A 67-year-old female presents with pancytopenia, a markedly enlarged spleen, and extramedullary hematopoiesis. Her blood smear is shown here. She is found to have a JAK-2 mutation. What is the diagnosis?
- Chronic myelofibrosis
- Chronic myeloid leukemia
- Hairy cell leukemia
- Metastatic breast carcinoma
- Renal cell carcinoma
The diagnosis in this case is chronic myelofibrosis. Chronic myelofibrosis is one of the four main chronic myeloproliferative disorders (the others are chronic myeloid leukemia, essential thrombocythemia, and polycythemia vera). In this disorder, the bone marrow is initially hypercellular, with proliferation of all of the myeloid cell lines (neutrophils, red cells, and megakaryoblasts). Over time, however, the marrow becomes progressively fibrotic. Eventually, there is not enough room for normal hematopoiesis, and the body starts making hematopoietic cells elsewhere (most notably in the spleen, which becomes markedly enlarged).
In these later stages of chronic myelofibrosis, the blood is characterized by pancytopenia (a decrease in white cells, red cells and platelets). Teardrop-shaped red cells (dacryocytes) may also be seen as a result of the red cells wending their way through a fibrotic marrow. Red cell precursors, such as the normoblast present in this image, are also commonly present, as there is less and less room for red cells to mature fully before leaving the marrow.
These blood smear findings are not specific for chronic myelofibrosis. Teardrop-shaped red cells may be seen when the marrow is fibrotic for other reasons, such as metastatic cancer, and pancytopenia and normoblasts may be seen in many other conditions. The JAK-2 mutation, however, is seen most frequently in three of the four chronic myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and chronic myelofibrosis.
-Kristine Krafts, MD, is an Assistant Professor of Pathology at the University of Minnesota School of Medicine and School of Dentistry and the founder of the educational website Pathology Student.