A 66-year-old man has experienced fatigue, a 5-kg weight loss, night sweats, and abdominal discomfort for 10 months. On physical examination, he has marked splenomegaly; there is no lymphadenopathy. Laboratory studies show hemoglobin, 10.1 g/dL; hematocrit, 30.5%; MCV, 89 gm3; platelet count, 94,000/mm3; and WBC count, 14,750/mm3 with 55% segmented neutrophils, 9% bands, 20% lymphocytes, 8% monocytes, 4% metamyelocytes, 3% myelocytes, 1% eosinophils, and 2 nucleated RBCs per 100 WBCs. The peripheral blood smear also shows teardrop cells. The serum uric acid level is 12 mg/dL. A bone marrow biopsy specimen shows extensive marrow fibrosis and clusters of atypical megakaryocytes. Which of the following is most likely to account for the enlargement in this patient's spleen?
Myelofibrosis with myeloid metaplasia is a myeloproliferative disorder that is also a stem cell disorder in which neoplastic megakaryocytes secrete fibrogenic factors leading to marrow fibrosis. The neoplastic clone then shifts to the spleen, where it shows trilineage hematopoietic proliferation (extramedullary hematopoiesis), in which megakaryocytes are prominent. The marrow fibrosis and the extramedullary hematopoiesis in the spleen fail to regulate orderly release of leukocytes into the blood. The peripheral blood has immature RBC and WBC precursors (leukoerythroblastic picture). Hematopoietic cell proliferation and turnover increases purine metabolism and uric acid production. Teardrop RBCs are misshapen RBCs that are seen when marrow undergoes fibrosis. Marrow injury also can be the result of other causes (e.g., metastatic tumors, irradiation). These causes also can give rise to a leukoerythroblastic picture, but splenic enlargement with trilineage proliferation usually is not seen. The other causes mentioned - Hodgkin lymphoma, portal hypertension, and Histoplasma capsulatum infection - can cause splenic enlargement, but not marrow fibrosis. Metastases to the spleen are uncommon.
Extramedullary hematopoiesis
Granulomas with Histoplasma capsulatum
Hodgkin lymphoma
Metastatic adenocarcinoma
Blood