Beyond the peripheral count: multiorgan leukemic infiltration in the absence of hyperleukocytosis, an autopsy case report

• AML with monocytic differentiation shows extramedullary infiltration and poor outcome. • Pulmonary leukemic infiltration can mimic atypical pneumonia and delay diagnosis. • No response to antimicrobial therapy should raise suspicion for hematological disorder. • Autopsy helps achieve diagnostic clarity when antemortem diagnosis is unclear. Acute myeloid leukemia (AML) is a hematological malignancy of predominantly older adults but also occurs in younger patients who have a better prognosis. Despite favorable cytogenetics and higher treatment tolerance, early mortality can still occur especially in cases where the underlying malignancy masquerades as benign conditions, such as infection. We report the case of a 28-year-old previously healthy woman who presented with progressive dyspnea and non-productive cough. Imaging revealed ground-glass opacities and interlobular septal thickening, initially attributed to atypical pneumonia. Despite broad-spectrum antibiotics, her condition deteriorated rapidly, culminating in death shortly after the initiation of chemotherapy. Laboratory investigations revealed leukocytosis, anemia, thrombocytopenia, and circulating blasts. Bone marrow biopsy demonstrated 90% cellularity with diffuse infiltration by myeloid blasts. Flow cytometry revealed an aberrant immature monocytic immunophenotype: CD4, CD9, CD11b (partial), CD11c, CD15, CD33, CD38, CD45, CD56, CD58, CD64, CD117 (partial) were positive; whereas MPO, CD7, CD13, CD14 (essentially negative), CD34, HLA-DR, and other B or T lineage-specific markers were negative. Next-generation sequencing identified KMT2A::MLLT3 fusion with KRAS G13D, KRAS G12V, and NRAS G12D mutations, without FLT3 , NPM1 , IDH1/2 , or TP53 alterations. Autopsy revealed diffuse leukemic infiltration of the lungs, heart, liver, spleen, kidneys, and thyroid in the absence of hyperleukocytosis. This case illustrates the potential for early, widespread extramedullary disease in young AML patients and highlights the diagnostic challenge posed by pulmonary leukemic infiltration mimicking infection. It underscores the importance of considering hematological malignancy in unexplained systemic illness and the value of autopsy in uncovering a clinically silent disease.