De novo acute myeloid leukemia with monocytoid blasts and erythrophagocytosis

Abstract

Key Clinical Message

Acute myeloid leukemia (AML) with t(8:16) is an infrequent acute leukemia subtype. It can occur de novo or more frequently therapy-related. The presence of blasts with monocytoid morphology and erythrophagocytosis suggest the presence of the t(8;16).

Introduction

A 50-year old woman with a history of low-grade carcinoid tumor of the jejunum treated with surgery presented, 14 months after this diagnosis, with epistaxis, shortness of breath, and pancytopenia. Bone marrow core biopsy demonstrated hypercellularity (Fig.1A; 200×) with 80% blasts in the aspirate smear and mild trilineage dysplasia. The blasts were intermediate to large with monocytic features and small cytoplasmic vacuoles. The blasts were positive for CD4, CD68, and myeloperoxidase and negative for CD34. Some blasts contained in the cytoplasm erythroid cells (Fig.1B, 500×) or fragments of erythrocytes/erythroid precursors (Fig.1C and D; 400×, 500×). Cytogenetic studies revealed a complex karyotype: 45,XX,t(6;12)(q21;q12),t(8;16)(p11;p13),der(8)dic(8;18)(q22;p11.2) trp(8)(q11.2q22)[cp14]/46,XX[3]; that included the t(8;16)(p11;p13) (Fig.1E). The presence of trp(8)(q11.2;q22) indicates triplication of this chromosomal region, confirmed by Flourescent In-Situ Hybridization (FISH) that showed three copies of the RUNX1T1 gene. The patient subsequently underwent standard induction chemotherapy with daunorubicin and cytarabine. Two subsequent bone marrow samples showed normal morphology and normal karyotypes. The patient is awaiting allogenic bone marrow transplant.

Figure 1.

Representative image of the blasts in the core biopsy specimen (A) and in the aspirate smears (B–D). Note the monocytoid appearance of the blasts with abundant cytoplasm, small cytoplasmic vacuoles, and erythrophagocytosis. Conventional kariotyping revealed a complex karyotype that included the t(8;16)(p11;p13). The chromosomes with rearrangements are indicated by arrows (E).

Acute myeloid leukemia (AML) with t(8:16) is an infrequent leukemia subtype. This leukemia is more frequent in women, has an aggressive course, frequent extramedullary involvement, disseminated intravascular coagulation, poor prognosis and often has monocytic differentiation [1,2]. It can occur de novo or more frequently therapy-related. The t(8;16) fuses MYST3 (at 8p11) with CREBBP (at 16p13) [3,4]. MYST3 is a histone acetyltransferase which modulates transcription through co-activation of RUNX1. CREBBP interacts with the DNA-binding protein CREB and has also histone acetyltransferase activity. Erythrophagocytosis by blasts has been most frequently associated with monocytic leukemias with cytogenetic abnormalities involving (8p11). The presence of monocytoid blast morphology with eryhtrophagocytosis suggested the presence of the t(8;16) in this AML.

Conflict of Interest

None declared.