Clinicopathological differences between T-lymphoblastic leukemia/lymphoma, early T-precursor lymphoblastic leukemia/lymphoma, and mixed-phenotype acute leukemia with T lineage: An analysis of 41 adult cases

The histopathological diagnosis of T-lymphoblastic leukemia/lymphoma, NOS (T-ALL), is based on morphology and positivity for CD3 and TdT. Early T-precursor lymphoblastic leukemia/lymphoma (ETP-ALL) and mixed-phenotype acute leukemia (MPAL), T/M, and/or B rarely occur and are usually diagnosed using flow cytometry. Using only formalin-fixed paraffin-embedded tissue raises the risk of misdiagnosis due to underestimation. Immunostaining markers for T cell (CD1a, CD4, CD5, CD8), B cell (CD19, CD10, CD22, CD79a), and stem/myeloid-related cell (CD33, CD34, CD117, MPO, lysozyme) diagnosed 25 T-ALL cases (61%), 7 MPAL (17%), 6 ETP-ALL (15%), and 3 near ETP-ALL (7%), with subsequent analysis of their clinicopathological characteristics. Patients with MPAL had significantly poorer 2-year progression-free survival (14.3% vs. 60.4%, P = 0.012) and 5-year overall survival (28.6% vs. 65.9%, P = 0.011) than did those with T-ALL, whereas ETP-ALL and near ETP-ALL did not. Of the seven patients with MPAL, three were classified as T/B, two as T/M, and two as T/M/B. Because most MPALs (6/7) share the ETP-ALL phenotype, immunohistochemistry for CD19 and MPO should be performed to avoid misdiagnosing MPAL as ETP-ALL. All three patients with TdT-negative MPAL died of the disease. Four patients with MPO-positive MPAL relapsed during the early phase (1–9 months). Five patients received the ALL regimen, but two patients received acute myeloid leukemia and lymphoma regimens, respectively. In this study, MPAL exhibited a poorer prognosis compared to T-ALL, unlike ETP-ALL. Thus, immunohistochemical classification with multiple antibody panels is useful for accurate diagnosis and treatment.