An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors

Abstract

BackgroundPathological examination combined with tumor markers has become a standard for the diagnosis of intracranial germ cell tumors (ICGCTs), but the current concept of ‘secreting germ cell tumors’ and three empirically highly specific diagnostic criteria (β-hCG ≥ 50 IU/L or αFP ≥ 10 ng/mL; β-hCG ≥ 100 IU/L or αFP ≥ 50 ng/mL; β-hCG > 50 IU/L or αFP > 25 ng/mL) are not based upon pathology examination or CSF cytology. Further investigation is needed to re-evaluate their value.MethodsA multidisciplinary diagnostic team was created. Valid β-hCG/αFP data were collected from cases of ICGCTs confirmed by pathology and CSF cytology (n = 58) between 1991 and 2012, and from suspected ICGCTs cases (n = 17) between 2011 and 2012 as controls [Langerhans cell histiocytosis (LCH), n = 12; and other intracranial tumor (ICT), n = 5]. The cut-off points for β-hCG and αFP were calculated using receiver operating characteristic (ROC) curves.ResultsThis study clarifies the relative rationality of one criteria (β-hCG > 50 IU/L and αFP > 25 ng/mL); confirms new β-hCG diagnostic cut-off points: CSF β-hCG ≥ 8.2 IU/L and serum β-hCG ≥ 2.5 IU/L (sensitivity of 47 and 34 %, respectively, specificity of 100 %, both; P < 0.05); and empirically adjusts the criteria for αFP to ≥ 3.8 ng/mL in CSF and to ≥ 25 ng/mL in serum. The total diagnostic sensitivity for ICGCTs finally increased from 34.6 to 65.4 % (P < 0.05, diagnostic value of CSF β-hCG exceeds 90 %). Subtype diagnosis improved with αFP in 16.7 % of non-geminomatous germ cell tumor cases.ConclusionNew evidence-based criteria of β-hCG and αFP can help improving early and formal diagnosis of ICGCTs, and is of great clinical significance.

Cytological diagnosis of primary pineal germ cell tumour with a yolk sac component in cerebrospinal fluid

“…CSF cytology together with magnetic resonance imaging study, are extremely important for the diagnosis of the potential leptomeningeal infiltration. CSF dispersal stages are categorised as M0 (no tumour cells found in CSF), M1 (varied numbers of neoplastic cells found in CSF), M2 (involvement of ventricles and subarachnoid region), M3 (involvement of the spinal cord) and M4 (extracranial metastases) . Our case was an M2 case.…”

Difficulties in cerebrospinal fluid βhCG interpretation in a patient with an infundibular lesion

“…Elevated serum levels occur in other malignancies, tumor lysis syndrome, primary hypogonadism and precocious puberty. Elevated CSF levels occur in pituitary adenomas, craniopharyngiomas, arachnoidal cysts and Langerhans cell histiocytosis ( 5 ).…”

Method Validation of Human Chorionic Gonadotropin and α-Fetoprotein in Cerebrospinal Fluid: Aiding the Diagnosis of Intracranial Germ Cell Tumors

“…The decision limits were recently reassessed in a study comparing hCG and AFP values in 58 GCTs confirmed by pathology. This study concluded that serum and CSF should have different decision limits, and lower decision limits of ≥8.2 IU/L for hCG and ≥3.8 μg/L AFP in CSF were proposed (7).…”

“…This result subsequently helps direct appropriate treatment (2)(3)(4) and reduces the risk of surgery-related complications in this subset of patients (5). Increased concentrations of AFP in CSF support the diagnosis of yolk sac tumors/yolk sac components of mixed GCTs, whereas high concentrations of hCG in CSF support the diagnosis of choriocarcinomas/ choriocarcinomatous components of mixed GCTs (6,7).…”

“…Detection of an increased concentration of AFP or hCG in CSF is diagnostically more sensitive and reliable than serum measurement and can be used to monitor response to treatment (7)(8)(9). After successful treatment, new-onset elevations of AFP and hCG in CSF are sensitive markers of tumor recurrence and may precede radiologic or symptomatic detection, allowing for better management.…”