T-lymphoblastic leukemia/lymphoma: a comprehensive review of pathology, molecular features, and differential diagnosis

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive neoplasm of immature T-lymphoid precursors that is classified as T-cell acute lymphoblastic leukemia when the primary site of involvement is the bone marrow and peripheral blood and as T-cell lymphoblastic lymphoma when it presents as a solid mass, most commonly in the anterior mediastinum. The neoplastic cells are defined by expression of T-lineage antigens (cytoplasmic or surface CD3) together with one or more markers of immaturity (terminal deoxynucleotidyl transferase, CD1a, CD34, CD99, or CD117) and must not fulfill criteria for early T-cell precursor acute lymphoblastic leukemia (ALL). This entity shows a marked male predominance (male:female ≈ 2:1) and predominantly affects children, adolescents, and young adults, accounting for approximately 15% of childhood ALL and 20%–25% of adult ALL cases. Pathologic diagnosis increasingly relies on recurrent molecular alterations such as activating NOTCH1 mutations (>60% of cases), transcription factor rearrangements, and cell-cycle regulator inactivation. Although intensive multiagent chemotherapy regimens have substantially improved outcomes, particularly in pediatric patients, adults and high-risk molecular subgroups continue to experience inferior survival. This review provides a practical, pathology-oriented update on the epidemiology, pathogenesis, diagnostic criteria, differential diagnosis, prognostic factors, and current treatment approaches for T-ALL/LBL.