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).