Clinical Diagnosis of Classical Cornelia de Lange Syndrome Made From Postmortem Examination of Second Trimester Fetus With Novel NIPBL Pathogenic Variant.

Classical Cornelia de Lange syndrome (CdLS) is a rare genetic disorder which is associated with distinctive facial features, growth retardation, significant intellectual disability and global developmental delay, hirsutism, and upper-limb reduction defects. Classical CdLS is associated with pathogenic variants in NIPBL. We present a clinical diagnosis of classical CdLS made in a second trimester male fetus with advanced maceration who had undergone intrauterine death at 15 + 6 weeks gestation. The diagnosis was suspected after multiple congenital anomalies were identified on fetal postmortem examination. These included intrauterine growth retardation, upper limb anomalies, ventricular septal defect and diaphragmatic hernia, and skeletal and genitourinary abnormalities. Related prenatal screening findings included a raised nuchal translucency and low maternal serum pregnancy-associated plasma protein-A. Targeted molecular sequencing of genes associated with CdLS identified a novel de novo frameshift pathogenic variant in NIPBL, which confirmed the diagnosis. This report describes our case and reviews the current literature on prenatal diagnosis of CdLS. In summary, we demonstrate that clinical diagnosis of CdLS in a second trimester fetus, through postmortem examination findings, is possible, with confirmation through molecular testing.

Fine needle aspiration cytology (FNAC) of salivary gland tumours: repeat aspiration provides further information in cases with an unclear initial cytological diagnosis.

INTRODUCTION: Fine needle aspiration cytology (FNAC) for salivary gland tumours requires expertise in interpretation. When a diagnosis is not clear (despite a cellular aspirate), published work is lacking on the value of repeating the test. METHODS: A retrospective study of 135 patients who had FNAC followed by definitive excision for a suspected salivary gland tumour. Accuracy was compared among those requiring repeat FNAC on one more occasion because of a non-diagnostic initial cytology report. RESULTS: 33 patients (24% of study group) had repeat FNAC. A definite cytological diagnosis was subsequently made in 27/33 patients (82%). The sensitivity (84%) and specificity (93%) of repeat FNAC in distinguishing benign from malignant tumours was similar to initial FNAC (70% and 95%, respectively). CONCLUSIONS: Repeat FNAC may provide a cytological diagnosis in cases where the initial diagnosis is not clear, although cytology should be used in conjunction with other investigations of salivary tumours, including image-guided biopsy examination where appropriate. Ideally salivary gland FNAC should be interpreted by a specialist pathologist.