Chapter 15: Myeloproliferative Neoplasms

The discussion centers on the three primary "classical" conditions: polycythemia vera, essential thrombocythemia, and primary myelofibrosis, alongside rarer entities like mastocytosis and chronic neutrophilic or eosinophilic leukemias. Central to the pathology of these diseases are acquired genetic alterations that disrupt normal signaling pathways, particularly mutations in the Janus-associated kinase 2 (JAK2), calreticulin (CALR), and the thrombopoietin receptor (MPL). These driver mutations often lead to constitutive activation of intracellular signaling, allowing cells to proliferate even in the absence of external growth factors. Polycythemia vera is specifically marked by a significant increase in red blood cell mass, resulting in hyperviscosity—a thickening of the blood that leads to clinical signs like facial plethora, headaches, and a characteristic itching sensation following a warm bath. Essential thrombocythemia involves a sustained, massive elevation of platelet counts, posing significant risks for both blood clots (thrombosis) and excessive bleeding (hemorrhage). Primary myelofibrosis is the most severe of the three, characterized by progressive bone marrow scarring or fibrosis, which forces blood production to shift to the spleen and liver—a process known as extramedullary hematopoiesis—resulting in massive organ enlargement. Diagnosis of these conditions has been revolutionized by molecular testing and bone marrow biopsies, which allow clinicians to identify specific clonal markers and differentiate these neoplasms from reactive states caused by smoking, altitude, or inflammation. Management strategies are tailored to the specific disease and patient risk profile, ranging from therapeutic phlebotomy (bloodletting) and low-dose aspirin to cytoreductive medications like hydroxycarbamide. Modern targeted therapies, such as the JAK inhibitor ruxolitinib, have also become vital for managing symptoms and improving quality of life. Furthermore, the chapter explores systemic mastocytosis, which is often driven by KIT mutations and presents with skin lesions or systemic organ involvement. A critical concern across all these neoplasms is their potential to transform over time into more aggressive bone marrow failure states or acute myeloid leukemia.