A 66-year-old woman comes to the office due to 2 months of worsening fatigue and dyspnea with moderate exertion. The patient has a history of breast cancer treated with surgery and combination chemotherapy 6 years ago. She has no other medical conditions. Vital signs are within normal limits. Physical examination reveals normal jugular venous pressure, clear lungs, and normal heart sounds; there is no hepatosplenomegaly, lymphadenopathy, or extremity edema. Laboratory results are as follows: Peripheral blood smear shows oval macrocytic red cells and hyposegmented neutrophils. Bone marrow biopsy of this patient is most likely to reveal which of the following?

Question

A 66-year-old woman comes to the office due to 2 months of worsening fatigue and dyspnea with moderate exertion.  The patient has a history of breast cancer treated with surgery and combination chemotherapy 6 years ago.  She has no other medical conditions.  Vital signs are within normal limits.  Physical examination reveals normal jugular venous pressure, clear lungs, and normal heart sounds; there is no hepatosplenomegaly, lymphadenopathy, or extremity edema.  Laboratory results are as follows:  Peripheral blood smear shows oval macrocytic red cells and hyposegmented neutrophils.  Bone marrow biopsy of this patient is most likely to reveal which of the following?

Quizplus · Accepted Answer

11ec160b_398b_62a0_9249_776020ee4ba3_MD0001_00 This patient's previous chemotherapy, pancytopenia, and cellular dysplasia (eg, hyposegmented neutrophils, oval macrocytic erythrocytes) indicate likely myelodysplastic syndrome (MDS). MDS is a clonal hematologic malignancy associated with the development of driver mutations due to advanced age, previous chemo-/radiotherapy, or exposure to environmental toxins. MDS is marked by the following: ≥1 cytopenias: normal hematopoiesis is impaired due to neoplastic cell replication in the bone marrow; therefore, patients usually present with symptoms of ≥1 cytopenia such as fatigue/dyspnea on exertion (anemia), bleeding/bruising (thrombocytopenia), or infections (leukopenia). Because erythrocyte production is impaired, reticulocyte count will be low despite significant anemia. However, significant extramedullary hematopoiesis does not occur, so hepatosplenomegaly is rare. Dysplasia of erythrocytes and neutrophils: peripheral blood smear usually shows normocytic or macrocytic erythrocytes with a variety of abnormalities (eg, oval macrocytes). Neutrophils are typically hypolobulated and hypogranular. Bone marrow biopsy typically reveals a hypercellular marrow with dysplasia of ≥1 cell lines. Myeloblasts are increased (but <20% of total cells), and granulocytes show evidence of impaired maturation such as abnormalities in size, granulation, or lobulation. Erythrocytes also show signs of abnormal development, including large size and nuclear lobation/budding. (Choice A) Metastatic adenocarcinoma (atypical gland-forming cells) can infiltrate the bone marrow, leading to pancytopenia. Although reticulocytes would be diminished, peripheral blood smear would not show signs of abnormal granulocyte development (eg, hyposegmentation). (Choice C) Hypercellular marrow with sheets of plasma cells is seen in multiple myeloma. Although it occasionally causes pancytopenia (anemia alone is more common), peripheral smear shows rouleaux formation due to increased monoclonal proteins; dysmorphic granulocytes would not be seen. In addition, multiple myeloma is not strongly associated with chemotherapy exposure. (Choice D) Anemia of chronic disease is associated with increased retention of iron in reticuloendothelial macrophages. Although low reticulocyte count is common, patients usually have normocytic anemia and relatively normal peripheral smear findings (eg, no dysplasia). In contrast, MDS can be associated with ringed sideroblasts (iron-laden erythrocyte precursors) in the bone marrow. (Choice E) Collagen deposition in the bone marrow is associated with myelofibrosis, a chronic myeloproliferative disorder that causes anemia and variable platelet/leukocyte counts. However, patients typically have marked splenomegaly due to extramedullary hematopoiesis. Educational objective: Myelodysplastic syndrome is a clonal hematologic neoplasm marked by ≥1 cytopenias and cellular dysplasia (eg, oval macrocytic erythrocytes, hyposegmented granulocytes). Bone marrow evaluation usually reveals a hypercellular marrow, a mild or moderate increase in myeloblasts (<20% of total cells), and dysplastic erythrocytes/granulocytes.

A 66-Year-Old Woman Comes to the Office Due to 2