Metastatic Bifocal Germinoma With Dramatic Early Steroid Response, Utility of Circulating miR-371a-3p and Vinblastine Monotherapy Prior to Definitive Craniospinal Irradiation

Abstract

Central nervous system (CNS) germ cell tumours (GCTs) are rare and heterogeneous due to different anatomical sites, subtypes, and variable serum and cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) marker expression (1). As a result, diagnosis and management are challenging (1). CNS GCTs are typically segregated into pure germinoma (two-thirds of cases) and the more aggressive non-germinomatous GCTs (NGGCTs), the latter needing more intensive therapy for cure (1). In Europe, CNS pure germinomas are diagnosed by both serum and CSF AFP and HCG levels being below specific thresholds [25ng/ml (20.8 kU/L) and 50IU/L, respectively] and histological confirmation (1). The exception is for ‘bifocal’ germinoma (occurring in both the pineal and suprasellar region), which can be diagnosed without recourse to biopsy where clinical presentation is typical [patient age >8–10 years of age and central diabetes insipidus (DI) present], along with serum and CSF AFP and HCG below threshold values, and with expected radiological findings (2, 3). In such cases, a diagnosis of germinoma can be assumed, and patients treated accordingly (2, 3). If there is any diagnostic uncertainty, a low threshold for considering biopsy must be maintained, as very rarely, NGGCT may similarly be present (3). Importantly, in a recent large bifocal cohort of 89 cases, no tumours other than GCTs were observed, and although three NGGCT cases were identified, none had a full set of serum/CSF AFP/HCG markers (4). Thus, in patients with complete tumour marker work-up, only pure germinoma was identified (4).