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WHO Classification of Tumours
Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1


Myeloproliferative and lymphoid neoplasms associated with rearrangement of PDGFRA ,PDGFRB and FGFR1 constitute three rare specific disease groups, which have some shared features and some that differ. All result from formation of a fusion gene encoding an aberrant tyrosine kinase. Eosinophilia is characteristic but not invariable. It has been established that, in the case of PDGFRA and FGFR1-related neoplasms, the cell of origin is a mutated pluripotent (lymphoid-myeloid) stem cell. It is possible that this is also true for PDGFRB-related neoplasms, but this has yet to be established.

All three disorders can present as a chronic myeloproliferative neoplasm (MPN), but the frequency of manifestation as a lymphoid neoplasm varies. The clinical and haematological features are also influenced by the partner gene involved. In the case of PDGFRA-related disorders, presentation is usually as chronic eosino­philic leukaemia (CEL) with prominent involvement of the mast cell lineage and sometimes of the neutrophil lineage. Less often, presentation is as acute myeloid leukaemia (AML) or precursor-T lympho­blastic lymphoma (T-LBL), in both instances with accompanying eosinophilia. In the case of PDGFRB-related disease, the features of the MPN are more variable but are often those of chronic myelo­monocytic leukaemia (CMML) with eosinophilia. Proliferation of aberrant mast cells can again be a feature. Acute transformations that have been described to date have been myeloid. In the case of FGFR1-related disease, a lymphomatous presentation is common, particularly T-LBL with accompanying eosinophilia. Other patients have had CEL, precursor-B lymphoblastic leukaemia/ lymphoma or AML.

The importance of recognizing these disorders is that the aberrant tyrosine kinase activity can make the disease responsive to tyrosine kinase inhibitors. This hope has already been realized for MPN with rearrangement of PDGFRA or PDGFRB, which are responsive to imatinib and some related tyrosine kinase inhibitors. Similar specific therapy has not yet been developed for FGFR1-related disease. Relevant cytogenetic analysis, molecular genetic analysis or both should be carried out in all patients in whom MPN with eosinophilia is suspected and also in patients presenting with an acute leukaemia or lymphoblastic lymphoma with eosinophilia. Recognition of PDGFRA-related disease usually requires molecular genetic analysis, since the majority of cases result from a cryptic deletion, whereas cytogenetic analysis will reveal the causative abnormality in the case of PDGFRB- and FGFR1-related disease.







Barbara J. Bain
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Barbara J. Bain
Department of Haematology
Imperial College Faculty of Medicine, St. Mary’s Hospital
London
UK




D. Gary Gilliand
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D. Gary Gilliand
Brigham and Women's Hospital
Harvard Medical School
Boston
USA




Hans-Peter Horny
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Hans-Peter Horny
Institute of Pathology
Clinic of Ansbach
Ansbach
Germany




James W. Vardiman
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James W. Vardiman
Department of Pathology
University of Chicago Medical Center
Chicago
USA





Flow diagram showing the diagnostic process in hypereosinophilia.
Flow diagram showing the diagnostic process in hypereosinophilia.