A 6-year-old boy from Mumbai presents with a 2-month history of progressive pallor, bone pain, and recurrent infections. On examination, he has hepatosplenomegaly and generalized lymphadenopathy. Complete blood count shows: Hb 6.8 g/dL, WBC 8,500/μL (65% blasts), platelets 45,000/μL. Bone marrow examination reveals >90% blasts that are TdT+, CD10+, CD19+, CD20−, cIg−. Cytogenetics shows t(12;21)(p13;q22). What is the most likely diagnosis?

Explanation

## Diagnosis: B-cell Acute Lymphoblastic Leukemia (B-ALL) with t(12;21) — ETV6-RUNX1 Fusion ### Clinical Presentation The patient is a **6-year-old child** — the **peak age for ALL is 2–5 years**, and this case fits the typical presentation: - **Bone pain** — due to leukemic infiltration of bone marrow - **Hepatosplenomegaly & lymphadenopathy** — extramedullary involvement - **Cytopenias** — Hb 6.8 (anemia), WBC 8,500 (low-normal, NOT hyperleukocytosis), platelets 45,000 (thrombocytopenia) - **Blasts 65%** in peripheral blood — diagnostic for leukemia ### Immunophenotype & Morphology | Feature | B-ALL (Common) | T-ALL | Burkitt | This Case | |---------|---|---|---|---| | **TdT** | + | + | − | + ✓ | | **CD10** | + (common ALL) | − | − | + ✓ | | **CD19** | + (B-lineage) | − | + | + ✓ | | **CD20** | − or weak | − | + (strong) | − ✓ | | **cIg** | − (immature) | − | + (surface Ig) | − ✓ | | **Cytogenetics** | t(12;21) is favorable | t(9;22), t(1;19) | t(8;14) | t(12;21) ✓ | **Key Point:** The **CD10+ CD19+ CD20− cIg− TdT+** immunophenotype defines **common B-ALL** (cALL), which accounts for ~80% of childhood ALL. This is the **most favorable ALL subtype** in children. ### Cytogenetic Significance: t(12;21) — ETV6-RUNX1 **High-Yield:** The **t(12;21)(p13;q22)** translocation results in the **ETV6-RUNX1 fusion gene** and is: - **Present in 20–25% of childhood B-ALL** — the most common translocation in pediatric ALL - **Associated with excellent prognosis** — >90% 5-year event-free survival with modern chemotherapy - **Detectable by RT-PCR** — more sensitive than conventional cytogenetics - **NOT associated with t(9;22) (Philadelphia chromosome)** — which has poor prognosis **Clinical Pearl:** ETV6-RUNX1 fusion is a **favorable risk factor** that allows for **reduced-intensity chemotherapy** in some protocols, whereas t(9;22) (BCR-ABL) requires **tyrosine kinase inhibitors** (imatinib) + intensive chemotherapy. ### Why This Is B-ALL and Not Other Subtypes 1. **TdT+ CD19+ CD20−** → **Immature B-lineage** (not mature B-cell lymphoma) 2. **cIg−** → **Precursor B-ALL** (not Burkitt, which has surface Ig+) 3. **CD10+** → **Common ALL** (favorable subtype) 4. **t(12;21)** → **ETV6-RUNX1** (pathognomonic for this B-ALL subtype) **Mnemonic:** **CALLA** = Common Acute Lymphoblastic Leukemia Antigen (CD10); **ETV6-RUNX1** = Excellent prognosis in childhood B-ALL. ### Prognosis & Treatment - **Chemotherapy:** Standard risk stratification; ETV6-RUNX1+ cases are **low-risk** and have excellent outcomes - **Remission rate:** >95% CR in children - **5-year EFS:** >90% (compared to ~50% for high-risk subtypes) [cite:Robbins 10e Ch 13; Harrison 21e Ch 110]