Page 77 - Haematologica Atlas of Hematologic Cytology

CHAPTER 10 - Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement
Chapter 10. MYELOID/LYMPHOID NEOPLASMS WITH EOSINOPHILIA AND GENE REARRANGEMENT
Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement are rare disorders generally arising from a pluripotent stem cell, characterized by myeloproliferative, or myelodysplastic/myeloproliferative and/ or lymphoproliferative features with possible evolution to acute, myeloid or lymphoid leukemia, and associated with eosinophilia and rearrangement of genes resulting in the expression of an aberrant tyrosine kinase. Accor- ding to the World Health Organization (WHO) classification (Bain et al., 2017), they include three groups of disor- ders and a provisional entity (Table 1).
Table 1. Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement characteris c features.
n ty
ommon presenta on
ytogene cs
Molecular gene cs
Myeloid/lymphoid neoplasms with
PDGFRA rearrangement
Chronic eosinophilic leukemia with involvement of the mast cell lineage
Normal with a cryp c del(4)(q12) or transloca ons with a 4q12 breakpoint
FIP1L1-PDGFRA fusion gene or a variant fusion gene with rearrangement of PDGFRA
Myeloid/lymphoid neoplasms with PDGFRB rearrangement
Chronic myelomonocy c leukemia with eosinophilia
t(5;12)(q32;p13.2) or variant transloca ons with a 5q32 breakpoint
ETV6-PDGFRB fusion gene or a variant fusion gene with rearrangement of PDGFRB
Myeloid/lymphoid neoplasms with FGFR1 rearrangement
Myeloprolifera ve neoplasm, acute myeloid leukemia, T- or B-lymphoblas c leukemia/ lymphoma, mixed phenotype acute leukemia (usually associated with eosinophilia)
t(8;13)(p11.2;q12.1) or variant transloca ons with a 8p11 breakpoint
ZMYM2-FGFR1 fusion gene or a variant fusion gene with rearrangement of FGFR1
Myeloid/lymphoid neoplasms with
PCM1-JAK2*
Myeloprolifera ve or myelodysplas c/myelopro- lifera ve neoplasm (usually associated with eosinophilia)
t(8;9)(p22;p24.1)
or variant transloca ons with a 9p24 breakpoint
PCM1-JAK2 fusion gene or a variant fusion gene with rearrangement of JAK2
*Provisional en ty
The finding of a myeloid or lymphoid neoplasm associated with eosinophilia suggests the diagnosis, which must be confirmed by the demonstration of specific cytogenetic and/or molecular abnormalities. In some cases, eosinophil morphology is normal, whereas in other cases, the same morphological abnormalities of reactive eo- sinophilia may be observed: hypogranulation, smaller than normal granules, purplish granules, nuclear hyper- or hyposegmentation, increased eosinophil size. Eosinophil or neutrophil precursors, and even blasts, can be pre- sent in the peripheral blood, and bone marrow blast cells may be increased. Sometimes, in the bone marrow, there is also mast cell proliferation, often with atypical morphology.
The clinical picture of these disorders may be characterized by the involvement of various organs, such as he- art, lungs, nervous system, skin, and gastrointestinal tract due to tissue infiltration by eosinophils and/or tissue damage caused by substances released by eosinophil granules.
Cytogenetic and/or molecular genetic analysis is essential for a differential diagnosis from idiopathic hype- reosinophilic syndrome, chronic eosinophilic leukemia not otherwise specified, systemic mastocytosis, or other myeloid or lymphoid neoplasms with eosinophilia. The identification of these disorders is important especially with regard to prognosis and therapy: in the forms with PDGFRA or PDGFRB rearrangement, the response to imatinib is usually very good, while myeloid/lymphoid neoplasms with PCM1-JAK2 may respond to ruxolitinib. Un- fortunately, myeloid/lymphoid neoplasm with FGFR1 rearrangement is not responsive to tyrosine kinase inhibitor therapy, and only allogeneic stem cell transplantation appears to offer a chance of cure.
Reference
Bain BJ, Horny HP, Arber DA, Te eri A, Hasser ian RP. Myeloid/lymphoid neoplasms with eosinophilia and rearran- gement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2. In: Swerdlow SH, Campo E, Harris NL et al (Eds). WHO Classi ca on of Tumours of Hematopoie c and Lymphoid Tissues (Revised 4th edi on). IARC: Lyon; 2017. p. 72-79.
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