Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (355 page)

   Laboratory Findings

   
CBC

   RBCs: Normochromic, normocytic progressive anemia caused by hemolysis, ineffective hematopoiesis, splenic sequestration, bleeding, and a variety of other cases. Peripheral blood smear (PBS) shows marked anisocytosis and poikilocytosis with teardrop RBCs (dacrocytes), polychromasia, and nucleated red cells (part of a leukoerythroblastic picture). Reticulocyte count is increased.

   WBCs may be decreased, normal, or increased; abnormal or immature forms may be present and increase with time. The blasts are initially <5%, but as the disease progresses, the WBCs and blasts in the peripheral blood may increase and may reflect transformation into blast crisis/acute myeloid leukemia. Basophils and eosinophils may be increased.

   Platelets may be decreased, normal, or increased. Thrombocytopenia becomes more profound with disease progression. Abnormal or large forms are present. Deficient aggregation with collagen or epinephrine is common.

   
Bone marrow
shows progressive fibrosis that can be visualized with silver stain for reticulin and trichrome stain for mature collagen. Bone marrow sinusoids are expanded, and there is intravascular hematopoiesis. Early on the bone marrow may be hypercellular with minimal fibrosis (prefibrotic or cellular phase of PMF). Frequently, the bone marrow aspirate results in a dry tape. The biopsy shows a progressively hypocellular marrow replaced by fibrosis. Megakaryocytes are the last remaining hematopoietic elements, most of which have abnormal morphology.

   
Lymph node biopsy
(usually not necessary) shows extramedullary hematopoiesis involving all three cell lines. Foci of extramedullary hematopoiesis may occur in almost any organ.

   
Genetics and flow cytometry

   The JAK2 V617F gene mutation is present in approximately 50–60% of cases.

   MPL (W515K/L): Activating mutations affecting MPL thrombopoietin receptors are present in 5–7% of cases.

   Elevated CD34+ hematopoietic precursors can be detected in peripheral blood and distinguishes PMF from PV and ET in which they are absent in the chronic phases.

   Chromosome abnormalities occur in 35–50% of patients at diagnosis. Favorable abnormalities include sole deletions in 13q or 20q or trisomy 9. Deletion of 5q, 7q, or 12p, trisomy 8, or >3 aberrations predict a poor survival. Patients with abnormalities 17p− have the poorest survival. Additional karyotypic abnormalities that may develop during the course of the disease may further affect prognosis.