Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 65-year-old man is evaluated for a 1-month history of headaches and blurred vision, early satiety, and itching that occurs after showering. He has a 90-pack-year smoking history. He has no history of cardiopulmonary or sleep disorders, no other medical problems, and he takes no medications.
On physical examination, temperature is normal, blood pressure is 160/90 mm Hg, pulse rate is 90/min, and respiration rate is 18/min. BMI is 35 kg/m2. Oxygen saturation is 97% with the patient breathing ambient air and does not decrease with exertion. His face is erythematous, and engorged retinal veins are noted on funduscopic examination. Cardiopulmonary and neurologic examinations are normal. Abdominal examination shows splenomegaly.
|Hemoglobin||19 g/dL (190 g/L)|
|Leukocyte count||13,500/µL (13.5 × 109/L); normal differential|
|Platelet count||595,000/µL (595 × 109/L)|
The findings on the complete blood count are confirmed. The remaining laboratory studies, including liver chemistry tests, are normal.
Which of the following is the most appropriate next step in diagnosis?
A: BCR-ABL gene analysis
B: Bone marrow biopsy
C: JAK2 V617F mutational analysis
MKSAP Answer and Critique
The correct answer is C: JAK2 V617F mutational analysis. This item is available to MKSAP 16 subscribers as item 6 in the Hematology/Oncology section.
MKSAP 16 released Part A on July 31. More information is available online.
The most appropriate next step in the management of this patient is to obtain a JAK2 V617F analysis. Polycythemia vera (PV) should be suspected in patients with an increased hemoglobin level or hematocrit and an oxygen saturation greater than 92%. The suspicion for PV is increased in patients with other manifestations of the disease, including erythromelalgia (a burning sensation in the palms and soles, possibly caused by platelet activation), plethora, warm water-induced pruritus, and thrombotic and bleeding symptoms. Previously, diagnosis of PV relied on detection of an increased red blood cell mass in the absence of other causes of secondary erythrocytosis. Assessment of red cell mass is no longer available at most laboratories. However, an elevated red cell mass can be identified indirectly by the presence of a hemoglobin level greater than 18.5 g/dL (185 g/L) in men or greater than 16.5 g/dL (165 g/L) in women. Concomitant leukocytosis (often with basophilia) and thrombocytosis further support the diagnosis. The diagnosis of PV can be confirmed with a JAK2 V617F analysis in patients with elevated hemoglobin or hematocrit levels and no evidence of conditions that may cause secondary erythrocytosis. This mutation is found in more than 97% of patients with PV.
The BCR-ABL (Philadelphia chromosome) is associated with chronic myeloid leukemia (CML). The diagnosis of CML requires the identification of this oncogene in a patient who has a leukoerythroblastic peripheral blood smear (increased granulocytes with a marked left shift plus early erythrocyte precursors) and hypercellular bone marrow with marked myeloid proliferation. These findings are not present in this patient.
Bone marrow biopsy is usually reserved for patients in whom a myeloproliferative disorder is suspected but in whom JAK2 mutation testing results are negative. Bone marrow findings usually show a hypercellular marrow with clusters of abnormal megakaryocytes. Increased reticulin fibrosis may also be seen. These findings are nonspecific but can be used to confirm the suspicion of a myeloproliferative neoplasm.
Polysomnography (a sleep study) can be performed in patients in whom nocturnal oxygen desaturation secondary to obstructive sleep apnea is suspected as a cause of secondary erythrocytosis; however, obstructive sleep apnea is not associated with postbathing pruritus, splenomegaly, leukocytosis, or thrombocythemia, all of which are present in this patient.
- Identification of the JAK2 V617F mutation in patients with a hemoglobin level greater than 18.5 g/dL (185 g/L) in men or greater than 16.5 g/dL (165 g/L) in women, with concomitant leukocytosis, thrombocytosis, and hepatosplenomegaly, is diagnostic of polycythemia vera.
Learn more about ACP’s MKSAP 16.
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