Initially Suspected Acute Promyelocytic Leukemia: A Case-Based Narrative Review of Diagnostic Mimics and Diagnostic Revision

Abstract

Abstract

Acute promyelocytic leukemia (APL) is a hematologic emergency in which all-trans retinoic acid (ATRA) should be initiated as soon as the disease is suspected; however, neoplastic and non-neoplastic conditions can closely mimic APL. This case-based narrative review examines findings that prompted suspicion of APL and those that led to diagnostic revision. A broadened literature search and patient-level extraction yielded 41 selected patients from 34 primary reports. Larger overlapping molecular cohorts and mechanistic studies were used for qualitative interpretation without adding their patients to the quantitative denominator. Median age was 48 years (range, 1.25–77), and 20 patients (48.8%) were female. Morphologic findings and an APL-like immunophenotype contributed to suspicion in 39/41 (95.1%) and 30/41 (73.2%), respectively; coagulation abnormalities contributed in 17/41 (41.5%). Negative PML::RARA or RARA-related testing contributed to diagnostic revision in 40/41 (97.6%), and identification of an alternative fusion or mutation contributed in 35/41 (85.4%). RARG rearrangements were identified in 14/41 patients (34.1%). All frequencies are descriptive and depend on reporting and variable-specific assessability. An APL-like phenotype is not equivalent to molecularly defined APL: rapid PML::RARA testing should accompany immediate empiric ATRA, and negative or equivocal results should prompt review of assay coverage and, when appropriate, orthogonal and broader molecular testing.