Human chorionic gonadotropin (hCG) is a hormone that may be abnormally secreted in several tumour types, including intracranial germ cell tumours. In pineal region tumors, hCG is a key tumor marker. In fact, mild elevation typically suggests a germinoma with syncytiotrophoblastic cells, whereas a markedly elevated level indicates a choriocarcinoma or a mixed germ cell tumor with trophoblastic differentiation. While histopathological confirmation remains the diagnostic gold standard, the anatomical situation of the pineal gland makes biopsy very challenging. In certain situations, diagnosis may therefore rely on a constellation of clinical, radiological, and biochemical findings, including cerebrospinal fluid (CSF) β-hCG levels. However, the differential diagnosis of pineal region tumours includes other primary neoplasms of the pineal parenchyma, which differ markedly in both prognosis and therapeutic management. Here, we report two cases of pineoblastoma with unexpectedly elevated CSF β-hCG levels, which might have led to a misdiagnosis of intracranial germinoma. These cases highlight the need for the development of novel, non-invasive biomarkers to improve the diagnostic accuracy of intracranial tumours.

Non-germinomatous germ cell tumors (NGGCTs) are rare, histologically diverse malignancies that primarily affect children and adolescents. Unlike germinomas, NGGCTs are less responsive to chemotherapy and radiation, resulting in a less favorable prognosis and necessitating intensified multimodal therapy. This chapter provides a comprehensive overview of NGGCTs, including histological subtypes, clinical presentation, diagnostic strategies, and established as well as emerging treatment paradigms. We discuss current classification systems, the roles of tumor markers and neuroimaging, and challenges in histopathologic diagnosis. Treatment approaches vary globally but typically include intensive chemotherapy combined with craniospinal or whole-ventricular irradiation. Long-term outcomes remain suboptimal for high-risk subtypes, especially those with yolk sac tumor, choriocarcinoma or embryonal carcinoma components. Recent genomic and epigenomic studies have revealed recurrent alterations in the RTK/MAPK and PI3K/mTOR pathways, along with distinctive methylation signatures and copy number aberrations, offering insights into tumorigenesis and potential therapeutic targets. Ongoing trials continue to focus on refining risk stratification and minimizing treatment-related toxicities. These efforts, along with advances in molecular characterization, may ultimately improve survival and long-term quality of life in patients with CNS NGGCTs.

We have previously shown that valproic acid (VPA) alters the expression of placental carriers of essential nutrients, including folates. Here, we exposed a placental cell line to VPA, its central nervous system-active amide derivative sec-butylpropylacetamide (SPD), and its individual stereoisomers to address the question of whether folate carrier expression can predict the teratogenicity of VPA-related compounds. We additionally conducted a pilot analysis of folate transfer across placental cell monolayers to estimate the translation of altered carrier expression to carrier activity. BeWo cells were incubated for 2 or 5 days with racemic SPD, its stereoisomers (2S,3S)-SPD, (2R,3S)-SPD, and (2R,3R)-SPD (previously found to be teratogenic at high doses in mice; .5 or 1 mmol·L-1), VPA (1 mmol·L-1 = 144 mg/L), or their vehicle. Expression of FOLR1 (folate receptor alpha), SLC19A1 (reduced folate carrier), and ABCG2 (breast cancer resistance protein) was measured by real-time polymerase chain reaction. Folate transfer across monolayers of BeWo b30 cells exposed to .5 mmol·L-1 (2R,3R)-SPD or 1 mmol·L-1 VPA was quantified by liquid chromatography-mass spectrometry analysis. At 1 mmol·L-1, racemic SPD, (2S,3S)-SPD, and (2R,3S)-SPD reduced by twofold SLC19A1 expression, similar to VPA (p < .001). SPD and its enantiomers induced FOLR1 expression by up to twofold (p < .05) or did not significantly affect it, and racemic SPD increased ABCG2 expression (p < .01). After 5 days, VPA, but not (2R,3R)-SPD, enhanced both maternal-to-fetal and fetal-to-maternal folate transfer (p < .01), resulting in a 15% increase in net transfer in the fetal direction. Altered expression of the studied carriers could not explain the folate transfer kinetics across placental cell monolayers. Future studies should assess the effects of VPA and other antiseizure medications on transplacental transfer of essential compounds in vivo and the ability to predict it by functional in vitro assays. This PDQ cancer information summary has current information about the treatment of childhood central nervous system germ cell tumors. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board. This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood central nervous system germ cell tumors. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Primary central nervous system (CNS) germ cell tumors (GCTs) are rare brain tumors that encompass two subtypes: germinomas and non-germinomatous germ cell tumors (NGGCTs), NGGCTs have less favorable outcome and require multi-modality treatment. Biopsy is recommended for disease diagnosis, the specimen may not adequately reflect the entire tumor. This study aimed to assess distinct imaging characteristics to differentiate between GCT subgroups and to identify possible initial image and subgroup features that influence survival. This retrospective study, conducted from January 2006 to March 2023, analyzed patient data and MRI findings of primary CNS GCTs. It evaluated tumor characteristics including cysts, seeding, multifocality, and hemorrhage. Tumor volumes and apparent diffusion coefficient (ADC) values of both tumoral and normal-appearing contralateral white matter were measured. These factors were correlated with overall and 5-year survival rates. This study included 51 participants with CGTs, comprising 19 germinoma and 32 NGGCTs cases. GCTs with hemorrhage had worse overall (P = 0.03) and 5-year (P = 0.01) survival rates. No survival difference between germinoma and non-hemorrhagic NGGCT. NGGCTs were more likely to bleed (P < 0.001) than germ cell tumor, especially those with choriocarcinoma or yolk sac tumor components (P = 0.001). The ADC ratios of germinomas were significantly lower than those of NGGCTs (P = 0.03 for whole tumor; P < 0.01 or solid part), The ADC ratios of choriocarcinoma were also lower than mixed tumor (P = 0.01; P = 0.02). Hemorrhage indicates worse prognosis. Intratumoral hemorrhage and ADC ratios differentiate germinoma from NGGCTs. Larger cohorts and advanced MR techniques are needed for future study.

Ultra high-risk gestational trophoblastic neoplasia (GTN) refers to patients with World Health Organization prognostic risk scores of at least 13. The mortality risk for these patients averages 30%. Ultra high-risk GTN more frequently presents with higher tumor volume, liver and/or brain metastases, and very high human chorionic gonadotropin levels. The diagnostic evaluation must include a thorough evaluation for central nervous system disease. Prompt initiation of cisplatin - etoposide induction chemotherapy reduces the risks of early death. Collaborative services such as neurosurgery, radiation oncology, and interventional radiology may be required to manage hemorrhagic lesions.