Cytopenic AML with marrow fibrosis and multihit TP53 abnormalities

A 73-year-old man presented with myocardial infarction, fever, and pancytopenia (hemoglobin, 7.2 g/dL; white cell count, 0.5 × 10⁹/L; platelet count, 29 × 10⁹/L) without splenomegaly. Blood smear showed marked leukopenia without teardrop cells (panel A, ×200 original magnification). Marrow aspirate was aparticulate, with 5% blasts (panel B, ×200 original magnification), which were CD34⁺/CD117⁺/CD13⁺/CD33(weak⁺)/CD7⁺/myeloperoxidase (MPO; cytoplasmic)^– on flow cytometric analysis. Trephine biopsy showed hypercellular marrow with reticulin fibrosis grade 2 and trilineage proliferation (panels C and D, ×400 original magnification). Foci of blasts (25% of marrow cells), other myeloid precursors, erythroblasts, and megakaryocytes are highlighted by immunostains for CD34, MPO, glycophorin A, and CD61, respectively (panels E-H, ×400 original magnification). Immunostaining for p53 protein showed moderate-to-strong nuclear positivity in 80% of the cells involving all 3 cell lineages (panel I, ×400 original magnification). Cytogenetics showed complex karyotype with del(5q) and monosomy 17. Next-generation sequencing showed TP53 mutation (p.Y220C; variant allele frequency, 39%) and multiplex ligation-dependent probe amplification showed loss-of-heterozygosity in TP53, suggesting multihit TP53 abnormalities. The patient died due to sepsis before commencing treatment for the disease.

Previously, this case would have been diagnosed as acute panmyelosis with myelofibrosis (per the revised 4th edition of the World Health Organization [WHO] classification), but now it is classified as acute myeloid leukemia with multihit TP53 abnormalities, per the latest International Consensus Classification of myeloid neoplasms and acute leukemias. The p53 immunostain correlated with the TP53 mutation status in this case.

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