PMC6925828_01
Morphologic, immunohistochemical, flow cytometric, and cytogenetic characteristics of the patient's leukemia. A1-A3 represent bone marrow evaluation at initial diagnosis. Bone marrow biopsy (A1, H&E, 400x) and aspirate (A2, Wright stain 100x, oil) showing numerous small-sized B-lymphoblasts which are strongly positive for PAX5 (A3). B1-B3 represent biopsy of the breast mass (B1, H&E, 400x) and touch imprint (B2, Wright stain, 100x, oil) showing numerous large-sized blasts with monocytic differentiation, which are patchy positive for lysozyme (B3). C1-C3 represent bone marrow biopsy (C1, H&E, 400x) and aspirate (C2, Wright stain, 100x, oil) showing sheets of myeloblasts which are patchy positive for lysozyme (C3). D1-D3 represent bone marrow evaluation six weeks after cessation of blinatumomab. Core biopsy (D1, H&E, 400x) and aspirate (D2, Wright stain, 100x, Oil) show a dimorphic population of blasts: small-sized B-lymphoblasts which are positive for PAX5 (D3) and large-sized myeloblasts which are positive for lysozyme (data not shown here). E1 represents the karyogram of bone marrow specimen at myeloblastic transformation. E2-E4 represent karyograms and AFF1/KMT2A fusion of bone marrow specimen with B/myeloid mixed phenotype acute leukemia. F-H represent flow cytometric features of the leukemic blasts. F represents flow cytometry performed on the bone marrow aspirate at the initial diagnosis showing a large population of B-lymphoblasts (green) in dim CD45 region expressing CD19, CD34 (partial), and CD15 (dim), G represents flow cytometry of the bone marrow aspirate while administration of blinatumomab showing a population of myeloblasts (blue) expressing CD33 and CD64 (dim) and was negative for CD19 and CD34. H represents flow cytometry of the bone marrow aspirate six weeks after cessation of blinatumomab showing two populations: B-lymphoblasts (green) expressing CD19, CD34 (dim), and cytoCD79a, and myeloblasts (blue) expressing CD33, CD64 (dim), and MPO (data not shown here).
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fig1
Bone marrow evaluation revealed a hypercellular bone marrow (90%) composed of numerous small-to-intermediate-sized blasts with similar morphology as the blasts are identified in peripheral blood smear (Figure 1, A1 and A2). Flow cytometry of bone marrow aspirate revealed a large population of blasts immunophenotypically identical to the blasts detected in peripheral blood (Figure 1, F). The blasts were strongly positive for PAX5 (Figure 1, A3), CD19, and CD79a; focally positive for CD34; but were completely negative for MPO (data not shown). The biopsy from the mass showed sheets of large-sized blastic cells (Figure 1, B1 andB2) which were positive for lysozyme (B3) but negative for CD19, PAX5, and other B-cell markers (data not shown) by immunohistochemistry, consistent with a diagnosis of myeloid sarcoma. A bone marrow evaluation revealed a hypercellular marrow (90%) composed of sheets of blasts with monocytic features (Figure 1, C1 andC2). Flow cytometry from the bone marrow aspirate detected a population of blasts expressing CD33 and CD64 (dim), but was negative for CD19 and CD34 (Figure 1, G). Immunohistochemical study performed on bone marrow biopsy showed the blasts were positive for lysozyme (Figure 1, C3). Conventional chromosome analysis from the bone marrow aspirate revealed t(4; 11)(q21; q23) and additional chromosomal abnormalities (Figure 1, E1; Table 1). Six weeks after discontinuation of blinatumomab, a repeat bone marrow biopsy and aspirate demonstrated a hypercellular marrow (80%) with a dimorphic population of blasts composed of mixed small-and large-sized blasts (Figure 1, D1-D2). Flow cytometry and immunohistochemical studies confirmed the presence of two populations of blasts: (1) B-lymphoblasts phenotypically identical to those in the patient's initial bone marrow specimen expressing CD19, CD34 (dim), and cytoCD79a and (2) myeloblasts phenotypically similar to those in her second bone marrow specimen expressing CD33 and CD64 (Figure 1, H).