Monthly Cell Challenge #3 / 2024

A case of acute leukemia with cup-like blasts.
Recognition of these cells on Cellavision guided molecular testing.
Description:
74-year-old male presented to the emergency department with weakness, shortness of breath, abdominal pain, and unexplained bruising.
CBC results:
Test | Result | Units |
WBC | 205 | x109/L |
HGB | 7.3 | g/dL |
MCV | 83.3 | fL |
PLT | 26 | x109/L |
Blood smear analysis on CellaVision DC-1
WBC Differential | % | x109/L |
Neutrophils | 5 | 10.3 |
Lymphocytes | 3 | 6.2 |
Monocytes | 1 | 2.1 |
Basophils | 1 | 2.1 |
Blasts | 90 | 184.5 |
NRBCs | 3 /100 WBC |

A side-by-side review of the blasts on CellaVision revealed similar invaginated nuclei in many cells. The lab scientist added a comment to the differential describing the blasts.

The neutrophils appeared hypogranular.

When the hematologist saw the differential results, she used Cellavision Remote Review to access the blood smear, confirmed the presence of blasts with cup-like nuclei, and immediately requested follow-up testing for NPM1 and FLT3 gene mutations.
Diagnosis:
Molecular testing confirmed the mutations, and the patient was diagnosed with acute myeloid leukemia (AML) with NPM1 mutation*.
Discussion:
NPM1 mutations are common in AML. When present, the leukemia diagnosis does not require > 20% blasts in blood and/or bone marrow. Hypogranular neutrophils and other dysplastic cells may be present in up to 25% of cases.
Blasts with cup-like (“fish-mouth”) nuclear morphology are strongly associated with mutations in both NPM1 and FLT3.
In this case, detecting distinctive nuclear abnormalities with Cellavision helped streamline follow-up testing. Understanding the link between cup-like blasts and mutations in NPM1 and FLT3 may enable faster diagnosis and aid in therapeutic decisions.
Reference
*WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. 5th ed. vol 11. WHO classification of tumours series. international Agency for Research on Cancer; 2024.