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

A 72-year-old man goes to his primary care provider for a checkup after some blood work showed lymphocytosis 3 months ago. He says he has been feeling a bit more tired lately but doesn’t complain of any other symptoms. Past medical history is significant for hypertension and hyperlipidemia. He takes lisinopril, hydrochlorothiazide, and atorvastatin. Additionally, his right hip was replaced three years ago due to osteoarthritis. Family history is noncontributory. He drinks socially and does not smoke. Today, he has a heart rate of 95/min, respiratory rate of 17/min, blood pressure of 135/85 mm Hg, and temperature of 36.8°C (98.2°F). On physical exam, he looks well. His heartbeat has a regular rate and rhythm and lungs that are clear to auscultation bilaterally. Additionally, he has mild lymphadenopathy of his cervical lymph nodes. A complete blood count with differential shows the following: Leukocyte count 5,000/mm3 Red blood cell count 3.1 million/mm3 Hemoglobin 11.0 g/dL MCV 95 um3 MCH 29 pg/cell Platelet count 150,000/mm3 Neutrophils 40% Lymphocytes 40% Monocytes 5% A specimen is sent for flow cytometry that shows a population that is CD 5, 19, 20, 23 positive. Which of the following is the most likely diagnosis?

Immune thrombocytopenic purpura

A 39-year-old man presents to the emergency department with the complaint of ‘cola-colored’ urine that he noticed this morning. Additionally, he complains of malaise and reports that he has not been able to be productive at work since last week. Lab results revealed a hemoglobin of 6.7 g/dL, leukocyte total count of 1,000 cells/mm3, and a reticulocyte count of 6%. Coomb test is negative and flow cytometry shows CD55/CD59-negative red blood cells. Concerned about the results of his complete blood count, his physician explains the diagnosis to the patient. Which of the following sets of events best describes the mechanism underlying the development of neutropenia?

↓ production of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules

↑ release of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules

↓ activation of neutrophil adhesion molecules and ↓ production of neutrophils in the bone marrow

↑ activation of neutrophil adhesion molecules, ↓ destruction of neutrophils, and ↓ production of neutrophils in the bone marrow

↑ activation of neutrophil adhesion molecules, ↓ release of neutrophils in the bone marrow, and ↑ destruction of neutrophils

White blood cell disorders for USMLE Step 2 CK: High-Yield Pathology Lessons

WBC Basics - The Body's First Responders

Function: Key mediators of inflammation and the immune response.
Normal Range: 4,000-11,000/μL.
- Leukocytosis: >11,000/μL (indicates infection, stress, or inflammation).
- Leukopenia: <4,000/μL (suggests immunosuppression, marrow failure).
Differential Count:
- 📌 Mnemonic (most to least abundant): Never Let Monkeys Eat Bananas (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils).
Absolute Neutrophil Count (ANC):
- $ANC = \text{WBC Count} \times (% \text{Neutrophils} + % \text{Bands})$.
- Severe Neutropenia: ANC <500/μL; high risk for life-threatening infections.

⭐ A "left shift" indicates an acute inflammatory response (esp. bacterial infection), characterized by the premature release of immature neutrophils (e.g., bands, metamyelocytes) from the bone marrow.

Neutrophil Maturation: Myelocyte to Segmented Neutrophil

Myeloid Neoplasms - Precursor Pandemonium

Clonal hematopoietic stem cell disorders causing overproduction of one or more myeloid lineages. Spectrum ranges from ineffective hematopoiesis (MDS) to hyper-proliferation (MPN) to acute leukemia (AML).

Myelodysplastic Syndromes (MDS): Pancytopenia despite hypercellular marrow. Risk of AML transformation.
Myeloproliferative Neoplasms (MPN):
- CML: BCR-ABL fusion gene.
- Polycythemia Vera, Essential Thrombocythemia, Primary Myelofibrosis: Primarily JAK2, CALR, MPL mutations.

⭐ Auer Rods, eosinophilic needle-like inclusions in cytoplasm, are pathognomonic for Acute Myeloid Leukemia (AML).

Auer rods in acute myeloid leukemia blood smear

Lymphoid Leukemias - Clonal Chaos Crew

Acute Lymphoblastic Leukemia (ALL):
- Most common childhood malignancy; blasts are TdT+.
- B-ALL: CD10+, CD19+, CD20+. Good prognosis with t(12;21).
- T-ALL: Can present as a mediastinal mass in a teenager.
Chronic Lymphocytic Leukemia (CLL):
- Affects adults > 60; often asymptomatic with lymphocytosis.
- Key finding: Smudge cells on peripheral smear.
- Co-expression of CD5 and CD20.
- Can undergo Richter transformation to an aggressive lymphoma.
Hairy Cell Leukemia:
- Affects older males; cells have fine, hair-like projections.
- Stains TRAP+ (Tartrate-Resistant Acid Phosphatase).
- Causes massive splenomegaly and pancytopenia.

⭐ In CLL, smudge cells are fragile neoplastic lymphocytes crushed during peripheral blood smear preparation. Their presence is characteristic but not pathognomonic.

CLL peripheral blood smear with smudge cells and lymphocytes

Plasma Cell Dyscrasias - M-Protein Mayhem

Multiple Myeloma (MM): Malignant plasma cells producing monoclonal Ig (IgG > IgA).
- 📌 CRAB criteria: ↑ Calcium (>11 mg/dL), Renal insufficiency, Anemia, lytic Bone lesions.
- Labs: M-spike on SPEP, Bence-Jones proteinuria, Rouleaux formation (RBC stacks).
Waldenström Macroglobulinemia: IgM M-spike leading to hyperviscosity syndrome (blurry vision, Raynaud).
MGUS (Monoclonal Gammopathy of Undetermined Significance): Asymptomatic; precursor with risk of progression.

⭐ Multiple Myeloma is the most common primary malignant bone tumor in adults.

Multiple Myeloma in Bone Marrow Biopsy

High‑Yield Points - ⚡ Biggest Takeaways

Leukemoid reaction is distinguished from CML by a high LAP score; CML has a low LAP score and the Philadelphia chromosome (t(9;22)).

Acute leukemias (ALL, AML) show >20% blasts in the marrow; Auer rods are pathognomonic for AML.

CLL is characterized by smudge cells and lymphadenopathy in the elderly.

Hodgkin lymphoma is identified by Reed-Sternberg cells and typically spreads contiguously.

Multiple myeloma presents with CRAB findings (hypercalcemia, renal failure, anemia, bone lesions) and an M-spike.

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