A 6-year-old boy from Mumbai presents with a 2-month history of recurrent infections, bone pain, and easy bruising. His mother reports he has been unwell with fever on and off. On examination, he has generalized lymphadenopathy, hepatomegaly (5 cm), and splenomegaly (6 cm). Blood count shows hemoglobin 8.5 g/dL, WBC 120,000/μL with 92% blasts, and platelets 25,000/μL. Bone marrow shows >95% blasts that are TdT-positive, CD19+, CD10+, and CD34+. Cytochemistry shows negative MPO and negative PAS. What is the most likely diagnosis?

Explanation

## Diagnosis: Acute Lymphoblastic Leukemia, Common B-Cell Type (B-ALL, CD10+) ### Clinical Presentation A 6-year-old child with acute leukemia presenting with fever, infections, bone pain, and hemorrhagic manifestations. Hepatosplenomegaly and lymphadenopathy are prominent. The age (peak incidence of ALL is 2–5 years, with continued high incidence to age 10) and presentation are classic for pediatric acute leukemia. ### Immunophenotypic & Cytochemical Profile **Key Point:** The immunophenotype **CD19+ (B-lineage marker), CD10+ (common ALL antigen), CD34+ (immature marker), and TdT+ (terminal deoxynucleotidyl transferase)** is diagnostic of B-ALL. **High-Yield:** **Negative MPO** rules out myeloid lineage (AML). **Negative PAS** (periodic acid-Schiff) is typical for lymphoblasts; AML blasts may show PAS+ granules. ### Immunophenotypic Classification of ALL | Feature | Pro-B ALL | Common B-ALL (CD10+) | Pre-B ALL | Mature B-ALL | |---------|-----------|----------------------|-----------|---------------| | **CD19** | + | + | + | + | | **CD10 (CALLA)** | − | + | − | − | | **CD34** | + | +/− | − | − | | **TdT** | + | + | + | − | | **CD20** | − | − | − | + | | **Frequency** | 5% | 60–70% | 20–25% | 5% | | **Prognosis** | Intermediate | Best | Intermediate | Poor | **Clinical Pearl:** Common B-ALL (CD10+) is the most frequent subtype in children (~70% of childhood ALL) and has the best prognosis with modern chemotherapy (cure rates >85%). ### Why This is B-ALL and Not AML 1. **MPO negativity** is the single most important finding distinguishing lymphoid from myeloid lineage. AML blasts are MPO+; ALL blasts are MPO−. 2. **TdT positivity** is a marker of lymphoid precursor cells and is positive in >95% of ALL but negative in AML. 3. **CD19+ CD10+ CD34+** phenotype is pathognomonic for B-ALL, common type. 4. **PAS negativity** (or weak positivity) is typical for ALL; AML blasts may show coarse PAS+ granules. ### Why CD10+ (Common B-ALL) Rather Than Other ALL Subtypes **Pro-B ALL (CD10−, CD34+, TdT+):** Would lack CD10 expression. This patient is CD10+, so Pro-B ALL is excluded. **Pre-B ALL (CD10−, CD34−, TdT+):** Would be CD10− and usually CD34−. This patient is CD10+, so Pre-B ALL is excluded. **Mature B-ALL (CD10−, CD20+, TdT−):** Would be CD10−, CD20+, and TdT−. This patient is CD10+, CD34+, and TdT+, so mature B-ALL is excluded. ### Cytochemistry Correlation **Myeloperoxidase (MPO):** - **Positive** in AML, acute promyelocytic leukemia, and some AML-M5 (monocytic). - **Negative** in ALL (lymphoid lineage). **Periodic Acid-Schiff (PAS):** - **Positive (coarse granules)** in AML, especially M2 and M3. - **Negative or weakly positive (fine granules)** in ALL. **Sudan Black B:** - **Positive** in AML (lipid-rich myeloid granules). - **Negative** in ALL. [cite:Robbins 10e Ch 13]