An Unusual Extramedullary Presentation of an NPM1-Mutated Acute Myeloid Leukemia (AML) in a Young Adult

Abstract Introduction/Objective Pleural effusion presentation of AML, particularly without leukemic disease, has been rarely described in the literature. This case serves to investigate the value of an identified NPM1 mutation. Methods/Case Report A 25-year-old male with Down syndrome presented with dyspnea. Computerized tomography scan identified a moderate pleural effusion and pelvic lytic bone lesions. A complete blood count was normal. Pleural fluid cytologic evaluation showed a spectrum of immature myeloid precursors, and flow cytometry identified a 23% CD117 positive myeloblast population expressing CD33, CD13, and dim CD45 but lacking CD34 and HLA-DR. Fluorescence in-situ hybridization testing was negative for a PML-RARA fusion. Given the phenotype, molecular testing was initiated and confirmed an NPM1 mutation. Testing revealed additional pathogenic variants in DNMT3A and IDH1 with no FLT3 mutations. Peripheral blood smear and bone marrow evaluations yielded no clear leukemic involvement, and cytogenetics from bone marrow showed 47,XY,+21c[20]. The significance of this myeloid infiltrate was initially not entirely clear with no established leukemic involvement or tumor-forming mass as required for the World Health Organization diagnosis of myeloid sarcoma. However, the finding of the NPM1 mutation lent high confidence for a diagnosis of an extramedullary presentation of acute myeloid leukemia, though the lytic bone lesions were not biopsied to possibly demonstrate a myeloid sarcoma. Results (if a Case Study enter NA) N/A. Conclusion The identified NPM1 mutation was instrumental in diagnosing an unusual presentation of AML where material was limited. Subsequent to this presentation the patient developed more overt leukemic disease at an outside institution, additionally supporting this diagnosis.