Low-Level Cerebrospinal Fluid β-hCG Elevation in Patients with Pineal Parenchymal Tumors: A Four-Case Series and Diagnostic Caution

Background: Pineal region tumors (PRTs) are rare and biologically heterogeneous neoplasms with overlapping clinical and radiological features. Low-level cerebrospinal fluid (CSF) beta-human chorionic gonadotropin (β-hCG) may support a clinical diagnosis of germinoma (GE); however, its pathological specificity remains uncertain. Methods: We retrospectively reviewed four patients with low-level CSF β-hCG elevation whose available tissue specimens demonstrated pineal parenchymal tumors (PPTs). Tissue was obtained before systemic treatment in two patients and after platinum-based chemotherapy in two. Results: All four patients were male and aged 8 to 19 years. Pretreatment specimens from two patients demonstrated pineal parenchymal tumors of intermediate differentiation (PPTID), whereas postchemotherapy specimens from the other two demonstrated pineoblastoma (PB). Serum β-hCG was <0.1 IU/L in all patients, while CSF β-hCG ranged from 2.86 to 18.29 IU/L; serum and CSF alpha-fetoprotein (AFP) levels were normal. Two patients received platinum-based chemotherapy for presumptive intracranial germ cell tumors before tissue diagnosis, achieving stable disease or partial response. Because their specimens were obtained after chemotherapy, an occult pretreatment germ cell component could not be excluded. Conclusions: Although contemporary diagnostic protocols allow a clinical diagnosis of GE with characteristic imaging findings and low-level β-hCG elevation, isolated low-level CSF β-hCG immunoreactivity may also coexist with tissue specimens demonstrating PPT and should therefore not be considered pathognomonic for GE or interpreted in isolation. Early tissue acquisition with integrated histopathological and molecular evaluation is essential to avoid diagnostic misclassification and ensure appropriate treatment.