This is a 62-year-old female with past medical history of hypertension , rheumatoid arthritis and  depression was found to have leukocytosis of more than 70,000 WBCs/ul on a pre-operative work up done for knee surgery. The patient was then promptly referred to oncology, where her initial white cell count was 100, 000 WBC/ul with 93 % blasts in peripheral blood. Her hemoglobin was 7.3 g/dl and platelets were 61,000/ul. The D-dimer was >20 uG/ul. The peripheral blood smear showed numerous blasts with cup-like nuclear indentations as shown in Figure 1 and 2. Bone marrow biopsy was done and it was consistent with acute myeloid leukemia with blasts positive for CD68, CD117, lysozyme, and myeloperoxidase and negative for CD34.  Cytogenetics showed normal female karyotype and molecular studies showed concurrent FLT3-ITD/TKD and NPM1 mutation. The patient was started on induction chemotherapy with idarubicin, cytarabine and midostaurin. The bone marrow biopsy on day 22 did not showed any residual leukemia.

“Cup-like blasts” have been described in the literature and they are strongly associated with mutation of both NPM1 and FLT3-ITD or TKD. Only AMLs with isolated NPM1 mutations are classified as AML with NPM1 mutations. Cases with double FLT3/NPM1 have a worse outcome compared to cases with isolated NPM1 mutation.