Institution: Dartmouth-Hitchcock Medical Center
Additional authors:David Ng
Session: Acute leukemias of ambiguous lineage
HISTORY
A 17 year old female presented with leukocytosis, anemia and thrombocytopenia (193 x 10^9/L, 43 g/Land 20 x 10^9/L respectively).
DETAILS
Her peripheral smear showed 99% blasts with fine nuclear chromatin and inconspicuous nucleoli. A subset displayed 'hand mirror' morphology (L1 subtype by FAB classification).
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometric analysis revealed that greater than 90% of the blasts expressed cytoplasmic CD3 (supportive of a T cell lineage), TdT, and CD34 as well as surface co-expression of myeloid associated antigens CD13 and CD117. About 10% of the blast gated cells, also co-expressed cytoplasmic myeloperoxidase (cMPO), and cytochemical stains revealed MPO activity in 10% of blasts (Figure 1).
CYTOGENETIC FINDINGS
Cytogenetic analysis revealed a normal female karyotype.
INTERESTING FEATURES
The findings of cytoplasmic CD3 by flow analysis and cytoplasmic MPO by flow and cytochemical stain, fulfilled the requirements for a Mixed Phenotype Acute Leukemia (MPAL), T/myeloid type, as per The WHO 2008 monogram [1]. Cytogenetic analysis revealed a normal female karyotype. While the WHO 2008 is unclear as to cut-off values for MPO positivity by either flow cytometry or cytochemistry, the previously published EGIL criteria utilized a 10% cut off for cytoplasmic anti-MPO, CD3 and CD79a and a 20% cut off for other antibodies [2]. A more recent study of MPAL cases utilized MPO positivity in over 5% of blasts, with immunocytochemical or cytochemical confirmation, as a cutoff for evidence of myeloid differentiation in MPAL [3].]. This further emphasizes the need to continue cytochemical staining in all cases of acute leukemia, a progressively dying art in some laboratories. At this low level of MPO positivity, cytochemical interpretation based on visualization of stain within the blasts can be more specific than that seen in flow analysis where the small signal maybe interpreted as signal from more maturing granulocytes within the blast gate. The WHO criteria for MPAL are stricter than EGIL and require MPO as a specific marker for myeloid lineage differentiation. The WHO considers CD13 and CD117 as myeloid associated antigens but not specific enough to identify MPALs [1, 2].
References1 Borowitz M, Bene MC, Harris NL, et al. Acute leukemia of ambiguous lineage. In: World health organization Classification of tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, France: IARC Pres; 2008:150-1552 Bene MC, Castoldi G, Knapp W, et al. Proposals for immunological classification of acute leukemias. Leukemia 1995; 9:1783-1786.3 Matutes E, Pickl WF, Veer MV, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011; 117:3163-3171.PROPOSED DIAGNOSIS
Mixed Phenotype Acute Leukemia (MPAL), T/myeloid type, as per the WHO 2008 monogram [1].
CONSENSUS DIAGNOSIS
Mixed phenotype acute leukemia, T/myeloid