This rare entity is characterized by marrow fibrosis, myeloid metaplasia with extramedullary hematopoiesis, and splenomegaly. Evaluation of a blood smear reveals teardrop-shaped RBC, nucleated RBC, and some early granulocytic forms, including promyelocytes. However, many entities may lead to marrow fibrosis and extramedullary hematopoiesis, and the diagnosis of primary idiopathic myelofibrosis is made only when the many other potential causes are ruled out. The following diseases are in the differential diagnosis: CML, polycythemia vera, Hodgkin's disease, cancer metastatic to the marrow (especially from breast and prostate), infection (particularly granulomatous infections), and hairy cell leukemia. Supportive therapy is generally used; novel inhibitors of JAK2 and telomerase have shown activity in reducing splenomegaly and marrow fibrosis in some cases; however, no study has yet shown a particular drug therapy to improve survival. Cases that do not have JAK2 mutations often have mutations in CALR.