Idiopathic or primary myelofibrosis indicates a myeloproliferative neoplasm (MPN) characterized by reactive bone marrow fibrosis. The causative mutation is in a multipotent or, more likely, a pluripotent haemopoietic stem cell. A multitude of names have been used for this condition, which indicates that none is wholly satisfactory. The International Working Group for Myelofibrosis Research and Treatment recommended use of the term 'primary myelofibrosis'  and this was accepted for the 2008 WHO classification. However, the condition is not idiopathic nor is it primary. The myelofibrosis is reactive, secondary to a myeloid neoplasm. Myelofibrosis with myeloid metaplasia has also been used but 'myeloid metaplasia', a term used in this context to indicate extramedullary haemopoiesis, can also occur with other forms of bone marrow disease with myelofibrosis, e.g. in the inherited condition, osteopetrosis. Since the condition is not of unknown origin (agnogenic), agnogenic myeloid metaplasia is similarly an unsatisfactory term. Chronic granulocytic-megakaryocytic myelosis is not inaccurate but does not convey the information that myelofibrosis is a characteristic disease feature. Chronic megakaryocytic leukaemia has also been suggested. 'Myeloproliferative myelofibrosis' could be suggested as a more appropriate name than those that are customarily used. The incidence is 0.3-1.5/100 000/year with a median age of onset of 65 to 75 years.
A similar condition can occur following polycythaemia vera or essential thrombocythaemia, in which case the terms 'post-polycythaemia myelofibrosis' and 'post-essential thrombocythaemia myelofibrosis' are used. The disease may evolve into an accelerated phase with an increasing white cell count (WBC) and increasing blast cells and can transform into acute myeloid leukaemia (AML).
Clinical features may be absent in the early stages of the disease. With disease progression, the spleen becomes palpable and later there is hepatomegaly. In late stage disease there may be massive splenomegaly and hepatomegaly. Other disease features relate to cytopenia and include the clinical features of anaemia and thrombocytopenia. Some patients have gout or renal calculi as a result of hyperuricaemia. With advanced disease there is fatigue, weight loss, low-grade fever, night sweats, generalized wasting and haemorrhage as a result of thrombocytopenia. Cardiac failure and portal hypertension can occur.
Haematological and pathological features
In early stage disease there may be neutrophilia and thrombocytosis. As the disease advances, there is progressive pancytopenia. The blood film is leucoerythroblastic and shows poikilocytosis. Teardrop poikilocytes are particularly characteristic (Figures 8.1 and 8.2). Platelets show abnormal variation in size, including giant forms, and they may also be hypogranular. Ultrastructural examination shows morphological abnormalities of platelets (Figure 8.3) In addition to circulating erythroblasts, myelocytes and promyelocytes, there may also be blast cells (Figure 8.4) and occasional bare megakaryocyte nuclei or micromegakaryocytes (Figures 8.5 and 8.6).
Peripheral blood film of a patient with primary myelofibrosis showing anisocytosis, poikilocytosis, teardrop poikilocytes and a myelocyte. MGG, high ...