Submitting Author: Chakhachiro, Zaher, MD
Institution: UT MD Anderson Cancer Center
Additional authors:Jeffrey L Jorgensen M.D., Ph.D. and Rachel L Sargent M.D.
Session: Therapy-related myeloid neoplasms

The patient is a 30 year old male with a history of acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA diagnosed and treated in Saudi Arabia in 2005. Family and social histories were unremarkable. The pateint was followed by a local oncologist every 3-6 months, until in May of 2012 when he presented with progressive leukocytosis and increased peripheral blasts. A bone marrow biopsy performed in Saudi Arabia led to a diagnosis of acute myeloid leukemia. The patient started induction chemotherapy and then came to our institution for a second opinion and therapeutic recommendations.

A formalin, fixed right posterior iliac crest bone marrow biopsy and clot specimen as well as bone marrow aspirate smears were submitted for morphologic evaluation.

The bone marrow biopsy and clot specimens showed bone marrow with a cellularity of approximately 90-100%. The normal hematopoietic elements were essentially replaced by a diffuse infiltrate of intermediate sized, immature mononuclear cells with round to oval and slightly irregular nuclei, finely dispersed chromatin, occasional prominent nucleoli and scant to moderate cytoplasm.

The aspirate smears showed 52% blasts that are variably sized, with round to oval and slightly irregular nuclei, finely dispersed chromatin, single and occasionally multiple prominent nucleoli and scant to moderate basophilic cytoplasm. Occasional blasts show fine cytoplasmic granules and/or vacuoles. Auer rods are not identified.

Immunophenotyping by flow cytometry showed two distinct blast populations. The first population, approximately 30% of total blasts, had a precursor B-lymphoblastic phenotype, positive for CD13 partial, CD19, CD20 small subset (~11%), surface CD22, CD34, cytoCD79a, CD81 dim, and TdT, and negative for CD10, CD15, CD25, CD33, CD117, surface light chains, and myeloperoxidase (MPO). The second population, approximately 70% of total blasts, showed an aberrant immature myeloid phenotype, positive for CD7 partial, CD13 partial, CD15 partial, surface CD22, CD25 partial, CD33, CD34, CD38, CD64 dim/partial, CD117, HLA-DR, TdT dim and MPO small subset (~4%) and negative for CD14, CD41, CD56, CD81 and all other tested B-cell and T-cell markers.

In addition, less than 3% of blasts were positive for MPO by cytochemistry. Immunofluorescence staining for the promyelocytic leukemia protein oncogenic domain (POD) was negative.

45,XY,-7[15]/46,XY[5].

FISH and PCR studies were negative for t(15;17)/PML-RARA. Mutational studies for mutations within the CEBPA, FLT3, DNMT3a, IDH1, IDH2, KITA, NPM1, KRAS and NRAS genes were negative.

This is a case of therapy-related acute leukemia, in a patient with a previous history of acute promyelocytic leukemia. Based on cytogenetic and molecular studies, the current leukemia represents an independent primary.

While the phenotype is borderline for WHO classification as mixed phenotype acute leukemia, the current leukemia clearly has distinct B-lymphoblastic and myeloid blast populations (“bilineal”).

Therapy-related myeloid neoplasm, mixed phenotype acute leukemia (bilineal, B/myeloid)

Case 18