Benign Hematogone-Rich Lymphoid Proliferations Can Be Distinguished From B-Lineage Acute Lymphoblastic Leukemia by Integration of Morphology, Immunophenotype, Adhesion Molecule Expression, and Architectural Features

Abstract

Distinction of normal B-lymphoid proliferations including precursors known as hematogones from acute lymphoblastic leukemia (ALL) is critical for disease management. We present a multiparameter assessment of 27 bone marrow samples containing at least 25% hematogones (range, 25%-72%) by morphologic review. We used flow cytometry to evaluate B-cell differentiation antigen and adhesion molecule expression and immunohistochemistry on clot sections to evaluate architectural distribution. Flow cytometry revealed that intermediately differentiated cells (CD19+, CD10+) predominated, followed in frequency by CD20+, surface immunoglobulin-positive cells, with CD34+, terminal deoxynucleotidyl transferase (TdT)-positive cells as the smallest subset. Adhesion molecules (CD44, CD54) were expressed more heterogeneously compared with expression in acute lymphoblastic leukemia. Immunohistochemistry revealed that CD34+, TdT-positive cells were dispersed without significant clustering, while CD20+ cells exceeded CD34/TdT-positive cells in 24 of 25 cases. This multidisciplinary study demonstrates that hematogone-rich lymphoid proliferations exhibit a spectrum of B-lymphoid differentiation antigen expression with predominance of intermediate and mature B-lineage cells, heterogeneity of adhesion molecule expression, and nonclustered bone marrow architectural distribution.

Mixed-phenotype acute leukemia: historical overview and a new definition

“…31 In addition, hematogones tend to be dispersed throughout the marrow, whereas blasts form small clusters. 32 These differences help to distinguish hematogones that can be present in AML from bilineal MPAL.…”

Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry

“…3,7,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] In some instances they constitute 5% to more than 50% of cells. 3,5,8,25,26 Increased numbers of hematogones may cause problems in diagnosis because of the morphologic features they commonly share with the neoplastic lymphoblasts of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. 3 Their immunophenotype also has features in common with neoplastic B-cell precursor lymphoblasts.…”

“…The reports of increased hematogones in specific diseases are mostly retrospective studies based on relatively small patient cohorts, lacking broad control populations. [3][4][5]9,13 Furthermore, in most flow cytometry studies hematogones have been reported as the percent of total lymphocytes or of B lymphocytes 8,17,26,[34][35][36] and in only a few reports as a percent of total events. 9,10,37 Finally, prior studies have not addressed the effects of the specimen-processing method and marrow involvement with neoplastic cells on the percentage of hematogones.…”

Abnormally expanded pro‐B hematogones associated with congenital cytomegalovirus infection

“…Their morphology and immunophenotype (CD19, CD10, CD34 surface antigen, and nuclear terminal deoxynucleotidyl transferase/TdT positive) is similar to that of B-precursor cells [3,4]. Occasionally, an hematogone increase may mimic acute lymphoblastic leukemia (ALL), raising diagnostic problems [5]. Here, we review the case of a newborn with congenital cytomegalovirus (CMV) infection and a marked atypical expansion of pro-B hematogones that had to be differentiated from infant ALL cells.…”