A 41-year-old man comes to the office due to worsening fatigue and dyspnea on exertion. Over the past week, he has been feeling short of breath while riding his bike to work, which is unusual for him. He has had no chest pain, palpitations, syncope, or pedal edema. The patient has no prior medical conditions and takes no medications. He occasionally drinks alcohol but does not use tobacco or illicit drugs. Temperature is 37.2 C (99 F), blood pressure is 130/80 mm Hg, pulse is 96/min, and respirations are 18/min. Physical examination shows moist mucous membranes, normal thyroid, clear lungs, and normal heart sounds. The abdomen is soft and nontender with normal bowel sounds. Laboratory results are as follows.
| Hemoglobin | 8.8 g/dL |
| Platelets | 78,000/mm3 |
| Leukocytes | 2,600/mm3 |
Peripheral blood smear shows numerous atypical leukocytes, some of which contain cytoplasmic inclusions, as shown below.
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This patient is at greatest risk of which of the following due to his current condition?
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This patient's pancytopenia and atypical myeloid cells with Auer rods on peripheral blood smear raises suspicion for acute promyelocytic leukemia (APL), a clinically unique form of acute myelogenous leukemia (AML) that primarily affects young and middle-aged adults.
In APL, clonal promyelocytes fill the bone marrow and interfere with normal hematopoiesis, leading to pancytopenia with anemia (eg, dyspnea on exertion, fatigue), thrombocytopenia (eg, bleeding complications), and neutropenia (eg, infections). The diagnosis is often suspected when a peripheral blood smear shows numerous atypical promyelocytes (large myeloid cells with intracytoplasmic violet granules) that contain Auer rods (seen with other forms of AML). However, confirmation of the diagnosis of APL requires cytogenic analysis for the characteristic mutation, the fusion of the promyelocytic leukemia gene and the retinoic acid receptor alpha gene (t[15;17]).
APL is considered a medical emergency due to the high risk of pulmonary/cerebrovascular hemorrhage from tumor-induced consumptive coagulopathy. Although the exact mechanism is unclear, APL appears to promote a bleeding diathesis via the activation of tissue factor (disseminated intravascular coagulation) and the increased generation of plasmin (primary hyperfibrinolysis). Urgent treatment with all-trans retinoic acid, which promotes differentiation of the atypical promyelocytes, is required to prevent life-threatening bleeding complications and induce long-term remission.
(Choice B) Plasma cell neoplasms, particularly Waldenstrom macroglobulinemia, can cause hyperviscosity syndrome (eg, blurred vision, diplopia, confusion). However, a peripheral blood smear generally shows rouleaux formation, not abundant atypical myelocytes with Auer rods.
(Choice C) Dermatomyositis, an inflammatory myopathy, can be associated with certain solid tumors (eg, cervical, lung, ovary, gastric, pancreatic). APL is not strongly associated with dermatomyositis.
(Choice D) Hematologic malignancies associated with massive splenomegaly (eg, myelofibrosis, splenic lymphoma) can lead to spontaneous splenic rupture. Although APL impairs hematopoiesis, significant extramedullary hematopoiesis (eg, splenomegaly) does not generally occur. Therefore, splenic rupture is not generally seen.
(Choice E) Vitamin B12 deficiency can cause subacute combined degeneration of the dorsal columns (leading to loss of vibratory sensation/proprioception and gait ataxia) and the lateral corticospinal tracts (leading to positive Babinski sign and hyperreflexia). This condition is often associated with megaloblastic changes on peripheral smear (eg, hypersegmented neutrophils, macrocytosis), not Auer rods.
Educational objective:
Acute promyelocytic leukemia (APL), a unique form of acute myelogenous leukemia, generally presents with symptoms related to pancytopenia. Individuals with APL are at an extremely high risk for catastrophic hemorrhage due to tumor-induced consumptive coagulopathy. Therefore, patients require urgent treatment with all-trans retinoic acid, which differentiates the abnormal promyelocytes into mature myelocytes and rapidly reduces bleeding risk.