Mixed phenotype acute leukemia (MPAL) is rare and clinically aggressive, particularly when accompanied by TP53 deletion and complex karyotype. Nodal presentations can mimic lymphoma, delaying definitive therapy. We report a young woman with MPAL (B/Myeloid) and extensive nodal involvement who achieved complete remission (CR) with HyperCVAD plus azacitidine.

Single-patient case review of prospectively collected data. Diagnostic work-up included complete blood counts, bone marrow (BM) aspirate/biopsy with immunohistochemistry (IHC), multiparameter flow cytometry, cytogenetics/FISH, PCR panel for recurrent fusions, and FDG PET-CT. Treatment consisted of HyperCVAD combined with azacitidine. Response was assessed morphologically, by PET-CT, and by minimal residual disease (MRD) testing.

A 37-year-old woman presented with fatigue, bilateral cervical and axillary lymphadenopathy, and pancytopenia. BM was normo–to-hypersellular (cellularity ∼50–65%) with blast proliferation; reticulin 0–1/4. IHC showed CD34+, CD117+, CD33+, heterogeneous CD3 and rare TdT; PAX5 was positive in marrow sections, while CD20, MPO, and CD13 were negative. Excisional axillary-node pathology revealed blast infiltration (CD34+, CD117+, CD33+, CD3+, CD5+, CD10+, BCL2+, Ki-67 ∼30%; PAX5 and MPO negative), supporting leukemic involvement. Flow cytometry identified a 53% blast population expressing CD33, HLA-DR, and aberrant CD7, negative for CD19, CD10, surface CD3, and MPO—consistent with MPAL (B/Myeloid) in the aggregate clinicopathologic context.Cytogenetics demonstrated complex hyperdiploidy (85–92 chromosomes) with trisomy 8 and tetrasomy 10; FISH detected TP53 (17p) deletion. TEL/AML1, PML/RARA, BCR/ABL, AML/ETO were negative by FISH; PCR for BCR-ABL, PML-RARA, and FLT3 was negative. Baseline PET-CT showed widespread FDG-avid nodal disease (cervical, axillary, mediastinal, abdominal, retroperitoneal; SUVmax ∼4–10) without visceral uptake.

First-line HyperCVAD plus azacitidine was administered with standard supportive care. End-of-treatment evaluation demonstrated morphologic CR, MRD negativity, and metabolic complete response by PET-CT. The patient remained in remission on early surveillance.

This case highlights three practice points. (1) Nodal MPAL can masquerade as lymphoma; integrated BM, node histology, flow, and molecular profiling are essential to prevent misclassification and treatment delay. (2) TP53 deletion with complex karyotype portends high risk; nonetheless, HyperCVAD plus azacitidine achieved deep response, suggesting potential synergy of epigenetic priming with intensive chemotherapy in adverse-genetic MPAL. (3) Discordant lineage signals (e.g., PAX5 IHC positivity with B-lineage markers absent on flow, and MPO negativity despite myeloid antigen expression) illustrate real-world diagnostic ambiguity in MPAL and the need to rely on the totality of evidence rather than any single assay.

In TP53-deleted, complex-karyotype MPAL with extensive nodal disease, HyperCVAD plus azacitidine induced MRD-negative CR with metabolic clearance. This experience supports considering epigenetic-augmented intensive regimens in high-risk MPAL and underscores the diagnostic value of coordinated marrow–node evaluation.