Acute myeloid leukemia (AML) is a clonal hematopoietic neoplasm due to acquired oncogenic mutations that disrupts differentiation, resulting in the accumulation of immature myeloid blasts in the marrow. NPM1 is one of the most common recurrent genetic abnormalities of AML, especially in patients with normal cytogenetics.

Patients typically present with leukocytosis, anemia, and thrombocytopenia. Other sites of involvement include lymph node, skin and gingiva.

Blasts with nuclear cup-like morphology is a common microscopic feature and is highly suggestive of NPM1 and/or FLT3 mutations. Myelomonocytic or monocytic differentiation is also a frequent finding. Up to 25% of the cases have multilineage dysplasia but this does not change the classification.

These neoplasms are characterized by bright CD33 expression and dim/variable CD13. They are also frequently positive for CD117, CD123, and CD110, and often negative for HLA-DR and CD34. CD34+ cases have worse prognosis. Immunohistochemical detection of cytoplasmic NPM1 on paraffin section is predictive of NPM1 mutations.

AMLs with NPM1 mutation usually have good prognosis, especially in cases of normal karyotype and absent FLT3-ITD.

This slide shows H&E stain of the bone marrow biopsy. See related content for CD34, CD117 stains and peripheral blood slide.