Institution: UT MD Anderson Cancer Center
Additional authors:Xiaohong I. Wang, Mark Routbort, Keyur Patel, Carlos E. Bueso-Ramos, C. Cameron Yin
Session: AML with recurrent genetic mutations Part II
HISTORY
The patient is a 68-year-old woman with a history of myelodysplastic syndrome (MDS) that was diagnosed in 2008. She had not received any treatment for MDS. She was in her usual state of health until January 16, 2013, when she presented to a local hospital with chest discomfort and worsening dyspnea on exertion. A complete blood cell count (CBC) was done which revealed marked leukocytosis with a white blood cell (WBC) count of 180,000 K/uL and circulating blasts. She was referred to our hospital for further treatment options.
Upon presentation at our hospital, her CBC showed WBC 163.0 K/uL, hemoglobin 11 g/dL, platelet count 43 K/uL, with 72% blasts. Her serum lactate dehydrogenase level was 3264 IU/L, and her b2-microglobulin was 4.5 mg/L. A bone marrow (BM) biopsy confirmed a diagnosis of acute myeloid leukemia (AML) arising from MDS. She was treated with 5-azacitidine and midostaurin.DETAILS
The peripheral blood smear shows normochromic, normocytic anemia, thrombocytopenia, left-shifted leukocytosis with 72% blasts.
Bone marrow biopsy and aspirate specimens show hypercellular (100%) marrow with left-shifted granulopoiesis, megakaryocytic and erythroid hypoplasia and 57% blasts. The blasts are medium to large in size with fine chromatin, prominent nucleoli, and scant to moderate amount of cytoplasm.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry immunophenotypic analysis of the BM aspirate material demonstrated a dinstinct population of blasts that were positive for CD4 (dim), CD13, CD33, CD34, CD38, CD45, CD49d, CD64 (subset), CD117, CD123, and myeloperoxidase, and were negative for CD2, CD3 (surface and cytoplasmic), CD5, CD7, CD10 CD14, CD15, CD19, CD22, CD36, CD41, CD56, and HLA-DR.
CYTOGENETIC FINDINGS
Cytogenetics showed 46,XX[20].
MOLECULAR FINDINGS
A next generation sequencing-based analysis for the detection of frequently reported mutations in a total of 53 genes was performed on DNA extracted from the BM aspirate sample. The following four mutations were detected: internal tandem duplication (ITD) in FLT3 gene, a 4 base pair insertion in exon 12 of the NPM1 gene, mutation in codon 882, exon 23 of the DNMT3A gene (c.2644C>T, p.R882C), and mutation in codon 192, exon 6 of the TP53 gene (c.574C>T, p.Q192*).
INTERESTING FEATURES
The patient has a history of long-standing MDS without treatment. She suddenly developed AML with diploid Karyotype. Next generation sequencing detected mutations in four genes which included FLT3, NPM1, DNMT3A and TP53.
PROPOSED DIAGNOSIS
Acute myeloid leukemia arising from myelodysplastic syndrome, diploid karyotype, with mutations in FLT3, NPM1, DNMT3A and TP53.
CONSENSUS DIAGNOSIS
Acute myeloid leukemia with myelodysplasia-related changes, with NPM1 mutation, FLT3 ITD mutation, DNMT3A mutation, and TP53 mutation