The role of cancer predisposition syndrome in children and adolescents with very rare tumours

Germline predisposing pathogenic variants (GPVs) are present in approximately 8–10 % of children with all cancer types. Very rare tumours (VRTs) represent many different diseases, defined with an annual incidence < 2 / 1,000,000, and correspond to 11 % of all cancers in patients aged 0–14 years. Some of these VRTs, including cancer typical for adults, develop in children with a cancer predisposition syndrome (CPS). Classically, three situations lead to consider this association: Some patients develop a VRT for which histology itself strongly suggests a GPV related to a CPS; others are referred for germline genetic testing because of a family or personal history and finally, a systematic molecular genomic tumour analysis, reveals a PV typical to a CPS. Depending on the samples tested and type of analysis performed, information can be directly available about the germline status of such a PV. Depicting the association between CPS and VRT is clinically important as some of these tumour types require adapted therapy, sometimes in the frontline setting, and the proposal of a specific surveillance programme to detect other malignancies. The diagnosis of CPS necessitates a careful familial evaluation and genetic counselling regarding the risks faced by the child or other family members. The aim of this paper is to propose a literature review of solid VRTs occurring in paediatric and young adult patients associated with CPSs.