LQCL2608 - CMLE - Microgranular Variant of Acute Promyelocytic Leukemia-LQCL2608

LQCL2608 - Educational Activity

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The document is an ASCP LabQ Hematology 2026 learning module focused on acute promyelocytic leukemia (APL), particularly the microgranular (hypogranular) variant. It outlines goals for recognizing APL morphology, clinical features/complications, immunophenotypic and genetic hallmarks, diagnostic criteria, and treatment/prognosis.<br /><br />A pediatric case is presented: a 12-year-old boy with malaise, petechiae, and fever, with CBC showing leukopenia, anemia, and thrombocytopenia and 35% abnormal cells. Peripheral blood and marrow smears demonstrate many abnormal promyelocytes with bilobed nuclei and largely agranular/hypogranular cytoplasm; occasional Auer rods/granules are present. Flow cytometry shows aberrant myeloid cells strongly MPO-positive with markers including CD13, CD33, CD64, CD117, and partial CD34 and CD2 (an atypical pattern that can delay recognition). FISH and karyotyping confirm PML::RARA rearrangement with t(15;17), and qPCR identifies a short-form PML::RARA transcript; NGS detects CREBBP, KMT2A, and FLT3 mutations. The diagnosis is APL with PML::RARA, microgranular variant.<br /><br />The module explains APL pathogenesis: PML-RARA acts as a transcriptional repressor that blocks myeloid differentiation at the promyelocyte stage. APL commonly involves blood and marrow and is strongly associated with life-threatening coagulopathy/DIC, making rapid presumptive diagnosis essential even before genetic confirmation. Morphologically, classic APL is hypergranular with prominent granules/Auer rods, while microgranular APL may appear hypogranular but often shows bilobed nuclei and at least rare granulated cells.<br /><br />Treatment is ATRA (tretinoin) plus arsenic trioxide (ATO), with added chemotherapy for high-risk patients (risk stratified by WBC and platelets). With modern therapy, cure rates approach ~90%. The case patient achieved MRD-negative remission after induction and consolidation and remained in remission at 1 year.

Keywords

acute promyelocytic leukemia (APL)

microgranular (hypogranular) variant

PML::RARA fusion

t(15;17) translocation

disseminated intravascular coagulation (DIC)

promyelocyte morphology

flow cytometry immunophenotype (CD13 CD33 CD117 MPO)

ATRA (tretinoin) therapy

arsenic trioxide (ATO)

minimal residual disease (MRD) monitoring