NPM1-Mutated Acute Myeloid Leukemia with Uterine Myeloid Sarcoma: A Diagnostic Challenge

Introduction: Acute myeloid leukemia( AML) NPM1+ represents a distinct entity, frequently associated with normal cytogenetics and favorable prognosis in the absence of other adverse mutations. In certain cases though the clinical and paraclinical presentation can appear as other forms of AML, especially APL variants, that imposes the initiation of treatment in an emergency setting due to the vital risk associated with severe coagulopathy. Methods: This paper reports the case of a 56 years old patient, that came to the emergency department with a severe hemorrhagic syndrome, severe leukocytosis and severe bicytopenia with signs of disseminated intravascular coagulation (DIC) highly suggestive of APL. The peripheral blood smear outlined blasts with specific morphology – cup like cells-suggestive for AML NPM1+. Immunophenotyping exam confirmed the myeloid lineage SSC medium/high cMPO+, CD34 -, HLA-DR-, CD117+, CD33+ , CD64+ CD15+/-, CD9-, CD56- and molecular testing identified NPM1 mutation, PML-RARA negative. Imaging exams showed the presence of a tumor localized in the uterus, the biopsy confirming extramedullary involvement – myeloid sarcoma- with the same phenotyping profile. Additionally at the diagnosis the patient had multiple infectious complications (flu type A, and E.coli faringoamigdalitis). Results: It is well-established that the morphological and immunophenotypic distinctions between APL and NPM1-mutated AML are exceedingly subtle. When clinical presentation also suggests APL, as observed in our case, establishing a timely diagnosis before cytogenetic and molecular test results become available can be challenging. The presence of disseminated intravascular coagulation (DIC) at presentation added complexity to the diagnostic process. Coagulopathy is a characteristic feature of acute promyelocytic leukemia (APL), frequently necessitating prompt initiation of all-trans retinoic acid therapy. Nonetheless, severe infections and sepsis are also well-established causes of DIC. In this case, the concurrent infectious pathology and APL-like morphological features resulted in significant diagnostic uncertainty. Although application of the ISTH DIC scoring system confirmed overt DIC, it was insufficient to distinguish between leukemia-associated and infection-induced mechanisms. Nevertheless, additional features can aid in the differential diagnosis. The white blood cell (WBC) count was markedly elevated, a finding that is atypical for acute promyelocytic leukaemia (APL). Importantly, increased median WBC counts and high percentages of bone marrow blasts have most frequently been reported in cases of acute myeloid leukaemia (AML) harbouring NPM1 mutations. Conclusion: This atypical clinical presentation AML NPM1 positive with APL like coagulopathy and myeloid sarcoma outlines the challenges in differential diagnosis for acute leukemias accompanied at diagnosis with coagulopathies, and the importance of integrating morphology, immunophenotype and molecular data for avoiding therapeutical errors in a context of hematological emergency.