In 80% of infertile men with obstructive azoospermia caused by a congenital bilateral absence of the vas deferens (CBAVD), mutations are identified in the cystic fibrosis transmembrane conductance regulator gene (CFTR). For the remaining 20%, the origin of the CBAVD is unknown. A large cohort of azoospermic men with CBAVD was retrospectively reassessed with more stringent selection criteria based on consistent clinical data, complete description of semen and reproductive excurrent ducts, extensive CFTR testing, and kidney ultrasound examination. To maximize the phenotypic prioritization, men with CBAVD and with unilateral renal agenesis were considered ineligible for the present study. We performed whole-exome sequencing on 12 CFTR-negative men with CBAVD and targeted sequencing on 14 additional individuals. We identified three protein-truncating hemizygous mutations, c.1545dupT (p.Glu516Ter), c.2845delT (p.Cys949AlafsTer81), and c.2002_2006delinsAGA (p.Leu668ArgfsTer21), in ADGRG2, encoding the epididymal- and efferent-ducts-specific adhesion G protein-coupled receptor G2, in four subjects, including two related individuals with X-linked transmission of their infertility. Previous studies have demonstrated that Adgrg2-knockout male mice develop obstructive infertility. Our study confirms the crucial role of ADGRG2 in human male fertility and brings new insight into congenital obstructive azoospermia pathogenesis. In men with CBAVD who are CFTR-negative, ADGRG2 testing could allow for appropriate genetic counseling with regard to the X-linked transmission of the molecular defect.

In the authors' practice, TPS helped to better characterize the categories of AUC, low-grade urothelial neoplasm, and suspicious for HGUC, which were associated with a higher risk of HGUC compared with the authors' previous classification. Cancer Cytopathol 2018;126:430-6. © 2018 American Cancer Society.

The cytopathology of salivary glands presents major challenges due to the heterogeneity of benign and malignant neoplasms, which is reflected in the large range of WHO 2017 Classifications. Fine needle aspiration (FNA) of salivary gland tumours is still the favoured initial approach as it results in good sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018 and comprises seven categories. We report results from a 4-year retrospective analysis of 328 salivary gland FNAs which were reviewed and classified according to the MSRSGC. We assess the risk of neoplasm, the risk of malignancy and the contribution of ancillary studies to the diagnosis. Benign neoplasms were the most frequent diagnosis (44.2%). Malignant and suspicious for malignancy were identified in 11.3% and 4.9% of diagnosed cases, respectively. Histopathological analysis after surgery was available for 216 (65.8%) of the cases. All malignant cases were confirmed post-surgery, and 68.8% of suspicious for malignancy were confirmed as malignant tumours. Immunocytochemistry was informative in 72.3% of cases. Immunocytochemistry and FISH provided the definitive diagnosis in 23.7% and 33% of cases, respectively. In conclusion, the MSRSGC is more effective when specific features of neoplasms can be identified. Ancillary studies help to further characterise salivary gland tumours and thereby increase the accuracy of MSRSGC.