Incidental Detection of Diffuse Large B-cell Lymphoma by Non-invasive Prenatal Testing: A Case Report

Non-invasive prenatal testing (NIPT) is widely used for prenatal screening of common fetal aneuploidies through analysis of cell-free DNA (cfDNA) in the maternal plasma. Because cfDNA originates from both placental and maternal sources, genome-wide NIPT may incidentally reveal acquired chromosomal abnormalities associated with maternal malignancies. We report the case of an asymptomatic pregnant woman whose first-trimester NIPT revealed multiple complex chromosomal imbalances incompatible with a fetal origin and suggestive of circulating tumor-derived cfDNA. Extensive biological and radiological investigations performed during pregnancy and early postpartum follow-up were initially non-contributive. After structured multidisciplinary monitoring, radiological progression of a vertebral lesion led to the diagnosis of an isolated diffuse large B-cell lymphoma of the spine, nearly one year after the initial NIPT. Chromosomal abnormalities detected by NIPT persisted postpartum and closely matched copy number alterations identified by molecular karyotyping of the tumor biopsy. This case suggests that NIPT may detect tumor-derived cfDNA at a very early stage, potentially preceding clinically detectable disease by several months in selected cases. However, such findings should be interpreted with caution, as alternative explanations cannot be excluded. Taken together, these observations highlight both the potential and the current limitations of cfDNA-based approaches and underscore the importance of structured longitudinal follow-up with multidisciplinary evaluation when NIPT results are highly suggestive of maternal malignancy.