Synchronous del5q myelodysplastic syndrome (del5qMDS) and adult B‐cell acute lymphoblastic leukemia (B‐ALL) with TET2 and TP53 mutations

An 81-year-old female presented with a 3-month history of progressive weakness, fatigue, and shortness of breath. Initial physical examination was unremarkable except for pallor. Her hemoglobin was 4.9 g/L, white blood cell 2.5 3 10/L, platelets 78 3 10/L, and MCV 99 fL. Peripheral blood smear showed anisopoikilocytosis, giant platelets, and tear drop cells. A bone marrow (BM) aspiration and biopsy revealed a hypercellular marrow (80–100%) with sheets of blasts. Aspirate smears showed medium-sized blasts (about 80%), with open nuclear chromatin, and scant agranular basophilic cytoplasm without Auer rods. There was multilineage dysplasia. Numerous small monolobated megakaryocytes were noted (Image 1A,B). Immunohistochemistry showed that the neoplastic cells expressed CD19, CD22, CD34, CD79a, CD20, and TdT (Image 1C,D) but not CD3, CD10, CD61, and MPO. BM flow cytometry analysis identified a distinct population of blasts expressing CD19, CD20, CD22, TdT, and dim CD13, CD33, CD34, CD45, and HLA-DR. The blasts did not express CD10, CD25, CRLF2, CD5, CD15, T/NK-cell, or other myeloid markers. In addition, a small population of aberrant myeloid blasts (9% of the CD34-positive cells) was also detected. Conventional cytogenetic analysis showed 46, XX, del (5) (q13q33) in 14/20 metaphases. Fluorescent in situ hybridization (FISH) analysis using dual color probe LSI EGR1/D5S23, Image 1. Features of the bone marrow aspirate/biopsy and cytogenetics/FISH. (A) Markedly increased blasts with open nuclear chromatin, inconspicuous nucleoli, and scant agranular basophilic cytoplasm. Dysplastic erythrocytes noted in the background (arrows) (Wright–Giemsa stain, 3500). (B) Sheets of immature medium size cells are seen interspersed with monolobated megakaryocytes (H&E, 3500). (C, D) Immunohistochemistry showing strongly positive CD20 and terminal deoxynucleotidyl transferase (TdT) (3500). (E, F) Combined morphologic and FISH analysis—FISH with D5S721, D5S23/EGR1 probes. Arrow: dysplastic myelocytes and granulocyte, showing two green and one red signals, indicating 5q31 deletion. Arrow head: blasts, showing two green and two red signals—normal pattern.