Case 89

Submitting Author: Xie, Ming, MD
Institution: William Beaumont Hospital, OUWB School of Medicine, Troy, MI 48085
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

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HISTORY

In 2010, this 73 year old male patient presented with thrombocytosis and underwent a bone marrow biopsy. The diagnosis of essential thrombocythemia was made, with positive JAK2 study. Cytogenetic study was normal. FISH study was negative for BCR/ABL1. He received chemotherapy.

In 2012, a repeat bone marrow biopsy showed acute myeloid leukemia arising from the previously diagnosed essential thrombocythemia.

Cytogenetic study showed abnormal cell lines.

After further chemotherapy, the AML showed remission, but bone marrow biopsy shows persistent essential thrombocythemia/myeloproliferative neoplasm, with minimal residual AML disease, with similar abnormal cytogenetic findings.

DETAILS

Bone marrow biopsies collected in 2010 and 2012 were formalin fixed and embedded in paraffin.

In 2010, bone marrow biopsy shows hypercellularity, markedly increased megakaryocytes with abnormal morphology, mild reticuline fibrosis and no increase in blasts, morphologically consistent with essential thrombocythemia.

In 2012 before chemotherapy, bone marrow biopsy shows prominent granulocytic hyperplasia with increased blasts 30-40%, consistent with AML.

In 2012 s/p chemotherapy for AML, bone marrow biopsy shows slightly increased immature granulocytes and blasts. The morphological features are more consistent with persistent MPN/ET.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

In 2010, immunohistochemical studies show increased CD61+ megakaryocytes. No increase in CD34+ blasts.

In 2012, flow cytometry study reveals 31% myeloid blasts, consistent with AML.

In 2012 after chemotherapy, flow cytometry evaluation shows 4% myeloid blasts, consistent with minimal residual AML disease.

CYTOGENETIC FINDINGS

In 2010 with essential thrombocythemia, the cytogenetic study was normal.

In 2012 with AML, before and after chemotherapy, cytogenetics show two abnormal cell lines: 46 XY, del(12)(p12p13) [5]/46, XY, del(12)(p12p13),i(17)(q10)[15]

MOLECULAR FINDINGS

JAK2 gene mutation studies were positive in 2010 and 2012.

FISH study in 2010 was negative for BCR/ABL1.

FISH study in 2012 with AML was positive for three copies of RARA gene in 67/200 nuclei consistent with I(17q)

INTERESTING FEATURES

Acute myeloid leukemia arising from the previously diagnosed essential thrombocythemia, with cytogenetic evolution.

After chemotherapy, the bone marrow biopsy shows persistent essential thrombocythemia/MPN, with minimal residual AML.

PROPOSED DIAGNOSIS

1. Acute myeloid leukemia arising from the previously diagnosed essential thrombocythemia.

2. Persistent myeloproliferative neoplasm/essential thrombocythemia, with minimal residual AML.

CONSENSUS DIAGNOSIS

Blast phase of myeloproliferative neoplasm/essential thrombocythemia, JAK2 mutation positive: acute myeloid leukemia (JAK2 mutation positive)