CBFA2T3::GLIS2-positive acute leukemia with RAM and mixed T/megakaryocytic phenotype

Abstract

Herein, we present a rare case of acute myeloid leukemia (AML) with CBFA2T3-rearrangement and the expression of megakaryocytic and lymphoid markers, highlighting the need for a high suspicion index in differential diagnosis and applying adequate workup to avoid misdiagnosing this entity. CBFA2T3::GLIS2-positive AML is primarily found in infants with non-down syndrome acute megakaryoblastic leukemia (non-DSAMKL). Flow cytometry immunophenotyping plays an important role in recognizing the unique immunophenotype of bright CD56 expression with dim/negative expression of HLA-DR, CD38, and CD45 termed the RAM immunophenotype in this entity. Still, CBFA2T3::GLIS2-positive acute leukemia with T/megakaryocytic markers could be misdiagnosed as T-lymphoblastic leukemia/lymphoma, early T-cell precursor acute lymphoblastic leukemia/lymphoma, NK lymphoblastic leukemia, AML with minimal differentiation, or AML with myelodysplasia-related changes.

Keywords: CBFA2T3; GLIS2; acute megakaryoblast leukemia; mixed phenotype acute leukemia.

FIGURE 1

Flow cytometry Immunophenotyping of the peripheral blood using an SSC/CD45 gating strategy, a CD45‐dim to negative blasts, 19% of total events (circled in SSA vs. CD45) are positive for cytoCD3 (partially bright), CD19 (dim), CD33, CD34, CD38 (dim), CD41 (dim), CD42b (partial, moderate), CD56 (bright), CD117, and CD123. Blasts are negative for CD1a, CD7, CD10, and HLA‐DR.

FIGURE 2

Histologic and immunohistochemical findings of bone marrow examination (aspirate smear and core biopsy) and right axillary lymph node. (A) The bone marrow aspirate smear shows small‐ to intermediate‐sized blasts with smooth open chromatin, small nucleoli, and a small amount of agranular basophilic cytoplasm (stain: Wright‐Giemsa; original magnification, ×1000), (B) The bone marrow biopsy is hypercellular with an increased number of blasts and foci of necrosis. Many eosinophils are seen in the inset image (stain: hematoxylin and eosin; original magnification, ×100 and ×600, respectively), (C) CD3(original magnification, ×400), (D) CD42b (original magnification, ×400), (E) lysozyme (original magnification, ×400), (F) cytochemical stain for myeloperoxidase is negative in blasts (arrowhead; original magnification, ×500), (G) Sections of the lymph node is entirely replaced by blasts. Mitotic figures and many scattered eosinophils are easily identified (stain: hematoxylin and eosin; original magnification, ×600), (H) CD42b (original magnification, ×400), and (I) CD56 (original magnification, ×400).