Mast cell differentiation of leukemic blasts in diverse myeloid neoplasms: A potential pre‐myelomastocytic leukemia condition

Abstract

Introduction: Myeloid neoplasm with blasts showing mast cell (MC)-differentiation and MC-component less than 10% of all nucleated cells but not fulfilling the criteria for systemic mastocytosis with associated hematological neoplasm (SM-AHN) or myelomastocytic leukemia (MML) has not been described in the literature. Herein, we report a study of diverse myeloid malignancies with blasts showing MCdifferentiation but not meeting the criteria for SM-AHN or MML. We also evaluated the utility of flow-cytometric immunophenotyping (FCI) in the characterization of immature-MCs (iMCs). Methods:We identified nine patients of myeloid neoplasms and studied their morphological, FCI, immunohistochemistry, cytogenetic and molecular characteristics.We also compared the immunophenotypic features of MCs from patient samples with control samples. Results:The study included patients with newly-diagnosed acute myeloid leukemia (n = 4), chronic myelomonocytic leukemia (n = 1), and chronic myeloid leukemia on follow-up (n = 4) showing MC differentiation in leukemic-blasts. These patients had mildly increased MCs (range, 0.5%-3%) in bone-marrow morphology, including immature-forms and did not meet the criteria for either SM-AHN or MML. On FCI, iMCs were positive for bright-CD117, heterogeneous-CD34, dim-to-negative-HLADR, and moderate-CD203c expression. Expression-levels of CD123 and CD38 were higher (p < 0.001) but CD33 and CD45 were lower in iMCs compared to mature-MC from control samples (p = 0.019 and p = 0.0037). Conclusion:We reported a rare finding of MC differentiation of leukemic blasts in diverse myeloid neoplasms and proposed it as a potential pre-myelomastocytic leukemia condition. We described the distinct immunophenotypic signature of immature-MCs using commonly used markers and highlighted the utility of FCI for the diagnosis of this entity.

Issue Highlights — May 2021

“…This contrasts with more limited data that exists on the potential diagnostic utility of immunophenotyping in MPN, HES, or the altered proliferation profiles in these and other, myeloid neoplasms (Shameli et al, 2020;Ouyang et al, 2015;Herborg et al, 2018;Matarraz et al, 2012;Matarraz et al, 2011). In this issue of Cytometry B six original research papers and a case report have used flow cytometry to study MDS, MDS/MPN, MPN and HES (Shestakova et al, 2021;Davydova et al, 2021;Mestrum et al, 2021;Panda et al, 2021;Vijayasekharan et al, 2021;Hu et al, 2021;Espasa et al, 2021). In the first of these six papers, Shestakova et al (2021) explored the utility of automated leucocyte parameters including cell volume, conductivity and light scatter properties (VCS parameters) as assessed in an automated hematological analyzer, as a read-out for dysplastic MDSassociated features.…”

“…These consisted of increased Ki67 expression at all maturation stages of all three lineageassociated cell compartments in MPN, while a decreased expression of Ki-67 was observed in the earliest maturation stages in MDS, and an increased percentage of Ki-67 + cells restricted to the more mature cell compartments was detected in MDS/MPN cases (Mestrum et al, 2021). In the following manuscript, Panda et al (2021) investigate mast cell differentiation of blast cells in patients with myeloid neoplasias not fulfilling diagnostic criteria for systemic mastocytosis or myelomastocytic leukemia (Swerdlow et al, 2017). Overall, 9 patients showed blasts with a CD117 hi CD34 het HLADR -/lo CD203c + immature mast cell-associated immunophenotype, supporting the potential existence a small percentage of underdiagnosed myelomastocytic leukemia cases; diagnosis of these nine patients corresponded to CML at any phase of the disease (n=4), to newly diagnosed and secondary AML (n=4) and to one chronic myelomonocytic leukemia, whose features are described in detail in the manuscript (Panda et al, 2021) Finally, the sixth manuscript on myeloid neoplasms reports on flow cytometry immunophenotypic findings in seven patients diagnosed with lymphocytic variant of HES, out of a series of 136 patients referred to a single institution for the diagnostic work-up of eosinophilia (Hu et al, 2021).…”

“…In the following manuscript, Panda et al (2021) investigate mast cell differentiation of blast cells in patients with myeloid neoplasias not fulfilling diagnostic criteria for systemic mastocytosis or myelomastocytic leukemia (Swerdlow et al, 2017). Overall, 9 patients showed blasts with a CD117 hi CD34 het HLADR -/lo CD203c + immature mast cell-associated immunophenotype, supporting the potential existence a small percentage of underdiagnosed myelomastocytic leukemia cases; diagnosis of these nine patients corresponded to CML at any phase of the disease (n=4), to newly diagnosed and secondary AML (n=4) and to one chronic myelomonocytic leukemia, whose features are described in detail in the manuscript (Panda et al, 2021) Finally, the sixth manuscript on myeloid neoplasms reports on flow cytometry immunophenotypic findings in seven patients diagnosed with lymphocytic variant of HES, out of a series of 136 patients referred to a single institution for the diagnostic work-up of eosinophilia (Hu et al, 2021). In this report, Hu et al (2021) showed that flow cytometry immunophenotyping was critical (and complementary to molecular analyses) for systematic demonstration of aberrant CD3-CD7-/lo CD4+ CD5+ CD2+ CD8-T-cells associated with T cell clonality, in all seven patients.…”

“…In the following manuscript, Panda et al (2021) investigate mast cell differentiation of blast cells in patients with myeloid neoplasias not fulfilling diagnostic criteria for systemic mastocytosis or myelomastocytic leukemia (Swerdlow et al, 2017). Overall, 9 patients showed blasts with a CD117 hi CD34 het HLADR ‐ /lo CD203c + immature mast cell‐associated immunophenotype, supporting the potential existence a small percentage of underdiagnosed myelomastocytic leukemia cases; diagnosis of these nine patients corresponded to CML at any phase of the disease (n=4), to newly diagnosed and secondary AML (n=4) and to one chronic myelomonocytic leukemia, whose features are described in detail in the manuscript (Panda et al, 2021). In the fifth paper of this series of manuscripts on myeloid neoplasias, Vijayasekharan et al (2021) report on a retrospective analysis of the value of identifying a population of haematopoietic precursor cells with mixed‐lineage phenotype in a series of 12 pediatric patients diagnosed with chronic phase CML.…”

A novel case of primary myelofibrosis with mastocytic differentiation; the characteristic CD117 vs HLA‐DR dot plot on flow cytometry

“…In a prior case series, this feature had been demonstrated in patients of chronic myeloid leukemias (CMLs), chronic myelomonocytic leukemias as well as acute myeloid leukemias. 1 In resemblance with the normal ontogeny, leukemic blasts show a typical immunophenotypic pattern of mast cell maturation on flow cytometry immunophenotyping (FCMI) in such cases that is, gain of CD117 with simultaneous loss of HLA-DR. Herein, we report a novel case of primary myelofibrosis (PMF) showing mastocytic differentiation in myeloid blasts on FCMI.…”