Which myeloproliferative neoplasm is characterized by a fibrotic bone marrow, extramedullary hematopoiesis of the spleen or liver, and leukoerythroblastosis with poikilocytosis?

Primary Myelofibrosis is the Myeloproliferative Neoplasm Characterized by Fibrotic Bone Marrow, Extramedullary Hematopoiesis, and Leukoerythroblastosis with Poikilocytosis

Primary myelofibrosis (PMF) is the myeloproliferative neoplasm characterized by a fibrotic bone marrow, extramedullary hematopoiesis of the spleen or liver, and leukoerythroblastosis with poikilocytosis. 1

Diagnostic Features of Primary Myelofibrosis

Primary myelofibrosis is distinguished from other myeloproliferative neoplasms by several key pathological features:

1. Bone Marrow Fibrosis:

   • Characterized by reticulin and/or collagen fibrosis (grade 2 or 3) 1
   • Megakaryocyte proliferation and atypia with aberrant nuclear/cytoplasmic ratio 1
   • Hyperchromatic and irregularly folded nuclei with dense clustering 1

2. Extramedullary Hematopoiesis:

   • Palpable splenomegaly due to hematopoietic cells relocating to the spleen 1
   • Hepatomegaly may also be present 2

3. Peripheral Blood Findings:

   • Leukoerythroblastosis (immature white cells and nucleated red cells in peripheral blood) 1
   • Poikilocytosis with characteristic teardrop-shaped red cells (dacryocytes) 3
   • Anemia not attributed to comorbid conditions 1

Differentiating from Other Myeloproliferative Neoplasms

Essential Thrombocythemia (ET):

• Features platelet count ≥450 × 10^9/L
• Megakaryocyte proliferation with large and mature morphology
• Lacks significant bone marrow fibrosis
• Absence of leukoerythroblastosis 1

Polycythemia Vera (PV):

• Characterized by increased red cell mass
• Hemoglobin >16.5 g/dL in men or >16 g/dL in women
• Trilineage myeloproliferation with pleomorphic megakaryocytes
• Subnormal serum erythropoietin level 1

Chronic Myelogenous Leukemia (CML):

• Defined by presence of BCR-ABL1 fusion gene (Philadelphia chromosome)
• PMF specifically requires absence of BCR-ABL1 1

Molecular and Pathophysiological Features

PMF is associated with specific genetic mutations:

• JAK2, CALR, or MPL mutations are present in approximately 90% of cases 4
• 10% of cases are "triple-negative" 4
• Additional mutations in genes like ASXL1, EZH2, TET2, SRSF2, or SF3B1 may help determine the clonal nature of the disease 1

Clinical Significance and Prognosis

Primary myelofibrosis has the poorest prognosis among the Philadelphia-negative myeloproliferative neoplasms:

• Characterized by progressive bone marrow failure
• Constitutional symptoms (fatigue, weight loss, night sweats)
• Risk of leukemic transformation
• Median survival ranges from 1.3 to 15.4 years depending on risk stratification 4

Treatment Considerations

Treatment options include:

• Allogeneic hematopoietic stem cell transplantation (only potentially curative option) 4, 5
• JAK inhibitors (e.g., ruxolitinib) for symptom palliation and reduction in spleen size 2
• Cytoreductive agents (e.g., hydroxyurea) 6
• Management of anemia with transfusions, erythropoiesis-stimulating agents, androgens, and immunomodulatory agents 6

In conclusion, the combination of fibrotic bone marrow, extramedullary hematopoiesis, and leukoerythroblastosis with poikilocytosis is pathognomonic for primary myelofibrosis, making option B the correct answer.