Background: Acute myeloid leukemia (AML) exhibiting mature plasmacytoid dendritic cell (PDC)-like immunophenotype or plasmacytoid dendritic cell differentiation or proliferation is rare and underrecognized. This phenotype can mimic blastic plasmacytoid dendritic cell neoplasm (BPDCN), particularly when associated with aberrant expression of markers such as CD303, CD123, CD43, and CD68. While case reports exist, comprehensive descriptions of this phenotype in genetically heterogeneous AML subtypes remain limited.

Aims: To describe the clinical, cytogenetic, molecular, immunophenotypic, and treatment characteristics of AML cases exhibiting plasmacytoid dendritic cell differentiation identified at the National Center for Cancer Care and Research (NCCCR) in Qatar.

Methods: We conducted a retrospective case series analysis of adult patients diagnosed with AML between 2014 and 2024 at National Center for Cancer Care and Research (NCCCR) in Qatar who demonstrated PDC-like or mature plasmacytoid dendritic cell proliferation Data collected included demographics, ELN risk stratification, cytogenetics, molecular mutations, treatment regimens, and outcomes. Flow cytometry and immunohistochemistry panels were reviewed for expression of PDC-associated markers.

Results: Six adult patients with acute myeloid leukemia (AML) exhibiting plasmacytoid dendritic cell (PDC) differentiationwere identified. The median age at diagnosis was 52.5 years (range 22–81), and the majority were male (5 out of 6).All patients displayed immunophenotypic evidence of PDC-associated differentiation. CD123, CD43, and CD68 were universally expressed. CD56 was detected in three cases, and CD303 performedand positive in one patient, initially raising concern for blastic plasmacytoid dendritic cell neoplasm (BPDCN). However, integration of morphology, clinical context, and broader flow cytometric findings supported a diagnosis of AML with PDC differentiation in all cases. Myeloid blasts uniformly expressed CD34, CD117, CD13, and CD33, with aberrant expression of markers such as CD7and CD15 in selected patients. A monocytic component was prominent in half of the cohort, supported by expression of CD14, CD64, and CD11b.Cytogenetic profiles were heterogeneous. Two patients had favorable-risk AML characterized by inv(16)/t(16;16). Three others demonstrated high-risk karyotypes, including monosomy 7, inv(3), del(6q), and trisomy 21, either alone or in complex combinations. One patient had intermediate-risk features. Molecular testing revealed recurrent mutations in FLT3-TKD, KRAS, NRAS, and c-KIT; no patient was FLT3-ITD or NPM1 positive. One patient with relapsed secondary AML following a prior diagnosis of acute promyelocytic leukemia (APL) did not have available molecular data at relapse.

All patients received intensive induction therapy, including3+7, FLAG-IDA, or venetoclax-based regimens, and three underwent haploidentical allogeneic stem cell transplantation in first complete remission. Despite initial responses, three patients experienced relapse. Two patients died during follow-up—one from septic shock and the other from disease progression. Of the remaining four, two are in remission (one post-transplant), and two are alive with relapsed or persistent disease. One of these patients developed chronic lung graft-versus-host disease and remains on therapy withruxolitinib and belumosudil. Conclusion: AML with plasmacytoid or plasmacytic differentiation is a rare but clinically relevant subset that spans diverse genetic and molecular backgrounds and may behave more aggressively than suggested by standard ELN risk classifications. Some patients with favorable-risk cytogenetics experienced poor outcomes, highlighting the limitations of current risk models in this group. Accurate recognition requires the use of extended immunophenotyping panels including markers such as CD123, CD303, CD43, and CD68 to distinguish this phenotype from entities like BPDCN. Greater awareness and refined diagnostic approaches are essential to improve risk stratification and inform tailored therapeutic strategies.

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2025
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