Institution: Wake Forest Baptist Health
Additional authors:Citabria Holley, MD, Mark Pettenati, PHD, David Grier, MD, Michael Beaty, MD
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN
HISTORY
A 76-year-old male presented with shortness of breath. The patient had a history of multiple malignancies including polycythemia vera (Jak2 V617F) with hydrea therapy initiated 4 years ago; stage IV bronchioalveolar adenocarcinoma status-post stereotactic body radiotherapy (45 Gy) 5 years ago; renal cell carcinoma, status-post right nephrectomy 12 years ago and bladder cancer, status-post transurethral resection of bladder tumor 12 years ago. A bone marrow biopsy showed acute myeloid leukemia. He developed tumor lysis syndrome and died 1 week after the diagnosis of leukemia.
DETAILS
The bone marrow core biopsy was B+ fixed, paraffin embedded, and stained with hematoxylin-eosin. Bone marrow aspirate smears were stained with Wright-Giemsa.
Bone marrow and peripheral blood at diagnosis: The bone marrow biopsy showed hypercellular marrow (90-100% cellularity) with increased blasts (28% by manual differential count). Blasts had irregular nuclei with prominent nucleoli and dark, basophilic, vacuolated cytoplasm. Erythroid precursors appeared megaloblastic, occasional nuclear irregularity and maturational dyssynchrony. Myeloid dysplasia was present. Numerous hypersegmented granulocytes were present. The peripheral blood smear revealed leukocytosis with 6% circulating blasts.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Blast immunophenotype by flow cytometry: CD45+/CD33+/CD36+/CD71+/CD4 (dim)/glycophorin A-/CD34-/CD117-/cMPO-/CD38-/HLA-DR-/CD13-/CD15-/CD14-/CD64-/CD11b-/CD56-/CD3-/CD19-.
CYTOGENETIC FINDINGS
GTG-banded metaphases analysis showed an abnormal clonal cell line with a t(9;22)(q34;q11.2) (Philadelphia chromosome positive). Another cell line was hypodiploid in nature missing 9 chromosomes and having a derived chromosome 22 from the 9;22 translocation (see figure).
FISH study showed loss of chromosome 5 and 7. FISH using a DNA probe specific for the CBFB gene region of 16q22 showed a loss of the second copy of the CBFB gene suggesting either a 16q- or loss of chromosome 16. GTG-banded metaphases analysis two years prior showed normal chromosomes and FISH for BCR/ABL was negative.INTERESTING FEATURES
t(9;22)(q34;q11.2) (Philadelphia chromosome) is primarily seen in chronic myelogenous leukemia and B lymphoblastic leukemia. Here we report a case of therapy-related acute myeloid leukemia with t(9;22)(q34;q11.2). Patient developed acute leukemia several years after chemotherapy (hydrea) and radiotherapy. t(9;22)(q34;q11.2) is extremely rare in therapy-related AML and its prognosis and response to chemotherapy are not known. In our case, the patient died one week after the diagnosis due to tumor lysis syndrome.
PROPOSED DIAGNOSIS
Acute myeloid leukemia with t(9;22)(q34;q11.2), favor therapy-related. However, given the history of polycythemia vera, a progression from previous myeloproliferative neoplasm cannot be completely ruled out.
CONSENSUS DIAGNOSIS
Therapy related myeloid neoplasm, acute myeloid leukemia with t(9;22)(q34;q11.2) and complex karyotypic abnormalities, in patient with polycythemia vera