Oncology · Hematologic Malignancies
The facts most likely to be tested
Acute Lymphoblastic Leukemia is the most common malignancy in children, typically presenting between the ages of 2 and 5 years old.
Patients present with bone marrow failure symptoms including pallor, fatigue, petechiae, and recurrent infections due to anemia, thrombocytopenia, and neutropenia.
Physical examination frequently reveals hepatosplenomegaly, lymphadenopathy, and bone pain caused by marrow expansion.
The diagnosis is confirmed by a bone marrow biopsy showing hypercellularity with >20% lymphoblasts.
Flow cytometry typically demonstrates TdT (terminal deoxynucleotidyl transferase) positivity, a marker of pre-B and pre-T cells.
The t(12;21) translocation (ETV6-RUNX1) is associated with a favorable prognosis in pediatric patients.
Central nervous system involvement is common, necessitating prophylactic intrathecal chemotherapy (e.g., methotrexate) as part of the treatment regimen.
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A 4-year-old boy is brought to the clinic by his parents due to a 3-week history of increasing fatigue and intermittent fevers. On physical exam, he appears pale and has multiple petechiae on his lower extremities. Palpation of the abdomen reveals hepatosplenomegaly, and the child complains of bilateral leg pain when walking. Laboratory studies show a hemoglobin of 7.2 g/dL, a platelet count of 45,000/mm³, and a white blood cell count of 42,000/mm³ with circulating blasts on the peripheral smear.
What is the most likely diagnosis?
Acute Lymphoblastic Leukemia (ALL)
The patient's presentation of pancytopenia, hepatosplenomegaly, and bone pain in a young child is classic for ALL, which is confirmed by the presence of blasts on the peripheral smear.
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High yield triage
Etiology / Epidemiology
Most common malignancy in children (peak age 2-5). Associated with Down syndrome.
Clinical Manifestations
Presents with bone pain, hepatosplenomegaly, and lymphadenopathy. Signs of pancytopenia.
Diagnosis
Bone marrow aspiration showing >20% lymphoblasts. Flow cytometry confirms lineage.
Treatment
Combination chemotherapy (e.g., vincristine, prednisone, L-asparaginase). Tumor lysis syndrome risk.
Prognosis
Highly curable in children with >85% 5-year survival rate.
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Epidemiology & Etiology
ALL is the most frequent pediatric cancer, representing 80% of childhood leukemias. Increased risk is noted in patients with Down syndrome and Li-Fraumeni syndrome. Exposure to high-dose radiation or prior chemotherapy are established environmental triggers.
Pertinent Anatomy
The disease originates in the bone marrow, leading to the crowding out of normal hematopoietic stem cells. Extramedullary infiltration commonly involves the CNS and testes, which serve as sanctuary sites for leukemic cells.
Pathophysiology
Malignant transformation of lymphoid progenitor cells results in the rapid proliferation of immature lymphoblasts. These cells fail to differentiate, leading to bone marrow failure and the clinical triad of anemia, thrombocytopenia, and neutropenia. Genetic mutations often involve Philadelphia chromosome (t(9;22)) in high-risk adult cases.
Clinical Manifestations
Patients present with constitutional symptoms including fever, fatigue, and weight loss. Physical exam reveals hepatosplenomegaly, lymphadenopathy, and bone pain due to marrow expansion. CNS involvement may manifest as headache, stiff neck, or cranial nerve palsies. Bleeding diathesis (petechiae/ecchymosis) is common due to low platelets.
Diagnosis
Bone marrow aspiration is the gold standard, demonstrating >20% lymphoblasts. Flow cytometry is required to distinguish B-cell vs T-cell lineage. Lumbar puncture is mandatory at diagnosis to assess for CNS infiltration.
Treatment
Treatment involves multi-phase combination chemotherapy including induction, consolidation, and maintenance. Intrathecal methotrexate is used for CNS prophylaxis. Tumor lysis syndrome is a major emergency requiring aggressive IV hydration and allopurinol or rasburicase.
Prognosis
Pediatric prognosis is excellent with >85% cure rates. Adult prognosis is significantly worse, often requiring allogeneic stem cell transplant for high-risk disease. Long-term monitoring for cardiotoxicity from anthracyclines is essential.
Differential Diagnosis
Acute Myeloid Leukemia: Auer rods present on peripheral smear
Aplastic Anemia: Bone marrow hypocellularity without blasts
Infectious Mononucleosis: Lymphocytosis with atypical lymphocytes, not blasts
ITP: Isolated thrombocytopenia without systemic symptoms
Neuroblastoma: Solid tumor mass, usually abdominal, not marrow-derived