Marked Eosinophilia. Workup?
Cytogenetic result: t(8,9)(p11.2,q34)
Diagnosis: Myeloproliferative neoplasm with eosinophilia and rearrangement of FGFR1
Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1
Specific disease groups resulted from formation of a fusion gene encoding an aberrant tyrosine kinase. Eosinophilia is characteristic. The cell of origin is a mutated pluripotent stem cell.
PDGFRA-related disorders: chronic eosinophilic leukaemia (CEL) with prominent involvement of the mast cell lineage and sometimes of the neutrophil lineage.
PDGFRB-related disease: MPN are more variable but are often those of chronic myelomonocytic leukaemia (CMML) with eosinophilia. FGFR1-related isease: a ymphomatous presentation is common, particularly T-LBL with accompanying eosinophilia.
The importance of recognizing these disorders is that the use of tyrosine kinase inhibitors for aberrant tyrosine kinase activity.
Myeloid and lymphoid neoplasms with PDGFRA rearrangement
Rare. M:F=17:1. Peak between 25 and 55 years old.
Presentation: CEL but can be as AML, T-LBL or both simultaneously. Organ damage occurs as a result of leukaemic infiltration or the release of cytokines, enzymes or other proteins by the eosinophils or mast cells.
The PB and BM are always involved. Tissue infiltration in a number of organs. Spleen involved in the majority. Endomyocardial fibrosis leads to restrictive cardiomyopathy. Thromboembolism
Usually cytogenetic analysis is normal, with the FIP1L1-PDGFRA fusion gene resulting from a cryptic del(4)(q12).
The fusion gene can be detected by RT-PCR. Deletion can also be detected by fluorescence in situ hybridization (FISH, a probe for the CHIC2 gene uniformly deleted)
Others: KIF5B-PDGFRA fusion gene involving chromosomes 3, 4 and 10; t(2;4)(p24;q12) STRN-PDGFRA fusion gene; t(4;12)(q2?3;p1?2), ETV6-PDGFRA fusion gene. Patients with t(4;22)(q12;q11) and a BCR-PDGFRA fusion gene, intermediate between those of FIP1L1-PDGFRA-associated eosinophilic leukaemia and those of BCR-ABL1-positive chronic myelogeneous leukaemia;
Myeloid neoplasms with PDGFRB rearrangement
Rare, M:F=2:1, wide age range (8–72 years) with the peak in middle-age.
Presentation: CMML(usually with eosinophilia) most common;Other: atypical chronic myeloid leukaemias (aCML) (usually with eosino philia), CEL and MPN with eosinophilia
Cytogentics: t(5;12)(q31~33;p12), or other partner genes.
Myeloid and lymphoid neoplasms with FGFR1 abnormalities
Rare, M:F= (1.5:1, wide age range (3–84 years) median age around 32 years old
Presentation may be as CEL, AML,T-LBL or, least often, precursor B lymphoblastic leukaemia/lymphoma.
Tissues primarily involved: BM, PB, lymph nodes, liver and spleen. Lymphoblastic lymphoma appears to be more common in patients with t(8;13) than in those with variant translocations
Patients who present in chronic phase usually have eosinophilia and neutrophilia and, occasionally, monocytosis.
Overall about 90% of patients have PB or BM eosinophilia.
The eosinophils belong to the neoplastic clone.
Basophilia: BCR-FGFR1 fusion
Polycythaemia vera: t(6;8)/FGFR1OP1-FGFR1 fusion
Cases should be classified as leukaemia/ lymphoma associated with FGFR1 rearrangement, followed by further details of the specific presentation
Genetics:
A variety of translocations with an 8p11 breakpoint; secondary chromosomal rearrangements occur, esp., trisomy 21
The prognosis is currently poor.
Specific disease groups resulted from formation of a fusion gene encoding an aberrant tyrosine kinase. Eosinophilia is characteristic. The cell of origin is a mutated pluripotent stem cell.
PDGFRA-related disorders: chronic eosinophilic leukaemia (CEL) with prominent involvement of the mast cell lineage and sometimes of the neutrophil lineage.
PDGFRB-related disease: MPN are more variable but are often those of chronic myelomonocytic leukaemia (CMML) with eosinophilia. FGFR1-related isease: a ymphomatous presentation is common, particularly T-LBL with accompanying eosinophilia.
The importance of recognizing these disorders is that the use of tyrosine kinase inhibitors for aberrant tyrosine kinase activity.
Myeloid and lymphoid neoplasms with PDGFRA rearrangement
Rare. M:F=17:1. Peak between 25 and 55 years old.
Presentation: CEL but can be as AML, T-LBL or both simultaneously. Organ damage occurs as a result of leukaemic infiltration or the release of cytokines, enzymes or other proteins by the eosinophils or mast cells.
The PB and BM are always involved. Tissue infiltration in a number of organs. Spleen involved in the majority. Endomyocardial fibrosis leads to restrictive cardiomyopathy. Thromboembolism
Usually cytogenetic analysis is normal, with the FIP1L1-PDGFRA fusion gene resulting from a cryptic del(4)(q12).
The fusion gene can be detected by RT-PCR. Deletion can also be detected by fluorescence in situ hybridization (FISH, a probe for the CHIC2 gene uniformly deleted)
Others: KIF5B-PDGFRA fusion gene involving chromosomes 3, 4 and 10; t(2;4)(p24;q12) STRN-PDGFRA fusion gene; t(4;12)(q2?3;p1?2), ETV6-PDGFRA fusion gene. Patients with t(4;22)(q12;q11) and a BCR-PDGFRA fusion gene, intermediate between those of FIP1L1-PDGFRA-associated eosinophilic leukaemia and those of BCR-ABL1-positive chronic myelogeneous leukaemia;
Myeloid neoplasms with PDGFRB rearrangement
Rare, M:F=2:1, wide age range (8–72 years) with the peak in middle-age.
Presentation: CMML(usually with eosinophilia) most common;Other: atypical chronic myeloid leukaemias (aCML) (usually with eosino philia), CEL and MPN with eosinophilia
Cytogentics: t(5;12)(q31~33;p12), or other partner genes.
Myeloid and lymphoid neoplasms with FGFR1 abnormalities
Rare, M:F= (1.5:1, wide age range (3–84 years) median age around 32 years old
Presentation may be as CEL, AML,T-LBL or, least often, precursor B lymphoblastic leukaemia/lymphoma.
Tissues primarily involved: BM, PB, lymph nodes, liver and spleen. Lymphoblastic lymphoma appears to be more common in patients with t(8;13) than in those with variant translocations
Patients who present in chronic phase usually have eosinophilia and neutrophilia and, occasionally, monocytosis.
Overall about 90% of patients have PB or BM eosinophilia.
The eosinophils belong to the neoplastic clone.
Basophilia: BCR-FGFR1 fusion
Polycythaemia vera: t(6;8)/FGFR1OP1-FGFR1 fusion
Cases should be classified as leukaemia/ lymphoma associated with FGFR1 rearrangement, followed by further details of the specific presentation
Genetics:
A variety of translocations with an 8p11 breakpoint; secondary chromosomal rearrangements occur, esp., trisomy 21
The prognosis is currently poor.