TOX as a new diagnostic marker for T cell large granular lymphocytic leukaemia

Abstract

AimsT cell large granular lymphocytic leukaemia (T‐LGLL) is a rare disorder that may underlie otherwise unexplained cytopenias. The identification of T‐LGLL cells in bone marrow biopsies can be a challenge, because a robust immunohistochemistry marker is lacking. The markers currently in use (granzyme B, TIA‐1 and CD8) are difficult to interpret or lack specificity. Therefore, we investigated whether immunohistochemistry for thymocyte selection‐associated high‐mobility group box (TOX), a transcription factor that associates with chronic T cell stimulation, could be a reliable tool for the identification of T‐LGLL cells.Methods and resultsIn this retrospective study, expression of TOX in CD8+ cells in bone marrow biopsies of T‐LGLL patients (n = 38) was investigated and compared to bone marrow of controls with reactive T cell lymphocytosis (n = 10). All biopsies were evaluated for TOX staining within the CD8‐positive T cell population. The controls were essentially negative for TOX, whereas all T‐LGLL cases were positive (median = 80%, range = 10–100%), even when bone marrow involvement was subtle.ConclusionTOX is a highly sensitive marker for the neoplastic cells of T‐LGLL and we recommend its use, especially in the diagnostic work‐up of patients with unexplained cytopenias.