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).