![]() ![]() Myeloproliferative neoplasms: From JAK2 mutations discovery to JAK2 inhibitor therapies. Passamonti F, Maffioli M, Caramazza D, et al.Incidence of JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. De Stefano, V, Fiorini, A, Rossi, E, et al.Homeostatic and pathogenic extramedullary hematopoiesis. A case of perirenal extramedullary hematopoiesis in a patient with primary myelofibrosis. While EMH is a rare finding, it should prompt an investigation for an underlying MPN. Depending on the extent of involvement and location, EMH may require treatment with low dose radiation. 4 Patients with EMH can have symptoms related to the site of involvement. In addition to being a driver of proliferation, it is thought that JAK2 mutations make hematopoetic stem and progenitor cells more sensitive to growth factors and can cause the cells to mobilize to the liver and spleen. EMH most commonly occurs in the spleen and liver, but has been described in many other sites including the mediastinum and lymph nodes. Ultimately, this can lead to extramedullary hematopoesis. Increasing fibrosis can eventually result in pancytopenia as the fibrosis takes over the marrow space in addition to altering the bone marrow environment so that it is unable to support normal hematopoiesis. In PMF, there is generally a proliferation of myeloid cells in addition to marrow fibrosis. 3 The patient in case 2 had a bone marrow biopsy with features concerning for primary myelofibrosis. This suggests that he may have an underlying MPN, however JAK2 mutations have been found in patients with venous thrombosis, but without overt evidence of MPNs. 2 The patient in case 1 was found to have a JAK2 mutation during the work-up for hypercoagulability. ![]() This mutation leads to constitutive activation of the JAK/STAT pathway and is a driver of myeloproliferation. 1 JAK2V617F mutation is the most frequent mutation associated with MPNs, found in roughly 96% of patients with PV and 65% of patients with ET and PMF. Myeloproliferative neoplasms (MPN) are a group of clonal hematopoetic stem cell disorders that include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). It can occur in both normal and pathologic states and has been seen in several hematologic disorders including chronic myeloproliferative neoplasms. Taken together, the findings are consistent with extramedullary hematopoiesis.Įxtramedullary hematopoiesis (EMH) is defined as hematopoiesis that occurs outside of the bone marrow. CD34 highlights vessels and only rare CD34-positive cells are seen. CD71 highlights erythroid precursors, which comprise 20-30% of the cellularity. Myeloperoxidase highlights myeloid precursors, which comprise 70-80% of the cellularity. The lymphocytes are a mixture of CD3 positive T cells and CD20 positive B cells with focal B cell predominance. Multiple small to medium sized lymphoid aggregates are also seen, composed of small and mature appearing lymphocytes. The lymph node biopsy shows fragments composed of adipocytes and maturing trilineage hematopoiesis. Lymph node biopsy 10X Lymph node biopsy 40X Myeloperoxidase CD71 CD61 CD34 CD3 CD20 Recent bone marrow biopsy showed mildly hypercellular bone marrow with megakaryocytic and myeloid hyperplasia, and increased stromal reticulin with concern for primary myelofibrosis. In the setting of a positive JAK2 V617F mutation, this constellation of findings is consistent with a myeloproliferative neoplasm.įifty-nine year old man with a history of hypertension and alcohol abuse with posterior mediastinal lymphadenopathy. Sections show liver parenchyma with changes of the patient’s known history of venous outflow obstruction, as well as extramedullary hematopoiesis, including scattered megakaryocytes (arrows) and erythroid precursors (circle). Liver core biopsy 40X Liver core biopsy 40X JAK2 Mutations Analysis The case was sent to hematopathology for further review. Occasional megakaryocytes and nucleated red blood cell precursors were noted. The liver biopsy showed extensive hemorrhage, hepatocellular necrosis and collapse with mild portal and lobular mixed inflammation. Liver core biopsy 2X Liver core biopsy 10X A liver biopsy was performed and a hypercoagulability work-up, including JAK2 mutation analysis was initiated. ![]() Sixty-one year old man with new diagnosis of Bud-Chiari syndrome and extensive peripheral, splenic and hepatic venous thrombosis with increasing fatigue, abdominal discomfort and abnormal liver function tests. ![]()
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