Institution: University Health Network, University of Toronto
Additional authors:Anna Porwit, MD
Session: Acute leukemias of ambiguous lineage
HISTORY
This 26-year-old man presented with a 6-week history of intermittent fever, sweats, shoulder pain and shortness of breath on exertion. A CT chest showed a 6 cm anterior mediastinal mass in the thymic position. He also developed left supraclavicular lymphadenopathy, which was sampled by FNA and diagnosed as T-lymphoblastic leukemia/lymphoma by cytology and flow cytometry using a limited antibody panel. As a result, a needle core biopsy of the lymph node and staging bone marrow aspirate/biopsy were performed. After the diagnosis of mixed-phenotype acute leukemia (MPAL) was established the patient received chemotherapy (hyper-CVAD) followed by complete remission and consolidation with FLAG-IDA. Six months following initial diagnosis, he underwent allogeneic bone marrow transplant from an unrelated donor and remains in remission.
DETAILS
- Bone marrow biopsy (right iliac crest, 10% formalin fixed, sections submitted): Hypercellular bone marrow with 35% blasts (large cells with high N/C ratio, prominent nuclear irregularities and nucleoli, no Auer rods). Severe dysmegakaryopoiesis with numerous micromegakaryocytes. Mild dysgranulopoiesis. Some hypogranulated eosinophils present. 11% blasts in peripheral blood.
- Lymph node core biopsy (Left supraclavicular, 10% formalin fixed): Lymph node replaced by cohesive infiltrates of blastic cells.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
- Lymph node FNA flow cytometry: CD45-dim blasts positive for CD34 (bright), CD3 (dim), CD5 (dim), CD7 (variable) and show very dim CD4/CD8 co-expression. Negative for CD2. The findings were thought to be most consistent with T lymphoblastic leukemia/lymphoma.
- Bone marrow flow cytometry: blasts positive for CD34, CD33, HLA-DR, CD7, myeloperoxidase, cytoplasmic CD79a, weakly for cyt.CD3 and cyt.CD22. A fraction of blasts positive for CD5 and CD19. Negative for TdT, CD2, CD4, CD8, membranous CD3, and other myeloid and monocyte markers. - Lymph node biopsy immunohistochemistry: blasts positive for CD34, CD33, CD99, CD5, CD56 (weak), CD7 (weak), myeloperoxidase, CD79a and PAX-5. Negative for cyt.CD3, CD4, CD8, CD2, CD10, CD123, CD117 and TdT.CYTOGENETIC FINDINGS
Results by G-banded karyotype: Abnormal clonal proliferation with a complex near-tetraploid karyotype including an unbalanced 3q rearrangement, 1p deletion, and unbalanced 12p rearrangement.
80~85<4n>,XXY,-Y,add(1)(p36),-2,add(2)(q31)x1~2,-3,add(3)(q12~21)x2,-6,-7,der(7)t(7;8)(p15;q13),-8,-8,-9,-9,add(12)(p11.2)x2,-13,-13,-15,-15,-16,-16,-17,-17,-18,+3~9mar[cp9]/46,XY[16]MOLECULAR FINDINGS
Not performed
INTERESTING FEATURES
This is an unusual case of MPAL with near-tetraploid complex karyotype showing co-expression of B-cell (CD19 [weak], CD79a, PAX-5, cyt.CD22 [weak]), T-cell (cyt.CD3 [weak], CD5, CD7), and myeloid antigens (MPO). Weak expression of CD19 is corroborated by 3 other B-cell associated antigens. Thus B-myeloid phenotype can be established. Weak cyt.CD3 expression does not fulfill the T-cell differentiation criteria but there are also two other T-cell associated markers. The case also illustrates the potential pitfalls in the diagnosis of MPAL, particularly in limited samples, such as with the initial FNA diagnosis of T-cell leukemia/lymphoma
PROPOSED DIAGNOSIS
Mixed-phenotype acute leukemia (MPAL), B-myeloid
CONSENSUS DIAGNOSIS
Mixed phenotype acute leukemia, B/myeloid (with near tetraploidy)