Masked Acute Promyelocytic Leukemia with Monosomy 17 and Marker Chromosome: Importance of Multimodal Molecular Diagnosis

Background: Acute promyelocytic leukemia (APL) is typically characterized by t(15;17)(q24;q21)/PML::RARA and is highly responsive to all-trans retinoic acid (ATRA) and arsenic trioxide. Cryptic PML::RARA rearrangements and additional cytogenetic abnormalities may obscure diagnosis by conventional karyotyping, potentially delaying life-saving therapy.

Case Presentation: A 58-year-old woman with hepatitis C virus-related chronic liver disease presented with persistent pancytopenia. Bone marrow examination demonstrated abnormal promyelocytes with folded nuclei and granular cytoplasm, positive Sudan Black B staining and strong myeloperoxidase expression, raising suspicion for APL. Conventional cytogenetic analysis revealed 46,XX,-17,+mar[20], without an apparent t(15;17). Hypofibrinogenemia (121 mg/dL) further supported the clinical suspicion of APL. Given the discordance between morphology and cytogenetics, fluorescence in situ hybridization (FISH) was performed and confirmed PML::RARA fusion, establishing APL with a cryptic rearrangement. FISH also demonstrated TP53/17p13.1 deletion. As FISH detects chromosomal deletion rather than sequence-level mutations, the specific TP53 nucleotide/amino acid variant and variant allele frequency (VAF) could not be determined.

Discussion: This case highlights the diagnostic challenge of cryptic PML::RARA rearrangement in the presence of monosomy 17 and a marker chromosome. Complementary molecular techniques are essential when morphology and conventional cytogenetics are discordant. The TP53/17p13.1 deletion and additional cytogenetic abnormalities may reflect genomic instability and potentially adverse prognostic biology. Reliable longitudinal clinical outcome data were unavailable because the specimen was received through our outreach service and the absence of a centralized national health information system limits patient follow-up across healthcare facilities.

Conclusion: A multimodal approach integrating morphology, cytogenetics, FISH, and molecular testing is essential for timely diagnosis of cryptic APL and appropriate therapeutic intervention.