From the Guidelines
Immunohistochemistry (IHC) is a crucial diagnostic tool in lymphoma diagnosis, providing essential information for accurate diagnosis and subtype classification. IHC works by using antibodies to detect specific cellular antigens, allowing pathologists to identify lymphoma subtypes based on their immunophenotypic profiles. For B-cell lymphomas, key markers include CD20, CD79a, and CD10, while T-cell lymphomas typically express CD3, CD4, CD8, and CD2.
Key Markers for Lymphoma Diagnosis
- CD20, CD79a, and CD10 for B-cell lymphomas
- CD3, CD4, CD8, and CD2 for T-cell lymphomas
- CD30 and CD15 for Hodgkin lymphoma
Importance of IHC in Lymphoma Diagnosis
IHC helps assess proliferation rates (Ki-67), identify aberrant protein expression (cyclin D1 in mantle cell lymphoma, MYC in Burkitt lymphoma), and detect prognostic markers like CD5 and CD10. The interpretation requires correlation with morphology, clinical features, and often molecular studies. A standard lymphoma panel typically includes lineage markers (CD20, CD3), proliferation markers (Ki-67), and subtype-specific markers based on morphologic impression, as recommended by the European Society for Medical Oncology (ESMO) guidelines 1. Proper tissue handling with adequate fixation is crucial for accurate results, as overfixation or poor preservation can lead to false negatives or uninterpretable staining.
Recommended IHC Panel
A suggested immunohistochemical panel would include CD20, CD79a, BCL6, CD10, MYC, BCL2, Ki67, IRF4, CyclinD1, CD5, and CD23, as well as EBER-1 staining to identify the Epstein–Barr virus-positive DLBCL subtype of the elderly population 1.
From the Research
Role of Immunohistochemistry in Lymphoma Diagnosis
- Immunohistochemistry (IHC) is a crucial technique in lymphoma diagnosis, enabling the identification of specific proteins in cells through antigen-antibody interactions 2.
- IHC has several key applications in lymphoma diagnosis, including:
- Identifying cell lineage and phase of maturation
- Detecting specific genetic alterations
- Visualizing the degree of cell proliferation
- Identifying therapeutic targets
Markers Used in Lymphoma Diagnosis
- CD3 is a pan T-cell marker expressed on most mature T/NK-cell lymphomas, except for anaplastic large cell lymphoma 2.
- CD20 is a pan B-cell marker expressed on most mature B-cell lymphomas, while CD79a may be used as an alternative in cases where CD20 is lost due to plasmocytic differentiation or rituximab administration 2.
- CD56 is used as an NK cell marker in lymphoma diagnosis, and CD30 is a useful marker for identifying Reed-Sternberg cells in classical Hodgkin's lymphoma 2, 3.
- Ki-67 reflects the degree of tumor cell proliferation, indicating cells in cell cycle phases other than G0 2.
Association with EBV and Therapeutic Targets
- Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) is associated with Hodgkin's lymphoma, particularly in the nodular sclerosis subtype 3.
- IHC can identify therapeutic targets, such as programmed death-ligand 1 (PD-L1), CD19, and CD30, which are useful in immunotherapy 2.
Efficiency and Cost-Effectiveness of IHC
- A deductive reasoning "decision tree" approach can be used to efficiently select and interpret IHC markers, allowing for cost-effective diagnosis of lymphomas 4.
- This approach relies on recognition of basic morphologic patterns and can be used to classify node-based malignancies according to the World Health Organization schema.
Comparison with Flow Cytometry
- IHC and flow cytometry (FC) have a substantial degree of agreement (κ=0.69) in the diagnosis of malignant hematologic diseases, including lymphomas 5.
- IHC has the advantage of combining markers, morphology, and tissue immunoarchitecture, making it beneficial in lymphoma diagnosis, while FC is faster and plays an important role in minimal residual disease detection 5.