CD19-negative B-lineage acute lymphoblastic leukemia: A diagnostic and therapeutic challenge

B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B-lymphocyte precursors that express the pan B-cell marker CD19 in all the cases. Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16-year-old male presented with complaints of pain abdomen, on and off fever, joint pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry, gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10. Immunohistochemistry study showed positivity for TdT, CD34, CD10 (focal), and PAX 5 and negativity for CD20, CD3, MPO, CD117, and CD68. Lack of awareness of negative CD19 expression in B-ALL can lead to incorrect immunophenotypic diagnosis, treatment, and monitoring of B-ALL. Proper diagnosis should be based on clinical features, immunophenotypic profiles, immunohistochemistry findings, and molecular analysis.