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Paracortical infiltrate of blasts in a lymph node biopsy. (Image A) The blasts are medium to large in size with eosinophilic granular cytoplasm. Nuclei are irregular with open chromatin and distinct nucleoli. Few immature eosinophils are also seen admixed in the background. The sparing of lymphoid follicles with interfollicular extension of leukemic cells is typical of blastic processes involving nodes. 

Blasts are positive for myeloperoxidase (MPO) (Image B) supporting myeloid lineage and CD34 (Image C) confirming their immature nature. Immunostains are crucial for diagnosis of this disease and may have varied results depending on the morphological variants. Aberrant expression of B and T cell markers can be observed and should not rule out the diagnosis of Myeloid sarcoma. NPM1 mutated AML are more commonly associated with Extra-medullary myeloid tumor compared to other AMLs and such cases frequently have myelomonocytic/monoblastic morphology and are negative for CD34 expression. Immunohistochemistry for mutated NPM1 is often helpful in confirming the underlying genetic alteration.