Masked polycythemia vera in a patient 5 years after gastric bypass surgery: A diagnostic pitfall

Abstract

A 66-year-old woman presented with a fever and symptoms of urinary tract infection. A complete blood count showed: white blood cells (WBC) 26.2 × 10⁹/L(normal, 4–11 × 10⁹/L), red blood cells (RBC) 7.2 × 10¹²/L(normal 3.99–5.46 × 10¹²/L), hemoglobin 12.4 g/dL(normal, 12.2–15.3 g/dL), hematocrit 45.3%(normal 36.4%–46.8%), mean corpuscular volume 63 fL(normal, 82–99 fL) and platelets 631 × 10⁹/L(normal, 160–397 × 10⁹/L). Serum iron was 15 µg/dL and ferritin was 10 ng/mL. A review of the peripheral blood smear (panel A) showed microcytic RBCs and pencil cells on the peripheral blood smear suggestive of iron deficiency. However, the high RBC count did not fit with iron deficiency, and thus bone marrow evaluation was performed. The biopsy specimen was hypercellular (∼90%) with panmyelosis and pleomorphic megakaryocytic hyperplasia without dysplasia or increased blasts (panels B–D). Absent storage iron was seen on iron stain performed on an aspirate smear. Further work-up showed that serum erythropoietin (EPO) was low and a detailed review of the medical history revealed the patient underwent gastric bypass surgery ∼5 years ago. Ultrasound abdomen detected mild splenomegaly (15.5 cm). Next-generation sequencing study showed JAK2 p.V617F(VAF:83%) mutation and conventional cytogenetics showed a normal diploid female karyotype. These results confirmed the diagnosis of “masked” polycythemia vera (PV) with concurrent iron deficiency likely due to gastric bypass (Figure 1).

According to the current World Health Organization classification and the International Consensus Classification, the diagnosis of PV requires three major criteria or two major with one minor criterion [1, 2]. The three major criteria are 1) An elevated hemoglobin (≥16.5 g/dL in men and ≥16.0 g/dL in women) or elevated hematocrit (≥49% in men and ≥48% in women); 2) Bone marrow biopsy specimen with age-adjusted hypercellularity with panmyelosis and pleomorphic megakaryocytic proliferation, and 3) Presence of JAK2 p.V617F or JAK2 exon 12 mutation; the minor criterion is a subnormal EPO level [1, 2]. Gastric bypass surgery compromises iron absorption by bypassing the portion of the small intestine where iron is absorbed, thus decreasing gastric acid production as a feedback loop. Furthermore, calcium and zinc may compete with iron for absorption and cause iron deficiency. Normal hemoglobin and hematocrit levels in the setting of chronic iron deficiency create a diagnostic pitfall when trying to meet diagnostic criteria for PV [3, 4]. This scenario is a diagnostic pitfall and can delay the diagnosis of PV or even result in misdiagnosis as essential thrombocythemia or pre-fibrotic myelofibrosis. Awareness and knowledge of gastric bypass as an etiology of iron deficiency can help in the appropriate diagnosis, management, and risk stratification in PV patients. To our knowledge, no case of masked PV in patient(s) who underwent gastric bypass surgery has been reported. This case illustrates the importance of correlating the history with a high RBC count (instead of hemoglobin or hematocrit levels). Low serum EPO level and appropriate bone marrow morphology with JAK2 mutation are useful clues for an accurate diagnosis and management in masked PV patients with iron deficiency due to gastric bypass surgery. Furthermore, the diagnosis of masked PV is not equivalent to a more indolent clinical course as risk stratification criteria are similar to that of non-masked PV patients [5].

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