A 67-year-old woman is evaluated for worsening fatigue and exertional dyspnea. She has no prior medical conditions and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs and consumes a balanced diet. Vital signs are within normal limits. Physical examination is notable for mucosal pallor. Stool testing for occult blood is negative. Laboratory studies reveal that hemoglobin is 6.7 g/dL, white blood cell count is 35,000/mm³, and platelets are 45,000/mm³. Peripheral blood flow cytometry of the white blood cell population is shown below. Which of the following is the most likely diagnosis?

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This patient's symptomatic anemia (eg, fatigue, weakness), thrombocytopenia, and leukocytosis are associated with a predominance of CD20-positive cells (a B-cell surface marker), raising strong suspicion for chronic lymphocytic leukemia (CLL). In CLL, mature B cells progressively accumulate in the bone marrow and peripheral blood due to oncogenic mutations that inhibit apoptosis. Although most patients are asymptomatic for years, accumulation of B cells in the bone marrow eventually chokes out normal hematopoiesis, leading to symptomatic anemia, thrombocytopenia, and infections (due to neutropenia). Patients with CLL usually have dramatic elevations in peripheral leukocyte count (often >100,000/mm³) and characteristic findings on peripheral blood smear (eg, numerous small lymphocytes, smudge cells). The diagnosis is supported by flow cytometry of peripheral blood revealing a clonal population of leukocytes with expression of B-cell surface markers such as CD19, CD20, and CD23. (Choice A) T-cell leukemia is marked by the clonal expansion of a leukocyte population with T-cell surface markers such as CD2, CD3, and CD4. However, this patient's flow cytometry shows very few CD3-positive cells. (Choice B) Aplastic anemia is characterized by bone marrow failure and is usually triggered by an infection, medication, radiation, toxic substance, or autoimmune disease. Patients have pancytopenia (not leukocytosis) and bone marrow biopsy shows a hypocellular marrow with morphologically normal hematopoietic cells; a clonal population of B cells would not be seen. (Choice D) Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by peripheral leukocytosis due to numerous circulating granulocytes (eg, neutrophils in different stages of maturation). Diagnosis is generally made when cytogenetic studies reveal the BCR-ABL fusion gene. A predominant population of CD20-positive cells (B cells) would not be seen. (Choice E) Classic Hodgkin lymphoma usually causes localized peripheral lymphadenopathy and B-symptoms (eg, fever, night sweats). The diagnosis is made by lymph node excision, which usually reveals Reed-Sternberg cells that are characteristically positive for CD15 and CD30 immunohistochemical stains. Anemia, thrombocytopenia, and leukocytosis would be atypical. Educational objective: Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the progressive accumulation of mature B cells. Most patients are asymptomatic for years but eventually develop anemia, thrombocytopenia, and/or neutropenia. The diagnosis is generally made when complete blood count reveals dramatic leukocytosis, and flow cytometry subsequently shows a clonal population of leukocytes with B-cell markers such as CD19, CD20, and CD23.

A 67-Year-Old Woman Is Evaluated for Worsening Fatigue and Exertional