A 72-year-old man presents to his primary care physician for a general checkup. He states that he has been a bit more fatigued lately but believes it is secondary to poor sleep at his new house. The patient is otherwise healthy and takes no medications. His temperature is 98.0°F (36.7°C), blood pressure is 141/90 mmHg, pulse is 82/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable only for minor pallor but is otherwise unremarkable. Basic laboratory studies are ordered as seen below.

Hemoglobin: 10 g/dL
Hematocrit: 30%
Leukocyte count: 67,500/mm^3
Platelet count: 119,000/mm^3

Serum:
Na: 141 mEq/L
Cl: 103 mEq/L
K: 4.0 Eq/L
HCO3-: 24 mEq/L
BUN: 22 mg/dL
Glucose: 109 mg/dL
Creatinine: 1.2 mg/dL
Ca: 10.0 mg/dL

Which of the following is the most likely diagnosis?
Chronic lymphocytic leukemia
Acute lymphoblastic leukemia
Hairy cell leukemia
Chronic myelogenous leukemia
Chronic lymphocytic leukemia
This elderly patient is presenting with minor fatigue, anemia, thrombocytopenia, and a leukocyte count >50,000/mm^3, which is most likely caused by chronic lymphocytic leukemia (CLL).

CLL is a monoclonal proliferation of incompetent mature B-cells. It is common in elderly men and is the most common form of leukemia in the United States. Patients are often asymptomatic when the diagnosis is made or may present with vague constitutional symptoms including fatigue, malaise, and weight loss. It is important to note that symptoms may be subtle or absent. Other findings include non-tender lymphadenopathy and splenomegaly. The diagnosis is supported when the white blood cell count is >50,000/mm^3 and can be supported with a peripheral smear which will show smudge cells. The cells in CLL may be CD5, CD20, and CD23 positive. The most common cause of death in this population is infection given the lack of competent B-cells.

Hallek reviews CLL. They discuss updated guidelines on the diagnosis and management of CLL. They recommend the use of targeted agents in initial therapy and acknowledge the need for further clinical trials to guide therapy.

Incorrect Answers:
Answer A: Acute lymphoblastic leukemia (ALL) is a common malignancy seen in children and presents with pancytopenia, anemia, fatigue, leukopenia (leading to recurrent infections), and thrombocytopenia (leading to bleeding). Other findings may include fever, bone pain, lymphadenopathy, splenomegaly, and hepatomegaly. Translocations in ALL include: t(12:21) which is the most common and denotes a favorable prognosis and t(9:22) (the Philadelphia chromosome) which is less common and denotes a poor prognosis

Answer B: Acute myelogenous leukemia occurs secondary to the proliferation of myeloblasts and presents in older patients. Patients will present with fatigue, malaise, weight loss, anorexia, fever, leukocytosis, anemia, thrombocytopenia, and neutropenia. Auer rods are frequently present on a blood smear.

Answer D: Chronic myelogenous leukemia is a neoplastic proliferation of myeloid stem cells and presents with a leukocyte count often >50,000/mm3. The increased myeloid lines include red blood cells, granulocytes, monocytes, and platelets. Many patients present in the chronic phase with minimal symptoms; however, the blast phase can lead to a hematologic emergency termed a blast crisis which may cause a hyperviscosity syndrome. This condition is more symptomatic and less common than CLL.

Answer E: Hairy cell leukemia occurs when there is a neoplastic proliferation of mature B cells with abundant cytoplasm with “hairy” cytoplasmic processes. The cells are tartrate-resistant acid phosphatase positive. Patients will present with splenomegaly, pancytopenia, weakness, and fatigue. This is a more rare diagnosis when compared to CLL.

Bullet Summary:
Chronic lymphocytic leukemia (CLL) presents in elderly patients with malaise, fatigue, and other nonspecific signs (but can also be asymptomatic), with anemia, thrombocytopenia, and a white blood cell count often >50,000/mm^3.