Submitting Author: Vasef, Mohammad A., MD
Institution: University of New Mexico Health Sciences Center
Additional authors:Carla S. Wilson
Session: Therapy-related myeloid neoplasms

The patient is a 62 year old female who was diagnosed with T3N1 invasive lobular carcinoma of the right breast in 2011. She was treated with adjuvant chemotherapy consisting of Adriamycin and Cytoxan every 3 weeks for 4 cycles followed by Taxol weekly. A total of 12 treatments were planned; however, treatment was stopped after 10 cycles due to toxicity including peripheral sensory neuropathy. She then underwent modified radical mastectomy in 2012 that revealed a T1BN0 (i+), ER/PR positive and HER2 negative residual lobular carcinoma. She has been on aromatase inhibitor (Arimidex) since mid-2012. She now presents with worsening leukopenia. A bone marrow biopsy was performed.

A complete blood cell count performed in late 2012 revealed WBC of 1.6x10^9/L, hemoglobin of 14.2 g/dL, hematocrit of 40%, MCV of 105 fL, and a platelet count of 174,000. Review of peripheral blood smear shows moderate neutropenia with rare blasts (<1%). A differential count includes: 54% neutrophils, 35% lymphocytes, 4% monocytes, 6% eosinophils, 1% basophils.

Wright-stained bone marrow aspirate smears reveal intact erythropoiesis, decreased neutrophilic myelopoiesis and increased blasts (21%). Blasts contain large oval to indented nuclei with fine chromatin, frequent distinct nucleoli and moderate amounts of pale blue cytoplasm with occasional intra-cytoplasmic small azurophilic granules without Auer rods. No significant dysplasia is seen in erythroid, myeloid or megakaryocytic lineages. The H&E-stained, post AZF-fixed, and decalcified trephine biopsy sections show a normocellular bone marrow with intact erythropoiesis, decreased neutrophilic myelopoiesis, adequate numbers of megakaryocytes, and patchy aggregates of blasts.

Flow cytometric analysis performed on bone marrow aspirate revealed an increased population of monocytic blasts (25% of total events) expressing CD64, CD4, CD36, CD13, CD33, HLA-DR, CD15, subset CD14, and minor subset CD117 and showing increased side scatter signal.

Karyotype: 46,XX,t(8;16)(p11.2;p13.3)[17]/ 46,XX[3].

The 8;16 translocation is associated with a MYST3-CREBBP fusion in most cases.

Not done.

The interesting features of this therapy-related myeloid neoplasm include:

1. The short interval between cytotoxic therapy and the development of acute myeloid leukemia without preceding myelodysplastic phase.

2. Acute myeloid leukemias with a balanced 8;16 translocation are rare but cases in the literature have distinctive morphologic features (myelomonocytic or monocytic), myelomonocytic immunophenotype with lack of significant CD34 or CD117 expression, and a unique gene expression profile.

3. Although the t(8;16) is more frequently seen in therapy-related AML rather than de novo AML, the prognosis has been uniformly poor in patients with this rare translocation. Should AML with t(8;16) be considered a specific subtype of AML?

Proposed diagnosis: Therapy-related myeloid neoplasm (acute myeloid leukemia with monocytic differentiation)

Therapy-related myeloid neoplasm, acute myeloid leukemia (monocytic), with t(8;16)(p11.2;p13.3)

Case 19