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Idiopathic Hypereosinophilic Syndrome

Definition

  • Persistent eosinophilia with tissue damage but without proven clonality or increase in blasts

Diagnostic Criteria

  • All of the following must be demonstrated
    • Persistent peripheral blood eosinophilia ≥1.5 x 103/μL
      • Duration ≥6 months
      • Eosinophils may have hyper or hyposegmented nuclei
        • May have nuclear enlargement
    • Reactive (allergy etc.) and secondary (T cell lymphoma etc.) eosinophilia should be excluded (see Differential Diagnosis)
    • Evidence of organ involvement with tissue damage must be present
      • Endomyocardial fibrosis is the most significant complication
      • May also involve lungs, nervous system, skin and gastrointestinal tract
      • If no tissue damage, consider Idiopathic Hypereosinophilia
    • No evidence of clonality on cytogenetic or molecular studies
    • No increase in myeloblasts or dysplastic features
  • As defined, Hypereosinophilic Syndrome is probably a mixed group
    • Some may be unrecognized reactive or secondary and some may be unrecognized clonal neoplasms
    • Patients should be followed for subsequent development of evidence of clonality, an increase in myeloblasts or overt T cell lymphoma

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

By definition, no clonal molecular or cytogenetic alteration is present in hypereosinophilic syndrome

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

Hypereosinophilia*
  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

Clinical

  • Complications due to tissue infiltrates of eosinophils
    • Most significant is endocardial fibrosis
      • Constrictive heart failure
      • Valvular scarring with thromboembolism
    • Nervous system disorders, central and peripheral
    • Pulmonary, cutaneous, gastrointestinal disorders
  • Variable prognosis, not well defined

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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  • 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.
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  • 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
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