In an adult (>60 years) with CD5⁺, CD23⁺, CD10⁻, CD103⁻, weak surface Ig J and low‑intensity CD20 immunophenotype, what is the diagnosis and the appropriate staging and initial management?

Diagnosis: Chronic Lymphocytic Leukemia (CLL)

The immunophenotype CD5⁺, CD23⁺, CD10⁻, CD103⁻, with weak surface immunoglobulin and dim CD20 expression is diagnostic of chronic lymphocytic leukemia (CLL). 1

Diagnostic Confirmation

This immunophenotype profile meets all three defining features of B-CLL established by international guidelines 1:

• Co-expression of CD5 with B-cell markers (CD19, CD20, CD23) in the absence of pan-T-cell markers 1
• Monoclonal B-cell population with kappa or lambda light chain restriction 1
• Low-density surface immunoglobulin expression 1

The dim CD20 intensity and weak surface immunoglobulin are characteristic features that distinguish CLL from other lymphoproliferative disorders 1, 2. The CD10-negative and CD103-negative profile effectively excludes follicular lymphoma and hairy cell leukemia respectively 1.

Critical Differential: Excluding Mantle Cell Lymphoma

Despite the CD5 positivity, the presence of CD23 expression strongly argues against mantle cell lymphoma (MCL), which typically lacks CD23. 1, 3

However, given the clinical importance of this distinction, you must perform additional testing 3, 4:

• Cyclin D1 immunohistochemistry (mandatory) 3, 4
• FISH for t(11;14)(q13;q32) translocation (mandatory) 3, 4
• CD200 expression by flow cytometry—CD200 positivity strongly favors CLL over MCL, as MCL is typically CD200-negative 3, 4

If cyclin D1 is negative but clinical suspicion remains high, SOX11 immunohistochemistry should be performed to exclude the rare (~5%) cyclin D1-negative MCL cases 3, 4.

Required Staging Evaluation

Once CLL is confirmed, perform clinical staging using either the Rai or Binet system 1:

Binet Staging (preferred in Europe) 1:

• Assess number of involved lymphoid areas (head/neck, axillae, groins, liver, spleen) 1
• Measure hemoglobin and platelet count 1
• Stage A: <3 areas involved, Hb ≥10 g/dL, platelets ≥100,000/μL 1
• Stage B: ≥3 areas involved, Hb ≥10 g/dL, platelets ≥100,000/μL 1
• Stage C: Hb <10 g/dL and/or platelets <100,000/μL (regardless of areas) 1

Modified Rai Staging (commonly used in North America) 1:

• Low risk (Rai 0): Lymphocytosis only 1
• Intermediate risk (Rai I-II): Lymphadenopathy and/or organomegaly 1
• High risk (Rai III-IV): Anemia (Hb <11 g/dL) or thrombocytopenia (platelets <100,000/μL) 1

Essential Prognostic Testing

After confirming CLL and excluding MCL, obtain the following prognostic markers 1, 3:

• FISH panel for del(17p), del(11q), trisomy 12, and del(13q14) 1, 3
• TP53 mutation analysis 3
• IGHV mutation status 1, 3
• Stimulated karyotype 3

These markers are critical because they identify high-risk disease (particularly del(17p) and TP53 mutations) that requires different therapeutic approaches 1, 3.

Initial Management Strategy

For asymptomatic patients with early-stage disease (Binet A/B without symptoms or Rai 0-II without symptoms), observation with "watch and wait" is the standard approach. 1

Monitor with:

• Blood counts and clinical examination every 3 months 1
• Assessment for disease progression indicators 1

Indications to initiate treatment (transition from observation to active therapy) 1:

• Binet stage C or Rai stage III-IV 1
• Symptomatic disease with B-symptoms 1
• Rapid disease progression (lymphocyte doubling time <6 months) 1
• Cytopenias not caused by autoimmune phenomena 1
• Symptomatic lymphadenopathy, splenomegaly, or hepatomegaly 1

Critical Pitfall to Avoid

Do not confuse this presentation with monoclonal B-lymphocytosis (MBL). If the absolute B-lymphocyte count is <5 × 10⁹/L without lymphadenopathy, organomegaly, cytopenias, or symptoms, the diagnosis is MBL rather than CLL 1. MBL progresses to CLL at a rate of 1-2% per year and requires less intensive monitoring 1.