Baseline characteristics/demographics
Fifty-five children (52 from Royal Marsden Hospital and 3 from San Raffaele Hospital) were included. The characteristics of the study population are detailed in Table 1 . The median age at tumour diagnosis was 12 (IQR 9–16) years, with a peak age between 9 and 10 years. Adolescents aged >11years accounted for 60% of cases. Most patients were boys (67.3%) and prepubertal at the time of diagnosis (54.5%).
Germinomas comprised most diagnoses (63.6% of the cohort). Children <5 years old (n=2) were diagnosed with teratoma, whilst germinoma occurred more frequently in older patients (p=0.052), especially in the 11-18 age group (n=24, 75%). Seven biopsies reported mixed GCT, all with a germinoma component.
Regarding the distribution of histology according to tumour locations, germinomas were significantly dominant in the suprasellar region (82.5%, p=0.047); together, NGGCTs accounted for 57.9% of the pineal tumours. Teratomas were also found in suprasellar region (n=3) and in atypical sites (n=2, right cerebro-pontine angle and thalamus). Seven cases occurred bifocally (7/55, 12.7%); among them, five were germinomas and two did not receive a histopathological diagnosis.
Six tumours were metastatic at diagnosis (10.9%), of which 4/6 were germinomas.
Serum AFP and beta-HCG were available for 53/55 (96.4%) and 52/55 (94.5%) subjects, respectively (Table 1) . For cytological detection of microdissemination, sampling of CSF was obtained; however, data on CSF tumour markers were missing for 6/55 subjects. Of the 4 tumours with severely elevated serum HCG, one case was teratoma and the remaining 3 cases had a mixed histology. Similarly, serum AFP was severely raised only in NGGCTs (2 yolk sac tumour, 1 teratoma and 1 mixed histology). On the contrary, normal levels of serum AFP and HCG were reported in 41 cases and 39 cases, respectively; they were all germinomas, aside from one teratoma that showed normal serum HCG levels and moderate elevation of both CSF HCG and AFP. PLAP results on biopsy samples prior to treatments were available in 30/55 cases (54.4%) and all of those that showed a positive PLAP staining were then diagnosed with germinoma, except for one (mixed histology with a predominant yolk sac component).