Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER–Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.

Introduction: Interstitial lung diseases (ILDs) can be caused by mutations in theSFTPA1andSFTPA2genes, which encode the surfactant protein (SP) complex SP-A. Only 11SFTPA1orSFTPA2mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenicSFTPA1orSFTPA2mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.Methods: The consequences of the 11SFTPA1orSFTPA2mutations were analysed bothin vitro, by studying the production and secretion of the corresponding mutated proteins andex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented.Results: For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28SFTPA1 or SFTPA2mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.Discussion: This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenicSFTPA1orSFTPA2mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

Renal tumors comprise approximately 7% of all malignant pediatric tumors. This is a highly heterogeneous group of tumors, each with its own therapeutic management, outcome, and association with germline predispositions. Histopathology is the key in establishing the correct diagnosis, and therefore pathologists with expertise in pediatric oncology are needed for dealing with these rare tumors. While each tumor shows different histologic features, they do have considerable overlap in cell type and histologic pattern, making the diagnosis difficult to establish, if based on routine histology alone. To this end, ancillary techniques, such as immunohistochemistry and molecular analysis, can be of great importance for the correct diagnosis, resulting in appropriate treatment. To use ancillary techniques cost-effectively, we propose a pattern-based approach and provide recommendations to aid in deciding which panel of antibodies, supplemented by molecular characterization of a subset of genes, are required.

Children with ABCA3 mutations may survive beyond infancy and reach adulthood. Genetic mechanisms should always be examined in adult patients with childhood onset ILD and molecular analysis should be performed accordingly in specialised referral centres. http://bit.ly/2LzMNOE.

Pre- and post-pubertal testicular tumors are two distinct entities in terms of epidemiology, diagnosis and treatment. Most pre-pubertal tumors are benign; the most frequent are teratomas, and the most common malignant tumors are yolk-sac tumors. Post-pubertal tumors are similar to those found in adults and are more likely to be malignant. Imaging plays a pivotal role in the diagnosis, staging and follow-up. The appearance on ultrasonography (US) is especially helpful to differentiate benign lesions that could be candidates for testis-sparing surgery from malignant ones that require radical orchidectomy. Some specific imaging patterns are described for benign lesions: epidermoid cysts, mature cystic teratomas and Leydig-cell tumors. Benign tumors tend to be well-circumscribed, with decreased Doppler flow on US, but malignancy should be suspected when US shows an inhomogeneous, not-well-described lesion with internal blood flow. Imaging features should always be interpreted in combination with clinical and biological data including serum levels of tumor markers and even intra-operative frozen sections in case of conservative surgery to raise any concerns of malignity. This review provides an overview of imaging features of the most frequent testicular and para-testicular tumor types in children and the value of imaging in disease staging and monitoring children with testicular tumors or risk factors for testicular tumors.