How does Chronic Lymphocytic Leukemia (CLL) usually present?

Clinical Presentation of Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia (CLL) most commonly presents as an incidental finding of lymphocytosis on routine blood tests in asymptomatic patients, with the majority of cases diagnosed during early stages of the disease. 1

Diagnostic Findings

Laboratory Abnormalities

• Sustained increase of peripheral blood lymphocytes ≥5 × 10^9/L for at least 3 months 1
• Clonal B-cell population confirmed by flow cytometry 1
• Characteristic small, mature-appearing lymphocytes with narrow cytoplasmic border and dense nucleus in blood smear 1

Immunophenotypic Profile

• Distinctive immunophenotype: CD5+, CD19+, CD20+ (dim), CD23+, surface immunoglobulin (dim), CD79b low, FMC7- 1, 2
• Light chain restriction (either kappa or lambda) 2

Clinical Presentation

Asymptomatic Presentation (Most Common)

• 63% of patients present with early-stage disease (Binet A) 1
• Incidental finding of lymphocytosis on routine blood tests 1, 3
• No physical symptoms or clinical manifestations 1

Symptomatic Presentation

When symptoms do occur, they may include:

• Lymphadenopathy (38% of symptomatic cases) - most common presenting symptom requiring treatment 4
• Night sweats (34% of symptomatic cases) 4
• Progressive marrow failure (31% of symptomatic cases) 4
• Fatigue (29% of symptomatic cases) 4
• Splenomegaly (25% of symptomatic cases) 4
• Progressive lymphocytosis (21% of symptomatic cases) 4

Advanced Disease Presentation

• Anemia (Hb <10 g/dL) - Binet stage C 1
• Thrombocytopenia (<100 × 10^9/L) - Binet stage C 1
• Significant lymphadenopathy in ≥3 lymphoid sites - Binet stage B 1

Staging and Risk Stratification

Binet Staging System

• Stage A: Hb ≥10 g/dL, platelets ≥100 × 10^9/L, <3 involved lymphoid areas (63% of patients) 1
• Stage B: Hb ≥10 g/dL, platelets ≥100 × 10^9/L, ≥3 involved lymphoid areas (30% of patients) 1
• Stage C: Hb <10 g/dL and/or platelets <100 × 10^9/L (7% of patients) 1

Rai Staging System

• Low-risk (Stage 0): Lymphocytosis only (30% of patients) 1
• Intermediate-risk (Stages I-II): Lymphocytosis with lymphadenopathy and/or hepatosplenomegaly (60% of patients) 1
• High-risk (Stages III-IV): Lymphocytosis with anemia and/or thrombocytopenia (10% of patients) 1

Clinical Pitfalls and Caveats

• Differential diagnosis: Must distinguish CLL from other CD5+ B-cell lymphoproliferative disorders, particularly mantle cell lymphoma (typically CD23-) and marginal zone lymphoma 1, 2
• Small Lymphocytic Lymphoma (SLL): Same entity as CLL but with <5 × 10^9/L B lymphocytes and presence of lymphadenopathy/splenomegaly 1
• Monoclonal B Lymphocytosis (MBL): <5 × 10^9/L monoclonal B lymphocytes without lymphadenopathy, organomegaly, cytopenias, or symptoms; progresses to CLL at rate of 1-2% per year 1
• Age distribution: While median age at diagnosis is 69 years, approximately 11-14% of CLL patients are younger than 55 years 1

Management Approach for Newly Diagnosed CLL

• Early, asymptomatic disease (Binet A, Rai 0-II without symptoms): Watch and wait strategy with blood counts and clinical examinations every 3-6 months 1
• Advanced or symptomatic disease: Treatment initiation based on disease activity and patient characteristics 1
• Genetic testing: FISH analysis for del(17p) and TP53 mutation testing recommended before starting therapy due to treatment implications 1

CLL is predominantly an incidental finding in asymptomatic patients, with the majority presenting with early-stage disease. Recognition of the characteristic immunophenotype and careful staging are essential for appropriate management decisions.