Terminal deoxynucleotidyl transferase (TdT) in acute nonlymphocytic leukemia. A clinical, morphologic, cytochemical,...

The classification of acute leukemia is essential for proper therapy and may be based on morphologic, cytochemical, immunologic, or even ultrastructural studies. Terminal deoxynucleotidyl transferase (TdT) is expressed in most patients with acute lymphocytic leukemia (ALL) and a minority of patients with acute nonlymphocytic leukemia (ANLL). Thirteen patients with ANLL and greater than 30% blasts positive for TdT were studied to establish the clinical, light microscopic, cytochemical, immunologic, and ultrastructural correlates of this phenomenon. Most patients demonstrated some morphologic and cytochemical features of monocytic differentiation. On cytochemical stains, nine had greater than 3% Sudan black-positive blasts. Diffuse alpha naphthyl acetate esterase (ANAE) staining of leukemic cells was present in nine cases, though extremely weak in seven. Blasts in ten patients did not express any other markers of lymphoid differentiation except TdT. However, two patient's immature cells bore CD10 common ALL antigen (CALLA) and CD19 (B4). Ultrastructural studies confirmed nonlymphoid differentiation in all ten patients studied, with a prominent monocytic component present in nine. In no case was a second population of lymphoblasts identified to account for TdT positivity. These patients responded poorly to conventional therapy for ANLL, with complete remissions in 3 of 13 (23%). With conventional therapy for ALL, complete remission was achieved in only two of nine (22%) patients. However, four of seven (57%) patients had a complete remission with high-dose cytosine arabinoside regimens. The authors' studies suggest that patients with TdT-positive ANLL represent a distinct subset that usually displays ultrastructural evidence for monocytic differentiation and is clinically significant in that these patients respond poorly to conventional therapy for both ALL and ANLL. Recognition of the monocytic lineage of these cases by light microscopic examination is difficult because they are often poorly differentiated morphologically and express only weak nonspecific esterase positivity.