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August 2023 – Hematopathology

By MCL Education • August 11, 2023

An 81-year-old man presented with neutropenia and thrombocytopenia. Peripheral blood showed 9% blasts and bone marrow aspirate/biopsy showed 15% blasts (Figure 1) with basophilic cytoplasm, perinuclear clearing, and occasional cytoplasmic azurophilic granules. In the background was maturing granulopoiesis (>10% of total bone marrow cellularity). A subset of neutrophils were hypogranular and had Pelger Huet-like nuclei (Figure 2). Flow cytometry showed a blast population that was positive for CD34, CD45, CD117, HLA-DR, CD33(dim), and CD15(partial). Conventional cytogenetics revealed a t(8;21) (q22;q22.1) translocation in 8/20 metaphases (Figure 3).

Figure 1: Myeloid blast with basophilic cytoplasm, with a perinuclear hof, and fine azurophilic granules.

Figure 2: Peripheral blood showing a neutrophil with hypogranular cytoplasm.

Figure 3: 8 out of 20 metaphases with t(8;21) (q22;q22.1).

Figure 4: Using a dual color, dual fusion probe strategy, the two fusion signals
(red and green superimposed on one another, indicated by the arrows) represent the *RUNX1::RUNX1T1* fusion.

How will you diagnose this case as per the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours?

Acute myeloid leukemia with RUNX1::RUNX1T1
Myelodysplastic neoplasm with increased blasts - 2
Acute myeloid leukemia with maturation, not otherwise specified (NOS)
Acute myeloid leukemia without maturation, not otherwise specified

The correct answer is ...

Acute myeloid leukemia with RUNX1::RUNX1T1.

As per the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours, AML with RUNX1-RUNX1T1 is a defining genetic abnormality and is considered to be acute leukemia regardless of the blast count.¹ The RUNX1-RUNX1T1 fusion was confirmed with a dual color double fusion probe set (Figure 4). The leukemic blasts in AML with RUNX1-RUNX1T1 exhibit a characteristic immunophenotype that includes expression of CD34, aberrant expression of the B-cell associated lymphoid markers CD19 and cytoplasmic CD79a, myeloid markers (CD13 and CD33) and CD56 is positive in some cases. Acute myeloid leukemia with maturation, NOS and acute myeloid leukemia without maturation, NOS are diagnoses of exclusion and do not fulfill criteria for any of the other categories of AML (e.g., recurrent genetic abnormality). Myelodysplastic neoplasm with increased blasts – 2 is a myeloid neoplasm with cytopenia(s) and dysplasia, lacks defining genetic abnormalities, and shows 5%-19% bone marrow blasts and/or 2%-19% peripheral blood blasts.

References

Khoury JD, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-1719.