Acute biphenotypic leukaemia: immunophenotypic and cytogenetic analysis

Abstract

The incidence of acute biphenotypic leukaemia has ranged from less than 1% to almost 50% in various reports in the literature. This wide variability may be attributed to a number of reasons including lack of consistent diagnostic criteria, use of various panels of antibodies, and the failure to recognize the lack of lineage specificity of some of the antibodies used. The morphology, cytochemistry, immunophenotype and cytogenetics of acute biphenotypic leukaemias from our institution were studied. The diagnostic criteria took into consideration the morphology of the analysed cells, light scatter characteristics, and evaluation of antibody fluorescence histograms in determining whether the aberrant marker expression was arising from leukaemic blasts or differentiated bone marrow elements. Fifty-two of 746 cases (7%) fulfilled our criteria for acute biphenotypic leukaemias. These included 30 cases of acute lymphoblastic leukaemia (ALL) expressing myeloid antigens, 21 cases of acute myelogenous leukaemia (AML) expressing lymphoid markers, and one case of ALL expressing both B- and T-cell associated antigens. The acute biphenotypic leukaemia cases consisted of four major immunophenotypic subgroups: CD2+ AML (11), CD19+ AML (8), CD13 and/or CD33+ ALL (24), CD11b+ ALL (5) and others (4). Chromosomal analysis was carried out in 42/52 of the acute biphenotypic leukaemia cases; a clonal abnormality was found in 31 of these 42 cases. This study highlights the problems encountered in the diagnosis of acute biphenotypic leukaemia, some of which may be responsible for the wide variation in the reported incidence of this leukaemia. We suggest that the use of strict, uniform diagnostic criteria may help in establishing a more consistent approach towards diagnosis of this leukaemic entity. We also suggest that biphenotypic leukaemia is comprised of biologically different groups of leukaemia based on immunophenotypic and cytogenetic findings.

Acute lymphoblastic leukemia with the phenotype of a putative B‐cell/T‐cell bipotential precursor

“…Using the EGIL criteria [4], the blasts scored 7.5 points for B-lymphoid markers (Cyt CD79a, 2; CD22, 2; CD19, 1; CD20, 1; CD10, 1; TdT, 0.5) and 5 points for T-lymphoid markers (Cyt CD3, 2; CD5, 1; CD10, 1; CD7, 0.5; TdT, 0.5), establishing it as a B-cell/T-cell BAL. To our knowledge, this is the first reported case of a well-characterized de novo B-cell/T-cell BAL, although the existence of this leukemic entity has been alluded to in case series [5][6][7][8]. The lack of monoclonal TCR-and IgH gene rearrangements may appear contradictory.…”

“…Using this scoring system, BALs are uncommon, generally accounting for less than 5% of all acute leukemias [5][6][7][8][9]. Most of these are of combined myeloid/B-cell or myeloid/T-cell lineage, whereas B-cell/ T-cell BALs are exceedingly rare.…”

Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system

“…The prevalence of BAL has ranged from 2% to almost 20% of ALs in various reports. [5][6][7] This wide variability may be attributed to a number of reasons including a lack of consistent diagnostic criteria, use of differing panels of antibodies, and failure to recognize the lack of antigen specificity of some of the antibodies used.…”

Flow cytometric immunophenotyping of hematological malignancies: the way forward in Nigeria

“…Extensive studies [6][7][8][9][10][11][12][33][34][35][36][37] have been done on the factors that affect the results of immunophenotyping, including: 1. The type and quality of samples.…”

“…[6][7][8][9][10][11][12]33,34 Assessments of the lineage and differentiation stage of the pathology represent the basis of current IMPT diagnosis and classification of hematological malignancies. It is however well established that leukemic cells display immunophenotypic features that are different from those present in healthy cells …”