Leukemia with Megakaryocytic Differentiation following Essential Thrombocythemia and Myelofibrosis

Abstract

Leukemias of megakaryocytic lineage are rare and heterogeneous clinical entities. The nomenclature published in the literature is confusing and perhaps inappropriate to designate these primary myeloproliferative disorders. We describe a patient with essential thrombocythemia who evolved through myelofibrosis and myeloid metaplasia to a final picture of leukemia with megakaryocytic differentiation in the peripheral blood. This case illustrates different aspects of a chronic myeloproliferative disorder where myelofibrosis and myeloid metaplasia are frequent but secondary events. We have reviewed the literature focusing on the role of clonal megakaryocytic proliferation in myelofibrosis and on the clinical characterization of leukemias with megakaryocytic phenotype. We also present our interpretation of the literature which indicates that a formal review of the nomenclature is urgently needed.

Chronic lymphocytic leukaemia in a patient with essential thrombocythaemia

“…Essential thrombocythaemia (ET), a myeloproliferative disorder characterized by platelet counts persistently above 600 × 10 9 /l (Murphy et al 1986), has been recognized as a clonal disorder of the myeloid stem cell (Fialkow et al 1981;Singal et al 1983). About 2% of ET patients eventually progress to either acute myeloid (Chistolini et al 1990;Peterson et al 1994), lymphoid (O'Hea et al 1986;Murphy et al 1995;Krafts & Litz 1996), or megakariocytic leukaemia (Chistolini et al 1990;Patino-Sarcinelli et al 1996), especially following therapy with alkylating agents or radioactive phosphorus. Cases evolving into a myelodysplastic form (Messora et al 1996) or multiple myeloma (Prosper et al 1992;Arlan & Golkland 1995;Kelsey & Patel 1995) have also been described, but in all of them the second neoplasia could have been induced by chemotherapy.…”

Idiopathic Myelofibrosis with Nodal, Serosal and Parenchymatous Infiltration

“…About 10% of the patients develop a blast crisis and die of an acute leukemic transformation [5, 6]. Extramedullary hematopoiesis in IMF is designated in almost all cases as ‘metaplastic’, i.e.…”

“…Hepatosplenomegaly, anisopoikilodakryocytosis and leukoerythroblastosis in the peripheral blood, and progressive bone marrow fibrosis with clustered hyperlobulated megakaryocytes are hallmarks of this disease [1, 2]. IMF patients are at increased risk of infectious and hemostatic complications due to severe pancytopenia and about 10% develop an acute leukemia [2, 3, 4, 5, 6, 7]. Rarely, IMF takes an unpredictable course, with extramedullary hematopoiesis involving the serosal surfaces, the lymph nodes and the parenchymatous organs [8, 9].…”

Leukaemic Transformation in a Case of Thrombocythaemia

“…Another case, suggestive of ET, described by Patiño-Sarcinelli et al [9], evolved through myelofibrosis and myeloid metaplasia to a final picture of leukaemia with megakaryocytic differentiation in the peripheral blood. In the terminal phase, the patient presented deletion of chromosome 5, as seen in myelodysplastic syndromes.…”