Myelodysplastic Neoplasm with Biallelic TP53 Mutations Presenting with Myelofibrosis and CD42b Expression: A Case Report.

Introduction: Myelodysplastic neoplasms (MDS) with biallelic TP53 mutations (MDS-biTP53) represent a rare and aggressive MDS subtype associated with a poor prognosis. The 5th edition of the WHO classification defines MDS-biTP53 as a high-risk entity with rapid progression to acute myeloid leukemia (AML).

Case presentation: A 69-year-old male presented with fatigue, pancytopenia, splenomegaly, fever, and elevated lactate dehydrogenase. Initial bone marrow smear revealed 10.5% plasma cell-like abnormal cells, leading to a suspected diagnosis of multiple myeloma. However, further bone marrow biopsy, immunophenotype, and next-generation sequencing confirmed the diagnosis of MDS-biTP53 with myelofibrosis and megakaryocytic differentiation, as evidenced by strong CD42b expression. Despite treatment with azacitidine, lenalidomide, and erythropoietin, the patient rapidly progressed to AML.

Conclusion: This case highlights the diagnostic challenges in differentiating MDS-biTP53 with CD42b-positive blasts from plasmablastic neoplasms. The presence of myelofibrosis and CD42b expression raises important questions regarding the biological role of megakaryocytic differentiation in MDS progression and potential implications for disease transformation.