Preoperative Evaluation of Thyroid Epithelial Lesions by DNA Ploidy and Galectin-3 Expression in FNAC

AIM: This study aimed to investigate the value of DNA ploidy and galectins-3 immunostain in the preoperative evaluation of thyroid epithelial lesions.MATERIAL AND METHODS: Sixty patients presenting with thyroid enlargement were included in this study and referred by clinicians for FNA. Routine cytological evaluation was done on PAP   stained slides according to the WHO criteria and at least three slides were prepared for routine cytological examinations. The nuclear DNA analysis was performed at the Pathology Department, National Research Center using the Leica Qwin 500 Image Analyzer (LEICA Imaging Systems Ltd, Cambridge, England). Galectin-3 expression was investigated in all tissues using streptavidin-biotin technique.RESULTS: Conventional Fine needle aspiration cytology (FNAC) of 60 cases could diagnose malignancy with a sensitivity of 60%, negative predictive value (NPV) 71.4%, and overall diagnostic accuracy of 80%. The aneuploidy was significantly associated with malignancy, with sensitivity 90.9%, specificity 83.3% and accuracy 88.3%. On using galectin-3 immunocytochemichal stain on cell blocks prepared from FNA the values were improved, sensitivity 93.3% specificity 86.7% and overall accuracy 90% and it was noticed that galectin-3 over expression was significantly associated with malignancy.CONCLUSIONS: From the results of this study we can consider that DNA ploidy and Galectin-3 could refine the FNA results and  increase its sensitivity as a screening test from sensitivity(60%) to reach sensitivity (93.3%), thus decreasing the false negative cases. From this study, it is concluded that the application of ancillary techniques as galectin-3 immunocytochemical markers may become a reliable indicator for surgical intervention, DNA ploidy measurements on the other hand may be of value in galectin-3 negative cases to determine the behavior of the lesion in such cases & refine the preoperative assessment by out ruling false negative cases

Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder

Purpose: To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder. Methods: A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization. Results: Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons. Conclusion: Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder