Pankit Vachhani, MD: There are a few challenges to the diagnosis of myelofibrosis worth mentioning. One is the presentation to a clinician. Many patients who have some symptoms tend to ignore those or blame it on other causes. There can be times when we discover abnormalities in hematologic parameters, and we tend not to dwell deep into the possible etiologies that may be causing those. Aside from those factors—meaning the time to diagnosis point—there are a few other challenging points from a diagnostic perspective of myelofibrosis. One is that the lab parameters, as well as symptoms—night sweats and constitutional symptoms, including weight loss, fatigue, pruritus, and hepatosplenomegaly—can overlap with the other myeloproliferative neoplasms [MPNs]. It’s very important to distinguish myelofibrosis from other chronic MPNs, like polycythemia vera, ET [essential thrombocytopenia], and the Philadelphia chromosome–positive myeloproliferative neoplasm, CML [chronic myeloid leukemia]. That’s 1 point.

The second point is that primary myelofibrosis needs to be distinguished from other myeloid neoplasms that may present with some fibrosis. It’s not uncommon for MDS [myelodysplastic], or MDS/MPN overlap syndromes like CMML [chronic myelomonocytic leukemia], to have some fibrosis at either presentation or down the line. For example, some dyserythropoiesis, dysplastic changes in the bone marrow, or the presence of extreme cytopenias may suggest a diagnosis of MDS, but it’s by no means a diagnostic of 1.

Aside from that point, differentiating primary myelofibrosis from essential thrombocytosis is primarily dependent on bone marrow morphology, the degree of bone marrow fibrosis, and the presence of splenomegaly and leucoerythroblastosis. Bone marrow of primary myelofibrosis and essential thrombocytosis need to be distinguished, but the counterpart is that prefibrotic myelofibrosis or early myelofibrosis can mimic essential thrombocytosis as well. A very careful hematopathologic work-up needs to be done. I tend to emphasize that, in scenarios of MPNs, we must be in touch with their hematopathologists to make sure the diagnosis is right. As an example, in essential thrombocytosis, the megakaryocytes are usually large and appear mature, while those in prefibrotic myelofibrosis tend to have hyperchromasia or some irregularly folded nuclei. In other words, some abnormal maturation like pictures.

Outside the setting of myeloid neoplasms, there can be other reactive causes or malignancies that can also present with myelofibrosis. Other hematologic neoplasms include hairy cell leukemia, lymphoma, and multiple myeloma. Occasionally solid tumor cases can present with some amount of myelofibrosis. Thrombopoiesis-stimulating agents, like eltrombopag, can have some amount of bone marrow fibrosis. Not to overlook this, but some autoimmune diseases, like lupus, scleroderma, mixed connective tissue diseases, or secondary hyperparathyroidism with vitamin D deficiency, can also present with some amount of fibrosis. Once again, the key is making sure that the diagnosis is right, with appropriate genetic work-up and hematopathology consultations.

Transcript edited for clarity.