Description: any MPN leading to bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly

Epidemiology

Peak incidence is between 50 and 74 years of age.


Etiology


Pathophysiology

Genetic mutations → hyperplasia of atypical megakaryocytes → ↑ TGF-β → ↑ fibroblast activity → bone marrow obliteration due to fibrosis → displacement of hematopoietic stem cells → extramedullary hematopoiesis


Clinical features

  • Constitutional symptoms
  • Anemia
  • Symptomatic splenomegaly
  • Thromboembolic events
    • Due to thrombocytosis and leukocytosis in the prefibrotic proliferative phase
  • Petechial bleeding
  • Increased infections

Diagnostics

  • CBC
    • Classic presentation: anemia, thrombocytosis, and leukocytosis
    • Patients may additionally present with:
  • Leukocyte alkaline phosphatase, LDH
  • Peripheral blood smear: dacrocytes (teardrop cells)
  • JAK2 mutation
  • Bone marrow studies
    • Aspiration often fails (dry tap) because of severe marrow fibrosis.

Treatment