A 68-year-old man comes to the office due to severe fatigue for the last few months. He has also had 6.8-kg (15-lb) of unintentional weight loss over the same period. The patient has no significant medical history and has not seen a physician in many years. He takes no medications and does not use tobacco, alcohol, or illicit drugs. Physical examination shows mucosal pallor with no scleral icterus. The lungs are clear on auscultation, and heart sounds are normal. Abdominal examination shows mild hepatomegaly and a markedly enlarged spleen. Stool guaiac testing is negative. Laboratory results show pancytopenia, and peripheral blood smear is shown below. Bone marrow aspiration is attempted but yields no marrow, and a bone marrow biopsy is subsequently performed. Which of the following findings is most likely to be observed in this patient's bone marrow?

Question

A 68-year-old man comes to the office due to severe fatigue for the last few months.  He has also had 6.8-kg (15-lb) of unintentional weight loss over the same period.  The patient has no significant medical history and has not seen a physician in many years.  He takes no medications and does not use tobacco, alcohol, or illicit drugs.  Physical examination shows mucosal pallor with no scleral icterus.  The lungs are clear on auscultation, and heart sounds are normal.  Abdominal examination shows mild hepatomegaly and a markedly enlarged spleen.  Stool guaiac testing is negative.  Laboratory results show pancytopenia, and peripheral blood smear is shown below.  Bone marrow aspiration is attempted but yields no marrow, and a bone marrow biopsy is subsequently performed.  Which of the following findings is most likely to be observed in this patient's bone marrow?

Quizplus · Accepted Answer

11ec160b_398c_c233_9249_af610213db3a_MD0001_00 This patient with pancytopenia, hepatosplenomegaly, and teardrop cells on peripheral blood smear likely has primary myelofibrosis, a hematopoietic stem cell malignancy associated with the clonal expansion of megakaryocytes. Neoplastic megakaryocytes secrete the cytokine transforming growth factor-beta, which stimulates bone marrow fibroblasts to fill the medullary space with collagen. Subsequent bone marrow fibrosis usually leads to the following: Extramedullary hematopoiesis - Because the bone marrow is destroyed by fibrotic tissue, hematopoiesis occurs in secondary hematopoietic tissue such as the spleen and liver. This typically results in marked splenomegaly and a palpable liver edge on examination. Cytopenias - Extramedullary hematopoiesis is much less efficient than medullary hematopoiesis. Therefore, patients often have deficits in 1 or more cell lines (eg, anemia, pancytopenia). Dacrocytes on peripheral blood smear - The red cell membrane is damaged when squeezing out of the fibrotic bone marrow or passing through the enlarged spleen, which leads to the formation of teardrop-shaped red cells. The diagnosis of primary myelofibrosis requires bone marrow examination. Bone marrow aspiration frequently results in a dry tap (no marrow) due to significant bone marrow fibrosis. Therefore, bone marrow biopsy is usually required; the presence of a diffusely fibrotic marrow with occasional clusters of atypical megakaryocytes confirms the diagnosis. (Choice B) Multiple myeloma, a clonal disorder of plasma cells, is marked by a monoclonal spike (M-spike) on protein electrophoresis. Patients typically have anemia, hypercalcemia, bone pain (osteolytic lesions), and renal insufficiency. Bone marrow biopsy usually shows a clusters of monoclonal plasma cells. (Choice C) Anemia of chronic disease is associated with hepcidin-induced changes in iron metabolism that cause iron trapping within macrophages. Bone marrow biopsy with Prussian blue stain demonstrates increased iron within macrophages. Hepatosplenomegaly and teardrop cells would be unexpected. (Choice D) Myelodysplastic syndrome is a malignant stem cell cancer associated with the production of dysplastic, atypical blood cells. Although most patients with myelodysplasia have cytopenias, the bone marrow is usually hypercellular with multi-lineage dysplasia. (Choice E) Aplastic anemia results from injury (eg, drugs, radiation, viruses) to multipotent hematologic stem cells. It is usually associated with pancytopenia and a profoundly hypocellular bone marrow predominantly composed of adipose tissue. Extramedullary hematopoiesis is minimal and hepatosplenomegaly and dacrocytes are not typically present. Educational objective: Primary myelofibrosis is a myeloproliferative disorder associated with the clonal expansion of megakaryocytes. Bone marrow fibrosis accounts for most of the major manifestations, including hepatosplenomegaly, cytopenias, and blood smear evidence of dacrocytes. Bone marrow aspiration is usually dry, but bone marrow biopsy will show marked fibrosis with occasional clusters of atypical megakaryocytes.

A 68-Year-Old Man Comes to the Office Due to Severe