A 65-year-old woman presents with fatigue and splenomegaly. Peripheral blood smear shows small lymphocytes with scant cytoplasm and 'smudge cells.' Flow cytometry confirms chronic lymphocytic leukemia (CLL). Which of the following immunophenotypic findings is NOT typical of CLL?

Explanation

## Immunophenotype of CLL **Key Point:** CLL is a neoplasm of mature B lymphocytes with a characteristic and highly specific immunophenotypic profile. Understanding this profile is essential for diagnosis and differentiation from other B-cell lymphoproliferative disorders. ## Typical CLL Immunophenotype | Marker | Expression | Significance | |--------|------------|-------------| | CD5 | **Positive** | Co-expression on B cells is characteristic of CLL; also seen in mantle cell lymphoma | | CD19 | **Positive** | B-cell marker; present in CLL | | CD23 | **Positive** | Helps distinguish CLL from mantle cell lymphoma (which is CD5+, CD23−) | | Surface Ig | **Weak/Absent** | Clonal B cells with reduced immunoglobulin expression | | CD10 | **Negative** | Absent in CLL; present in follicular lymphoma | | FMC7 | **Negative** | Absent in CLL; present in other B-cell lymphomas | **High-Yield:** The **CD5+, CD19+, CD23+** profile with **weak/absent surface Ig** is pathognomonic for CLL. ## Why CD10 and FMC7 Are NOT Typical of CLL **Clinical Pearl:** CD10 and FMC7 are markers of germinal center B cells and are characteristic of **follicular lymphoma** and other germinal center-derived lymphomas, **NOT CLL**. CLL arises from pre-germinal center B cells and is CD10−, FMC7−. **Mnemonic:** **CLL = CD5, CD19, CD23** (the "CLL triad"). Anything else (CD10, FMC7) points away from CLL. ## Differential: CLL vs. Mantle Cell Lymphoma | Feature | CLL | Mantle Cell Lymphoma | |---------|-----|---------------------| | CD5 | + | + | | CD23 | **+** | **−** | | Surface Ig | Weak | Strong | | Cyclin D1/t(11;14) | − | + | [cite:Robbins 10e Ch 13]