Figure 1: Peripheral blood smear
Markedly decreased WBC count with occasional circulating blasts (top of the image) are seen on peripheral smear. Red cells demonstrate moderate anisopoikilocytosis with microcytes and macrocytes. Platelets are markedly decreased. There is no evidence of dysplastic neutrophils.
Figure 2: Bone marrow aspirate
Aspirate smears are cellular and demonstrate increased numbers of blasts accounting for 31% of all cells. The blasts are small to medium in size with scant to moderate basophilic cytoplasm, round nuclear contours, fine chromatin and prominent nucleoli (Black arrow-Top left image). Erythroid precursors show megaloblastoid maturation with occasional erythroid precursors demonstrating nuclear irregularities consistent with dysplastic changes. Several dysplastic micromegakaryocytes, frequently with hypolobated and widely separated nuclei are noted (White arrow-Top right image). Additionally, occasional dysplastic megakaryocytes exhibiting "pawn-ball" cytomorphology are seen (Green arrow-Bottom image). Such pawn-ball megakarytocytes are often described in patients with germine GATA2 mutations.
Figure 3: Bone marrow biopsy H&E
Core biopsy is normocellular as evident on low power (Top left image). High power images demonstrate increased number of large mononuclear cells with fine chromatin and prominent nucleoli, compatible with blasts (Black arrow-Top right image). Islands of erythroid precursors are also noted. Megakaryocytes are decreased and occasional micromegakaryocytes with separated nuclear lobes or a single nuclear lobe are identified (White arrow-Bottom image). Reticulin stain showed mild fibrosis.
Figure 4: Bone marrow biopsy-Prussian blue
Adequate histiocytic iron and some sideroblastic iron without ringed sideroblasts is noted.
Figure 5: Bone marrow biopsy-NPM1
Stain is negative for cytoplasmic expression of NPM1 in blast cells. Nuclear restricted expression indicates wild-type pattern.
Figure 6: Bone marrow biopsy-CD34
Blasts expressing CD34 (small CD34+ cells-Left image) are seen admixed with dysplastic megakaryocytes staining with CD34 (white arrow-Right image). Such aberrant staining by dysplastic megakaryocytes is non-specific and is frequently seen in malignant myeloid processes.
Figure 7: Bone marrow biopsy-CD61
CD61 is typically highlighting the micromegakaryocytes, which are frequently unilobated and bilobated.
Figure 8: Karyotype
Loss of chromosomes 5, 7, 16 and 17 is noted in the karyotype (Black arrow). Loss of chromosome 5 or 7 or deletion of a portion of the long arm of these chromosomes [del(5q) or del(7q)] are the most commonly encountered chromosome abnormalities in AML-MRC. Additionally, loss of chromosome 17 results in loss of TP53 located at chromosome band 17p13.1.
Figure 9: Next generation sequencing
This shows a mutation in exon 5 of the TP53 tumor suppressor gene producing an arginine to histidine substitution at amino acid 175, within the DNA binding domain of the p53 protein. Mutation at codon R175 in TP53 can affect the global conformation of p53 protein leading to functional conversion of TP53 from a tumor suppressor to an oncogene. In AML, TP53 mutations correlate with an unfavorable outcome.
