Polycythemia Vera

Definition

• Dysregulated expansion of the red blood cell mass

Diagnostic Criteria

• Prodromal, pre-polycythemic diagnosis is difficult to make
  • Borderline to mild erythrocytosis
  • Bone marrow biopsy showing panmyelosis with decreased erythropoietin may be helpful for diagnosis
• Proliferative phase diagnosis requires 2 major and 1 minor or 1 major and 2 minor criteria:
• Major criteria
• Hemoglobin >18.5 g/dl (men) or >16.5 g/dl (women)
  • If iron deficient, can be anemic but will still have prominent polychromasia
• JAK2V617F or other functional similar mutation
• Minor criteria
• Hypercellular bone marrow with panmyelosis
  • Erythroid hyperplasia often predominates
• Low serum erythropoietin (EPO)
• Endogenous erythroid colony formation in vitro
• Variable excess platelet or leukocyte production
• Post-polycythemic myelofibrosis phase requires both:
  • Previous diagnosis of PV
  • Bone marrow fibrosis
    • Grade 2-3 (coarse diffuse reticulin fibrosis with or without collagen fibrosis, European consensus system, Thiele 2005)
• AND any two of following
• Anemia or sustained loss of phlebotomy/cytoreduction treatment for erythrocytosis
• Leukoerythroblastic blood smear
• Increasing splenomegaly
• Development of >1 of following constitutional symptoms
• >10% weight loss in 6 months
• Night sweats
• Unexplained fever

Dita Gratzinger MD PhD
Tracy I George MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting: 10/23/11

Supplemental studies

• >99% JAK2V617F or exon 12 mutations
  • Found in all myeloid lineages
  • May also be found in Essential Thrombocythemia and Primary Myelofibrosis (50% of cases)
    • Also more rarely in a variety of other myeloid neoplasms (see DDX in left sidebar)
• Erythropoietin level should be low
• Absence of Ph’ or BCR-ABL1 negative if clinically indicated
• Karyotypic abnormalities (+8,+9/del(9p), del(13q), del (20q))
  • In 20% of cases at diagnosis
  • In 80-90% of post-PV myelofibrosis

Differential Diagnosis

Clinical

• Median age 60-65
  • Broad range 20-80 years
  • Rare in children
• Onset frequently insidious
  • Headaches, weakness, weight loss, pruritis
  • Hemorrhage, thrombosis, hyperviscosity symptoms
    • Includes deep vein thrombosis, stroke, myocardial infarction
  • Splenomegaly
• Low incidence of evolution to MDS/AML
  • 2-3% without cytotoxic agent chemotherapy
  • >10% with chemotherapy
• Median survival times >10 years overall
  • Most deaths due to thrombosis or hemorrhage
  • Up to 20% die with MDS or AML

Classification / Lists

WHO 2008 Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN)

• Chronic myeloid leukemia, BCR-ABL1 pos
• Chronic neutrophilic leukemia
• Chronic eosinophilic leukemia NOS
  • (see also Idiopathic hypereosinophilic syndrome)
• Polycythemia vera
• Essential thrombocythemia
• Primary myelofibrosis
• Mastocytosis
• Myeloproliferative neoplasm unclassifiable

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

• Chronic myelomonocytic leukemia (CMML)
• Atypical chronic myeloid leukemia, BCR-ABL1 negative
• Juvenile myelomonocytic leukemia
• Myelodysplastic / myeloproliferative neoplasm, unclassifiable
• Refractory anemia with ring sideroblasts associated with marked thrombocytosis
• Myelodysplastic / myeloproliferative neoplasm with isolated isochromosome 17q

Myelodysplastic Syndromes (MDS)

• Refractory cytopenia with unilineage dysplasia (RCUD)
  • Refractory anemia
  • Refractory neutropenia
  • Refractory thrombocytopenia
• Refractory cytopenia with multilineage dysplasia (RCMD)
• Refractory anemia with ring sideroblasts (RARS)
• Refractory anemia with excess blasts (RAEB)
• MDS associated with isolated del(5q)
• Childhood myelodysplastic syndrome
  • Refractory cytopenia of childhood
• MDS unclassifiable
• Additional features that may be superimposed on above classification:
  • MDS with fibrosis
  • MDS, hypocellular

Therapy Related Myeloid Neoplasms

Bibliography

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