Therapy-related acute myeloid leukemia with eosinophilia, basophilia, t(4;14)(q12;q24) and PDGFRA rearrangement: a case report and review of the literature

Abstract

The myeloid and lymphoid neoplasms with eosinophilia and PDGFRA gene rearrangements usually show a good response to Imatinib and are typically associated with a normal karyotype, occasionally exhibiting a secondary chromosomal abnormality associated with clonal evolution. Five variant translocations involving PDGFRA have been reported. Here, we report a rare case of therapy-related acute myeloid leukemia with PDGFRA rearrangement after chemotherapy for prior B lymphoblastic leukemia (B-ALL). The patient had a history of BCR-ABL negative, hypodiploid B-ALL in complete remission after chemotherapy. However, 15 months later the patient developed acute myeloid leukemia with rapidly increasing eosinophilia, basophilia and a complex karyotype that included a novel t(4;14)(q12;q24). FIP1L1 was not associated with the PDGFRA rearrangement. The patient had a very aggressive clinical course, and died from the disease shortly after diagnosis. This is the first case of a primary therapy-related myeloid neoplasm with secondary PDGFRA rearrangement. The t(4:14)(q12;q24) is joining the growing list of the variant translocations involving PDGFRA.

Keywords: Acute myeloid leukemia (AML); PDGFRA; basophilia; eosinophilia; therapy-related myeloid neoplasm.

Figure 1

B-lymphoblastic leukemia at initial diagnosis. A. Predominance of large lymphoblasts with round to indented nuclei, fine chromatin, and basophilic cytoplasm with cytoplasmic vacuoles (Aspirate smears, Wright stain, 1000 ×). B. Hypercellular marrow with sheets of blasts (Bone marrow core biopsy, H & E stain, 100 ×).

Figure 2

Restaging bone marrow biopsy after chemotherapy for B-ALL showed multilineage dysplasia and focal eosinophilia. A. Megakaryocytic dysplasia with hypolobulated nuclei (Aspirate smears, Wright stain, 100×); B. Erythroid dysplasia with prominent nuclear budding (Aspirate smears, Wright stain, 1000×); C. Focally increased eosinophils and precursors as well as erythroid dysplasia (Aspirate smears, Wright stain, 1000×); D. Hypercellular marrow with dysplastic megakaryocytes (Bone marrow core biopsy, H & E stain, 100×).

Figure 3

The absolute counts of peripheral blood with differential demonstrated marked leukocytosis with a rapid increase of eosinophils and basophils, along with circulating blasts.

Figure 4

Acute myeloid leukemia with eosinophilia, basophilia and FIP1L1-PDGFRA. A. Eosinophila, basophilia and circulating blasts (Peripheral blood smear, Wright-giemsa stain, 1000×); B. Eosinophilia, basophilia and increased myeloblasts (Aspirate smears, Wright stain, 1000×); C. Hypercellular marrow with hypolobulated dysplastic megakaryocytes (Bone marrow core biopsy, H & E stain, 100×); D. Markedly increased blasts (ALIP) as well as eosinophils and precursors (Bone marrow core biopsy, H & E stain, 200×); E. Approximately 20% CD34-positive blasts (Bone marrow core biopsy, immunostain, 100×); F. Normal number and morphology of tryptase-positive mast cells (Bone marrow core biopsy, immunostain, 100×).

Figure 5

Cytogenetic and FISH findings in acute myeloid leukemia with eosinophilia, basophilia and FIP1L1-PDGFRA. A. Complex karyotype with 45,XY,del(3)(p12), t(4;14)(q12;q24),der(5;21)(p10;q10),add(10)(q22). B and C. Complex karyotype with 50-51,XY,t(4;14)(q12;q24.3),+5,der(5;21)(p10;q10),+6,+8,+10,add(10)(q22)x2,+11,der(17)t(11;17)(q13;p11.2),+1-2mar. D. Interphase fluorescence in situ hybridization (FISH) tricolor 4q12 linked gene analysis: positive for loss of one FIP1L1 signal (green) and one CHIC2 signal (red) from the isolated PDGFRA signal (aqua).