A 4-year-old boy from rural Maharashtra presents with a 3-week history of progressive pallor, easy bruising, and petechiae. His mother reports he has been febrile on and off and complains of bone pain. On examination: pallor, petechiae over lower limbs, hepatomegaly (3 cm), splenomegaly (2 cm), and generalized lymphadenopathy. CBC shows: Hb 7.2 g/dL, WBC 85,000/μL (with 70% blasts), platelets 45,000/μL. Bone marrow aspirate reveals >90% lymphoblasts with fine chromatin and scanty cytoplasm. Cytochemistry: MPO negative, PAS positive (diffuse). What is the most likely diagnosis?

Explanation

## Diagnosis: Acute Lymphoblastic Leukemia (ALL) ### Clinical Presentation This 4-year-old presents with the classic triad of childhood ALL: - **Anemia** (pallor, Hb 7.2 g/dL) - **Thrombocytopenia** (petechiae, platelets 45,000/μL) - **Leukocytosis** with high blast burden (WBC 85,000/μL, 70% blasts) **Key Point:** Bone pain and hepatosplenomegaly are common presenting features due to leukemic infiltration of bone marrow and extramedullary sites. ### Morphologic & Cytochemical Clues | Feature | ALL | AML | APL | |---------|-----|-----|-----| | Blast morphology | Fine chromatin, scanty cytoplasm | Coarse chromatin, abundant cytoplasm | Abundant Auer rods | | MPO stain | **Negative** | Positive (>3% positive) | Positive | | PAS stain | **Positive (diffuse)** | Negative or focal | Negative | | Auer rods | Absent | May be present | Characteristic (bundles) | **High-Yield:** MPO-negative + PAS-positive (diffuse) = **ALL**, not AML. This is a critical discriminator. ### Epidemiology & Prognosis - ALL is the most common childhood malignancy (80% of pediatric leukemias) - Peak incidence: 2–5 years - B-cell ALL accounts for ~85% of cases (vs. T-cell ~15%) - Favorable prognostic factors in this case: age 4 years (2–10 years is favorable), WBC <50,000/μL at presentation **Clinical Pearl:** The presence of hepatosplenomegaly and lymphadenopathy in ALL reflects extramedullary leukemic infiltration, which is common but does not necessarily indicate worse prognosis if other favorable factors are present. ### Why B-Cell Type? Without immunophenotyping data explicitly stated, the morphology (fine chromatin, scanty cytoplasm, PAS-positive) is consistent with common ALL (cALL, ~60% of pediatric ALL), which is B-cell derived and typically has a better prognosis than T-cell ALL. **Mnemonic: ALL cytochemistry** — **"MPO Negative, PAS Positive"** = ALL (remember: "ALL are PAS-positive, AML are MPO-positive"). [cite:Robbins 10e Ch 7]