Diagnostic intervals analysis
Overall, the TDI ranged from 0.25 to 58.5 months (median 4 months, mean
12 months); most patients were diagnosed within 10 months after the
onset of symptoms. A statistically significant difference was found in
subgroup analysis of TDI by tumour location and histology
(p<0.001 and p=0.006, respectively). Pineal GCTs had the
shortest interval compared with other locations, with a median TDI of 1
month (range 0-17) versus a median TDI of 24 months (range 0.25-58.5) in
suprasellar GCTs (Fig. 2 ). Ranking of tumour histology
identified germinoma as the one with the longest interval, but also with
the most skewed distribution, with a median TDI of 7 months (range
0.25–58.5) and a mean TDI of 16.5 months. Patients aged <5
years and aged 5–11 years had similar TDI (median 6.3 months and 7.4
months, respectively), whilst older patients displayed a shorter TDI but
with a wider range (median 3 months, 1–19), although without
statistical significance (p=0.88).
TDI >6 months was observed in 26/55 patients (47.3%),
whose demographic and clinical characteristics are summarized inTable 2. There was no significant correlation for TDI
>6 months with age, histology, and metastatic disease at
diagnosis, but we found a negative correlation with height at diagnosis
(p=0.043). Regarding location of disease, pineal site was observed less
frequently in those with TDI >6 months (3/26 patients;
11.5%) than in those with a TDI ≤6 months (17/29 patients; 58.6%)
(p<0.001), whereas suprasellar tumours were predominant in the
TDI >6 months group (17/26; 65.4%) (p=0.002). TDI
>6 months was less associated with boys (86.2% vs 46%;
p=0.003), although the role of sex was confounded by the 100% male
predominance among pineal GCTs and the 67.3% among the whole cohort.
The pattern of presenting symptoms differed significantly in those with
TDI >6 months. Endocrine symptoms were more frequent
(n=17/26; 65.4%) in those with TDI >6 months compared with
those who were diagnosed in less than 6 months (n=0)
(p<0.001). In contrast, RICP was an infrequent initial symptom
(n=4/26; 15.4%) in those with TDI >6 months but was
typically observed in those with TDI ≤6 months (n=20/29; 69%)
(p<0.001).
Eight patients (14.5%) were followed with serial MRI for a median of 27
months (range 0.25–58.5) before the eventual diagnosis of IC-GCT.
Nearly all (7/8; 87.5%) presented with central DI; the remaining
patient exhibited poor growth. In the first MRI study, all cases
demonstrated pituitary stalk thickening. Serum and CSF markers were
initially mildly raised only in one patient. Progressive changes in the
size of the infundibulum and/or development of new symptoms (especially
hydrocephalus) led to biopsy, that was diagnostic for germinoma in all
patients but one who did not undergo biopsy for the neuroradiological
evidence of bifocal tumour.
In a subgroup of patients with endocrinopathies as presenting symptoms
(17/55; 30.9%), we performed subgroup analysis of different lag
intervals, referred as PI, HI and TI, stratified by age groups. PI and
HI account for 78% of the TDI, collectively. PI did not differ
significantly among the three age groups (p=0.83), although the
>11 age group had the longest PI with a range from 8 to
26.5 months (median 18 months), compared with <5 age group
(median 12) and the 5-11 age group (median 7.5). SI was also similar
across age groups (median 1.0 vs 1.0 vs 1.8 months, p=0.19). Finally,
the longest TI was found in subjects aged >11 years
(p=0.14).