Stanford School of Medicine

Surgical Pathology Criteria

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Chronic Neutrophilic Leukemia


  • 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


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


  • 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



  • Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2008
  • Anastasi J. The myeloproliferative neoplasms: insights into molecular pathogenesis and changes in WHO classification and criteria for diagnosis. Hematol Oncol Clin North Am. 2009 Aug;23(4):693-708.
  • George TI, Arber DA. Pathology of the myeloproliferative diseases. Hematol Oncol Clin North Am. 2003 Oct;17(5):110
    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.
  • Wadleigh M, Tefferi A. Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria. Int J Hematol. 2010 Mar;91(2):174-9. 1-27.
  • Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999 Apr 29;340(17):1330-40.
  • Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A,  Cazzola M, Skoda RC. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005 Apr 28;352(17):1779-90.
  • Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR; Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-61. Erratum in: Lancet. 2005 Jul 9-15;366(9480):122.
  • James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-8.
  • Thiele J, Kvasnicka HM, Schmitt-Graeff A, Zankovich R, Diehl V. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients.  Am J Hematol. 2002 Aug;70(4):283-91.
  • Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003 Mar 27;348(13):1201-14.
  • Gotlib J, Cools J, Malone JM 3rd, Schrier SL, Gilliland DG, Coutré SE. The
    FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood. 2004 Apr 15;103(8):2879-91.
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