Dr. Ayesha Warsi

If the bone marrow biopsy is completed during an early or pre-fibrotic stage of the disease, the bone marrow can actually appear hypercellular with little fibrosis.

In the overt myelofibrotic stage, the bone marrow will demonstrate significant fibrosis, suggesting a more advanced stage of disease.

The bone marrow samples should also be sent for molecular testing, looking for JAK2, CalR, and NPL mutations, as well as for cytogenetic testing, which is relevant for prognostication.

Imaging should be guided by suspicion of organ systems involved in extramedullary hematopoiesis.

All patients should, at minimum, receive an abdominal ultrasound to assess for hepatospinomegaly.

Finally, it is also important to consider alternative differential diagnoses that may result in bone marrow fibrosis.

Other hematological malignancies such as myelodysplastic syndrome, lymphoproliferative disorders, and plasma cell dyscrasias can also result in a degree of cytopenias and marrow fibrosis.

Solid tumor malignancies with metastatic marrow infiltration can present with a similar clinical picture.

Non-malignant causes of fibrosis to take into consideration include primary or secondary autoimmune myelofibrosis, granulomatous infections such as tuberculosis or histoplasmosis, or renal osteodystrophy to name a few.

Putting this all together, to diagnose myelofibrosis, we will review the World Health Organization's diagnostic criteria for overt primary myelofibrosis.

It requires the presence of all three major criteria.

Number one, megakaryocyte proliferation and atypia observed on bone marrow biopsy accompanied with fibrosis.

Number two, not meeting criteria for a different myeloproliferative neoplasm, myelodysplastic syndrome, or other myeloid neoplasms.

Number three, the presence of JAK2, CalR, or NPL mutation, or in the absence of these mutations, the presence of another clonal marker.

In addition, the diagnosis also requires at least one of the following minor criteria on two occasions.

1.

Anemia not due to an alternative comorbidity.

2.

Leukocytosis greater than 11.

Number three, palpable splenomegaly.