Intracranial germ cell tumors: an underrecognized diagnostic consideration in adults with sellar/suprasellar lesions

Sellar/suprasellar intracranial germ cell tumors (iGCTs) predominantly occur in children and adolescents, while adult-onset cases are rare and poorly characterized. We aimed to characterize adult-onset iGCTs and improve their differential diagnosis.

Patients with iGCTs and onset age ≥ 18 years were enrolled in a single center. Adult-onset LYH patients served as comparison. iGCT and LYH were diagnosed using predefined pathological or clinical criteria incorporating characteristic clinical presentations, laboratory findings, MRI features, and treatment response. A nomogram was developed to distinguish iGCTs from LYH and was internally validated using 1,000 bootstrap resamples.

Forty-eight adult patients with iGCTs were enrolled, including 36 with germinoma and 12 with nongerminomatous germ cell tumors. The median age at onset was 23.4 years (range 18.1-53.5), and 87.5% were male. Forty-six patients with LYH were included for comparison. CSF β-hCG accurately diagnosed iGCTs from LYH (AUC 0.897, 95% CI 0.821-0.973). The optimal cutoff was 2.52 U/L, yielding a sensitivity of 78.6% and a specificity of 95.5%. The nomogram incorporating sex, log-transformed serum β-hCG, hyperprolactinemia, and pituitary stalk thickening differentiated iGCTs from LYH with an AUC of 0.939 (95% CI 0.875-1.000). Among patients with documented treatment regimens, 17 (53.1%) underwent radiotherapy, and 15 (46.9%) received chemoradiotherapy. During a median follow-up of 1.7 years (range 0.2-13.5), four patients developed progression or recurrence.

iGCT represents a rare yet possible etiology of suprasellar/sellar lesions in adults. CSF β-hCG and the proposed nomogram may aid differential diagnosis, although external validation in independent cohorts is still required.