Incidental Diagnosis of Occult Maternal Malignancy With Routine Noninvasive Prenatal Testing During Pregnancy

The noninvasive prenatal test (NIPT) for genetic screening has been adopted globally as an alternative to first-trimester and quad screening due to its high sensitivity and specificity. NIPT involves detecting and processing foreign fetal DNA in maternal circulation to screen for fetal aneuploidy. An incidental consequence of this process is the detection of foreign tumor cell DNA in maternal circulation in otherwise asymptomatic patients. Here, we present two such cases of maternal cancer that were initially suspected with routine NIPT during pregnancy. The first patient had an "atypical finding" on NIPT at 13 weeks, five days gestation. Diagnostic prenatal genetic testing with amniocentesis at 16 weeks gestation showed a normal fetal karyotype. Between 25 and 28 weeks gestation, she developed nonspecific symptoms and was ultimately diagnosed with stage IIIB intrahepatic cholangiocarcinoma. The second patient had a "non-reportable" NIPT at 11 weeks due to insufficient fetal DNA fraction. At 16 weeks gestation, NIPT was repeated and showed an "atypical finding of maternal origin". The patient was enrolled in the National Institute of Health Incidental Detection of Maternal Neoplasia Through Non-Invasive Cell-Free DNA Analysis (NIH IDENTIFY) study. She had a whole-body magnetic resonance imaging (MRI) that identified an adrenal mass. She was diagnosed with stage III high-grade adrenocortical adenocarcinoma. NIPT is not validated for cancer screening or diagnosis. Although the overall incidence of cancer diagnosed with NIPT in otherwise asymptomatic patients is extremely low, this finding presents unique ethical challenges. A multidisciplinary approach is recommended.