Myeloid and Lymphoid Neoplasms with Eosinophilia

Abstract

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 were first formally accepted as a set of entities in the 2008 edition of the World Health Organization’s Classification of Tumours of Haematopoietic and Lymphoid Tissues. In the 2016 edition, myeloid and lymphoid neoplasms with eosinophilia and t(8;9)(p22;p24.1);PCM1-JAK2 are now recognized as a provisional entity. Collectively, these represent a heterogeneous group of neoplasms in which eosinophilia is typical but not required. Most commonly, patients are men in their 40s or 50s, although they may present across a broad age range. Abnormalities of PDGFRA usually resemble chronic eosinophilic leukemia (CEL). Rarely, patients may display characteristics of acute myeloid leukemia (AML) or T lymphoblastic leukemia/lymphoma (T-ALL), although eosinophilia remains a consistent feature. Additionally, mast cells with abnormal immunophenotype may be increased in bone marrow biopsies, mimicking systemic mastocytosis (SM). Most abnormalities of PDGFRA are the result of a cryptic 4q12 (CHIC2) deletion, necessitating fluorescence in situ hybridization (FISH) analysis or polymerase chain reaction (PCR) for identification (Figs. 16.1, 16.2, 16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, and 16.10, Table 16.1). Patients with abnormalities of PDGFRB often present with features of chronic myelomonocytic leukemia (CMML) with eosinophilia, but atypical chronic myeloid leukemia (aCML), CEL, and juvenile myelomonocytic leukemia (JMML) phenotypes are also reported (Figs. 16.11, 16.12, 16.13, 16.14, 16.15, and 16.16, Table 16.2). The presentation of abnormalities of FGFR1 is highly variable and partly dependent on the specific gene rearrangement (Figs. 16.17, 16.18, 16.19, and 16.20, Table 16.3). In t(8;13)(p11;q12), lymphadenopathy is common, and a “bilineal lymphoma” phenotype is often seen. In t(8;9)(p11;q33), monocytosis and tonsillar involvement are characteristic. The t(6;8)(q27;p11–12) presents in an older age group with more prominent eosinophilia and erythrocytosis. Unlike abnormalities of PDGFRA, conventional karyotyping can detect most abnormalities associated with PDGFRB and FGFR1. The recognition of these neoplasms is vital, as patients with abnormalities of PDGFRA and PDGFRB are exquisitely sensitive to imatinib. Unfortunately, definitive, effective targeted monotherapy has not yet been discovered for patients with abnormalities of FGFR1, resulting in a poor prognosis. The use of ponatinib in combination with chemotherapy and possible allogeneic transplantation may improve the prognosis, however.