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

Definition

  • 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

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

  • 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

 

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.
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