Stanford School of Medicine

Surgical Pathology Criteria

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Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1


  • Any of several myeloproliferative neoplasms or lymphoid neoplasms with accompanying rearrangements or other mutations in PDGFRA, PDGFRB or FGFR1

Diagnostic Criteria

  • These disorders are defined by the tyrosine kinase involved :
    • No BCR-ABL1 or Philadelphia chromosome
    • Myeloid and lymphoid neoplasms with PDGFRA rearrangement
      • Most common rearrangement is FIP1L1-PDGFRA
        • Rare others involving PDGFRA may occur
        • Makes up 10-20% of idiopathic hypereosinophilias
        • Primarily seen in males
      • Most common neoplasm is chronic eosinophilic leukemia (CEL)
        • Peripheral eosinophilia >1 x 103/μL for >6 months
        • May also present as AML, T lymphoblastic lymphoma, CML
    • Myeloid neoplasms with PDGFRB rearrangement
      • Most common rearrangement is t(5;12)(q31-q33;p12)
    • Myeloid and lymphoid neoplasms with FGFR1 abnormalities
      • Most common is t(8;13)(p11;q12) involving FGFR1
        • Other rearrangements or fusion genes involving FGFR1 may be seen
        • Most frequent neoplasms are CEL, AML, T lymphoblastic lymphoma, precursor B lymphoblastic lymphoma/leukemia

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

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

  Idiopathic Hypereosinophilia Idiopathic Hypereosinophilic Syndrome Chronic Eosinophilic Leukemia NOS Hematolymphoid Neoplasms with Specific Genetic Abnormalities#
Hypereosinophilia Yes Yes Yes Yes
Tissue Damage No Yes Subset Subset
Clonality** No Not demonstrated Yes Yes
Blasts ≥20% No No No Subset
Abnormalities of BCR-ABL1, PDGFRA, PDGFRB, KIT, FGFR1 or CBFB No No No Yes

  • *Transient, reactive and secondary eosinophilia must be excluded
    • Causes of reactive eosinophilia, including
      • Drug reaction
      • Allergy, including bronchopulmonary aspergillosis
      • Parasites
      • Loeffler syndrome
      • Collagen vascular diseases
      • Kimura disease
      • Vasculitis
      • Cyclical eosinophilia
    • Aberrant T cell population associated eosinophilia
      • Also known as lymphocyte variant hypereosinophilia
      • Abnormal T cell population does not meet diagnostic criteria for leukemia or lymphoma
    • Causes of eosinophilia secondary to neoplasms
      • T cell lymphomas and leukemias
      • Hodgkin lymphoma
      • Systemic mastocytosis
  • #Neoplasms with specific genetic abnormalities are covered separately:
  • **Clonality may be demonstrated by cytogenetics or assumed due to >2% PB or >5% BM blasts or dysplastic features


  • Neoplasms involving PDGFRA
    • Male:female 17:1
    • Wide age range, peaks at middle age
    • Tissue damage from infiltrates
      • Cardiac failure due to endomyocardial fibrosis is most significant
    • Sensitive to imatinib
  • Neoplasms involving PDGFRB
    • Male:female 2:1
    • Wide age range, peaks at middle age
    • Tissue damage from infiltrates
      • Cardiac failure due to endomyocardial fibrosis is most significant
    • Sensitive to imatinib
  • Neoplasms involving FGFR1
    • Male:female 1.5:1
    • Wide age range, peaks around 30 years
    • May present as lymphoma or as myeloproliferative neoplasm
    • Not sensitive to imatinib
  • Chronic myelomonocytic leukemia with eosinophilia
    • t(5:12) involving PDGFR on conventional cytogenetics
    • Imatinib sensitive
  • Chronic eosinophilic leukemia with FIP1
    • Imatinib sensitive

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.
  • Gotlib J. World Health Organization-defined eosinophilic disorders: 2011 update on diagnosis, risk stratification, and management. Am J Hematol. 2011 Aug;86(8):677-88.
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