A 59-year-old man presents to his primary care physician for fatigue. In general, he has been in good health; however, he recently has experienced weight loss, abdominal pain, and general fatigue. He has a medical history of anxiety, diabetes, a fracture of his foot sustained when he tripped, and a recent cold that caused him to miss work for 1 week. His current medications include metformin, insulin, buspirone, vitamin D, calcium, and sodium docusate. His temperature is 99.5°F (37.5°C), blood pressure is 150/100 mmHg, pulse is 90/min, respirations are 18/min, and oxygen saturation is 98% on room air. Physical exam reveals a calm gentleman. A mild systolic murmur is heard in the left upper sternal region. The rest of the physical exam is within normal limits. Laboratory values are ordered as seen below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 66,500/mm^3 with normal differential Platelet count: 177,000/mm^3 Leukocyte alkaline phosphatase: elevated Serum: Na+: 139 mEq/L Cl-: 100 mEq/L K+: 4.3 mEq/L BUN: 20 mg/dL Glucose: 120 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.9 mEq/L AST: 12 U/L ALT: 10 U/L Which of the following is the most likely diagnosis?
Chronic lymphocytic leukemia
Chronic myeloid leukemia
Leukemoid reaction
Multiple myeloma
Leukemoid reaction
This patient is presenting with leukocytosis and an elevated leukocyte alkaline phosphatase suggestive of a leukemoid reaction.

A leukemoid reaction typically presents with a drastically elevated leukocyte count (typically > 50,000/mm^3) in the setting of an elevated leukocyte alkaline phosphatase score (LAP). This reaction typically occurs after a major infection and is an immunologic response to the pathogen that caused the illness. In contrast, chronic myeloid leukemia presents with a similar elevation in leukocytes but a low LAP score in addition to symptoms of general malaise, fatigue, and weight loss. The LAP score is the critical differentiating factor when comparing these 2 pathologies. Treatment for a leukemoid reaction is by addressing the underlying pathology.

Portich and Faulhaber review the evidence regarding the diagnosis of leukemoid reaction. They discuss how the most common cause is infection. They recommend considering paraneoplastic syndromes in patients without evidence of infection.

Incorrect Answers:
Answer A: Acute lymphoblastic lymphoma presents in a pediatric patient with pallor, fatigue, easy bruising, fever, bone pain, hepatomegaly, and splenomegaly. Treatment is with combination chemotherapy.

Answer B: Chronic lymphocytic leukemia can present similarly to a leukemoid reaction with non-specific systemic symptoms and lymphadenopathy but is a less likely diagnosis in this patient given his age and LAP score. Treatment is with ibrutinib and rituximab as well as other agents.

Answer C: Chronic myeloid leukemia presents with systemic symptoms, fatigue, malaise, weight loss, and abdominal pain with an elevated leukocyte count (typically > 50,000/mm^3) but a depressed LAP score. Treatment is with tyrosine kinase inhibitors.

Answer E: Multiple myeloma presents with systemic symptoms, weight loss, pathologic fractures, and hypercalcemia. It is not associated with an elevated leukocyte score and an elevated LAP score. Treatment is with steroids and chemotherapy.

Bullet Summary:
Both a leukemoid reaction and chronic myeloid leukemia present with an elevated leukocyte count (> 50,000/mm^3), but an elevated leukocyte alkaline phosphatase score is suggestive of a leukemoid reaction.