Case 131

Submitting Author: Chen, Mingyi, MD, PhD
Institution: UC Davis Medical Center
Session: Therapy-related myeloid neoplasms

HISTORY

52-year-old female with history of triple negative breast cancer, treated with lumpectomy and axillary dissection, chemotherapy with dose-dense AC-T(60 mg/m2 adria x 4) + Tamoxifen followed by breast radiation with no evidence of recurrence or metastases. After 3 years, she developed marked thrombocytopenia. Bone marrow biopsy confirmed the diagnosis of AML.

DETAILS

Left posterior iliac crest bone marrow biopsy was performed.

There are occasional (2%) circulating blasts in peripheral blood smear. The blasts are large in size with slightly irregular nuclear contour, fine chromatin, prominent nucleoli, and vacuolated basophilic cytoplasm. The Wright-Giemsa stained bone marrow aspirate smears shows numerous blasts, representing 60% marrow cellularity. The blasts shows essentially similar features as peripheral blasts. There are occasional eosinophilic granules in the cytoplasm of blasts. No definite Auer rods are identified. The residual trilineage hematopoiesis shows dysplastic features.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytomery: IMMATURE MYELOMONOCYTIC CELLS EXPRESSING: CD33+/CD34+/HLA-DR+/CD117+/CD7+ DIM/CD19 (SUBSET). LARGE PROPORTION OF THE MYELOID CELLS EXPRESSING MONOCYTIC PHENOTYPE: CD64+, CD11B+, CD14+ AND CD4+.

CYTOGENETIC FINDINGS

Cytogenetics: 46,XX,t(3;5)(q21;q31)[16]/46,xx[4]

FISH: no MDS panel abnormalities using deletion 5q33-q34, 7p31/CEP7, Trisomy 8, Deletion 20q probes

INTERESTING FEATURES

She was treated with induction: 7+3 (Cytarabine + Daunorubicin). On day 14, marrow was negative for leukemia with morphological remission, and sibling HLA matched allogeneic transplant was performed two months later. Post-transplant course was complicated by mucositis, culture negative neutropenic fevers, and skin GVHD. After 3 months, a bone marrow biopsy showed no evidence of recurrent AML. Chimerism studies showed 98% CD3 engraftment. The patient was persistent in remission after 1 year follow up.

The t(3;5)(q21-25;q31-35) chromosomal translocation is associated with myelodysplastic syndrome and acute myeloid leukemia (AML). The t(3;5) (q21;q31) chromosomal abnormality is a rare finding in acute myelogenous leukemia, and usually is associated with trilineage myelodysplasia. It was reported that the t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.

References:

1. Sharp RA, Robertson J, Heppleston AD. t(3;5)(q21;q31) in a myelodysplastic syndrome. Leuk Res. 1987;11(7):629-33.

2. Yoneda-Kato N, Look AT, Kirstein MN, Valentine MB, Raimondi SC, Cohen KJ, Carroll AJ, Morris SW The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene. 1996 ; 12 (2) : 265-275.

PROPOSED DIAGNOSIS

Therapy-related acute myeloid leukemia with myelodysplasia-related changes and t(3;5)(q21;q31)

CONSENSUS GROUP: ADDITIONAL INFORMATION/STUDIES

Additional immunostains performed by conference consensus group:

MPO: Positive in blasts
CD68: Positive in blasts
Glycophorin A: Negative

CONSENSUS DIAGNOSIS

Therapy related myeloid neoplasm, acute myeloid leukemia with t(3;5)(q21;q31)