A 64-year-old woman comes to the physician for her routine health maintenance examination. She feels well. She had cervical cancer and received radiotherapy 8 years ago. Her vital signs are within normal limits. On percussion, the spleen size is 15 cm. Otherwise, the physical examination shows no abnormalities. The laboratory test results are as follows: Hemoglobin 10 g/dL Mean corpuscular volume 88 μm3 Leukocyte count 65,000/mm3 Platelet count 500,000/mm3 Two images of the peripheral blood smear are shown on the image. Which of the following is the most appropriate next step in management?

Allogeneic stem cell transplantation

An 8-year-old girl is brought to the clinic by her parents for fever and easy bruising. Her parents report that the child has been bruising easily ever since an upper respiratory infection 3 months ago. For example, a bump into the table resulted in a large bruise on the side of her hip for a week. Three days ago, her mother noticed that the child felt warm and subsequently measured a temperature of 101.8°F (38.8°C) that did not respond to acetaminophen. The patient denies any chills, cough, rhinorrhea, pharyngitis, sick contacts, headache, or urinary symptoms. A physical examination demonstrates a nontender, firm, and rubbery node along her left neck and splenomegaly. Laboratory findings are shown below: Leukocyte count and differential: Leukocyte count: 19,000/mm³ Neutrophils: 39% Bands: 12% Eosinophils: 2% Basophils: 0.5% Lymphocytes: 40% Monocytes: 6.5% Hemoglobin: 9.7 g/dL Platelet count: 100,000/mm³ Mean corpuscular hemoglobin concentration: 30% Mean corpuscular volume: 76 μm³ Reticulocyte count: 0.7% What cytogenetic abnormality would be most likely in this patient?

t(12;21) - TEL-AML1 translocation

t(9;22) - Philadelphia chromosome (BCR-ABL)

t(15;17) - PML-RARA translocation

A 70-year-old retired police officer is being evaluated for fatigue. A peripheral smear shows extremely elevated numbers of immature myeloid cells, which are positive for myeloperoxidase and a translocation t(15,17). Which of the following statements is true regarding his condition?

The patient can be treated with a vitamin A derivative.

Myelodysplastic syndromes may give rise to the condition.

This condition is also developed early in life in patients with Down syndrome.

Philadelphia chromosome may be seen and indicates a poor prognosis.

Auer rods are responsible for gum hyperplasia and bleeding.

A 12-year-old boy is brought in by his mother for a routine checkup. The patient’s mother says he is frequently fatigued and looks pale. She also claims that he has recently become “much quieter” than normal and is no longer interested in playing baseball with his friends. The patient’s mother believes it may just be “growing pains.” The patient has no significant medical history. He is the 90th percentile for height and weight and has been meeting all developmental milestones. The patient is afebrile, and his vital signs are within normal limits. Physical examination reveals several small bruises on the patient’s right arm and on both thighs. Laboratory findings are significant for the following: Sodium 140 mEq/L Potassium 4.2 mEq/L Chloride 101 mEq/L Bicarbonate 27 mEq/L BUN 16 mg/dL Creatinine 1.2 mg/dL Glucose (fasting) 111 mg/dL WBC 3,400/mm3 RBC 4.20 x 106/mm3 Hematocrit 22% Hemoglobin 7.1 g/dL Platelet count 109,000/mm3 A peripheral blood smear reveals myeloblasts. Which of the following is the next best step in the management of this patient?

Packed red blood cell transfusion

Administration of oral ferrous sulfate

A 7-year-old girl is brought to the physician by her mother because of a 2-week history of generalized fatigue, intermittent fever, and progressively worsening shortness of breath. Physical examination shows pallor, jugular venous distention, and nontender cervical and axillary lymphadenopathy. Inspiratory stridor is heard on auscultation of the chest. The liver is palpated 3 cm below the right costal margin. Her hemoglobin concentration is 9.5 g/dL, leukocyte count is 66,000/mm³, and platelet count is 102,000/mm³. An x-ray of the chest shows a mediastinal mass. A bone marrow aspirate predominantly shows leukocytes and presence of 35% lymphoblasts. Which of the following additional findings is most likely in this patient?

Positive myeloperoxidase staining

Leukemias in children for USMLE Step 3: High-Yield Pediatrics Lessons

Leukemia Basics - Blood Cell Rebellion

Most common childhood malignancy (~33%).
Uncontrolled clonal proliferation of immature hematopoietic cells (blasts) in the bone marrow.
This "rebellion" leads to bone marrow failure:
- ↓ RBCs → Anemia (pallor, fatigue)
- ↓ Platelets → Thrombocytopenia (petechiae, bleeding)
- ↓ Neutrophils → Neutropenia (recurrent infections)
Blasts can infiltrate extramedullary sites: liver, spleen, lymph nodes (LNs), CNS, and testes.

⭐ Children with Down syndrome (Trisomy 21) have a 10-20x increased risk of developing acute leukemia, particularly ALL.

Leukemia: Uncontrolled proliferation of immature WBCs

Acute Lymphoblastic Leukemia (ALL) - The Lympho-Blast Off

Most common childhood cancer; peak incidence at 2-5 years.
Presentation: Abrupt onset of bone marrow failure symptoms (anemia, infection, bleeding), bone pain, and lymphadenopathy.
Diagnosis: Requires >25% lymphoblasts in bone marrow.
- B-ALL (85%): CD10, CD19, CD22, TdT+. Good prognosis.
- T-ALL (15%): CD2, CD3, CD5, CD7, TdT+. Often presents with a mediastinal mass.

Peripheral smear: Acute Lymphoblastic Leukemia (ALL)

⭐ CNS Prophylaxis: All ALL patients receive intrathecal chemotherapy (e.g., Methotrexate) as the CNS is a pharmacological sanctuary site.

Acute Myeloid Leukemia (AML) - Myeloid Mayhem

Accounts for 15-20% of childhood leukemias; less common than ALL.
Key Associations: Down syndrome (especially < 4 years), Fanconi anemia, neurofibromatosis type 1.
Clinical Hallmarks: Besides pancytopenia symptoms (fatigue, fever, bleeding), look for:
- Gingival hypertrophy (common in M4/M5 subtypes)
- Leukemia cutis (nodular skin infiltrates)
- Myeloid sarcoma (Chloroma): extramedullary solid tumor of blasts.
Diagnosis: Bone marrow aspirate showing ≥20% myeloblasts.
- Auer rods: Pathognomonic eosinophilic, needle-like cytoplasmic inclusions.
- Cytochemistry: Blasts are Myeloperoxidase (MPO) and Sudan Black B (SBB) positive.

Auer rods and myeloblasts in Acute Myeloid Leukemia

⭐ AML M7 (Acute Megakaryoblastic Leukemia) is strongly associated with Down syndrome, particularly in children < 4 years of age.

Diagnosis & Management - The Cancer Crackdown

Initial Workup: Complete Blood Count (CBC) with Peripheral Smear (PS) showing ↑ blasts, pancytopenia.
Confirmatory Test: Bone Marrow Aspiration & Biopsy is gold standard. Diagnosis requires >20% blasts.
Lineage & Risk: Flow cytometry (differentiates ALL/AML), cytogenetics, and molecular studies (e.g., t(9;22) Philadelphia) for risk stratification.

Peripheral smear: Acute Lymphoblastic Leukemia (ALL)

Management: Multi-agent chemotherapy is the mainstay.
- Phases (ALL): Induction → Consolidation → Interim Maintenance → Delayed Intensification → Maintenance.
- CNS Prophylaxis: Intrathecal Methotrexate is crucial to prevent CNS relapse.
- Supportive Care: Blood product transfusions, managing infections (neutropenic fever).

⭐ Auer rods (needle-like cytoplasmic inclusions) seen on peripheral smear are pathognomonic for Acute Myeloid Leukemia (AML).

Acute Lymphoblastic Leukemia (ALL) is the most common pediatric malignancy, with a peak incidence at 2-5 years.

Favorable prognosis in ALL is associated with hyperdiploidy and the t(12;21) translocation.

Poor prognostic markers include age <1 year or >10 years, WBC >50,000/μL, and the t(9;22) Philadelphia chromosome.

AML is less common and often presents with Auer rods in myeloblasts.

CNS prophylaxis is a mandatory component of ALL treatment to prevent relapse.

Be vigilant for Tumor Lysis Syndrome, an oncologic emergency.

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