Epidemiology, Natural History, and Optimal Management of Neurohypophyseal Germ Cell Tumors

Background: Intracranial germ cell tumors (iGCT) preferentially arise at the neurohypophysis—their second most common origination, following the pineal region. Neurohypophyseal iGCT present with stereotypic symptoms due to their suprasellar location, including pituitary dysfunction or visual field deficit.

Methods: This is a retrospective, single-institution cohort study of neurohypophyseal iGCT focused on the epidemiology, presentation, natural history, and treatment outcomes, 1988 to 2017.

Results: Thirty-five neurosurgically managed patients met inclusion criteria; median age was 18 years (3 months to 49 years), and 74% were males (n = 26). Thirty-one were germinomas and four were nongerminomatous GCTs. Presenting symptoms included pituitary insufficiency in 76% (n = 25), visual deficit in 40% (n = 14), and diabetes insipidus (DI) in 61% (n = 20). Index symptoms included isolated diabetes insipidus (DI) in 10 (36%), isolated hormonal deficiency in 14 (50%), and concomitant DI and hormonal deficiency symptoms in 4 (14%). Radiographic diagnostic latency was common, occurring at a median 363 days (range = 9–2,626) onset of first symptoms, and significantly associated with both DI and hormonal deficiency as the index symptom (360 vs. 1,083 days, p = 0.009; 245 vs. 953 days, p = 0.004). Biochemical abnormalities were heterogeneous: each pituitary-axis was dysfunctional in at least 1 patient, with most patients demonstrating ≥2 abnormalities, and pretreatment dysfunction demonstrating a nonsignificant trend toward association with long-term posttreatment hormonal supplementation. Among germinomas, whole-brain and whole-ventricle radiation demonstrated significantly improved progression-free and overall survival, as compared with local therapy (p = 0.009, p = 0.004).

Conclusion: Neurohypophyseal iGCT are insidious tumors that may pose a diagnostic dilemma, evidenced by the prototypically prolonged latency before radiographic confirmation. Serial imaging and close endocrine follow-up is recommended in patients with a characteristic clinical syndrome and negative imaging due to the propensity for radiographic latency. Pretreatment biochemical abnormalities may indicate higher risk of posttreatment pituitary insufficiency, and all patients should receive careful endocrine follow-up. Local radiotherapy is prone to treatment failure, while whole-ventricle treatment is associated with improved survival in germinomas.