A 72-year-old man presents to the office for a routine physical examination. He feels well, though he mentions being a bit more tired than usual over the past few months. He denies fever, drenching night sweats, or unintentional weight loss. On physical examination, he has nontender, mobile cervical and axillary lymphadenopathy. The tip of the spleen is palpable 2 cm below the left costal margin.
Laboratory studies show the following:
Hemoglobin: 13.5 g/dL
Platelet count: 185,000/μL
White blood cell count: 32,000/μL
Differential: 85% lymphocytes, 10% neutrophils, 5% monocytes
Peripheral blood smear: Numerous small, mature-appearing lymphocytes and several ruptured cells with indistinct margins (smudge cells).
Which of the following is the most likely immunophenotype of the predominant cells in this patient's peripheral blood?
The correct answer is:
B) CD5+, CD19+, CD23+
This patient is presenting with chronic lymphocytic leukemia (CLL), the most common leukemia in adults in Western countries. CLL is a neoplasm of mature B-cells. The clinical presentation is often asymptomatic, discovered incidentally on routine CBC as an isolated lymphocytosis. The diagnosis of CLL requires a persistent absolute lymphocyte count (ALC) > 5,000/μL. The characteristic peripheral smear finding is the smudge cell (or basket cell), which represents fragile leukemic lymphocytes that rupture during the preparation of the slide.
The immunophenotype of CLL is unique and highly diagnostic:
B-cell markers: CD19, CD20 (typically dim), and CD23.
T-cell marker: CD5. The expression of CD5 (normally found on T-cells) on a B-cell population is a hallmark of CLL and mantle cell lymphoma.
Answer choice A: CD3+, CD4+, CD7-, is incorrect. This describes a mature T-cell phenotype, often seen in Sézary syndrome or mycosis fungoides (T-cell lymphomas).
Answer choice C: CD10+, CD19+, TdT+, is incorrect. This is the immunophenotype for B-cell acute lymphoblastic leukemia (B-ALL). TdT is a marker of immature lymphoblasts, whereas the cells in CLL are mature lymphocytes.
Answer choice D: CD11c+, CD25+, CD103+, is incorrect. This is the classic triple threat immunophenotype for hairy cell leukemia. While Hairy Cell also presents with splenomegaly, it typically features pancytopenia rather than a profound lymphocytosis.
Answer choice E: CD19+, CD20+, CD5-, is incorrect. This describes a normal mature B-cell or certain other B-cell lymphomas (like follicular lymphoma). The absence of CD5 would rule against a diagnosis of CLL.
Key Learning Point
Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm (CD19+, CD20+) that aberrantly expresses the T-cell marker CD5. It is characterized by smudge cells on peripheral smear. Most patients are managed with observation ("watch and wait") until they develop active disease (e.g., severe cytopenias, massive lymphadenopathy, or systemic B-symptoms).
