A 5-year-old boy presents to his pediatrician with weakness. His father observed that his son seemed less energetic at daycare and kindergarten classes. He was becoming easily fatigued from mild play. His temperature is 98°F (37°C), blood pressure is 90/60 mmHg, pulse is 100/min, and respirations are 20/min. Physical exam reveals pale conjunctiva, poor skin turgor and capillary refill, and cervical and axillary lymphadenopathy with assorted bruises throughout his body. A complete blood count reveals the following: Leukocyte count: 3,000/mm^3 Segmented neutrophils: 30% Bands: 5% Eosinophils: 5% Basophils: 10% Lymphocytes: 40% Monocytes: 10% Hemoglobin: 7.1 g/dL Hematocrit: 22% Platelet count: 50,000/mm^3 The most specific diagnostic assessment would most likely show which of the following?

Bone marrow biopsy with ≥ 20% lymphoblasts

Fluorescence in situ hybridization analysis with 9:22 translocation

Peripheral blood smear with > 50% lymphoblasts

Flow cytometry with positive terminal deoxynucleotidyl transferase staining

Fluorescence in situ hybridization analysis with 12:21 translocation

A pathologist receives a patient sample for analysis. Cells in the sample are first labeled with fluorescent antibodies and then passed across a laser beam in a single file of particles. The light scatter and fluorescent intensity of the particles are plotted on a graph; this information is used to characterize the sample. This laboratory method would be most useful to establish the diagnosis of a patient with which of the following?

Pancytopenia and deep vein thrombosis with intermittent hemoglobinuria

Ventricular septal defect and facial dysmorphism with low T-lymphocyte count

Painless generalized lymphadenopathy with monomorphic cells and interspersed benign histiocytes on histology

Multiple opportunistic infections with decreased CD4 counts

Vesicular lesions with dermatomal distribution and dendritic corneal ulcers

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 3-year-old boy is brought to the physician by his mother because of a 2-week history of generalized fatigue, intermittent fever, and occasional bleeding from his nose. His temperature is 38.3°C (100.9°F). He appears pale. Physical examination shows cervical lymphadenopathy and multiple petechiae on his trunk. The spleen is palpated 3 cm below the left costal margin. His hemoglobin concentration is 9.3 g/dL, leukocyte count is 63,000/mm3, and platelet count is 30,000/mm3. A bone marrow aspirate predominantly shows immature leukocytes that stain positive for CD10, CD19, and terminal deoxynucleotidyl transferase (TdT), and negative for myeloperoxidase. Which of the following is the most likely diagnosis?

Pre-B-cell acute lymphoblastic leukemia

Acute megakaryoblastic leukemia

T-cell chronic lymphocytic leukemia

A 7-year-old boy presents to his primary care physician for a general checkup. The patient has been feeling poorly for the past several weeks and has been losing weight. He states that he often feels weak and too tired to play with his friends. He is no longer interested in many recreational activities he used to be interested in. The patient's parents state that a few of their child's friends have been sick lately. His temperature is 102°F (38.9°C), blood pressure is 77/48 mmHg, pulse is 110/min, respirations are 24/min, and oxygen saturation is 98% on room air. On exam, you note a fatigued appearing child who has lost 10 pounds since his last appointment. Left upper quadrant tenderness and a mass is noted on abdominal exam. Which of the following best describes the most likely diagnosis?

Smudge cells on peripheral smear

Infection sensitive to oseltamivir

Parental mistreatment of the child

Acute leukemias for USMLE Step 3: High-Yield Pathology Lessons

Acute Leukemias - When Blasts Go Bad

Sudden onset; bone marrow failure (anemia, infections, bleeding).
Defined by >20% blasts in bone marrow or blood.

Acute Myeloid Leukemia (AML)
- Affects older adults (~65 years).
- Myeloblasts with Auer rods (pathognomonic).
- 📌 Auer rods for Myeloid Leukemia.
Acute Lymphoblastic Leukemia (ALL)
- Most common childhood cancer.
- Lymphoblasts are TdT+.
- Requires CNS prophylaxis.

Peripheral blood smear showing lymphoblasts in ALL

⭐ Acute Promyelocytic Leukemia (APL), an AML subtype with t(15;17) translocation, is uniquely treated with all-trans-retinoic acid (ATRA), which induces differentiation of blasts.

ALL - Lymphoid Lineage Gone Wild

Malignant, clonal proliferation of lymphoid blasts (>20% in bone marrow). It's the most common cancer of childhood (peak age 2-5 years) and is associated with Down syndrome.
Hallmark Markers: Blasts are TdT+ (terminal deoxynucleotidyl transferase), a marker of immature lymphocytes. Cytoplasm often contains PAS+ aggregates.

ALL peripheral blood smear with numerous lymphoblasts

Subtypes & Prognosis
- B-ALL: Most common. Good prognosis associated with t(12;21). Poor prognosis with t(9;22) [Philadelphia chromosome].
- T-ALL: Less common, presents in adolescents.

⭐ T-ALL classically presents as a large anterior mediastinal (thymic) mass in a teenager, potentially causing Superior Vena Cava (SVC) syndrome or dysphagia.

📌 Remember ALL the children.

AML - Myeloid Mayhem

Malignant proliferation of myeloblasts (>20% in bone marrow). Primarily affects older adults (median age 65).
Presentation: Pancytopenia symptoms-anemia (fatigue), thrombocytopenia (bleeding), neutropenia (infections). Gingival hyperplasia is also characteristic.
Microscopy: Large blasts with punched-out nucleoli.
- Auer rods: Pathognomonic needle-like, reddish-pink cytoplasmic inclusions.
Key Subtypes & Genetics:
- APL (Acute Promyelocytic Leukemia): t(15;17) PML-RARα fusion gene.
  - Associated with DIC.
  - Treatment: All-trans-retinoic acid (ATRA) induces differentiation.
- t(8;21): Favorable prognosis.
- inv(16): Favorable prognosis.
📌 Mnemonic: "All Myeloblasts Look alike."

⭐ Acute Promyelocytic Leukemia (APL, M3 subtype) is a medical emergency due to high risk of disseminated intravascular coagulation (DIC) from granule release. Treatment with ATRA can rapidly resolve this.

Lab Lowdown - Telling Blasts Apart

Myeloblasts: Large size, fine chromatin, prominent nucleoli, cytoplasmic granules.
- Auer Rods: Pathognomonic needle-like inclusions.
Lymphoblasts: Scant agranular cytoplasm, condensed chromatin, inconspicuous nucleoli.

⭐ T-ALL can present as a mediastinal (thymic) mass in a teenager, potentially causing SVC syndrome or dysphagia.

📌 Mnemonic: T-cell markers for T-ALL (CD2-8). Think Be-TEN-NINETEEN-TWENTY for B-ALL (CD10, CD19, CD20).

High‑Yield Points - ⚡ Biggest Takeaways

Acute leukemias are defined by >20% blasts in the bone marrow, causing an abrupt onset of pancytopenia (fatigue, bleeding, infections).

ALL is the most common cancer in children; blasts are TdT+. The t(12;21) translocation carries a good prognosis.

AML primarily affects older adults (~65 years); blasts are MPO+ and may contain pathognomonic Auer rods.

APL (M3), an AML subtype with t(15;17), is a medical emergency treated with all-trans retinoic acid (ATRA).

The Philadelphia chromosome t(9;22) confers a poor prognosis in both ALL and AML.

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Acute leukemias