Is CLL a B Cell Lymphoma?
Yes, Chronic Lymphocytic Leukemia (CLL) is definitively classified as a B cell lymphoma according to the World Health Organization classification of hematopoietic neoplasias, which describes CLL as a leukemic, lymphocytic lymphoma. 1
Classification and Definition
CLL is characterized as:
- A low-grade B cell lymphoma with circulating cells 2
- The most common leukemia in Western countries 3
- A disease of neoplastic B cells, as per WHO classification 1
- Only distinguishable from Small Lymphocytic Lymphoma (SLL) by its leukemic appearance 1
CLL and SLL are considered different manifestations of the same disease entity:
- CLL requires ≥5 × 10^9 B lymphocytes/L in peripheral blood 1
- SLL has the same immunophenotype but with <5 × 10^9 B lymphocytes/L and presence of lymphadenopathy/splenomegaly 1
Diagnostic Criteria
The diagnosis of CLL requires:
- Presence of ≥5 × 10^9 B lymphocytes/L (5000/μL) in peripheral blood 1
- Confirmation of clonality by flow cytometry 1
- Characteristic morphology: small, mature lymphocytes with narrow cytoplasmic border and dense nucleus 1
- Distinctive immunophenotype (see below)
Immunophenotypic Profile
CLL cells have a specific immunophenotypic signature:
- Co-expression of the T-cell antigen CD5 and B-cell surface antigens CD19, CD20, and CD23 1, 4
- Characteristically low levels of surface immunoglobulin, CD20, and CD79b compared to normal B cells 1, 4
- Restriction to expression of either kappa or lambda immunoglobulin light chains 1, 4
Differential Diagnosis
CLL must be distinguished from other lymphoproliferative disorders:
- B-cell prolymphocytic leukemia (B-PLL): often CD5-negative in half of cases, with high levels of CD20 and surface Ig 1
- Mantle cell lymphoma: typically CD5+, CD23-, with t(11;14) translocation and cyclin D1 expression 1, 4
- Marginal zone lymphoma: typically CD5-, CD23-, and CD43 low 4
- Hairy cell leukemia and other leukemic lymphomas 1
Clinical Implications
Understanding CLL as a B-cell lymphoma has important implications:
- It explains the dual presentation as either leukemia (CLL) or lymphoma (SLL) 3
- It helps guide appropriate diagnostic workup and monitoring 1
- It informs treatment approaches targeting B-cell pathways, such as BTK inhibitors and BCL2 inhibitors 5
Pathophysiology Insights
CLL's B-cell origin explains several disease characteristics:
- CLL cells likely derive from a pool of auto/polyreactive CD5+ B cells 6
- The disease is highly dependent on B-cell receptor stimulation and microenvironment interactions 2
- Antigenic stimulation through the B-cell receptor appears involved in selection and expansion of the malignant clone 6
Understanding CLL as a B-cell lymphoma is crucial for proper diagnosis, risk stratification, and treatment selection, with significant implications for patient outcomes in terms of morbidity, mortality, and quality of life.