Here’s another case in our series of unknowns (the last one is here). This is the type of thing you might see in an unknown slide set if you were a pathology resident, or a medical student rotating through pathology (though they probably wouldn’t give you much of a history to go along with it!). Take a look at the photo, and see if you can answer the question…then scroll down for the answer and a short explanation.
The blood smear shown here is from a 67-year-old female with pancytopenia, a markedly enlarged spleen, and extramedullary hematopoiesis. She is found to have a Jak-2 mutation. What is the diagnosis?
A. Chronic myelofibrosis
B. Chronic myeloid leukemia
C. Hairy cell leukemia
D. Metastatic breast carcinoma
E. Renal cell carcinoma
The diagnosis in this case is chronic myelofibrosis. The teardrop-shaped red cells and normoblast in this blood smear are indicative of a fibrotic marrow. While other tumors can cause a myelophthisic process, JAK-2 mutations are seen most frequently in three chronic myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and chronic myelofibrosis. Jak-2 mutations are particularly characteristic of polycythemia vera – but given the markedly enlarged spleen and extramedullary hematopoiesis in this case, chronic myelofibrosis is a better guess (not to mention that polycythemia vera wasn’t one of the choices.).
The naming of the Jak-2 protein is kind of interesting. One early meaning of Jak was “Just Another Kinase” (at the time, it seemed like just one more kinase in a long line of newly-discovered kinases). However, Jak also stands for Janus kinase, which is a clever and satisfyingly appropriate name for this kinase. Janus was the Roman God of doorways, often shown with two faces looking in opposite directions. JAK has two domains that work in opposite directions too (one domain has kinase activity, and the other domain negatively regulates the first)! Nice naming job.
- dela said I got here after a few hours spent browsing the web for resources on chilblain lupus (being one of 7...
- Kristine said Hi Cynthia – Yes!! I totally agree. I remember learning that if you see any secondary granulat...
- Cynthia said I’m going to have agree with the granules being the most important. I’m also MT and I...
- AG said Thanks Kristine, very helpful!
- Frank MD said Succinctly explained. Excellent! Thank you so much!!
- kartik said Thanks,i am learner,when i think hypothtically,i think i may find confusing beetween promyelocyte an...
- Carol said Thanks…. Well explained
- Ulyses Yakovlevich said This looks like an awesome tool for future Pathologists to learn from :).
- Chief said Amazing explanation. No other website teaches this interesting and important medical lesson. Not eve...
- Dr.Kisor Kumar Pal said Very helpful and practical discussion.I learned a lot.
- Cheri said Thank you ! I’m a traveler in Pathology/Histology
- Dr. Syed Mahbub Baksh said During my residency years, I have read only two books: Robbins Pathology and Henry’s Clinical...