βF1+, CD5-, CD7+, CD56-, with cytotoxic granule proteins positive. 1
Cutaneous γδ T-cell lymphoma presents as CD2+, CD5-, CD7+/-, CD56+/-, with cytotoxic granule protein expression. 1
NK/T-cell lymphoma, nasal type shows CD2+, CD7-, CD56+, cytotoxic granule proteins positive, and is EBV+. 1
Biological Function and Structure
Molecular Characteristics
CD2 (also known as LFA-2) is a 50-58 kDa T-lymphocyte surface glycoprotein that appears early in thymocyte development and is present on all mature T cells and NK cells. 2, 3
CD2 functions as both an adhesion molecule and a signaling molecule, binding to its ligand LFA-3 (CD58) to mediate T-cell adhesion to antigen-presenting cells or target cells. 2, 4
The adhesion domain of CD2 is approximately 103 amino acids in length and binds to LFA-3 with micromolar affinity, requiring multivalent interactions to enhance binding avidity. 3
Clinical Significance of CD2-CD58 Interaction
The CD2-CD58 interaction is critical for T-cell activation and organization of the immunological synapse between T-cells and antigen-presenting cells. 5
Loss of CD2 expression on tumor-infiltrating lymphocytes has been associated with defective cytotoxicity, T-cell exhaustion, and represents a potential immune evasion mechanism in lymphomas, particularly DLBCL. 5
Practical Diagnostic Algorithm
When to Order CD2 Testing
Order CD2 immunophenotyping when evaluating any suspected T-cell or NK-cell lymphoproliferative disorder, as it is essential for establishing T-cell lineage. 1
Include CD2 in the initial diagnostic panel for lymphomas with non-anaplastic morphology in extranodal or nodal locations. 1
For cutaneous lymphomas, CD2 testing helps differentiate between primary cutaneous T-cell lymphomas and B-cell lymphomas. 1
Interpretation Considerations
CD2 positivity confirms T-cell or NK-cell lineage when combined with other T-cell markers (CD3, CD5, CD7). 1
Aberrant loss of CD2 expression in otherwise T-cell lineage tumors may indicate specific subtypes or immune evasion mechanisms. 5
The pattern of CD2 expression combined with CD4, CD8, CD56, and cytotoxic markers helps classify specific T-cell lymphoma subtypes. 1
Common Pitfalls to Avoid
Do not rely on CD2 alone for T-cell lineage determination—always use a panel including CD3, CD5, and CD7 for accurate classification. 1
Do not assume all T-cell lymphomas will be CD2 positive, as aberrant loss can occur and may indicate specific biological behavior or immune evasion. 5
For lymphoblastic lymphoma/leukemia, remember that CD2 is typically positive in T-lineage cases (CD2+, CD7+) but must be interpreted with TdT and other markers. 1
When evaluating cutaneous lymphomas, CD2 expression patterns must be correlated with clinical presentation, morphology, and other immunophenotypic markers—do not use CD2 results in isolation. 1