Case 1: AML with mutated NPM1

Blasts with this morphology are highly-associated with NPM1 mutations (particularly when there is a coexisting FLT3-ITD)

Note that the blasts are medium-sized, with high N:C ratio, and many have an indented nucleus, leading to a cup-like shape

This is especially apparent when viewed in profile, and can resemble a nucleolus when viewed head-on

On ultrastructural examination, these indentations are filled with mitochondria, lysosomes, and endoplasmic reticulum

🔎 AML with mutated NPM1 (4 bp insertion into exon 12) occurs in 25-35% of of adult AML. Generally associated with favorable prognosis, but is a clinically heterogenous group, as it is usually associated with other mutations (e.g. FLT3-ITD)

⚠️ Pitfalls:

• Features of AML w monocytic differentiation (like nuclear clefts and folding) can be reminiscent of cup-like nuclei
• Cup-like nuclei can resemble cleaved nuclei in APL, (esp since AML w mutated NPM1 often shows CD34➖and HLA-DR➖), but PML-RARA would be ➖

Thanks for following along! 🤗

Special thanks to Dr. Dan Larson for his excellent teaching on this case!

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