Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors

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OBJECTIVE

Placental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs.

METHODS

From 2004 to 2014, 74 patients (average age 19.6 ± 10.6 years) with intracranial GCTs were evaluated using PLAP from their CSF and histological samples. Chemiluminescent enzyme immunoassay was utilized to measure CSF PLAP in the following tumor sites: pineal (n = 32), pituitary stalk, suprasellar (n = 16), basal ganglia (n = 15), intraventricular (n = 9), and cerebellar (n = 5) regions. In addition to classifying GCT cases, all patients underwent tumor biopsy for correlation with tumor marker data.

RESULTS

PLAP in combination with other tumor markers resulted in extremely high sensitivity and specificity of the diagnostic value of intracranial GCTs. Intracranial GCT cases were classified into 1) germinomas, both “pure” and syncytiotrophoblastic giant cell types (n = 38); 2) nongerminomatous GCTs, choriocarcinomas (n = 9) and teratomas (n = 4); and 3) nongerminomas, other kinds of tumors (n = 23). Consequently, all patients received chemoradiation therapy based on elevation of PLAP and the histopathological results. It was also speculated that the level of PLAP could show the amount of intracranial germ cell components of a GCT. PLAP was 100% upregulated in all intracranial germinoma cases. The absence of CSF PLAP proved that the tumor was not a germinoma.

CONCLUSIONS

The current study is the first systematic and comprehensive examination of the diagnostic value of the tumor marker PLAP in pediatric patients with intracranial GCT. Using the level of PLAP in CSF, we were able to detect the instances of intracranial germinoma with very high reliability, equivalent to a pathological diagnosis.

ABBREVIATIONS AFP = α-fetoprotein; CBDCA = carboplatin; CDDP = cisplatin; CEA = carcinoembryonic antigen; CLEIA = chemiluminescent enzyme immunoassay; hCG = human chorionic gonadotropin; hCG-β = hCG;β-subunit; GCT = germ cell tumor; IgG = immunoglobulin G; PLAP = placental alkaline phosphatase; STGC = syncytiotrophoblastic giant cell; VP-16 = etoposide.

Article Information

Correspondence Yasuo Aihara: Tokyo Women’s Medical University, Tokyo, Japan. yaihara@twmu.ac.jp; yz3y-aihr@asahi-net.or.jp.

INCLUDE WHEN CITING Published online September 28, 2018; DOI: 10.3171/2018.3.JNS172520.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Bar graphs showing the differences between each tumor marker group. Differences were significant for both variables and every dependent variable: PLAP level, F(3, 70) = 89.0, p < 0.001, and hCG-β level, F(3, 70) = 70.5, p < 0.001. **p < 0.001.

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    Scatterplot showing that results of multiple comparisons (using the Bonferroni method) for germinomas and choriocarcinomas were significantly higher for the PLAP and hCG-β levels together compared with those for nongerminomas (p < 0.01). In addition, compared with the choriocarcinoma group, germinomas only had significantly lower hCG-β levels (p < 0.01).

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    A: Scatterplot that classified the value of the PLAP/hCG-β marker combination according to the current intracranial GCT grade classification. B: Scatterplot showing the new intracranial GCT classification (types 0–V) based only on PLAP and hCG-β value combination. C: Diagnostic flowchart indicating (with lines) the type of tumor according to a combination of value ranges of hCG and PLAP. As can be observed, some of the histological entities demonstrated more than one type of tumor marker characteristic and are presented as separate subtypes. Their clinical significance will be investigated later.

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    A: Case 1 (type I). T1-weighted Gd-enhanced MRI demonstrates acute hydrocephalus and a huge mass in the pineal region. Just 2–3 weeks after the first course of chemotherapy (CBDCA/VP-16), new MRI demonstrates the complete remission of the pineal region tumor. B: Case 2 (type IIIb). T1-weighted Gd-enhanced MRI demonstrates acute hydrocephalus and a huge mass in the suprasellar region and third ventricle. Just 2–3 weeks after the first course of chemotherapy (CBDCA/VP-16), the massive tumor disappeared rapidly and hydrocephalus improved without ventriculoperitoneal shunt placement. C: Case 3 (type V). T1-weighted Gd-enhanced MRI demonstrates a mass in the left basal ganglia. MRI of the brain at 2 and 4 weeks after the first course of chemotherapy revealed poor mass reduction of the tumor compared with the initial MRI. D: Case 4 (type V). T1-weighted Gd-enhanced MRI demonstrates acute hydrocephalus and tumor mass in the pineal region. MRI of the brain at 2 and 4 weeks after the first course of chemotherapy revealed poor mass reduction of the tumor compared with the initial MRI. Figure is available in color online only.

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