Primary Myelofibrosis: Understanding Your Pathology Report

Section Editor: David Li MD
June 25, 2026

Primary myelofibrosis is a type of blood cancer called a myeloproliferative neoplasm. It starts in the bone marrow, the soft tissue inside bones where blood cells are made. In this condition, abnormal blood-forming stem cells produce too many of certain blood cells, especially megakaryocytes (the cells that make platelets). Over time, these abnormal cells trigger fibrosis (scarring) of the bone marrow, which interferes with normal blood cell production. As the bone marrow becomes less able to produce blood cells, the body begins producing them outside the marrow, most often in the spleen, a process called extramedullary hematopoiesis, which causes the spleen, and sometimes the liver, to enlarge. Primary myelofibrosis can be diagnosed in an early, prefibrotic stage (pre-PMF) or in a more advanced fibrotic stage.

This article will help you understand the findings in your pathology report for primary myelofibrosis, what each term means, and why it matters for your care.

Where does primary myelofibrosis occur?

Primary myelofibrosis always involves the blood and bone marrow. In later stages, blood cell production shifts to other organs, particularly the spleen and sometimes the liver, which become enlarged. In advanced disease, abnormal blood-forming tissue can also appear in the lymph nodes, skin, lungs, or other organs.

What are the symptoms of primary myelofibrosis?

The symptoms of primary myelofibrosis vary widely and depend on the stage of disease. About one-third of patients have no symptoms at diagnosis and are identified after routine blood tests show abnormalities such as anemia or low platelet counts. Many patients experience symptoms due to increased energy expenditure and inflammation in the body, including fatigue, weakness, weight loss, loss of appetite, fever, and night sweats. These symptoms are important because their presence is linked to a less favorable outlook.

As the spleen enlarges, patients may feel fullness or pain in the upper-left abdomen and may feel full quickly when eating. Bone pain can also occur. Bleeding and blood clots are common complications, and anemia is frequent and may worsen as the disease progresses. Over time, primary myelofibrosis can transform into acute myeloid leukemia, which happens in about 20 to 25% of patients.

What causes primary myelofibrosis?

Primary myelofibrosis is caused by genetic mutations (changes in the DNA) that develop in blood-forming stem cells in the bone marrow. These mutations cause stem cells to produce abnormal cells, especially megakaryocytes, which release substances that stimulate scar tissue formation. Over time, this scarring interferes with normal blood cell production. The mutations are acquired, meaning they develop during a person’s lifetime and are not inherited or passed on to children. The specific genes involved are described in the next section.

What genetic changes are involved in primary myelofibrosis?

Most cases of primary myelofibrosis are driven by a mutation in one of three genes that control a signaling pathway called JAK/STAT, which normally regulates blood cell growth. A mutation keeps this pathway switched on, leading to uncontrolled cell production:

JAK2 — The most common, found in about 50 to 60% of cases.
CALR — Found in about 25 to 35% of cases.
MPL — Found in about 5 to 10% of cases.

About 10% of people have none of these three mutations, a situation sometimes called triple-negative. Many patients also carry additional mutations in other genes, such as ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1, or TP53. These extra changes are often called high-molecular-risk mutations because they are linked with a higher chance of progression or transformation to leukemia, and they help doctors estimate the outlook. Testing is usually performed on blood or bone marrow using next-generation sequencing (NGS), and a dedicated article explains JAK2 testing in more detail.

How is the diagnosis made?

The diagnosis of primary myelofibrosis is based on a combination of blood tests, a bone marrow examination, and molecular genetic testing. Blood tests often show anemia, abnormal platelet counts, and changes in white blood cell counts. In more advanced disease, immature blood cells may appear in the bloodstream, along with misshapen red blood cells called teardrop cells.

A bone marrow biopsy is essential for diagnosis and for determining the stage. Because the marrow is scarred, it often cannot be drawn out as a liquid (sometimes called a “dry tap”), so a solid core of bone marrow tissue is needed. A pathologist examines the sample for the abnormal, clustered megakaryocytes that are the hallmark of this disease and assesses the amount of scarring, which is graded using the system described later in this article. Immunohistochemistry and special stains help highlight the megakaryocytes and measure the degree of fibrosis.

Genetic testing for the JAK2, CALR, or MPL mutations described above supports the diagnosis. Testing also confirms that the BCR::ABL1 fusion gene, which is found in chronic myeloid leukemia, is absent, because that condition can look similar but is treated differently. Doctors also consider other causes of bone marrow scarring and other myeloproliferative neoplasms before confirming the diagnosis.

What does primary myelofibrosis look like under the microscope?

The appearance of primary myelofibrosis under the microscope varies with the disease stage.

Prefibrotic stage (pre-PMF): The bone marrow is usually hypercellular, meaning it contains too many blood-forming cells, with increased production of white blood cells (especially granulocytes) and relatively reduced red blood cell production. The most important feature is the presence of abnormal megakaryocytes, which are increased in number, arranged in loose clusters, and vary widely in size and shape, often with large, dark, bulbous nuclei that have a cloud-like pattern. These cells are frequently found in abnormal locations near blood vessels and bone surfaces. Scarring is minimal or absent, and immature blast cells are not increased.

Fibrotic stage: The bone marrow shows moderate to severe scarring, and the normal marrow space is progressively replaced by fibrous tissue and, later, by fat. The megakaryocytes are markedly abnormal and often found in tight clusters, sometimes appearing as “naked” nuclei without visible surrounding material. Normal red blood cell production is reduced, blood vessels in the marrow become prominent, and new bone formation (osteosclerosis) may occur in advanced cases.

WHO grading system for myelofibrosis

Pathologists use a standardized system developed by the World Health Organization (WHO) to grade the amount of fibrosis (scarring) in the bone marrow of primary myelofibrosis. The grade helps determine the stage of disease, monitor changes over time, and assess the response to treatment. It is based on the amount of scar tissue, its distribution, and whether there are changes in bone structure:

MF-0 (no fibrosis) — Normal or near-normal bone marrow, with only the thin fibers found in healthy marrow. This level may be seen in very early disease.
MF-1 (mild fibrosis) — A loose network of fine fibers, especially around blood vessels, with no widespread scarring. This grade is commonly seen in prefibrotic primary myelofibrosis.
MF-2 (moderate fibrosis) — A denser, more widespread network of fibers, with thicker collagen fibers beginning to form and more obvious bone thickening. This grade indicates established fibrotic disease.
MF-3 (severe fibrosis) — The bone marrow is extensively replaced by dense scar tissue and collagen, often with marked new bone formation, and normal blood cell production is severely impaired.

When the scarring is uneven, the final grade is the highest grade present in at least 30% of the bone marrow. The fibrosis grade correlates with the severity of anemia, the degree of spleen enlargement, the risk of progression, and prognostic scores such as DIPSS and MIPSS.

Accelerated phase and blast phase primary myelofibrosis

In some patients, primary myelofibrosis can progress into more advanced, faster-growing forms of the disease that signal a higher risk and usually prompt a change in treatment.

Accelerated phase — An intermediate stage between chronic disease and acute leukemia, defined by an increase in immature cells called blasts to 10 to 19% of cells in the bone marrow or blood. Patients may have worsening symptoms and more unstable blood counts. Although this is not leukemia, it indicates a higher risk of progression and closer monitoring.
Blast phase (leukemic transformation) — Occurs when blasts make up 20% or more of cells in the blood or bone marrow. At this point, the disease behaves like an acute leukemia, most often acute myeloid leukemia. Symptoms can progress quickly, and this phase requires urgent evaluation by a hematology team, often with intensive chemotherapy, targeted therapy, or consideration of a stem cell transplant.

What is the difference between primary myelofibrosis and myelofibrosis from essential thrombocythemia or polycythemia vera?

Myelofibrosis can develop in different ways. Primary myelofibrosis begins as myelofibrosis, with bone marrow scarring developing early in the disease, either gradually (prefibrotic stage) or more extensively (fibrotic stage). In contrast, myelofibrosis can also develop later in people initially diagnosed with essential thrombocythemia (ET) or polycythemia vera (PV), a condition then called post-ET or post-PV myelofibrosis. Although the scarring may look similar under the microscope, these conditions behave differently, with different risk patterns, so doctors use different prognostic scoring systems depending on how the myelofibrosis developed.

What is the prognosis for primary myelofibrosis?

The prognosis for primary myelofibrosis varies widely. Some people live for decades with mild disease, while others progress more quickly. Patients with prefibrotic disease generally have a better outlook than those with fibrotic disease, although prefibrotic disease often progresses over time. Doctors use prognostic scoring systems, such as DIPSS and MIPSS, that combine clinical features, blood counts, bone marrow findings, and genetic results to estimate risk and guide treatment. These scores are especially important when considering a stem cell transplant, which is the only potentially curative treatment. Your prognosis depends on your own combination of these factors, which your care team can explain in the context of your specific report.

What happens after a diagnosis of primary myelofibrosis?

After primary myelofibrosis is diagnosed, further testing is done to determine the risk category and guide treatment. For most patients, treatment focuses on controlling symptoms, improving blood counts, and reducing spleen size, rather than curing the disease. The pathology and risk findings help guide several decisions:

Observation — Patients with early or low-risk disease and no symptoms may be monitored closely without immediate treatment, since they can remain stable for a long time.
JAK inhibitors — Drugs that block the overactive JAK/STAT pathway, including ruxolitinib and fedratinib, can shrink an enlarged spleen and relieve symptoms. Pacritinib is used when platelet counts are very low, and momelotinib is helpful when anemia is a major problem.
Treatment of anemia — Blood transfusions and medicines that support red blood cell production may be used to manage anemia.
Stem cell (bone marrow) transplant — An allogeneic transplant, using blood-forming cells from a donor, is the only treatment that can cure primary myelofibrosis. It carries significant risks and is generally considered for higher-risk patients who are well enough, based on prognostic scores.

Care is provided by a hematology team, and regular blood tests, bone marrow examinations when needed, and genetic testing help detect early progression. Newer treatments are being studied in clinical trials, which may be an option to discuss. Decisions about treatment are made by the care team together with the patient, based on the specific findings in the report.

Questions to ask your doctor

Do I have prefibrotic or fibrotic primary myelofibrosis?
What grade of bone marrow fibrosis (MF grade) do I have?
Was a JAK2, CALR, or MPL mutation found, and were any high-risk mutations detected?
Was I tested for the BCR::ABL1 fusion gene to rule out chronic myeloid leukemia?
What is my risk category based on prognostic scoring?
Is my disease primary myelofibrosis, or did it develop from essential thrombocythemia or polycythemia vera?
Am I at risk for progression to leukemia, and what signs should I watch for?
Would a JAK inhibitor help my symptoms or spleen size?
How will my anemia or low platelet counts be managed?
Should I be evaluated for a stem cell transplant?
Are there clinical trials that I should consider?