Sites of hematopoiesis
The principal site of extramedullary hematopoiesis in myelofibrosis is the spleen, which is usually markedly enlarged, sometimes weighing as much as 4000 g. As a result of massive enlargement of the spleen, multiple subcapsular infarcts often occur in the spleen, meaning that due to interrupted oxygen supply to the spleen partial or complete tissue death happens. On the cellular level, the spleen contains red blood cell precursors, granulocyte precursors and megakaryocytes, with the megakaryocytes prominent in their number and in their bizarre shapes. Megakaryocytes are believed to be involved in causing the secondary fibrosis seen in this condition, as discussed under "Mechanism" above. Sometimes unusual activity of the red blood cells, white blood cells, or platelets is seen. The liver is often moderately enlarged, with foci of extramedullary hematopoiesis. Microscopically, lymph nodes also contain foci of hematopoiesis, but these are insufficient to cause enlargement.There are also reports of hematopoiesis taking place in the lungs. These cases are associated with hypertension in the pulmonary arteries.The bone marrow in a typical case is hypercellular and diffusely fibrotic. Both early and late in disease, megakaryocytes are often prominent and are usually dysplastic. Diagnosis
Epidemiologically, the disorder usually develops slowly and is mainly observed in people over the age of 50.Diagnosis is made on the basis of bone marrow biopsy. Fibrosis grade 2 or 3 defines overt PMF whereas grade 0 or 1 defines prefibrotic primary myelofibrosis.A physical exam of the abdomen may reveal enlargement of the spleen, the liver, or both.Blood tests are also used in diagnosis.
Primary myelofibrosis can begin with a blood picture similar to that found in polycythemia vera or chronic myeloid leukemia. Most people with myelofibrosis have moderate to severe anemia. Eventually thrombocytopenia, a decrease of blood platelets develops. When viewed through a microscope, a blood smear will appear markedly abnormal, with presentation of pancytopenia, which is a reduction in the number of all blood cell types: red blood cells, white blood cells, and platelets. Red blood cells may show abnormalities including bizarre shapes, such as teardrop-shaped cells, and nucleated red blood cell precursors may appear in the blood smear (leukoerythroblastic reaction). Normally, mature red blood cells in adults do not have a cell nucleus, and the presence of nucleated red blood cells suggests that immature cells are being released into the bloodstream in response to a very high demand for the bone marrow to produce new red blood cells. Immature white cells and platelets (large megakaryocytes) are also seen in blood samples, and basophil counts are increased. When late in the disease progression an attempt is made to take a sample of bone marrow by aspiration, it may result in a dry tap, meaning that where the needle can normally suck out a sample of semi-liquid bone marrow, it produces no sample because the marrow has been replaced with collagen fibers. A bone marrow biopsy will reveal collagen fibrosis, replacing the marrow that would normally occupy the space. Treatment
The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.