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A 68-year-old male presented with progressive fatigue, weakness and respiratory infections since last few days. A complete blood cell count showed anemia (hemoglobin 9 g/dL), hyperleukocytosis (139.3K/lL) and low platelets (50K/lL) with 95 % blasts in peripheral blood. Bone marrow aspirate demonstrated 93 % blasts which were positive for myeloperoxidase and showed normal male (46, XY) karyotype. These blasts were intermediate in size with folded nuclei (Fig. 1a; 5009 magnification), many with a nuclear invagination giving a cup-like nuclear indentation (see arrows), or ‘‘fish-mouth’’ appearance. Auer rods were not seen. Figure 1b from bone marrow aspirate smear demonstrates high resolution (10009 magnification) of these ‘‘cup-like’’ blasts. Flow cytometry studies demonstrate that the blasts were positive for CD33, CD13, CD117 and MPO confirming the diagnosis of acute myeloid leukemia (AML). The unusual morphology of blasts with cuplike nuclear indentation, also known as a fish-mouth shape, has been described in a subset of AML with NPM1 and FLT3 (ITD) mutations. Altered nucleocytoplasmic shuttling and accumulation of mitochondria due to increased flexibility of nuclear envelope in NPM1 mutations is proposed to be responsible for this alteration in the morphology of blasts.

“Cup-like” blasts and NPM1 and FLT3 (ITD) mutations in acute myeloid leukemia (AML)