Resident Program - Case of the Month

Discussion

The patient’s peripheral blood smear had circulating blasts and bone marrow biopsy showed a hypercellular marrow with sheets of blasts. The flow cytometry showed that the majority of blasts had T cell differentiation (cytoplasmic CD3, CD7, supported by CD3 IHC). In addition, there was expression of myeloid markers as well (CD13, CD15, CD117).  Occasional auer rods were seen in the aspirate and myeloperoxidase cytochemical stain highlighted a subset of blasts as well as the auer rods. Given these findings, a diagnosis is mixed phenotype acute leukemia specifically T/myeloid lineage is favored.

World Health Organization 2017 defines mixed phenotype acute leukemia (MPAL) as leukemias that consists of distinct blast populations with more than one lineage (bilineage) or one population of blasts with multiple antigens of different lineages on the same cells (biphenotypic). MPAL can be further classified into B/myeloid or T/ myeloid or a combination where the two lineages are specified. This diagnosis relies mainly on the immunophenotype.

In order to assign more than one lineage to a single blast population, certain requirements for lineage specific markers needs to be expressed. For myeloid lineage, there needs to be expression of MPO (by flow cytometry, IHC, or cytochemistry) or monocytic differentiation where there is 2 or more of the following markers: non-specific esterase, CD11c, CD14, CD64, and lysozyme. In order to demonstrate T cell lineage, cytoplasmic CD3 (by flow cytometry, IHC, or cytochemistry) or surface CD3 needs to be expressed.

MPAL (T/myeloid) accounts for less than 1% of all leukemias overall and can be seen in both in children and adults. Although the data on this specific type of MPAL is limited when comparing with other types of MPAL, T/Myeloid MPAL has a poor prognosis when compared with the more typical AML or ALL case. Previously, various combinations of myeloid and lymphoid directed treatments have been tried with variable response. At this time, the role of immunophenotypic and genetic markers in choosing the appropriate chemotherapy and post-remission regimen is unknown. However, Wolach et al study suggests that once MPAL is identified, patients should be treated with acute lymphoid leukemia like regimen.  

References:

1. Borowitz MJ et al: Acute leukaemias of ambiguous lineage. In Swerdlow SH et al: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC. 180-187, 2017
2. Wolach O et al: How I treat mixed-phenotype acute leukemia. Blood. 125(16):2477-85, 2015
3. Porwit A et al: Acute leukemias of ambiguous origin. Am J Clin Pathol. 144(3):361-76, 2015