What is the difference between Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)?

Difference Between CLL and SLL

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, with the primary difference being the location of malignant cells. 1

Key Differences

Distribution of Malignant Cells

• CLL: Significant number of abnormal lymphocytes are found in peripheral blood (≥5,000 B lymphocytes/μL for at least 3 months) in addition to bone marrow and lymphoid tissue 1
• SLL: Bulk of disease is in lymph nodes, bone marrow, and other lymphoid tissues, with few or no abnormal lymphocytes in peripheral blood (B lymphocytes should not exceed 5×10^9/L) 1

Diagnostic Criteria

• CLL diagnosis requires:

  • ≥5,000 B lymphocytes/μL in peripheral blood for at least 3 months
  • Clonality confirmed by flow cytometry
  • Characteristic immunophenotype (CD5+, CD19+, CD20+, CD23+)
  • Low expression of surface immunoglobulin, CD20, and CD79b
  • Restricted expression of either κ or λ light chains 1

• SLL diagnosis requires:

  • Presence of lymphadenopathy and/or splenomegaly
  • <5×10^9/L B lymphocytes in peripheral blood
  • Same immunophenotype as CLL
  • Confirmation by lymph node biopsy whenever possible 1

Staging Systems

• CLL: Typically staged using Rai or Binet staging systems 1
• SLL: Typically staged using the Lugano Modification of the Ann Arbor Staging System 1

Similarities

Cellular Characteristics

• Both diseases show identical immunophenotype: CD5+, CD19+, CD20+, CD23+ B-cells with low expression of surface immunoglobulin 1
• Morphologically, both present as small, mature lymphocytes with narrow cytoplasm and dense nucleus lacking discernible nucleoli 1

Genetic Features

• Both share similar genetic abnormalities, though some differences in frequency have been noted:
  • SLL may have higher incidence of trisomy 12 and lower incidence of del(13q) compared to CLL 2
  • Both can present with del(17p), del(11q), and other cytogenetic abnormalities that affect prognosis 1

Management Approach

• Treatment is identical for both conditions 1
• Treatment decisions are based on:
  • Disease stage
  • Presence of del(17p) or TP53 mutation
  • IGHV mutation status
  • Patient age and comorbidities 3
• Both conditions are managed with the same therapeutic agents, including:
  • BTK inhibitors
  • BCL-2 inhibitors
  • Chemoimmunotherapy regimens 1, 4

Clinical Implications

• Despite different presentations, studies show no significant differences in response rates, survival, or failure-free survival between CLL and SLL patients when treated with similar regimens 5
• Both conditions can be monitored without treatment until disease progression or development of symptoms 6
• Prognostic factors such as del(17p), TP53 mutations, and IGHV mutation status are important for both conditions 1, 4

Common Pitfalls in Diagnosis

• Failing to distinguish from other lymphomas such as mantle cell lymphoma (which is CD5+ but typically CD23-) 1
• Not confirming SLL diagnosis with lymph node biopsy when possible 1
• Overlooking the need for cytogenetic and molecular testing before treatment initiation 1, 4

In summary, while CLL and SLL have different clinical presentations based primarily on the distribution of malignant cells, they represent the same underlying disease and should be managed with identical treatment approaches.