Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the PIEZO1 gene diagnosed prenatally using exome sequencing (ES). Two variants in PIEZO1 (c.3206G>A and c.6208A>C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the PIEZO1 subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review PIEZO1 variants as a cause of GLD and discuss the uses of prenatal ES to date.

Introduction The Afirma test has been used in the diagnosis of cytologically indeterminate thyroid nodules to reduce diagnostic uncertainty and unnecessary surgeries. Gene Sequencing Classifier (GSC) was developed to improve the positive predictive value and overall test performance of Gene Expression Classifier (GEC). Here we present our experience comparing the performance of first‐generation assay of Afirma (GEC) with the new assay (GSC). Methods Retrospective analysis was performed on all Bethesda III and IV cytology thyroid nodules tested with GEC and GSC. Test performance was evaluated by surgical pathology outcomes. Results In total, 167 cases were tested with GEC, of which 49% were reported as benign. Fourteen cases had surgical follow‐up with 11 benign, one non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) and two malignant diagnoses. Of the 167 cases, 51% had suspicious GEC result. Fifty‐seven of these suspicious GEC cases had surgical follow‐up with 28 benign, nine NIFTP and 20 malignant histology. There 133 cases tested with GSC, of which 61% were reported as benign. Ten cases had surgical follow‐up, all of which showed benign results and 32% of the cases were tested as suspicious. Thirty‐six cases with suspicious GSC had surgical follow‐up. Fourteen of them had benign, five NIFTP, and 17 malignant surgical pathology. Based on molecular testing, surgical resection could have been be prevented 61% with GSC, compared to 49% with GEC test. Conclusion Our experience shows that GSC has a better test performance than GEC. Also, our data support that GSC identify more cases as benign and reduces the number of unnecessary surgeries compared to GEC.

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