Submitting Author: Wang, Xiaohong Iris, MD, PhD
Institution: MD Anderson Cancer Center, University of Texas
Additional authors:Lin Pei, M.D.
Session: AML with myelodysplasia-related changes

The patient is a 63-year-old man who was in his usual state of health until 09/2009 when a routine lab work showed an elevated ferritin and iron levels. Liver biopsy was performed and reported to show no specific abnormality. The patient was followed without further therapy. He then developed recurrent cellulitis and upper respiratory infections. In 01/201, he was found to have an abnormal CBC and was diagnosed as having hypoplastic myelodysplastic syndrome at an outside institution. The patient was started on Aranesp injections for anemia in 03/2011 and became transfusion dependent on red blood cells and platelets in 08/2011. He was also treated with Neupogen daily. He complained of weight loss (80 pounds in 1 year), night sweats and chronic shortness of breath. He was then referred to our hospital in 1/2013 for a second opinion and treatment options.

At our hospital, WBC: 2.8 K/uL, hemoglobin 8.7 g/dL, platelet count 34 K/uL, with 1% blasts. Neutrophils: 9%, lymphocytes: 55%, monocytes: 20%, eosinophils 1%, metamyelocytes 1%, blasts, 1%, myelocytes: 13%

His serum lactate dehydrogenase level was 4161 IU/L, and β 2-microglobulin 5.3 mg/L, ferritin 9173 ng/mL, erythropoietin 464 mIU/ml. total iron binding capacity: 156.4 ug/dL (250- 450), transferin: 111.7 mg/dL (188-341), AST: 118 IU/L (15-46)

Physical exam found that patient had hepatosplenomegaly

A bone marrow biopsy confirmed a diagnosis of myelodysplastic syndrome, best classified as refractory cytopenia with multilineage dysplasia and fibrosis, MF 1-2.

The peripheral blood smear showed pancytopenia with 1% blasts. Bone marrow biopsy and aspirate specimens showed hypercellular (90%) marrow with trilineage dysplasia, left shifted granulopoiesis and 4% blasts. Reticulin stain showed increased fibrosis.

Flow cytometry immunophenotypic analysis of the BM aspirate material demonstrated <3% of aberrant CD34+ myeloblasts with decreased CD38 expression and increased CD13 expression. The myelomonocytic components also showed an aberrant maturation pattern.

Cytogenetics showed 46,XY[20].

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. Mutations of NRAS and KRAS genes were identified. No other mutations including JAK2 and FLT3 were identified.

Mutation in codon 13, exon 2 of NRAS gene (c.37G>C, p.G13R)

Mutation in codon 12, exon 2 of the KRAS gene (c.34G>A, p.G12S)

HFE mutation (for hemochromatosis) was negative.

Studies for infectious diseases were negative.

The patient has myelodysplastic syndrome associated with hepatosplenomegaly, a high ferritin level, elevated LDH, and AST, and mutations in both KRAS and NRAS genes. Although some features are suggestive of a concomitant myeloproliferative process, the overall findings (marked cytopenias, mutations of NRAS and KRAS) are most consistent with myelodysplastic syndrome.

Myelodysplastic syndrome, best classified refractory cytopenia with multilineage dysplasia and fibrosis, MF 1-2, with mutations of K-RAS and N-RAS,

Refractory cytopenia with multilineage dysplasia and fibrosis, with mutations of KRAS and NRAS

Case 401