Incidental finding of maternal malignancy in an unusual non-invasive prenatal test and a review of similar cases

Abstract

We present a clinical case where a complex abnormal non-invasive prenatal test (NIPT) result in a research project revealed carcinoma of the breast in the pregnant woman. Furthermore, the NIPT result did not demonstrate the same fetal chromosomal aberration as the chorion villus sample. A literature search for similar cases was performed identifying 43 unique cases, where abnormal NIPT results were related to maternal malignancy. Malignancy is a rare but important cause of complex abnormal non-invasive prenatal test (NIPT) results and should be considered when fetal karyotype and abnormal NIPT results are discordant. Furthermore, a follow-up invasive sample is essential for correct fetal diagnosis when abnormal NIPT results are found.

Keywords: NIPT; cell‐free DNA; fetal diagnostics; genetics; malignancy; prenatal diagnostics.

FIGURE 1

(A) UNCULTURED CVS. Array‐CGH revealed a 5.6 Mb terminal deletion on chromosome 21q (arr[GRCh37] 21q22.2q22.3(42538181‐48090317)x1). (BI) CULTURED CVS. Array‐CGH revealed a 27 Mb duplication and the terminal deletion of 5.6 Mb of chromosome 21q (arr[GRCh37] 21q11.2q22.2(15390816‐42482129)x3,21q22.2q22.3(42518800‐48090317)x1). (BII) Multicolor mBAND21 confirmed the suspicion of duplication of chromosome 21 (q11.2q22.2) and terminal deletion of chromosome 21 (q22.2q22.3) in cultured CVS. Karyotyping, not shown, revealed one normal chromosome 21 and one iso‐chromosome 21 in all metaphases analyzed.

FIGURE 2

The whole genome Wisecondor results showing multiple events called by the sliding window method. The cfDNA profile shows the following aberrations: interstitial gain in 1q, terminal gain in 1q, gain in 3q, monosomy 5, loss in 8p and gain in 8q,gain in 12p and loss in 12q, gain in 13q, monosomy 14, and possible gain in 19p and 19q. Chromosome 21 was not called by window method, but it has an unusual pattern with a subtle interstitial gain and possible terminal loss. This was noticed likely only thanks to a priori knowledge of the CVS results.