Case 145

Submitting Author: Craig, Fiona E, MB BS
Institution: University of Pittsburgh Medical Center
Additional authors:Nidhi Aggarwal, MD, Robert L. Redner, MD
Session: Therapy-related myeloid neoplasms

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HISTORY

73 year-old male with history of high-grade sarcoma of the thigh (pleomorphic myxoid sarcoma grade 3- negative for CHOP translocation) diagnosed January 2012 status post resection and chemotherapy (Adriamycin and Ifosfamide). He presented in November 2012 with hematuria at an outside hospital in California where lab work demonstrated leukocytosis, anemia and thrombocytopenia. He was diagnosed with acute myeloid leukemia, likely therapy related, with morphologic features similar to that seen on the subsequent marrow (Images submitted). The patient was started on hydroxyurea 1000 mg/day on 11/14/2012. He was later also found to have leukemia cutis (biopsy of left thigh) 11/26/12. The performance status of the patient was not good and he refused induction chemotherapy. He was counseled regarding hypomethylating agents and a UPCI protocol 8-160 phase 1 trial (ATRA and Dasatinib). He chose to enroll for the trial. The submitted marrow is Day 28 status post chemotherapy (UPCI 08-160 protocol, phase 1 trial ATRA plus dasatinib).

Although the initial marrow obtained one month following transplant demonstrated engraftment with no evidence of leukemia, a marrow obtained on day 62 demonstrated relapse with 34% B lymphoblasts.

DETAILS

The followup bone marrow biopsy submitted was received in B+ fixative and consists of a single core of tan cancellous bone measuring 1.0 x 0.2 cm with an attached piece of brown friable clot measuring 1.6 x 0.2 cm and a few pieces of unattached brown friable clot measuring 0.7 x 0.5 cm in aggregate. Microscopic description: Hypercellular marrow with extensive replacement by blasts with some monocytic features that comprise 80-90% of all cells. Blasts are intermediate cell with moderate amount of cytoplasm, some with granules and erythrophagocytosis, nucleus with irregular nuclear indentation, fine chromatin and some with prominent nucleolus (Image 1). Cytochemical stains performed on aspirate smears demonstrated staining with Butyrate esterase that was inhibited with fluoride incubation.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometric immunophenotypic studies performed on the bone marrow aspirate demonstrate a population of monocytic cells representing approximately 86% of the total cells analyzed and expressing the following phenotype (Image 2): CD45 dim positive, CD14 dim positive in a small subset, CD36 positive, CD64 positive, CD15 positive, CD33 bright positive, CD4 positive, CD56 partial positive, CD2 mostly negative, CD34 negative, CD117 mostly negative, CD38 positive, and HLA-DR variable positive. In addition, there are few B-cells, few heterogeneous T-cells and few natural killer cells.

CYTOGENETIC FINDINGS

46,XY,t(8;16)(p11;p13)[19]/46,XY[1]

MOLECULAR FINDINGS

INTERESTING FEATURES

This case demonstrates features characteristic of AML with t(8;16), and is most likely therapy-related. AML with t(8;16) is a rare disorder, which has been reported to occur de novo or secondary to chemotherapy, and often has monocytic differentiation with associated erythrophagocytosis.

The patient is receiving novel therapy for AML. He is enrolled in the phase 1 UPCI108-160 protocol using ATRA and dasatinib for relapsed/refractory, and/or elderly, patients with acute myeloid leukemia, non-acute promyelocytic. There is interest in using ATRA in combination with other agents for the treatment of acute myeloid leukemias other that acute promyelocytic leukemia and myelodysplastic syndromes e.g. ATRA plus 5-azacytidine, valproic acid (Blood 2007 110: 2302-2308). Dasatinib, which is used most frequently in the treatment of chronic myelogenous leukemia, has been shown in vitro to promote ATRA-induced differentiation of AML cells (Leukemia 2010 24, 663-665).

PROPOSED DIAGNOSIS

Persistent acute myeloid leukemia with monocytic differentiation and t(8;16), likely therapy related.

CONSENSUS DIAGNOSIS

Therapy-related myeloid neoplasm, acute myeloid leukemia (monocytic) with t(8;16)(p11;p13)