Abstract
Introduction
Acute myeloid leukemia (AML) may initially present with vague, nonspecific symptoms that can be attributed to chronic illness, medication effects, or common outpatient conditions. Recognizing constitutional symptoms and promptly reviewing basic labs are critical to prevent delays in diagnosis and treatment.
Case Info
A 74-year-old man with type 2 diabetes mellitus, hereditary hemochromatosis (C282Y/H63D compound heterozygosity), and obstructive sleep apnea presented with several weeks of fatigue, polyuria, subjective postural hypotension, abdominal discomfort, and some tachypnea. One month prior, he was active, exercising regularly, and reported feeling well. Previous blood counts were overall unremarkable. Initially, his symptoms were ascribed to the recent addition of empagliflozin or possible infection, as he recently recovered from an ear infection.
Urinalysis was negative, no other medication changes were noted, and the physical exam was unremarkable. Subsequent testing demonstrated a white blood cell count of 11.3×10⁹/L, hemoglobin of 14.3 g/dL, platelets of 22×10⁹/L, and 31% circulating blasts on differential. Peripheral smear showed marked thrombocytopenia and large irregular blasts, prompting emergency department referral and hospitalization with expedited oncological workup. Repeat testing showed 23–37% peripheral blasts with progressive thrombocytopenia. Flow cytometry identified 39% myeloblasts with a CD34-negative, dim CD117-positive, HLA-DR-negative, cytoplasmic myeloperoxidase-positive phenotype concerning for acute promyelocytic leukemia. However, PML:RARA [t(15;17)] fluorescence in situ hybridization (FISH) was negative.
Bone marrow biopsy demonstrated 98% hypercellular marrow with 86% blasts/monoblasts and myeloid maturation arrest. Molecular testing identified FLT3 internal tandem duplication with high allelic ratio (0.82), two additional FLT3 insertions, NPM1 mutation, and IDH2 R140Q mutation; karyotype and AML/MDS FISH panels were normal. His diagnosis was AML with FLT3, NPM1, and IDH2 mutations and promyelocytic features. He began azacitidine and venetoclax, with gilteritinib added for FLT3-mutated AML. A day-21 marrow showed no morphologic, immunophenotypic, or flow-cytometric evidence of residual AML, although low-level FLT3-ITD molecular residual disease persisted. Subsequent marrow assessments remained morphologically negative for AML.
Disc Clinical
This case highlights the insidious onset and rapid progression of AML. Weeks before his clinic visit, he went to urgent care twice and an otolaryngologist with each visit noting apyrexia, negative constitutional symptoms, and localized otitis media treatment. In the clinic, the presenting symptoms were non-specific and confounded by recent illness and comorbidities. High clinical suspicion for underlying malignancy is paramount, especially in the elderly population. Fortunately, rapid workup and treatment by oncology led to a favorable response, with his most recent marrow biopsy without evidence of residual/recurrent AML.
Conclusion
AML is a rare, yet increasingly treatable hematologic malignancy emerging rapidly despite previously normal labs and apparent clinical stability. As such, the differential diagnosis for new or progressive constitutional symptoms must include malignancy, especially in the elderly population, as these may be the only presenting symptoms. A simple, inexpensive test such as a complete blood count with differential must be performed, as it can identify life-threatening hematologic disease and facilitate early intervention.