Papillary Glioneuronal Tumor Research Articles

Letter to editor: comment on, “Imaging manifestations of papillary glioneuronal tumors”

Letter to editor: comment on, “Imaging manifestations of papillary glioneuronal tumors”

Low-grade glioma of the temporal lobe and tumor-related epilepsy in children.

Low-grade glioma is the most common brain tumor among children and adolescents. When these tumors arise in the temporal lobe, patients frequently present with seizures that are poorly controlled with antiepileptic drugs. Here we summarize the clinical features, pathophysiology, preoperative evaluation, surgical treatment, and outcomes of pediatric patients with low-grade gliomas in the temporal lobe. We reviewed the literature on pediatric low-grade gliomas in the temporal lobe, focusing on cohort studies and systematic reviews that described surgical treatment strategies and reported both oncologic and epilepsy outcomes. The differential diagnoses of pediatric low-grade gliomas in the temporal lobe include ganglioglioma, dysembryoplastic neuroepithelial tumor, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, angiocentric glioma, and polymorphous low-grade neuroepithelial tumor of the young. There is no consensus on the optimal surgical approach for these tumors: lesionectomy alone, or extended lesionectomy with anterior temporal lobectomy, with or without removal of mesial temporal structures. Gross total resection and shorter preoperative duration of epilepsy are strongly associated with favorable seizure outcomes, defined as Engel Class I or Class II, approaching 90% in most series. The risk of surgical complications ranges from 4 to 17%, outweighing the lifetime risks of medically refractory epilepsy. Pediatric patients with temporal low-grade glioma and tumor-related epilepsy are best managed by a multidisciplinary epilepsy surgery team. Early and appropriate surgery leads to prolonged survival and a greater likelihood of seizure freedom, improving their overall quality of life.

Imaging manifestations of papillary glioneuronal tumors

To analyse the imaging findings of papillary glioneuronal tumors (PGNTs), in order to improve the accuracy of preoperative diagnosis of this tumor. The clinical and imaging manifestations of 36 cases of PGNT confirmed by pathology were analyzed retrospectively. A total of 17 males and 19 females, averaging 22.47 (± 11.23) years. Initial symptoms included epilepsy in ten, headache in seven, and others in 19 cases. 97.2% (35/36) of the lesions were located in the supratentorial area, and 80.5% (29/36) in the intraventricular or deep white matter adjacent to the lateral ventricles. Twenty-four of the lesions (66.7%) were mixed cystic and solid, four (11.1%) were cystic with mural nodules, four (11.1%) were cystic, and four (11.1%) were solid. Four cases of PGNT of cystic imaging showed a “T2-FLAIR mismatch” sign. 69.4% (25/36) had septations. Nine lesions (25%) were accompanied by edema, and 9 (25%) of the mixed cystic and solid lesions were accompanied by hemorrhage. Among the 18 patients who underwent computed tomography (CT) or susceptibility-weighted imaging (SWI), nine had lesions with calcification. PGNTs mostly manifest as cystic mass with mural nodules or mixed cystic and solid mass in the white matter around the supratentorial ventricle, and the cystic part of the lesion is mostly accompanied by septations. Pure cystic lesions may exhibit the sign of “T2-FLAIR mismatch”. PGNT is rarely accompanied by edema but sometimes by calcification and hemorrhage. Patients often present with seizures, headaches, and mass effect symptoms.

Papillary glioneuronal tumor: A rare case with recent updates as per 2021 CNS WHO 5th classification.

The papillary glioneuronal tumor is a WHO grade 1, rare neuronal-glial tumor and comprises 0.02% of all CNS tumors. Histologically, it is a mixture of glial and neuronal components showing a pseudopapillary pattern with hyalinized vessels. PGNT is considered a low-grade neoplasm, and surgical excision has been curative in most cases. In this paper, we report a new case of papillary glioneuronal tumor in a 44-year-old male having a divergent presentation, to analyze it due to the rarity of its occurrence as per the latest classification.

被误诊的乳头状胶质神经元肿瘤一例

被误诊的乳头状胶质神经元肿瘤一例

Varied histomorphology and clinical outcomes of FGFR3-TACC3 fusion gliomas.

Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.

The landscape of common genetic drivers and DNA methylation in low-grade (epilepsy-associated) neuroepithelial tumors: A review.

Low-grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long-term epilepsy-associated tumors (LEATs) includes a heterogenous group of low-grade, cortically based tumors, associated to drug-resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High-quality peer-reviewed original manuscripts and review articles with full-text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full-text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches.

Uncommon Glioneuronal Tumors: A Radiologic and Pathologic Synopsis.

Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors). Most of these tumors occur in young patients and are related to epilepsy. While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent. Advances in immunohistochemical and molecular diagnostics have improved the characterization of these tumors and favored the description of variants and new subtypes, some not yet classified by the World Health Organization. Not infrequently, the histologic findings of biopsies of glioneuronal tumors simulate low-grade glial neoplasms; however, some imaging findings favor the correct diagnosis, making neuroimaging essential for proper management. Therefore, the aim of this review was to present key imaging, histopathology, immunohistochemistry, and molecular findings of glioneuronal tumors and their variants.

Challenges in the Intraoperative Consultation of Low-Grade Epilepsy-Associated Neuroepithelial Tumors by Cytomorphology in Squash Preparations

Introduction: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) create a diagnostic challenge in daily practice and intraoperative pathological consultation (IC) in particular. Squash smears are extremely useful in IC for accurate diagnosis; however, the knowledge on cytopathologic features of LEATs is based on individual case reports. Here, we discuss the 3 most common and well-established entities of LEATs: ganglioglioma (GG), dysembryoplastic neuroepithelial tumor (DNT), and papillary glioneuronal tumor (PGNT). Methods: Thirty patients who underwent surgery for GG, DNT, and PGNT between 2001 and 2021 were collected. Squash smears prepared during intraoperative consultation were reviewed by 1 cytopathologist and an experienced neuropathologist. Results: Among the 30 tumors, 16 (53.3%) were GG, 11 (36.6%) DNT, and 3 (10%) PGNT. Cytomorphologically, all of the 3 tumor types share 2 common features such as dual cell population and vasculocentric pattern. GG smears were characteristically composed of dysplastic ganglion cells and piloid-like astrocytes on a complex architectural background of thin- to thick-walled vessels. DNT, on the other hand, showed oligodendroglial-like cells in a myxoid thin fibrillary background associated with a delicate capillary network. Common cytological features of PGNT were hyperchromatic cells with narrow cytoplasm surrounding hyalinized vessels forming a pseudopapillary pattern and bland cells with neuroendocrine nuclei dispersed in a neuropil background. Conclusion: A higher diagnostic accuracy can be obtained when squash smears are applied with frozen sections. However, it is important to integrate clinical and radiologic features of the patient as well as to know the cytopathologic features of the LEAT spectrum in the context of differential diagnosis to prevent misinterpretation in the IC.

Papillary Glioneuronal Tumor of Third Ventricle Endoscopically Treated: Case Report and Review of Literature

Introduction: Papillary Glioneuronal Tumor (PGNT) is a grade I tumor based on the new World Health Organization CNS tumor classification. Its special feature concerns its biphasic histologic pattern of both glial and neuronal elements. Because of the rarity of this entity, literature is mostly based on case reports. Research Question: The objective of this paper is to display our experience treating endoscopically a papillary glioneuronal tumor located into the third ventricle in an adult patient and to highlight the main points of the literature. Material & Methods: A 75-year-old patient with known Parkinson disease presented with episodes of loss of consciousness and gait disorders in our institution. Brain MRI demonstrated enlargement of ventricular system due to an obstruction caused by an intraventricular tumor in the third ventricle. Results: Patient underwent an endoscopic subtotal removal of the tumor. Postoperative brain CT scan revealed minor residual of the tumor and patient was discharged 2 days after surgery in good clinical condition. Histopathological analysis of the tumor samples matched the diagnosis of PGNT. Postoperative follow-up in 1 month demonstrated great neurological improvement. Discussion & Conclusion: Literature reports that total surgical resection is the treatment of choice in almost all cases of PGNT giving the most favorable clinical outcome. Only 4 cases of PGNT located in 3rd ventricle have been recorded and data for endoscopic management found only for one of the cases concerning a pediatric patient. Therefore, we report for first time removal of third ventricle papillary glioneuronal tumor in adult patients via the endoscopic technique.

P14.82 Glioneuronal tumors - a rare tumor entity with diagnostic and therapeutic challenges: report of two cases and review of literature

Abstract BACKGROUND The 2007 WHO classification of brain tumors first encompassed two new entities of glioneuronal tumors, including papillary glioneuronal tumors (PGNT) and rosette-forming glioneuronal tumours. The reviewed version of the 2016 WHO classification additionally included diffuse leptomeningeal glioneuronal tumours. The histopathological, genetic, and clinical understanding of glioneuronal tumors is currently evolving, however there are no guidelines for diagnostic and clinical management yet. MATERIAL AND METHODS We report two male patients with glioneuronal tumors and performed a review of literature. RESULTS The first patient was diagnosed with a PGNT (MIB-1 proliferation index = 5%) located in the right parietal lobe at the age of 33 years and received surgical resection. Two years later, the tumor recurred in the same location. A second tumor resection was performed followed by concomitant radiochemotherapy with temozolomide (60/2 Gray). A next-generation sequencing gene panel (Oncomine) confirmed the initial diagnosis of a PGNT. The patient has remained in remission for the past 10 years. The second patient developed complex partial seizures which were first misdiagnosed as anxiety disorder at the age of 26 years. An MRI scan revealed a contrast-enhancing bifrontal cystic lesions 5 years later and he received a gross total tumor resection. The diagnosis of a glioneuronal tumor was made, however molecular pathology and methylation analysis were not able to classify the tumor entity further. There was no evidence of tumor recurrence one year after surgery and he remained seizure-free with antiepileptic treatment. CONCLUSION Glioneuronal tumors encompass rare and heterogenous tumor entities which primarily present in young patients and often show a favorable clinical course. Although the increasing number of reports in the literature have improved our understanding of these tumors, uncertainty remains in diagnostic challenging cases and patients with progressive disease after surgery. The value of next-generation sequencing and the choice of adjuvant treatment modalities have not been systematically evaluated in this patient group.

Papillary glioneuronal tumors: Distinctive cytological characteristics and cyto-histologic correlation

Intraoperative cytological examination and cyto-histologic correlation of papillary glioneuronal tumors have rarely been described in detail in the literature. A 23-year-old female presented at our institution with seizure-like activity, and a 3.0 cm left temporal lobe hypoattenuating lesion. She was accurately diagnosed with papillary glioneuronal tumor on Intraoperative cytology. The patient subsequently proceeded to stealth-guided awake left temporal craniotomy, confirming the diagnosis. In this article, we present a detailed report of papillary glioneuronal tumor (extremely rare central nervous system neoplasm) describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature.

Sellar and parasellar lesions: multidisciplinary management.

SUMMARYIntroductionThe endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the ventral skull base. The advantage of the endoscope is enhanced visualization and improved panoramic view that can result in more complete removal of the tumor. An extensive knowledge of the anatomy is mandatory to approach this region.Materials and methodsFrom February 2009 to March 2020, the endoscopic endonasal approach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pituitary adenomas, 7 craniopharyngiomas, 3 Rathke’s cysts, a tuberculum sellae meningioma, an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma.ResultsThe most common surgical complications were cerebral spinal fluid leak (9), bleeding (2), pituitary abscess (2). Among endocrinological complications, the most important were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with meningitis. There were no visual worsening and no operative mortality. We had persistence of disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease.ConclusionsPre-operative planning and collaboration with several specialists are necessary in order to offer the patient the best treatment, minimizing complications.

Rosette-forming and papillary glioneuronal tumors - A clinicopathological and molecular analysis.

Rosette-forming glioneuronal tumors (RGNT) and papillary glioneuronal tumors (PGNT) account for < 1% of brain tumors. Genetic data regarding RGNT and PGNT is still evolving. We aimed to perform a detailed clinicopathological analysis on rosette-forming and papillary glioneuronal tumors and to evaluate these for common, known genetic mutations. Our cohort consisted of 6 cases of these rare glioneuronal tumors diagnosed over a period of 5 years. IDH1, ATRX, p53, and BRAF V600E mutations were evaluated on immunohistochemistry, and cases of RGNT were screened for the mutations in PIK3CA gene at hotspots exon 4, 9, and 20. Our findings confirm the presence of PIK3CA gene mutations in RGNT along with two novel mutations in PIK3CA gene, of which one is proposed to be of prognostic significance. .

Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA.

Papillary glioneuronal tumor (PGNT) is a WHO-defined brain tumor entity that poses a major diagnostic challenge. Recently, SLC44A1-PRKCA fusions have been described in PGNT. We subjected 28 brain tumors from different institutions histologically diagnosed as PGNT to molecular and morphological analysis. Array-based methylation analysis revealed that 17/28 tumors exhibited methylation profiles typical for other tumor entities, mostly dysembryoplastic neuroepithelial tumor and hemispheric pilocytic astrocytoma. Conversely, 11/28 tumors exhibited a unique profile, thus constituting a distinct methylation class PGNT. By screening the extended Heidelberg cohort containing over 25,000 CNS tumors, we identified three additional tumors belonging to this methylation cluster but originally histologically diagnosed otherwise. RNA sequencing for the detection of SLC44A1-PRKCA fusions could be performed on 19 of the tumors, 10 of them belonging to the methylation class PGNT. In two additional cases, SLC44A1-PRKCA fusions were confirmed by FISH. We detected fusions involving PRKCA in all cases of this methylation class with material available for analyses: the canonical SLC44A1-PRKCA fusion was observed in 11/12 tumors, while the remaining case exhibited a NOTCH1-PRKCA fusion. Neither of the fusions was found in the tumors belonging to other methylation classes. Our results point towards a high misclassification rate of the morphological diagnosis PGNT and clearly demonstrate the necessity of molecular analyses. PRKCA fusions are highly diagnostic for PGNT, and detection by RNA sequencing enables the identification of rare fusion partners. Methylation analysis recognizes a unique methylation class PGNT irrespective of the nature of the PRKCA fusion.

Tectal region papillary neuroglial tumour: a case report

Papillary glioneuronal tumor (PGNT) is a rare central nervous system neoplasm. Of reported cases, the vast majority are located in the frontal and temporal lobes. We present the case of a 39-year-old male who presented with a one day history of gait disturbance following chemotherapy treatment for metastatic rectal adenocarcinoma. Following MRI of the head showed a tectal mass. Following an occipital interhemispheric craniotomy for tumor resection, final pathology was diagnostic of a papillary neuroglial tumor, WHO grade I. To the best or out knowledge this is the only report of it arising from the tectal plate.

BRAF V600E mutation and clinicopathologic characteristics in 250 cases of brain tumors associated with epilepsy

Objective: To investigate the clinicopathologic characteristics and BRAF V600E mutation of brain tumors associated with epilepsy. Methods: Totally 250 patients with brain tumors associated with epilepsy were included from March 2008 to August 2017 retrospectively at Sanbo Brain Hospital, Capital Medical University.The clinical manifestations, histological features and BRAF V600E mutation results were collected and analyzed. Results: There were 132 males and 118 females, and the male to female ratio was 1.1∶1.0. The age of patients ranged from 2 to 67 years(mean 22 years). The tumors had obvious local space occupying effect on MRI. The temporal lobe was the most common site (44.4%, 111/250). There were 58.4% (146/250) of ganglioglioma (GG), 24.0% (60/250) of dysembryoplastic neuroepithelial tumor (DNT), 12.8% (32/250) of pleomorphic xanthoastrocytoma(PXA), 4.0% (10/250) of angiocentric glioma (AG) and 0.8% (2/250) of papillary glioneuronal tumor (PGNT). Mixed GG, PXA and DNT morphological structures were found in 9 of patients. Among 250 cases, 35 cases were accompanied by focal cortical dysplasia(FCD). BRAF V600E was seen in 43 of 74 (58.1%) GG and 13 of 28 (46.4%) PXA. The most common pathologic grade of GG, DNT, AG and PGNT was WHO I. Some of the tumor cells from GG (34 cases) showed higher proliferative activity (WHO Ⅱ/Ⅲ). Most cases of PXA were WHOⅡand high proliferative activity was seen in nine cases. Conclusions: The association of low-grade glioneuronal tumors with intractable epilepsy was well-recognized. The most common low-grade glioneuronal tumors were GG.GG may occur in any part of the central nervous system, with a predilection for temporal lobe. Each type of low-grade glioneuronal tumors has its own unique histological morphology, but some may show complex features with 2 or 3 mixed components. The occurrence of BRAF V600E mutations in GG is common, and their detection may be valuable for the diagnosis and treatment in GG.

Magnetic resonance imaging findings of mixed neuronal-glial tumors with pathologic correlation: a review.

Mixed neuronal-glial tumors are rare, and MRI diagnosis of them presents a challenge. In this review, we discuss the MRI findings of ganglioglioma, anaplastic ganglioglioma, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, and primary diffuse leptomeningeal glioneuronal tumor with clinicopathologic correlation. There is overlap of imaging features both with each other and some other tumors, which complicates diagnosis. The combination of imaging findings and the age, location, and appropriate clinical picture should allow the radiologist and the clinicians to raise a provisional diagnosis of a mixed neuronal glial tumor, and guide patient management.

Atypical Papillary Glioneuronal Tumor: A Neoplasm in Search of a Grade (P6.100)

Atypical Papillary Glioneuronal Tumor: A Neoplasm in Search of a Grade (P6.100)

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

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. 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. 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 therapy (χ2 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). 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.