T-bet Transcription Factor Detection Facilitates the Diagnosis of Minimal Hairy Cell Leukemia Infiltrates in Bone Marrow Trephines

Abstract

Diagnosis of minimal infiltration by hairy cell leukemia (HCL) cells in bone marrow trephines is challenging as its differentiation from interstitially distributed infiltrates of reactive B cells and small B-cell lymphomas other than HCL is difficult or impossible. The diagnostic utility of DBA.44, tartrate-resistant acid phosphatase (TRAP) and of the recently propagated Annexin A1 is limited in this diagnostic setting since DBA.44 does not always label all HCL cells, TRAP is frequently weakly expressed whereas the numerous Annexin A1-positive hematopoietic cells interfere with the immunohistochemical recognition of sparse HCL cells. Therefore, we searched for antibodies suitable for the identification of minimal HCL infiltrates in formalin-fixed bone marrow trephines. Among the antibodies tested those directed against the T-cell associated transcription factor T-bet showed the required specificity: (1) T-bet is highly expressed in all 85 cases of HCL including 31 cases showing only minimal infiltrates, and (2) T-bet is exclusively expressed only on a subset of reactive T cells which are rare in bone marrow. Although T-bet is also weakly expressed in a proportion of the tumor cells of some small B-cell lymphomas (n=32/69) other than HCL, a reliable distinction is nevertheless easily possible because (1) T-bet is strongly expressed by all hairy cells of all HCL cases and (2) T-bet is not coexpressed in HCL with markers typical for other small B-cell lymphomas/leukemias (ie, CD23, CD5, CD10, and/or BCL6). Therefore, the immunohistochemical detection of T-bet in infiltrated bone marrow trephines represents an important adjunct for the diagnosis of HCL.

An Assessment of the Usefulness of Immunohistochemical Stains in the Diagnosis of Hairy Cell Leukemia

“…T-bet, as a relatively newer antibody, has been suggested to have a 100% sensitivity but low specificity for HCL. 12 The results from our study showed that T-bet failed to stain a few cases of HCL (93.0% of cases were positive) and confirmed its previously described low specificity. Previous studies have shown that T-bet is expressed in several low-grade B-cell lymphomas and a variety of T-cell malignancies.…”

Predictive Value of Blood and Bone Marrow Flow Cytometry in B-Cell Lymphoma Classification: Comparative Analysis of Flow Cytometry and Tissue Biopsy in 252 Patients

“…30 It also reinforces the need for data to support an FCIP HCL diagnosis with TRAP cytochemical positivity and/or distinctive histologic features in the bone marrow biopsy specimen supplemented by diagnostic immunoperoxidase features such as Annexin A1 positivity. [31][32][33] CD10 + HCL is a commonly described phenotypic variant, whereas CD5 expression in HCL is infrequent. 34 The detection of CD5, rather than CD10, expression in a minor subset of the HCL cases included in this study likely reflects the small number of cases of this uncommon entity that were included.…”

Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry

“…[60][61][62] Although annexin A1 is specific for HCL, 58 its expression in normal hematopoietic cells, especially in neutrophils, makes it unsuitable for detection of minimal, residual HCL, but T-bet was reported to be useful in those cases. 63 Weak cyclin D1 staining can be observed in most HCLs (Figure 7, C), but there is no rearrangement of the cyclin D1 gene at 11q13 locus. 64 After excluding CD5 þ27 and/or CD10 þ46-48 DLBCL NOS, approximately 50% to 70% of de novo DLBCLs NOS are negative for both CD5 and CD10.…”