Paediatric renal tumours account for ~6% of all paediatric malignant tumours, of which ~90% are Wilms tumours (nephroblastoma) 1. Other renal non-Wilms tumours are rare entities and include mesoblastic nephroma, clear cell sarcoma of the kidney, rhabdoid tumour of the kidney, renal cell carcinoma and few other, even rarer tumour types 1. The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new study for all renal tumours of childhood, the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol) 2,3 , on the basis of the experiences from SIOP-2001 and the UK Improving Population Outcomes for Renal Tumours of Childhood (IMPORT) 2013 studies 2-4. The aim of the UMBRELLA protocol is to collect all clinical, biological and outcomes data from children with primary renal tumours in a comprehensive data registry, with central review of diagnostics (radiology, patho logy and surgery), standardized biobanking and precise treatment recommendations for the most common paediatric renal tumours. Molecular biology research within the protocol is primarily focused on the validation of the prognostic value of 1q gain, which might lead to a more personalized treatment approach (Box 1). Consequently, short-term and long-term outcomes might be improved for all children with renal tumours by increasing survival, but also by reducing treatment in specific subgroups, resulting in diminished direct and late adverse effects. Timely genetic analysis and step-wise extension to additional targets such as TP53 (refs 5-7) or several of the newly identified driver candidates for stratification and inclusion of liquid biopsies might help to reach this goal 8-10. The UMBRELLA protocol includes updated guidelines for pathologists for the handling and processing of tissue as well as criteria that are important for postoperative histological classification, staging and treatment stratification. These recommendations were established by a consensus of pathology experts within the SIOP-RTSG (chaired by G. M. Vujanić and I. Leuschner).

The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.