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Surgical Pathology Criteria

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Polycythemia Vera


  • 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

Disorder Molecular or Cytogenetic Alteration Test Used
Chronic myelogenous leukemia BCR-ABL1 CG, PCR
Polycythemia vera JAK2 V617F, JAK2 exon 12 PCR
Essential thrombocythemia JAK2 V617F, MPL W515K/L PCR
Primary myelofibrosis JAK2 V617F, MPL W515K/L PCR
Hematolymphoid neoplasms with FIP1L1-PDGFRA FIP1L1-PDGFRA CG, FISH with CH1C2 probe
Hematolymphoid neoplasms with eosinophilia ETV6-PDGFRB. various involving FGFR1 CG
Chronic eosinophilic leukemia NOS none specific, may have clonal CG abnormalities CG
Mastocytosis KIT D816V CG, PCR on BM, not PB
Acute myelogenous leukemia, even if <20% blasts inv or t(16)(p13.1q22); CBFB-MYH11 FISH
PCR = polymerase chain reaction, CG = conventional cytogenetics, FISH = fluorescent in situ hybridization

Differential Diagnosis

Common Myeloproliferative Neoplasms - Overview
Tyrosine kinase ABL JAK2 JAK2 or MPL JAK2 or MPL
Blood ↑WBC with IG, basophils Normo or hypochromatic anemia, may have ↑platelets & basophils Leukoerythroblastic with teardrops ↑Platelets, often abnormal
Marrow ↑↑Myeloids Panmyelosis, ± erythroid hyperplasia, atypical megas Panmyelosis, atypical megas ↑↑Megas
Marrow fibrosis Varies ↑In spent phase ↑↑In fibrotic phase Minimal
Splenomegaly ++ ++ +++ ±
Clinical Presentation /Other B symptoms Hypertension, thrombosis, pruritus,↓EPO B symptoms, bleeding, gout Thrombosis, hemorrhage
CML = chronic myeloid leukemia; PV = polycythemia vera; PMF = primary myelofibrosis; ET = essential thrombocythemia; IG = immature granulocytes; Megas = megakaryocytes; EPO = erythropoietin


Common Myeloproliferative Neoplasms - Peripheral Blood
  CML PV Cellular Phase PMF ET
RBC Normal or ↓ Normal, ↑ or ↓, may be hypochromatic or polychromatic ↓, teardrop cells Normal or ↓ (iron deficient anemia)
WBC ↑, left shifted, basophilia, eosinophilia, rarely monocytosis Normal or ↑, +/- basophils, (leukoerythroblastic ini fibrotic stage) ↑granulocytes if leukoerythroblastic Normal
Platelets Normal or ↑ Normal or ↑ Normal or ↑ ↑ (>450 x103/μL)
CML = chronic myeloid leukemia; PV = polycythemia vera; PMF = primary myelofibrosis; ET = essential thrombocythemia


Hematolymphoid Disorders with Thrombocytosis
  CML PV PMF, Cellular Phase ET RARS-T 5q-
Tyrosine kinase ABL p230 variant* JAK2 JAK2 or MPL 50% JAK2 or MPL 50% JAK2 50% JAK2 or MPL 10%
Blood ↑PMN, basophils, platelets Normo or hypochromatic anemia, may have ↑basophils, platelets Anemia, leukocytosis, ↑or nl platelets ↑platelets, often abnormal Dimorphic RBC, ↑platelets Macrocytic anemia, ↑or nl platelets
Marrow ↑↑Myeloids, ↑dwarf megas Panmyelosis, ±erythroid hyperplasia, atypical megas Panmyelosis, atypical tightly clustered megas ↑↑Megas Erythroid dysplasia, ring sideroblasts, ↑megas Erythroid hypoplasia, ↑small megas
Marrow Fibrosis Varies ↑ in spent phase ↑↑ in fibrotic phase Minimal Varies Minimal
Splenomegaly ++ ++ +++ ± ± Absent
Clinical/Other B symptoms Hypertension, thrombosis, pruritus, ↓EPO B symptoms, bleeding, gout Thrombosis, hemorrhage Anemia Anemia
EPO = erythropoietin, * rare p230 BCR-ABL1 isoform can present with thrombocytosis and /or neutrophilia



  • 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)

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

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Myelodysplastic Syndromes (MDS)

Therapy Related Myeloid Neoplasms



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