A newborn with congenital mixed phenotype acute leukemia with complex translocation t(10;11)(p12;q23) with KMT2A/MLLT10 rearranged – a report of an extremely rare case

Abstract

neonatal congenital leukemia (Cl) constitutes less than 1% of all childhood leukemia cases and is diagnosed in 1 to 5 per million live births. in the neonatal period acute myeloid leukemia (aMl) is described in 56-64% of cases, acute lymphoblastic leukemia (all) in 21-38% of cases and mixed-phenotype acute leukemia (Mpal) in less than 5% of cases. rearrangements of the mixed-lineage leukemia (kMt2a alias Mll) gene are found in > 70% of infant leukemia cases. the incidence of the most frequent kMt2a rearrangements in newborns with congenital Mpal is unknown. we report a male term newborn with "blueberry muffin" syndrome, which had been noted at birth, as a presenting sign of acute leukemia. eight-color multiparameter flow cytometry showed a blast population corresponding to a myeloid lineage with monocytic differentiation positive for CD33+/CD15+/CD11c+/CD64+/ hLa-dr+/cd4+, negative for mPo-/cd34-/cd19-/cd79a-/cd117-/cd13-/cd14-/cd36-/ccd3-/ cd2-/cd7-, and additionally positive for scd3 (40%). mixed-phenotype acute leukemia according to the world health organization (who) classification was diagnosed with complex translocation t(10;11)(p12;q23) with kMt2a/Mllt10 rearrangement. the patient had an unfavorable response to chemotherapy and died on the 5 th day of life.

An alternative approach to confirm mixed lineage involvement in acute leukemia with KMT2A rearrangement–an illustrative report

“…Currently, its diagnosis requires the demonstration of either bright CD19 and one or more B lineage antigens to define the B lineage, that is, CD10, cytoplasmicCD22, CD22, CD79a, or dim CD19, and at least two of the other B antigens along with more than one monocyte-associated antigen (CD11c, CD14, CD36, CD64, or lysozyme), or a diffuse positivity for non-specific esterase/NSE in cytochemistry analysis [2,3]. The patterns of immunophenotype in monocytes in the literature include CD11c, CD14, CD33, the immaturity marker CD34, and B lymphoid-associated markers, namely CD19 and cytoplasmic CD79a [5][6][7].…”

“…Diagnosis is not difficult if monocytes co-express B-lineage or immature markers. The presence of abnormal maturation patterns also helps confirm that they are part of the leukemic process [5]. However, a dilemma arises when the percentage of monocytes is low or immunophenotypically normal, or when limited flow cytometry panels do not allow for detailed immunophenotypic characterization of monocytes.…”