A 73-year-old man comes to the office due to 2 months of worsening fatigue. The patient used to walk 1-2 miles each day but recently began having difficulty covering this distance. He has had no chest pain, shortness of breath, fever, joint pain, or abdominal issues. The patient underwent coronary artery bypass grafting 5 years ago. His other medical problems include hypothyroidism, hypertension, hyperlipidemia, and benign prostatic hyperplasia. He quit smoking 10 years ago and drinks 1 or 2 glasses of wine with dinner almost every day. His medications include aspirin, levothyroxine, atorvastatin, tamsulosin, metoprolol, and lisinopril.
Temperature is 37 C (98.6 F) , blood pressure is 130/80 mm Hg, pulse is 78/min, and respirations are 14/min. Pulse oximetry shows 98% on room air. BMI is 29 kg/m². Examination reveals mucosal pallor. There is no jugular venous distension, thyromegaly, or lymphadenopathy. The lungs are clear to auscultation. No hepatosplenomegaly or peripheral edema is present. Neurological examination is unremarkable.
Laboratory results are as follows:
Peripheral blood smear shows ovalomacrocytic red cells and reduced granulocyte segmentation. Complete blood count was normal a year ago. Colonoscopy was normal 5 years ago.
Which of the following is the most appropriate next step in management of this patient?

Question

A 73-year-old man comes to the office due to 2 months of worsening fatigue. The patient used to walk 1-2 miles each day but recently began having difficulty covering this distance. He has had no chest pain, shortness of breath, fever, joint pain, or abdominal issues. The patient underwent coronary artery bypass grafting 5 years ago. His other medical problems include hypothyroidism, hypertension, hyperlipidemia, and benign prostatic hyperplasia. He quit smoking 10 years ago and drinks 1 or 2 glasses of wine with dinner almost every day. His medications include aspirin, levothyroxine, atorvastatin, tamsulosin, metoprolol, and lisinopril.
Temperature is 37 C (98.6 F) , blood pressure is 130/80 mm Hg, pulse is 78/min, and respirations are 14/min. Pulse oximetry shows 98% on room air. BMI is 29 kg/m². Examination reveals mucosal pallor. There is no jugular venous distension, thyromegaly, or lymphadenopathy. The lungs are clear to auscultation. No hepatosplenomegaly or peripheral edema is present. Neurological examination is unremarkable.
Laboratory results are as follows:

Peripheral blood smear shows ovalomacrocytic red cells and reduced granulocyte segmentation. Complete blood count was normal a year ago. Colonoscopy was normal 5 years ago.
Which of the following is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

11ec193a_982d_842c_853d_a1d6e5558fca_MD0002_00 This patient has anemia with an elevated mean corpuscular volume (MCV). His vitamin B₁₂, folate, and TSH levels are normal, and he is not currently taking any medication that can result in elevated MCV (eg, hydroxyurea, zidovudine). Given his older age and peripheral blood smear findings, the most likely underlying diagnosis is myelodysplastic syndrome (MDS). ₁₂ MDS is a group of malignant hematopoietic stem cell disorders characterized by progressive bone marrow failure leading to blood cell dysplasias and cytopenias. Most cases are discovered incidentally on routine laboratory evaluation, but patients can also present with fatigue, infection, or easy bruising/bleeding. Laboratory evaluation usually shows anemia (macrocytic or normocytic) with an inappropriately low reticulocyte response; leukopenia (~50%) with monocytosis, thrombocytopenia (~25%), and thrombocytosis (~8%) also commonly occur. MDS is a diagnosis of exclusion; alternate causes of cytopenias (eg, medications, vitamin B₁₂/folate deficiency) should be ruled out prior to considering the diagnosis. Diagnostic evaluation for suspected MDS includes: ₁₂ Peripheral blood smear - typically reveals significant dysplasia (eg, ovalomacrocytosis, hyposegmented neutrophils) in ≥1 cell lines.Bone marrow aspirate/biopsy - usually reveals a hypercellular marrow with single- or multilineage dysplasia (peripheral blood cytopenias are thought to occur due to increased intramedullary apoptosis). Cytogenetics should be performed to classify, risk stratify, and stage the disease. Peripheral blood smear - typically reveals significant dysplasia (eg, ovalomacrocytosis, hyposegmented neutrophils) in ≥1 cell lines. Peripheral blood smear - typically reveals significant dysplasia (eg, ovalomacrocytosis, hyposegmented neutrophils) in ≥1 cell lines. Bone marrow aspirate/biopsy - usually reveals a hypercellular marrow with single- or multilineage dysplasia (peripheral blood cytopenias are thought to occur due to increased intramedullary apoptosis). Cytogenetics should be performed to classify, risk stratify, and stage the disease. Bone marrow aspirate/biopsy - usually reveals a hypercellular marrow with single- or multilineage dysplasia (peripheral blood cytopenias are thought to occur due to increased intramedullary apoptosis). Cytogenetics should be performed to classify, risk stratify, and stage the disease. (Choice A) Although alcohol abuse is a common cause of macrocytosis, it does not usually present with anemia of this degree or MCV >110 µm³. ³ (Choice C) This patient's TSH is within normal limits; he does not require further levothyroxine dosage adjustment. In addition, hypothyroidism usually causes a normocytic anemia. (Choice D) Methylmalonic acid levels can be used to diagnose vitamin B₁₂ deficiency in patients with borderline levels (200-300 pg/mL). However, this patient's vitamin B₁₂ level of >300 pg/mL makes deficiency unlikely, and his monocytosis makes MDS a more likely cause of his macrocytosis. In addition, vitamin B₁₂ deficiency is usually marked by hyperlobulated (not hypolobulated) neutrophils on peripheral blood smear. ₁₂ ₁₂ ₁₂ (Choice E) Serum and urine protein electrophoresis are used to identify plasma cell disorders such as multiple myeloma. Multiple myeloma commonly causes anemia (usually normocytic, normochromic) as well as bone pain, hypercalcemia, and renal insufficiency. Educational objective: Myelodysplastic syndrome (MDS) should be suspected in patients who have ≥1 cytopenias with no clear alternate (eg, medications, B₁₂ deficiency) cause. Diagnostic evaluation requires peripheral blood smear and bone marrow aspirate/biopsy to assess for dysplastic cytologic features consistent with MDS. ₁₂ __________ References: NCCN clinical practice guidelines in oncology: myelodysplastic syndromes. (http://www.ncbi.nlm.nih.gov/pubmed/21233243)

A 73-Year-Old Man Comes to the Office Due to 2