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?

Question

Accepted Answer

A. CD10+ and FMC7+ B cell markers. ## 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]

Answer

B. CD5+ and CD19+ B lymphocytes

Answer

C. Weak or absent surface immunoglobulin expression

Answer

D. CD23+ B lymphocytes

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

Typical CLL Immunophenotype

Why CD10 and FMC7 Are NOT Typical of CLL

Differential: CLL vs. Mantle Cell Lymphoma

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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