Clinicoradiological features and surgical outcomes of primary intracranial medulloepitheliomas: a single-center experience and pooled analysis of individual patient data

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OBJECTIVE

Medulloepithelioma (MEPL) is a rare, malignant primitive neuroectodermal tumor with dismal survival rates. The authors aimed to define independent risk factors for progression-free survival (PFS) and overall survival (OS) and to propose an optimal treatment protocol for MEPL.

METHODS

The authors reviewed the clinicoradiological data obtained in 12 patients with MEPL who underwent surgical treatment at their institution between January 2008 and June 2016. In addition, they reviewed 55 cases of MEPL published in the literature from January 1957 to July 2017. A pooled analysis of individual patient data of these 67 patients was performed to evaluate risk factors.

RESULTS

The authors’ cohort included 5 males and 7 females with a mean age of 15.7 years. Gross-total resection (GTR) was achieved in 10 (83.3%) patients. Radiotherapy (mean total dose 42.8 Gy) and chemotherapy were administered to 7 and 4 patients, respectively. After a median follow-up of 21.7 months, 6 (50%) patients suffered recurrence and subsequently died, with median PFS and OS times of 5.5 and 13.9 months, respectively. Among the 55 patients in the literature, 13 (23.6%) patients received GTR, and 25 (49.0%) and 15 (29.4%) received radiotherapy (median total dose 53.2 Gy) and chemotherapy, respectively. After a median follow-up of 10.0 months, the recurrence and mortality rates were 69.7% (23/33) and 70.8% (34/48), respectively, and the median PFS was 6.0 months. Of the pooled cohort, the actuarial 5-year PFS and OS were 36.3% and 29.2%, respectively, and the estimated median survival time for PFS and OS were 12.8 and 15.2 months, respectively. A multivariate Cox model verified non-GTR (HR 5.537, p < 0.001) and no radiotherapy (HR 3.553, p = 0.008) as independent adverse factors for PFS. The 5-year PFS in patients with or without GTR was 63.8% and 6.3%, respectively, and in patients with or without radiotherapy was 42.7% and 23.1%, respectively. A multivariate model demonstrated non-GTR (HR 9.089, p < 0.001), no radiotherapy (HR 3.126, p = 0.004), and no chemotherapy (HR 3.621, p = 0.004) as independent adverse factors for poor OS. The 5-year OS in patients with GTR, radiotherapy, or chemotherapy was 72.1%, 44.0%, and 58.0%, respectively. In contrast, in patients without GTR, radiotherapy, or chemotherapy, the 5-year OS was 5.8%, 14.3%, and 15.8%, respectively. Overall, in patients receiving GTR plus chemoradiotherapy, the actuarial 5-year PFS and OS were both 87.5%.

CONCLUSIONS

MEPL is a rare neoplastic entity with a poor prognosis. There are no distinguishing radiological features apart from cystic degeneration. Via the pooled analysis, the authors identified independent adjustable factors associated with PFS and OS, from which they advocate for GTR plus chemoradiotherapy with a sufficient dose if tolerable as an optimal treatment to improve outcomes. Future studies with large cohorts will be necessary to verify our findings.

ABBREVIATIONS AuPBSCT = autologous peripheral blood stem cell transplantation; CSI = craniospinal irradiation; GTR = gross-total resection; KPS = Karnofsky Performance Scale; MEPL = medulloephithelioma; OS = overall survival; PFS = progression-free survival; PR = partial resection; STR = subtotal resection.

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Article Information

Correspondence Wang Jia: Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China. jiawangttyy@163.com.

INCLUDE WHEN CITING Published online July 6, 2018; DOI: 10.3171/2018.1.JNS172509.

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.

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Figures

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    Case 2. A: Preoperative CT scan revealing a right frontal lobe lesion with intralesional hemorrhage, peritumoral edema, and a mass effect. B–D: Preoperative axial T2-weighted (B), T1-weighted (C), and contrast-enhanced (D) MRI scans showing a cystic-solid lesion with enhancement. E and F: Postoperative axial T1-weighted (E) and contrast-enhanced (F) MRI scans showing total resection. In this case, total resection was evaluated according to the following signs. 1) The main solid and cystic components had been completely removed. 2) The resected extent had been extended and included regions approximately 0.5–1.0 cm surrounding the contrasted lesions and the cyst wall. 3) The peritumoral edema zone had been removed, which was absent on the postoperative MRI scans. 4) The frontopolar cortex and the anteromedial cyst wall (arrows in E) adjacent to the falx had been totally removed. 5) The notable contrast enhancement along the surgical cavity wall was significantly more intense and thicker than that in the preoperative cyst wall, and the postoperative radiological features after contrast enhancement were more likely associated with postoperative changes (i.e., minor bleeding and hemostasis material) rather than residuals; additionally, on the postoperative T1-weighted image (E), the hyperintense signal along the surgical cavity wall suggested postoperative changes that were quite different from signals of the preoperative MRI. 6) Because of an absence of parenchyma, the contrast enhancement along the falx and the frontopolar dura (F) precluded the possibility of residual. 7) Finally, most importantly, resection of this lesion was performed along the boundary between tumor and normal parenchyma, followed by extended resection that guaranteed total resection.

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    Histopathological examination revealed the typical morphology of MEPL. A–D: Based on H & E staining, MEPL displayed multipotential cellular lineages including a full spectrum of glioneuronal differentiation, and showed the structure of the primitive neuroepithelium arranged in tubular, ribbon-like, and/or papillary rosette formations lined by mitotic, pseudostratified columnar cells that resemble embryonic neural tube. E: Cytokeratin was focally presented in the neural tube–like structures. F: The Ki-67 proliferation index was calculated approximately up to 50%. G and H: Diffuse membranous CD99 and CD56 expression in neoplastic cells. I: GFAP immunoreactivity was evident in abundant primitive cells close to neuroepithelial structures. J: Neoplastic cells were strongly diffusely positive for MAP-2. K: Strong nestin immunoreactivity was seen in the epithelial structures. L: Local synaptophysin immunoreactivity was expressed. Figure is available in color online only.

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    Kaplan-Meier analyses illustrating the PFS (n = 38) and OS (n = 58) of MEPL based on the literature and our cohort (A), and showing the significantly different PFS (B) and OS (C) in patients reported before 2007 or later. This confounding factor was taken into consideration when performing the multivariate analysis. Chi-square values were obtained by log-rank (Mantel-Cox) testing during the Kaplan-Meier curve analysis. EMPT = estimated median PFS time; EMST = estimated median survival time. Figure is available in color online only.

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    Kaplan-Meier survival curves illustrating the different PFS (A–D) and OS (E–H) in patients with risk factors. Patients younger than 6 years (A), who did not undergo GTR (B), or had no radiotherapy (C) had a significantly worse PFS. Although the different PFS in patients with or without chemotherapy was not significant, the survival curve showed a poor outcome trend and shortened survival time in patients who did not undergo chemotherapy (D). The OS was significantly worse in patients younger than 6 years (E), those who did not undergo GTR (F), and had no radiotherapy (G) or chemotherapy (H). Chi-square values were obtained by log-rank (Mantel-Cox) testing during the Kaplan-Meier curve analysis. Figure is available in color online only.

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