330 Myelodysplastic Neoplasm with Multi-hit TP53 Mutation in a Young Adult: A Case Report

Introduction/Objective Updates in hematologic malignancy classifications have introduced distinct categories for TP53-mutated myeloid neoplasms, reflecting their aggressive behavior and poor prognosis. In myelodysplastic neoplasms (MDS), biallelic (type of multi-hit) TP53 mutations define a high-risk category, while monoallelic mutations have relatively better outcomes and are excluded. We present an uncommon clinical scenario of MDS with biallelic TP53 inactivation (WHO)/MDS with mutated TP53 (ICC) in a young adult patient. Methods/Case Report A 34-year-old male presented with hemoptysis, hematochezia, dyspnea, severe fatigue and transfusion-dependent pancytopenia. Bone marrow biopsy showed hypercellularity (95–100%), trilineage dysplasia, erythroid predominance, 3% myeloid blasts with aberrant CD7, 15% proerythroblasts, 5–10% ring sideroblasts, complex karyotype including del(5q), del(7) and trisomy 8, and two pathogenic biallelic TP53 mutations, p.Cys176X (47.0%) and p.Arg175His (50.0%) by next-generation sequencing, confirming the diagnosis. The patient received azacytidine+venetoclax and transfusion support, however, succumbed to septic shock secondary to profound neutropenia while awaiting allogeneic hematopoietic stem-cell transplantation Results NA Conclusion MDS is rare (<10%) in individuals under 50 years. Multi-hit TP53 mutations in younger patients may suggest germline predispositions, such as Li-Fraumeni syndrome, warranting genetic counseling/family screenings. This case underscores the importance of integrated multi-modality laboratory workups for diagnostic accuracy, while also contributing data to evolving classification schemes.