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Chronic Neutrophilic Leukemia

Definition

  • Very rare myeloproliferative neoplasm characterized by neutrophilia

Diagnostic Criteria

  • Reactive neutrophilia must be ruled out
  • Sustained peripheral blood leukocytosis with neutrophilia
    • WBC ≥25 x 103/μL
    • Segmented neutrophils and bands >80% (usually >95%)
      • May have toxic granulation
      • No dysplasia
    • Immature granulocytes <10%
    • Blasts <1%
  • Hypercellular bone marrow
    • Myeloid hyperplasia
      • Myeloblasts <5%
      • Normal granulocytic maturation
      • Megakaryocytes normal or left shifted
  • Hepatosplenomegaly
  • No Ph' or BCR-ABL1 or rearrangement of PDGFRA, PDGFRB or FGFR1
    • CML with p230 BCR-ABL1 is neutrophilic variant of CML, not CNL
  • PV, PMF, ET, MDS and MDS/MPN must be excluded

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

  • Occasional JAK2V617F mutations
  • Absence of Ph’ or BCR-ABL1
  • Cytogenetics normal in 90% of patients
    • Nonspecific clonal abnormalities seen include +8, +9, +21, del(20q)

Differential Diagnosis

  • Reactive neutrophilia
    • Infection, inflammation and neoplasm must be ruled out
      • Underlying plasma cell myeloma must be excluded
  • Other myelodysplastic syndromes, myeloproliferative neoplasms and MDS/MPN must be ruled out
    • No dysplasia
    • No involvement of other lineages
    • No Ph' or BCR/ABL1 or rearrangement of PDGFRA, PDGFRB or FGFR1
      • Specifically, CML with the p230 variant BCR/ABL can present with neutrophilia

Myeloproliferative and Mixed MDS/MPNs with Neutrophilia and/or Monocytosis
  CML-CP Atypical CML CMML-1 CNL
Ph Chromosome and/or BCR-ABL1 Translocation Almost 100% Absent Absent Absent

WBC

Left shifted neutrophilia* Left shifted neutrophilia Monocytosis, may have left shifted neutrophilia Neutrophilia
Blood basophils Increased Not increased Not increased Not increased
Blood monocytes Variable,** <1x103/μL Variable, <1x103/μL Always >1x103/μL <1x103/μL
Blood immature granulocytes >20% 10-20% Usually <10% <10%
Blood blasts Usually <2% >2% <5% <1%
Granulocytic dysplasia Absent ++ +/- Absent
*rare p230 BCR-ABL1 isoform may show mature neutrophilia, **rare p190 BCR-ABL1 isoform associated with monocytosis

Clinical

  • Variable survival
    • 6 months to >20 years
  • Progressive neutrophilia leads to anemia and thrombocytopenia
    • Mucocutaneous bleeding

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

 

Bibliography

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    Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008 Jan;22(1):14-22.
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