Atypical Chronic Lymphocytic Leukemia (CLL) with Atypical Immunophenotype
The immunophenotype described (CD19+/CD20+/CD5+/CD200+, dim CD43, lambda restriction, CD23-/CD10-/CD79b-) most likely represents an atypical variant of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), though the absence of CD23 is unusual and requires careful exclusion of mantle cell lymphoma (MCL).
Key Diagnostic Considerations
Primary Diagnosis: Atypical CLL/SLL
The immunophenotype shares several features with classic CLL/SLL but has critical atypical features:
Classic CLL/SLL features present:
- CD5+, CD19+, CD20 (though intensity not specified as dim), CD200+ 1
- Lambda light chain restriction indicating B-cell clonality 1
- CD10- (typical for CLL/SLL) 1
Atypical features requiring explanation:
- CD23 negativity is the most significant deviation, as typical CLL/SLL is CD23+ 1
- CD79b negativity is somewhat unusual but can occur in CLL (characteristically low/dim rather than completely negative) 1
- Dim CD43 rather than the typical CD43+/- pattern 1
Critical Differential: Mantle Cell Lymphoma
MCL must be definitively excluded because it shares CD5+/CD19+/CD20+/CD23- features with this case 1:
Against MCL in this case:
- CD200 positivity strongly argues against MCL, as MCL is typically CD200- 1
- CD43 is typically bright/positive in MCL, not dim 1
- FMC-7 status not provided (MCL typically FMC-7+) 1
Mandatory testing to exclude MCL:
- Cyclin D1 expression by flow cytometry or immunohistochemistry - must be negative to exclude MCL 1
- FISH for t(11;14)(q13;q32) - must be negative to exclude MCL 1
- If cyclin D1 negative, consider SOX11 immunohistochemistry to exclude rare cyclin D1-negative MCL 1
Diagnostic Algorithm
Step 1: Confirm B-cell Clonality
- Lambda light chain restriction is already established 1
- Peripheral blood count: if ≥5,000 monoclonal B lymphocytes/mcL, diagnose as CLL; if <5,000 with lymphadenopathy/splenomegaly, diagnose as SLL 1
Step 2: Exclude Mantle Cell Lymphoma (MANDATORY)
- Cyclin D1 by flow cytometry or IHC 1
- FISH for t(11;14) 1
- Evaluate CD200 expression (already positive, favors CLL over MCL) 1
- If cyclin D1 negative but high clinical suspicion, add SOX11 IHC 1
Step 3: Additional Prognostic Testing for CLL/SLL
Once MCL is excluded, obtain prognostic markers:
- FISH panel: del(17p), del(11q), trisomy 12, del(13q) 1
- TP53 mutation analysis by sequencing 1
- IGHV mutation status 1
- Stimulated karyotype for complex karyotype (≥3 unrelated abnormalities) 1
Step 4: Morphologic Correlation
- Review peripheral blood smear for characteristic small mature lymphocytes with narrow cytoplasm, dense nucleus, and smudge cells 1
- If prolymphocytes exceed 55%, consider prolymphocytic leukemia 1
- Lymph node biopsy if SLL suspected (peripheral lymphocytes <5,000/mcL) 1
Clinical Pitfalls and Caveats
Common diagnostic errors to avoid:
Assuming CD23 negativity excludes CLL - While unusual, CD23-negative CLL variants exist and CD200 positivity strongly supports CLL over MCL 1
Failing to exclude MCL - The CD5+/CD23- combination mandates cyclin D1 and t(11;14) testing, as MCL requires different treatment and has worse prognosis 1
Overlooking immunophenotypic heterogeneity - Approximately 18% of MCL cases show immunophenotypic aberrancies including CD23 coexpression or CD5 loss 2, 3, 4
Not recognizing CD200 as a discriminator - CD200 positivity is highly characteristic of CLL and atypical for MCL, making it a valuable distinguishing marker 1
Management Implications
If cyclin D1/t(11;14) negative (confirming atypical CLL/SLL):
- Stage using Rai or Binet staging systems 1
- If asymptomatic with low tumor burden, observation is appropriate 1
- Prognostic markers (del(17p), TP53 mutations, IGHV status, complex karyotype) guide treatment selection when therapy is indicated 1
- Repeat FISH and karyotype at time of treatment as cytogenetic abnormalities evolve 1
If cyclin D1/t(11;14) positive (MCL diagnosis):