Chronic megakaryocytic leukemia, misnamed chronic idiopathic myelofibrosis, has neoplastic not hyperplastic megakaryocytopoiesis

To the editor:

Ciurea et al¹  have provided further confirmatory evidence that a neoplastic accumulation of megakaryocytes is the “pivotal” factor in the pathobiology of what is called in the World Health Organization (WHO) classification by its pseudonym, chronic idiopathic myelofibrosis, focusing on an epiphenomenon, not the central pathobiologic feature of this clonal myeloid (leukemic) disorder.

I would like to make 2 points in this brief letter.

First, the repetitive use of the term “megakaryocytic hyperplasia” in the paper by Ciurea et al¹  should be replaced by “neoplastic accumulation of megakaryocytes.” The process is an accumulation of neoplastic, not hyperplastic, megakaryocytes as a result of an increased clonal production of megakaryocytes and a decrease in apoptotic signaling in the neoplastic megakaryocytes, as they have skillfully confirmed. The correct use of the term hyperplasia in nonclonal accumulations of megakaryocytes, such as in immune thrombocytopenia, reflects a quite different process from neoplasia. The distinctions among hypoplasia(aplasia), hyperplasia, metaplasia, dysplasia, and neoplasia should retain their classical patho-biologic meaning.^2,3  Of course, these experts understand these distinctions but it is important to consider the specificity of language for those trying to learn about these processes. Likewise, the structural aberrations in clonal myeloid disorders may result in the dysmorphia of neoplasia, but they are not “dysplastic.” Similarly, extramedullary neoplastic (clonal) hematopoietic cells or tumors, distant from the primary site (marrow) represent metastases, not “metaplasia,” probably the result, in part, of high concentrations of circulating clonal CD34+ cells capable of local extramedullary proliferation and partial differentiation.

Second, the centrality of neoplastic megakaryocytes in the disease is not unexpected, since it is, in fact, chronic megakaryocytic leukemia, as has been argued in a Commentary in the journal Leukemia.⁴ 

The members of the WHO committee who are responsible for nomenclature of the clonal myeloid diseases should permit nosology to advance with the science it is meant to encapsulate. The paper by Ciurea et al¹  adds important evidence to the centrality of neoplastic megakaryocytes in this disorder.