Institution: William Beaumont Hospital, Troy, MI
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN
HISTORY
65 year old male with long history of thrombocytosis.
In 1996, a bone marrow biopsy showed features consistent with myeloproliferative neoplasm/essential thrombocythemia.In 2007, the diagnosis of essential thrombocythemia was made based on bone marrow biopsy and positive for JAK-2 gene mutation. Cytogenetic studies were normal. Treated with Hydrea and Agrylin. Other medications include Lotensin, Nexium, hydrochlorothiazide, Toprol and Zocor.In 2012, presenting with neutropenia, anemia and features suggesting blastic transformation from his origin essential thrombocythemia. Both peripheral blood and bone marrow biopsy examination show acute B-lymphoblastic lymphoma/leukemia. JAK-2 is still positive. Cytogenetic studies report one abnormal cell line with del (9) (p13). Negative for BCR/ABL by FISH.DETAILS
Bone marrow biopsies were obtained in 1996, 2007 and 2012. The core biopsies were formalin fixed and paraffin embedded. In 1996 and 2007, bone marrow biopsies show hypercellularity with atypical megakaryocytic proliferation and reticulin fibrosis, consistent with myeloproliferative neoplasm/essential thrombocythemia. Blasts are 3% or less. In 2012, bone marrow biopsy shows diffuse blastic infiltrate, more than 80% blasts, decreased erythropoiesis and granulopoiesis, occasional large megakaryocytes. The blasts show features of lymphoblasts, consistent with acute lymphoblastic leukemia/lymphoma.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
In1996 and 2007, no flow cytometry study performed. Immunohistochemical studies on bone marrow biopsies show findings consistent with myeloproliferative neoplasm/essential thrombocythemia. No evidence of acute leukemia, blasts were 3% or less.
In 2012, flow cytometry evaluation was performed on both peripheral blood and bone marrow with similar results: a large population of B-lymphoblasts positive for CD10, CD19, CD20, CD34, CD38, CD45, CD58 and HLA-DR. Negative for the other markers studied (CD11c, CD13, CD14, CD15, CD16, CD33, CD36, CD41, CD64, CD71, CD117, CD2, CD3, CD4, CD5, CD7, CD8, CD56 and K/L light chains). The diagnosis is B-lymphoblastic lymphoma/leukemia.CYTOGENETIC FINDINGS
In1996 and 2007, cytogenetic studies were normal during essential thrombocythemia.
In 2012, cytogenetic studies report one abnormal cell line with chromosome 9p deletion: 46, xy, del (9) (p13), with transformation to B-lymphoblastic lymphoma/leukemia.MOLECULAR FINDINGS
In 2007, PCR study was positive for JAK-2 gene mutation.
In 2012, PCR study is positive for JAK-2 gene mutation, FISH study is negative for BCR/ABL.INTERESTING FEATURES
Myeloproliferative neoplasm/essential thrombocythemia, positive for JAK2 gene mutation, with normal cytogenetics, treated with Hydrea and Agrylin, transformed into B-lymphoblastic lymphoma/leukemia, with cytogenetic evolution (del 16p), positive JAK2, negative BCR/ABL
Possible therapy-related ?PROPOSED DIAGNOSIS
Myeloproliferative neoplasm/essential thrombocythemia with transformation into B-lymphoblastic lymphoma/leukemia, with cytogenetic evolution
CONSENSUS DIAGNOSIS
Blast phase of myeloproliferative neoplasm/essential thrombocythemia, JAK2 mutation positive: B-acute lymphoblastic lymphoma/leukemia (JAK2 mutation positive)