T-ALL

T-ALL arises from malignant transformation of T-cell precursors (lymphoblasts) in the thymus or bone marrow, driven by genetic alterations such as NOTCH1 mutations (>50% of cases), which promote uncontrolled proliferation and blocked differentiation. Other associated mutations include CDKN2A/B deletions, and translocations involving TAL1, TLX1, and TLX3 oncogenes with T-cell receptor gene loci.

Clinically, T-ALL classically presents in male teenagers/young adults with a rapidly enlarging anterior mediastinal mass (thymic origin), which can cause superior vena cava syndrome (facial swelling, distended neck veins, dyspnea) and pleural effusions. Unlike B-ALL, hepatosplenomegaly and CNS involvement can also occur, and peripheral cytopenias may be less pronounced initially since marrow involvement can be minimal.

Diagnosis involves flow cytometry showing TdT+ lymphoblasts expressing T-cell markers (CD2, CD3, CD5, CD7) with variable CD4/CD8 co-expression (unlike mature T-cells, blasts can be CD4+CD8+ double positive). Lymphoblasts lack myeloperoxidase (distinguishing from AML) and are TdT+ (distinguishing from mature lymphomas).

Treatment utilizes multiagent chemotherapy regimens similar to B-ALL (vincristine, corticosteroids, asparaginase, anthracyclines) with CNS prophylaxis, as T-ALL has higher propensity for CNS relapse. Prognosis in children is generally favorable (~85-90% cure rates) though historically worse than B-ALL, while adult T-ALL has a poorer prognosis. NOTCH1 mutations, paradoxically, are associated with better treatment response in some studies.

Key board associations: anterior mediastinal mass + young male = think T-ALL or thymoma; TdT+ blasts differentiate from mature lymphoid malignancies; NOTCH1 mutation is a classic buzzword.