BCL11B helps to define T-lineage in lymphomas/leukaemias with a mixed/ambiguous immunophenotype

BCL11B is a pan-T-cell transcription factor that plays a pivotal role in guiding T-cell differentiation and maturation. BCL11B is lineage specific, and its expression is confined to T cells; B, NK ​and myeloid cells are usually negative. In this study, we aim to explore the value of BCL11B in the diagnosis and differential diagnosis of lymphomas/leukaemias exhibiting an ambiguous immunophenotype or which simultaneously express both T- and B-cell markers. The study cohort included 23 cases with a mixed/ambiguous immunophenotype, including five cases of T-lymphoblastic leukaemia (T-ALL) with B-marker expression, 10 mature T-cell lymphomas either with B-marker expression or lacking the expression of most T markers, three diffuse large B-cell lymphomas with T-marker expression, one classic Hodgkin lymphoma positive for T-cell antigens, and four plasma cell neoplasms expressing T markers. Immunohistochemistry (IHC) analysis for BCL11B was performed using formalin-fixed, paraffin-embedded tissue sections. All five cases of T-ALL were positive for BCL11B, confirming T-lineage. Amongst 10 cases of mature T-cell lymphoma, eight were BCL11 positive, and the remaining two BCL11B-negative cases were anaplastic large-cell lymphoma (ALCL). All cases of B-cell lymphoma, classic Hodgkin lymphoma, ​and plasma cell neoplasm were negative for BCL11B, consistent with their non-T-lineage. In conclusion, BCL11B IHC is valuable in designating T-lineage in neoplasms with a mixed/ambiguous immunophenotype. As observed in this study, BCL11B expression is highly specific for T-cell lineage. Of note, the absence of BCL11B does not completely exclude a diagnosis of T-cell lymphoma or leukaemia, especially in cases with a potential diagnosis of ALCL.