Algorithm for using special techniques in lymphoma diagnosis.
| *Can be detected by gene expression (immunophenotype) or gene rearrangement (genetic techniques) |
| Abbreviations: CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; MALT, mucosa associated lymphoid tissue; Ig, immunoglobulin; DLBCL, diffuse large B-cell lymphoma; NK, natural killer cell; TdT, terminal deoxynucleotidyl transferase; ALK, anaplastic lymphoma kinase. |
| A. Morphology: Small lymphoid cells |
| 1. Benign vs malignant |
| *Immunoglobulin light chains (kappa and lambda) |
| *Bcl2 protein in follicles |
| Kappa/lambda polyclonal or Bcl2- follicles =Reactive |
| Kappa/lambda monoclonal or Bcl2+ follicles = Small B-cell lymphoma |
| 2. Classification of Small B-cell Neoplasms |
| CD5+: CLL/SLL vs mantle cell lymphoma |
| *Cyclin D1-, dim sIg, CD23+ = CLL/SLL |
| *Cyclin D1+, bright sIg, CD23− = Mantle cell lymphoma |
| CD5-: Follicular lymphoma vs Marginal zone lymphoma (MALT) |
| CD10+ = Follicular lymphoma |
| CD10− = Marginal zone lymphoma vs CD10− follicular lymphoma |
| Bcl6+, CD43−, *Bcl2+ follicles = follicular lymphoma |
| Bcl6−, CD43+, Bcl2− follicles = marginal zone lymphoma |
| B. Morphology: Large lymphoid cells |
| 1. Lymphoma vs nonlymphoid tumor |
| CD45 (leukocyte common antigen), pan- B and pan-T-cell antigens,* immunoglobulin light chains, cytokeratin, melanoma markers |
| 2. Subclassification of medium-sized and large cell lymphomas |
| Pan-B antigens (CD20, CD79a)+ = B-cell lymphoma |
| Ig+ = mature B-cell lymphoma (DLBCL vs Burkitt) |
| CD10+ bcl2- Ki67 >99% = favors Burkitt |
| CD10− bcl2+ Ki67 <90% = favors DLBCL |
| Ig- = mature B-cell vs lymphoblastic |
| TdT+ CD10+ = precursor B-lymphoblastic |
| TdT− CD10−/+ =DLBCL |
| Pan-T antigens + (CD3, CD2, CD45RO) = T/NK-cell lymphoma |
| TdT+ = precursor T-lymphoblastic |
| TdT− = mature T/NK-cell lymphoma |
| CD21+ FDC, CD10+ = angioimmunoblastic T-cell lymphoma |
| CD30+ ALK+ = anaplastic large cell lymphoma |
| *Can be detected by gene expression (immunophenotype) or gene rearrangement (genetic techniques) |
| Abbreviations: CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; MALT, mucosa associated lymphoid tissue; Ig, immunoglobulin; DLBCL, diffuse large B-cell lymphoma; NK, natural killer cell; TdT, terminal deoxynucleotidyl transferase; ALK, anaplastic lymphoma kinase. |
| A. Morphology: Small lymphoid cells |
| 1. Benign vs malignant |
| *Immunoglobulin light chains (kappa and lambda) |
| *Bcl2 protein in follicles |
| Kappa/lambda polyclonal or Bcl2- follicles =Reactive |
| Kappa/lambda monoclonal or Bcl2+ follicles = Small B-cell lymphoma |
| 2. Classification of Small B-cell Neoplasms |
| CD5+: CLL/SLL vs mantle cell lymphoma |
| *Cyclin D1-, dim sIg, CD23+ = CLL/SLL |
| *Cyclin D1+, bright sIg, CD23− = Mantle cell lymphoma |
| CD5-: Follicular lymphoma vs Marginal zone lymphoma (MALT) |
| CD10+ = Follicular lymphoma |
| CD10− = Marginal zone lymphoma vs CD10− follicular lymphoma |
| Bcl6+, CD43−, *Bcl2+ follicles = follicular lymphoma |
| Bcl6−, CD43+, Bcl2− follicles = marginal zone lymphoma |
| B. Morphology: Large lymphoid cells |
| 1. Lymphoma vs nonlymphoid tumor |
| CD45 (leukocyte common antigen), pan- B and pan-T-cell antigens,* immunoglobulin light chains, cytokeratin, melanoma markers |
| 2. Subclassification of medium-sized and large cell lymphomas |
| Pan-B antigens (CD20, CD79a)+ = B-cell lymphoma |
| Ig+ = mature B-cell lymphoma (DLBCL vs Burkitt) |
| CD10+ bcl2- Ki67 >99% = favors Burkitt |
| CD10− bcl2+ Ki67 <90% = favors DLBCL |
| Ig- = mature B-cell vs lymphoblastic |
| TdT+ CD10+ = precursor B-lymphoblastic |
| TdT− CD10−/+ =DLBCL |
| Pan-T antigens + (CD3, CD2, CD45RO) = T/NK-cell lymphoma |
| TdT+ = precursor T-lymphoblastic |
| TdT− = mature T/NK-cell lymphoma |
| CD21+ FDC, CD10+ = angioimmunoblastic T-cell lymphoma |
| CD30+ ALK+ = anaplastic large cell lymphoma |