Study design and population
We retrospectively analysed data of patients (<18 years old) who were diagnosed with IC-GCT between January 1996 and December 2019 at the Royal Marsden Hospital, Sutton, UK and at San Raffaele Hospital, Milan, Italy. Only patients affected by primary IC-GCT with available complete information were included.
Data collection included patient demographics, height and weight measurements, timing, and features of symptoms at diagnosis, laboratory data (tumour markers, hormonal levels), tumour location, histology and staging. Since laboratory tests were performed in different institutions, we stratified tumour markers into 4 categories: normal, mild, moderate, and severe elevation. We chose 5 IU/L and 10 ng/mL as cut-off values for normal HCG and AFP levels, respectively; 50 IU/L and 25 ng/mL as cut-off levels distinguishing mild and moderate HCG and AFP levels; >500 IU/L and > 1000 ng/mL for severe HCG and AFP levels. Placental alkaline phosphatase (PLAP) staining on pathologic specimens was reported when available. Brain and spine MRI were mandatory for diagnosis and staging. Metastatic IC-GCT was defined as the presence of >1 intracranial focus (except for bifocal disease), spinal metastases, metastases outside the CNS, or the presence of tumour cells in CSF cytology. Definition of bifocal disease required radiological synchronous detection of tumour in both the pineal gland and the suprasellar region. The diagnosis of IC-GCT was histologically confirmed in 52/55 cases (94.5%). For two pathological undetermined specimens clinic-radiologic suspicion of IC-GCT was confirmed by raised CSF tumour markers; one patient did not undergo any biopsy as presumptive diagnosis of IC-GCT was based on tumour localization (bifocal disease with leptomeningeal dissemination).
Symptoms at diagnosis were classified into four groups: 1)raised intracranial pressure, RICP (headache, vomiting); 2)visual impairment; 3)endocrinopathy (polyuria/polydipsia, poor growth); 4)other (neurological signs, ataxia, fatigue, behavioural changes, worsen school performance).