CD19-NEGATIVE B-LYMPHOBLASTIC LEUKEMIA/LYMPHOMA: A CASE REPORT

Abstract

Lymphoblasts in B-lymphoblastic leukemia/lymphoma are almost always positive for the B-cell markers CD19, cytCD79a and cytCD22 and, according to the revised 4th edition of the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues, expression of those markers in combination or at high intensity supports B-cell lineage assignment. We had a case of CD19-negative B-lymphoblastic leukemia/lymphoma, which represented a diagnostic challenge. Patient was a 20 year-old female with clinical suspicious of acute leukemia. At physical examination she had splenomegaly. Complete blood cell counts at admission showed hemoglobin of 4.9 g/dl, white blood cell of 5.1 ×109/l (neutrophils – 26%; lymphocytes – 72%) and platelet count of 36 ×109/l. Lactate dehydrogenase levels were increased. Flow cytometry immunophenotyping (FCI) assessment of a bone marrow sample revealed an immature population that expressed cytCD22, CD10bright, CD22, CD34, CD38, CD45weak, CD99, HLA-DR and nuTdT, and coexpressed CD123. Blast cells were negative for cytCD3, cytCD79a, cytIgM, cytMPO, CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD11b, CD11c, CD13, CD14, CD15, CD16, CD19, CD20, CD33, CD36, CD41, CD56, CD58, CD79a, CD71, CD81 and CD117. Assessment of CD19 expression was performed with CD19 PerCP (clone 4G7, from EXBIO, Praha, CZE) and CD19 APC (clone HIT2, from BD Biosciences, San Diego, USA). Assessment of peripheral blood and bone marrow smears were performed elsewhere and karyotype results were not available at the time of diagnosis. Patient's final FCI diagnosis was of CD19-negative B-lymphoblastic leukemia/lymphoma. Although CD19 is a reliable surface marker for B-cells, it is not expressed in a minor subpopulation of precursor B-cells throughout normal lymphopoiesis, such subset can be identified by CD22 expression. During B-cell ontogeny, CD19 surface expression can be detected around the time of immunoglobulin gene rearrangement, which explains the absence of cytoplasmic IgM in our case. There are few published cases of CD19-negative B-lymphoblastic leukemia/lymphoma and the precise diagnosis of this entity requires expanded FCI panels for the exclusion of other hematopoietic neoplasms. In conclusion, FCI has an important role in the diagnosis, classification and monitoring of hematopoietic neoplasms and it is necessary to test for the expression of all B-cell markers as recommended by the WHO for the correct assignment of B-cell lineage.