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BackgroundThe American College of Obstetrics and Gynecology (ACOG) and Maternal Fetal Medicine (MFM) Societies recommended that abnormal cfDNA fetal results should be confirmed by amniocentesis and karyotyping. Our results demonstrate that normal cfDNA results inconsistent with high-resolution abnormal ultrasounds should be confirmed by karyotyping following a substantial frequency of incorrect cfDNA results.MethodsHistorical review of our ~4,000 signed prenatal karyotypes found ~24% of reported abnormalities would not have been detected by cfDNA. Akron Children’s Hospital Cytogenetics Laboratory has completed 28 abnormal cfDNA cases among the 112 amniocenteses karyotyped.ResultsFollowing abnormal cfDNA results our karyotypes confirmed only 60% of the cfDNA results were consistent. Our cases found a normal cfDNA test result followed by a 20 weeks anatomical ultrasound detected a false negative trisomy 18 cfDNA result. One cfDNA result that reported trisomy 21 in the fetus was confirmed by karyotyping which also added an originally undetected balanced reciprocal translocation. Another reported karyotyped case followed by a repeated microarray of pure fetal DNA, together revealed one phenotypically normal newborn with a complex mosaic karyotype substantially decreasing the newborn’s eventual reproductive fitness. This second case establishes the importance of karyotyping the placenta and cord or peripheral blood when inconsistent or mosaic results are identified following an abnormal cfDNA result with a normal newborn phenotype without a prenatal karyotype.ConclusionsThese Maternal Fetal Medicine referrals demonstrate that positive NIPT results identify an increased abnormal karyotypic frequency as well as a substantial proportion of discordant fetal results. Our results found: (1) a normal NIPT test result followed by a 20 week anatomical ultrasound detected a false negative trisomy 18 NIPT result, (2) a substantial proportion of abnormal NIPT tests identify chromosomal mosaicism that may or may not be confined to the placenta, (3) follow up karyotyping should be completed on the newborn placenta and peripheral blood when the amniocyte karyotype does not confirm the NIPT reported abnormality in order to identify ongoing risk of developing mosaic symptoms, and (4) karyotyping all high risk fetuses tested by amniocentesis defines the 24% of chromosome abnormalities not currently screened by NIPT.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0569-y) contains supplementary material, which is available to authorized users.

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

Objective Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E. coli lipopolysaccharide (LPS). Methods Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U. parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion Acute U. parvum exposure (7d) can suppress LPS induced chorioamnionitis.