Background: Polycythemia vera is a myeloproliferative disease that sometimes evolves to myelofibrosis, causing splenomegaly and neutropenia. In this case report, we describe a patient with polycythemia vera and unexplained neutropenia who later turned out to also have hairy cell leukemia. Case presentation: A middle-aged Caucasian man with polycythemia vera presented to our hospital with chronic mouth ulcers. Later he developed leukopenia and pancytopenia. Bone marrow biopsies showed fibrosis. Further morphological analyses of bone marrow and blood smears revealed probable transformation into acute myeloid leukemia. However, there were also cells indicating hairy cell leukemia. Morphological and immunohistochemical analyses later confirmed the presence of hairy cell leukemia in biopsies that had been present for 3 years. Treatment with cladribine temporarily reversed the patient’s neutropenia. Conclusions: Hairy cell leukemia may mimic development to myelofibrosis in patients with polycythemia vera.

Background

The BCR-ABL-negative myeloproliferative neoplasms (MPN) polycythemia vera, essential thrombocythemia, and primary myelofibrosis are characterized by excessive production of terminally differentiated and functional blood cells. They clinically overlap, because primary myelofibrosis sometimes presents with thrombocythemia and may be difficult to distinguish from essential thrombocythemia, whereas both essential thrombocythemia and polycythemia vera can progress to myelofibrosis [1]. All three entities have a risk of transformation to acute myeloid leukemia (AML). Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are genetically characterized by clonal mutations in JAK2, CALR, or MPL. The MPN diseases are thought to arise from a somatically mutated hematopoietic stem cell that gives rise to all myeloid cells, B cells, and natural killer cells [2]. Patients with polycythemia vera usually live with the disease for many years, often decades, before it may transform into AML or secondary myelofibrosis [3]. The phase when polycythemia vera is about to transform to myelofibrosis is known as spent phase polycythemia vera and is characterized by reduced erythropoiesis and splenomegaly because of extramedullary hematopoiesis. More than 10% blasts in peripheral blood is unusual and may suggest a blast transformation to AML. Postpolycythemia myelofibrosis, and certainly AML, has a poorer prognosis than polycythemia vera and may therefore be considered for allogeneic stem cell transplant [4]. Hairy cell leukemia is a mature, indolent B-cell malignancy. Patients with hairy cell leukemia are characterized by fatigue, splenomegaly, and cytopenia, most often pancytopenia, and some patients may display bone marrow fibrosis [5]. The prognosis is good, and patients usually respond well to purine analogs such as cladribine or pentostatin [6, 7]. Mutation in the BRAF gene leading to a Val-to-Glu substitution in position 600 of the BRAF molecule (V600E) is probably the driving mutation in hairy cell leukemia [8], and a phase II trial testing the BRAF inhibitor vemurafenib in hairy cell leukemia showed promising results, with response in 25 of 26 patients [9]. We report diagnostic and therapeutic difficulties with a patient presenting with myelofibrosis secondary to polycythemia vera, further development to AML, and hairy cell leukemia. This case report illustrates that hairy cell leukemia in a patient with polycythemia vera may be interpreted as secondary myelofibrosis, that monocytopenia could have raised the suspicion of hairy cell leukemia earlier, and that AML does not always present with CD34-positive blasts.