A 45-year-old woman comes to the physician because of a 1-week history of fatigue and bruises on her elbows. Examination shows a soft, nontender abdomen with no organomegaly. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?

Sheets of abnormal plasma cells

Wrinkled cells with a fibrillary cytoplasm

Dysplastic bone with ringed sideroblasts

A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?

Repeated CBCs for several weeks and reassess

A 76-year-old woman presents to the physician for a follow-up examination. She had a hemoglobin level of 10.5 g/dL last month. She complains of mild dyspnea with exercise. She reports exercising daily for the past 30 years. She is relatively healthy without any significant past medical history. She occasionally takes ibuprofen for knee pain. She denies a prior history of alcohol or tobacco use. Her temperature is 37.1°C (98.8°F), the pulse is 65/min, the respiratory rate is 13/min, and the blood pressure is 115/65 mm Hg. The examination shows no abnormalities. Laboratory studies show: Laboratory test Hemoglobin 10.5 g/dL Mean corpuscular volume 75 μm3 Leukocyte count 6500/mm3 with a normal differential Platelet 400,000/mm3 Serum Iron 35 Total iron-binding capacity 450 μg/dL Ferritin 8 Ca+ 9.0 mg/dL Albumin 3.9 g/dL Urea nitrogen 10 mg/dL Creatinine 0.9 mg/dL Serum protein electrophoresis and immunofixation show a monoclonal protein of 20 g/L (non-IgM). Marrow plasmacytosis is 5%. A skeletal survey shows no abnormalities. In addition to the workup of iron deficiency anemia, which of the following is the most appropriate next step in management?

Annual follow-up with laboratory tests

No further steps are required at this time

A 9-year-old boy is brought to the physician by his mother because of a 3-day history of fever and bleeding after brushing his teeth. His mother also reports that her son has asked to be picked up early from soccer practice the past few days because of fatigue. He appears pale and ill. His temperature is 38.3°C (101.1°F), pulse is 115/min, and blood pressure is 100/60 mm Hg. The lungs are clear to auscultation. Examination shows a soft, nontender abdomen with no organomegaly. There are several spots of subcutaneous bleeding on the abdomen and shins. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?

Hypocellular fat-filled marrow with RBCs of normal morphology

Infiltration of the marrow with collagen and fibrous tissue

Hypercellular, dysplastic bone marrow with ringed sideroblasts

Sheets of abnormal plasma cells

A 7-month old boy, born to immigrant parents from Greece, presents to the hospital with pallor and abdominal distention. His parents note that they recently moved into an old apartment building and have been concerned about their son's exposure to chipped paint from the walls. On physical exam, the patient is found to have hepatosplenomegaly and frontal skull bossing. Hemoglobin electrophoresis reveals markedly increased HbF and HbA2 levels. What would be the most likely findings on a peripheral blood smear?

Microcytosis and hypochromasia of erythrocytes

Basophilic stippling of erythrocytes

Macrocytosis of erythrocytes with hypersegmented neutrophils

Schistocytes and normocytic erythrocytes

A 13-year-old girl is brought to the pediatrician due to a 4-month history of heavy vaginal bleeding during menstrual periods. She endorses episodes of bleeding gums after brushing her teeth and experienced prolonged bleeding after tonsillectomy 6 years ago. Her mother states that she bled significantly during childbirth and that the girl’s older brother has similar symptoms including easy bruising. Vitals were stable and physical exam was not revealing. Laboratory studies show: Platelet count: 72,000/mm^3 Bleeding time: 14 min Prothrombin time: 12 secs (INR = 1) Partial thromboplastin time: 40 secs Blood smear demonstrates increased megakaryocytes and enlarged platelets. Platelets do not aggregate to ristocetin. Which of the following is the most likely diagnosis?

Idiopathic thrombocytopenic purpura (ITP)

A 60-year-old woman comes to the physician because of lower back pain, generalized weakness, and weight loss that has occurred over the past 6 weeks. She also says that her urine has appeared foamy recently. Physical examination shows focal midline tenderness of the lumbar spine and conjunctival pallor. Her temperature is 100.5°F (38°C). A photomicrograph of a bone marrow biopsy specimen is shown. Further evaluation of this patient is most likely to show which of the following findings?

Grouped erythrocytes with stacked-coin appearance

Myeloblasts with needle-shaped cytoplasmic inclusions

Erythrocytes with cytoplasmic hemoglobin inclusions

Neutrophils with hypersegmented nuclear lobes

B-lymphocytes with radial cytoplasmic projections

Myelodysplastic syndromes for USMLE Step 3: High-Yield Pathology Lessons

MDS Intro - The Failing Factory

Clonal hematopoietic stem cell disorders causing ineffective hematopoiesis (a dysfunctional bone marrow factory).
Leads to peripheral cytopenias (anemia, neutropenia, thrombocytopenia) despite a normo- or hypercellular marrow.
Hallmark is dysplasia (abnormal cell morphology) in one or more myeloid lineages.
Considered a pre-leukemic condition with risk of transformation to Acute Myeloid Leukemia (AML), defined by ≥20% blasts.

⭐ The central paradox of MDS is a hypercellular, "packed" bone marrow that yields peripheral cytopenias due to defective, apoptotic cells.

Pseudo-Pelger-Huët neutrophil and dyserythropoiesis in MDS

Pathophysiology - Corrupted Blueprints

Clonal mutation in a hematopoietic stem cell (HSC) is the primary insult.
Leads to ineffective hematopoiesis: marrow is hypercellular but cells are defective (dysplastic) and undergo apoptosis.
- Results in peripheral blood cytopenias (anemia, neutropenia, thrombocytopenia).
- Dysplastic changes visible in one or more cell lines (e.g., pseudo-Pelger-Huët cells, ring sideroblasts).
Represents a pre-malignant state with a high risk of transformation to Acute Myeloid Leukemia (AML).

MDS: Dysplastic megakaryocytes and erythroid precursors

⭐ MDS with isolated del(5q) is a unique subtype with a favorable prognosis, often presenting with thrombocytosis, and showing a robust response to lenalidomide therapy.

Diagnosis & Features - Spotting the Sabotage

Complete Blood Count (CBC):
- Hallmark: Unexplained, persistent cytopenia(s), especially macrocytic anemia (↑ MCV).
Peripheral Blood Smear:
- Shows dysplastic features in ≥1 cell line.
- WBCs: Pseudo-Pelger-Huët cells (bilobed nuclei).
- RBCs: Ovalomacrocytes.
- Platelets: Giant or hypogranular platelets.
Bone Marrow Aspirate & Biopsy (Definitive Dx):
- Hypercellular marrow despite peripheral cytopenias.
- Dysplasia in ≥10% of cells in a lineage.
- Key: Myeloblasts < 20%.

⭐ A blast count of ≥ 20% in the bone marrow or blood signifies transformation to Acute Myeloid Leukemia (AML).

Morphology & Subtypes - A Rogues' Gallery

Hallmark: Ineffective hematopoiesis → peripheral cytopenias despite a hypercellular or normocellular bone marrow.
Key Feature (Dyspoiesis): Abnormal maturation in ≥1 cell line.
- Erythroid: Ring sideroblasts (>15% of precursors), megaloblastoid changes, nuclear budding.
- Myeloid: Pseudo-Pelger-Huët cells (bilobed nuclei), hypogranulation.
- Megakaryocytic: Micromegakaryocytes, "pawnball" nuclei (small, non-lobated).
Blasts: Bone marrow blasts are < 20%; reaching this threshold signifies transformation to AML.

Pseudo-Pelger-Huët cell and ring sideroblasts in MDS

⭐ MDS with isolated del(5q): Typically affects older women, presenting with macrocytic anemia, a normal or elevated platelet count, and carrying a favorable prognosis.

Prognosis & Treatment - Damage Control

Prognosis: Stratified by the IPSS-R score, which predicts survival and AML transformation risk. Key factors include marrow blast %, cytogenetics, and severity of cytopenias.
Supportive Care (Damage Control): The mainstay for lower-risk MDS, focused on managing marrow failure.
- Anemia: RBC transfusions for symptoms; ESAs if serum EPO is <500 U/L.
- Thrombocytopenia: Platelet transfusions for active bleeding.
- Neutropenia: G-CSF for recurrent infections.
- Iron Overload: Iron chelation for patients with chronic transfusion needs.

⭐ Isolated del(5q) syndrome is a unique entity with a favorable prognosis and high response rates to lenalidomide.

High‑Yield Points - ⚡ Biggest Takeaways

Clonal stem cell disorders in the elderly, leading to ineffective hematopoiesis and peripheral cytopenias.

Hallmark is dysplasia in one or more myeloid lineages, such as pseudo-Pelger-Huët cells and ring sideroblasts.

Bone marrow is paradoxically hypercellular despite low peripheral blood counts.

Patients often present with a macrocytic anemia (↑ MCV) resistant to standard therapies.

Carries a high risk of progression to Acute Myeloid Leukemia (AML).

The del(5q) syndrome subtype has a more favorable prognosis and often responds to lenalidomide.

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