Elsevier

World Neurosurgery

Volume 107, November 2017, Pages 534-541
World Neurosurgery

Original Article
Surgical Resection and Cellular Proliferation Index Predict Prognosis for Patients with Papillary Glioneuronal Tumor: Systematic Review and Pooled Analysis

https://doi.org/10.1016/j.wneu.2017.08.041Get rights and content

Background

Although the World Health Organization classifies papillary glioneuronal tumor (PGNT) as a grade I tumor, several malignant cases have been reported. In this study, we examined the clinical and prognostic characteristics of PGNT.

Methods

PubMed, Embase, and institutional databases were queried for patient-level reports of PGNT, resulting in identification of 138 cases. Descriptive and Kaplan–Meier survival analyses were conducted. The threshold of significance was 0.05.

Results

The mean age at presentation was 26.9 ± 16.3 years, and the incidence was higher in males (1.42:1). Tumors with a high Ki-67 index (≥5) were more likely to exhibit perilesional edema and ring enhancement on magnetic resonance imaging, trending toward significance (P = 0.114 and 0.113, respectively). Compared with tumors with a low Ki-67 index (<5), those with a high Ki-67 index were more likely to be treated with subtotal resection (STR) than with gross total resection (GTR) (Kruskal–Wallis test, P = 0.006) and with radiation therapy2 test, P = 0.010). At 5 years post-treatment, PGNT had a mean progression-free survival (PFS) of 85.9 ± 3.9%. Males had a better 5-year PFS than females (94.0 ± 3.4% vs. 74.8 ± 7.8%; Mantel–Cox test, P = 0.002). Two-year PFS was higher after GTR than after STR (91.9 ± 3.6% vs. 46.7 ± 21.4%; Mantel–Cox test, P < 0.001). A low Ki-67 index was associated with a higher 5-year PFS compared with a high Ki-67 index (94.8 ± 3.6% vs. 55.6 ± 12.9%; Mantel–Cox test, P < 0.001).

Conclusions

PGNT is a benign tumor of young adults, but can present atypically as high grade. Male sex, low cellular proliferation, and maximal surgical resection are positive prognostic indicators for PGNT.

Introduction

Papillary glioneuronal tumor (PGNT) is a rare brain tumor recently classified as a unique clinicopathologic entity in the 2007 World Health Organization (WHO) classification of central nervous system tumors.1 First characterized by Komori et al.,2, 3 PGNT is most commonly reported in young adults, occurring in the white matter of the cerebral hemispheres with proximity to the ventricular system. Patients often present with headaches, seizures, and mass effect symptoms.4

These tumors can demonstrate solid, cystic, and occasionally nodular components on magnetic resonance imaging (MRI).5 Histologically, they exhibit a mixed glial and neuronal differentiation. The glial component is characterized by glial fibrillary acidic protein (GFAP)-positive cuboidal cells arranged in a papillary architecture, overlaying hyalinized vessels. The neuronal component occurs in interpapillary regions, consisting of homogenous neurocyte-like cells, oligodendrocyte-like cells, and ganglioid cells.1 Using fluorescence in situ hybridization, several studies have identified SLC44A1-PRKCA, a novel and specific fusion product in PGNT consisting of a choline transporter-like protein and a serine/threonine-specific protein kinase.6, 7, 8 Routine diagnosis remains challenging and relies on neuroimaging and histology.

Although the 2007 and 2016 WHO classification of central nervous system tumors designated PGNT as a grade I tumor,1, 9 increasing numbers of cases of malignant or aggressive PGNT have been reported.10, 11, 12, 13, 14, 15, 16 Bourekas et al.17 reported a case of anaplastic PGNT in a 19-year-old patient who, after undergoing surgical resection, radiation therapy, and chemotherapy, presented with pleural metastases and subcarinal and retroperitoneal lymphadenopathy.

Several case series have attempted to characterize PGNT; however, because of its rarity, it has not yet been comprehensively described. The purpose of this study was to identify the common clinical characteristics of this rare tumor and to delineate predictors of long-term prognosis, information that can aid the diagnosis and management of PGNT.

Section snippets

Methods

PubMed and Embase were queried for “papillary glioneuronal tumor/tumour” or “PGNT” in a systematic review of the literature. PRISMA guidelines were followed, entailing the use of distinct inclusion and exclusion criteria, careful extraction of data, and a summarization of results.18 Inclusion criteria included patient-level data and English-language text. Purely histological or genetic analyses without patient data were excluded. The citations in all publications were cross-referenced for

Results

A total of 132 cases were identified in the literature, and 6 additional cases were identified in institutional databases, for a total of 138 cases.3, 5, 7, 8, 10, 11, 12, 13, 14, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68 The mean patient age at presentation for PGNT was 26.9 ± 16.3 years. More than 80% of cases were reported in

Discussion

It has been 20 years since PGNT was first reported in the literature.3, 19 Studies of the natural history of PGNT are limited by the tumor's rarity and geographic scarcity. Long-term data on such rare tumors are severely lacking. The present study represents the most comprehensive clinical examination of PGNT published to date.

PGNT is considered a tumor of young adults, as demonstrated here by the mean age at presentation of approximately 27 years. However, several cases were reported in the

Conclusion

PGNT is a benign tumor of young adults, but can present atypically as high grade and across the human lifespan. It has a higher incidence in males, and has a predilection for the ventricular system. Male sex, low Ki-67 cellular proliferation index, and maximal surgical resection are positive prognostic indicators for PGNT. This study represents the most comprehensive clinical information on this rare tumor published to date.

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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