Mixed glioneuronal tumor: A dysembryoplastic neuroepithelial tumor with rosette‐forming glioneuronal tumor component

Neuronal and mixed neuronal‐glial tumors of the CNS show a wide spectrum of components. Here, we report an unusual case of brain tumor with combined histological features of dysembryoplastic neuroepithelial tumor (DNT) and rosette‐forming glioneuronal tumor (RGNT) in a 23‐year‐old man. It arose in the left anterior cingulate cortex with a pseudo‐polycystic appearance on neuroimaging. Histological features contained the “specific glioneuronal element” mimicking DNT and the components of distinct neurocytic rosettes with a center of neuropil islands and pilocytic astrocytoma resembling RGNT. Although the mechanisms of mixed glioneuronal tumor are far from being well‐known, their co‐existence might suggest a possible etiologic relationship between DNT and RGNT.     

A peculiar histopathological form of dysembryoplastic neuroepithelial tumor with separated pilocytic astrocytoma and rosette‐forming glioneuronal tumor components

Dysembryoplastic neuroepithelial tumors (DNTs) mostly display typical clinical, neuroimaging and histopathological features, but sometimes they reveal heterogeneous or non‐specific morphology, which results in diagnostic dilemmas. We present a case of a young adult with longstanding, intractable epilepsy associated with a multinodular cystic lesion in the temporal lobe. The lesion consisted of morphologically different components. In particular, a few cortical nodules displayed a specific glioneuronal element with floating neurons typically found in DNT. Two large, well‐circumscribed nodules were entirely composed of biphasic, piloid, astroglial patterns that corresponded strictly to a pilocytic astrocytoma. The well‐defined areas, which contained numerous distinct neurocytic‐like rosettes, were identical with rosette‐forming glioneuronal tumors (RGNTs). This type of neurocytic rosette was widespread within the surrounding piloid background. Some solid nodules exhibited increased cellularity, oligodendroglioma‐like elements and a focal ribbon cell arrangement. The lesion was associated with advanced reactive gliosis and foci of dysplastic changes in the adjacent cortex. The clinico‐radiological and main histopathological features were consistent with a diagnosis of a complex variant of DNT composed of pilocytic and rosette‐forming glioneuronal components. Although both piloid tissue and rosette‐like formations have been occasionally mentioned in DNT lesions, the present case of DNT was unique in its well‐circumscribed, separate pilocytic and RGNT nodules. We concluded that it represented an unusual, mixed pilocytic/RGNT variant of DNT.     

18例罕见胚胎发育不良性神经上皮肿瘤的治疗

目的探讨胚胎发育不良性神经上皮肿瘤（dysembryoplastic neuroepithelial tumor，DNT）的临床治疗特点。方法对2001年至2007年治疗18例DNT病人的临床症状，影像学、电生理和病理资料进行回顾性分析。结果18例DNT病人表现癫痫发作，发作形式与部位有关，14例行脑电图描记，其中10例行术中皮层脑电图描记切除病灶，术后随访1月～6年，3例仍有癫痫发作，15例癫痫发作消失，无肿瘤复发。结论DNT属良性肿瘤，手术效果良好，行术中脑电图描记可有效切除癫痫灶。     

胚胎发育不良性神经上皮肿瘤的诊断和外科治疗

目的探讨胚胎发育不良性神经上皮肿瘤的临床特点、诊断及治疗。方法回顾性分析4例胚胎发育不良性神经上皮肿瘤的临床资料。肿瘤位于颞叶2例,额叶2例。临床表现为反复癫疒间发作。均行开颅肿瘤切除术,术中在脑电监测下对周边致疒间区给予切除。结果颞叶肿瘤脑电图间歇期及发作期均表现为与肿瘤部位相关的异常放电;额叶肿瘤脑电间歇期亦表现为与肿瘤部位相关的异常放电,而发作期则表现为全头或弥漫性放电。手术均全切除肿瘤,术后病理均为胚胎发育不良神经上皮肿瘤。随访6～15个月,无癫疒间发作,MRI显示肿瘤无复发。结论胚胎发育不良性神经上皮肿瘤经手术切除可治愈,术后不需放疗及化疗。     

Rosette‐forming glioneuronal tumor of the fourth ventricle with advanced microvascular proliferation – a case report

Rosette‐forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described novel type of primary brain tumor that was included into the current WHO classification of CNS tumors. It is a very rare, slowly growing, mixed neoplasm at cerebellar localization with distinctive morphological pattern. We present an unusual case of a 20‐year‐old patient with RNGT of the fourth ventricle with advanced microvascular proliferation. MRI revealed the solid‐cystic tumor mass largely involving the cerebellar vermis and left hemisphere with compression of the fourth ventricle. Microscopically, the tumor showed classical architectural pattern with two distinctive components. The main component consisted of neurocytic rosettes formed by round, isomorphic nuclei arranged around eosinophilic, fibrillar cores with strong synaptophysin expression. The perivascular rosettes with cell arrangement along blood vessels were observed only sporadically. The second neoplastic component consisted of spindle or stellate astroglial cells with piloid process and Rosenthal fibers, strongly resembling pilocytic astrocytoma. Focally, the astroglial cells showed increased cellularity but without marked nuclear atypia. The glial part of the tumor revealed advanced proliferation of microvessels. The vessels of glomeruloid type exhibited multilayered endothelial proliferation and marked mitotic activity. MIB1 labelling index was generally low; however, in areas exhibiting microvascular proliferation its expression was significantly increased up to 20%. This report demonstrates the unique case of RGNT with conspicuous microvascular proliferation of glomeruloid type and extensive endothelial proliferation. As there is still limited clinical experience with RGNT, further studies are necessary to evaluate the biology of this type of tumor.     

Olig2‐positive cells in glioneuronal tumors show both glial and neuronal characters: The implication of a common progenitor cell?

Glioneuronal tumors (GNTs) are rare neoplasms consisting of both glial and neuronal components. Among the GNTs, dysembryoplastic neuroepithelial tumors (DNTs), papillary glioneuronal tumors (PGNTs), and rosette‐forming glioneuronal tumors of the fourth ventricle (RGNTs) share the character of being mainly composed of small round Olig2‐positive tumor cells. Using immunohistochemistry and fluorescence in situ hybridization, we examined a series of 35 GNT cases (11 DNTs, 15 PGNTs and 9 RGNTs) on the characteristics of Olig2‐positive tumor cells. Histologically, Olig2‐positive cells showed small round forms in most GNTs; however, there were a small number of Olig2‐positive cells with neuronal morphology only in a PGNT case. These cells expressed both glial and neuronal markers by double immunostaining. With regard to labeling indices and intensity, only PGNT cells expressed neuronal markers, including α‐internexin and neurofilament. These findings also suggest that some Olig2‐positive PGNT cells may show neuronal differentiation. In GNTs, a considerable number of Olig2‐positive cells showed immunopositivity for cyclin D1 and/or platelet‐derived growth factor receptor alpha (PDGFRα), which are markers for oligodendrocyte progenitor cells. These immunostainings were particularly strong in DNTs. In RGNTs, Olig2‐positive cells formed “neurocytic rosettes”. Furthermore, they were also immunopositive for glial markers, including GFAP, PDGFRα and cyclin D1. These findings indicate the heterogeneous characteristics of Olig2‐positive cells in GNTs, and some of them also exhibited neuronal features. So it is possible that a part of Olig2‐positive GNT cells have characteristics similar to those of progenitor cells.     

胚胎发育不良性神经上皮肿瘤继发癫痫的外科治疗

目的 探讨胚胎发育不良性神经上皮肿瘤(DNT)继发癫痫的临床特点和手术疗效.方法 回顾性分析2014年12月至2019年1月手术治疗并经病理证实的53例DNT合并癫痫的临床资料.结果 肿瘤次全切除9例,全切除23例,扩大切除21例.术后病理检查结果均为DNT,其中合并局灶性脑皮质发育不良20例、海马硬化4例、神经节细胞...     

A case of recurrent epilepsy‐associated rosette‐forming glioneuronal tumor with anaplastic transformation in the absence of therapy

Rosette‐forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy‐associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5‐year‐old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET‐like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high‐grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild‐type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high‐grade regions. By immunohistochemistry there was loss of nuclear alpha‐thalassemia mental retardation syndrome, X‐linked (ATRX) expression only in the high‐grade region. Next‐generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high‐grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q‐codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole‐arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy.     

Review: Molecular characteristics of long‐term epilepsy‐associated tumours (LEATs) and mechanisms for tumour‐related epilepsy (TRE)

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour‐related epilepsy (TRE) has a profound impact on patients with brain tumours and these seizures are often refractory to anti‐epileptic treatments, resulting in long‐term disability and patient morbidity. Despite the drastic impact of epilepsy‐associated tumours on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards further understanding of the molecular and developmental backgrounds of specific epilepsy‐associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of TRE. In this review, we aim to summarize the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy‐associated tumours.     

Multifocal dysembryoplastic neuroepithelial tumours associated with refractory epilepsy

Dysembryoplastic neuroepithelial tumours (DNET) are a common cause of tumour‐associated epilepsy, and are usually located in the temporal lobes. We present a case of multifocal DNETs in both infra‐ and supra‐tentorial locations, in a 23‐year‐old man with a coincident Type I Chiari malformation, presenting with medically refractory focal seizures. The extensive anatomical distribution of the lesions suggests a genetic component in their tumourigenesis.     

Diffuse form of dysembryoplastic neuroepithelial tumour: the histological and immunohistochemical features of a distinct entity showing transition to dysembryoplastic neuroepithelial tumour and ganglioglioma

I. Bodi, R. Selway, P. Bannister, L. Doey, N. Mullatti, R. Elwes and M. Honavar (2012) Neuropathology and Applied Neurobiology 38, 411–425 Diffuse form of dysembryoplastic neuroepithelial tumour: the histological and immunohistochemical features of a distinct entity showing transition to dysembryoplastic neuroepithelial tumour and ganglioglioma Aims: A diffuse variant of dysembryoplastic neuroepithelial tumour (dDNT) has previously been described, which although composed of oligodendroglia‐like cells (OLC), astrocytes and mature neurones, lacks the multinodularity and ‘specific component’ of typical DNT. The dDNT poses a significant challenge to the neuropathologist. This study was undertaken to further characterize the histological and immunohistochemical features of dDNT. Materials and methods: Review of our archived material from epilepsy surgery identified 16 cases, in which features of dDNT predominated. Their histological and immunohistochemical features, including CD34 and nestin immunohistochemistry, were analysed. Results: Seven cases had the characteristics of pure dDNT. A further two cases of dDNT showed extension into the white matter with occasional dysplastic neurones. Two additional cases had similar features but with the presence of either single, or multiple small nodular clusters of OLC, in keeping with transition to classical DNT. Five cases showed ganglioglioma‐like areas, of which three cases had micronodule formation but with predominant dDNT pattern. In all the cases the dDNT areas showed strong CD34 and less intense nestin immunoreactivity and microglial activation highlighting the full extent of the lesions. There was variable overlap between CD34 and nestin positivity within the micronodular and/or ganglioglioma‐like areas. Conclusions: Immunoreactivity for CD34 and nestin characterizes the dDNT and helps to distinguish it from other lesions associated with epilepsy. Histological evidence indicative of transition of dDNT to other forms of DNT and ganglioglioma suggests that dDNT might be an early histogenetic form of these glioneuronal tumours.     

Focal epilepsy associated with dysembryoplastic neuroepithelial tumor in the area of the caudate nucleus

Dysembryoplastic neuroepithelial tumors (DNTs) are usually located within the supratentorial cortex, often in the temporal lobe and they are frequently associated with intractable complex partial seizures. DNTs in extracortical sites are rare. Thus far, 21 cases of 36 DNT-lesions occurring in these areas have been reported; only 8 out of them had epilepsy. We report a case of a 39-year-old woman who had pharmacoresistant epilepsy associated to a DNT in the caudate nucleus-periventricular area treated by lesionectomy. During a 4-year follow-up period, the patient was seizure free and the tumor did not recur. We discuss the hypothetical epileptogenic mechanism involved and we review the pertinent literature.     

The ‘rosette‐forming glioneuronal tumor’ of the fourth ventricle

Tumors containing both neuronal and glial components are a rare heterogeneous group with unique features that require further subclassification. The rosette‐forming glioneuronal tumor of the fourth ventricle is one of a number of recently described glioneuronal tumors, which has been accorded official WHO nosologic status only in 2007. We describe the clinical and pathologic features of two patients with rare rosette‐forming glioneuronal tumors of the fourth ventricle, one of which was associated with dysgenetic tricho‐rhinopharyngeal type I syndrome.     

胚胎发育不良性神经上皮肿瘤的致痫灶处理

目的 探讨胚胎发育不良性神经上皮肿瘤(DNT)伴药物难治性癫痫患者的外科手术治疗方法.方法 回顾性分析了第三军医大学新桥医院神经外科采用外科手术治疗14例此类患者的经验.术前和术中均进行致痫灶定位,术中在切除肿瘤的同时一并处理肿瘤外致痫灶.结果 14例患者肿瘤均得到全切,未行放疗和化疗,无肿瘤复发及恶性转化.11例患者癫痫发作得到完全控制(Engel Ⅰ级),2例患者稀少发作(Engel Ⅱ级),1例患者术后仍有频繁癫痫发作,再次手术切除肿瘤周围致痫灶后癫痫得到完全控制.结论 DNT应当按照皮质发育障碍来处理,除切除肿瘤外,积极处理肿瘤外致痫灶可获得较佳的癫痫控制结果.     

Cytogenetic study of glioneuronal tumor with neuropil‐like islands: A case report

Glioneuronal tumor with neuropil‐like islands (GTNI) is a recently recognized glioneuronal neoplasm but it was classified as an astrocytic tumor by the World Health Organization (WHO) in 2007. We performed a cytogenetic study in a case of GTNI arising in a 55‐year‐old man and analyzed its genetic alteration. It presented as a heterogeneously enhancing, multi‐lobulating solid mass on MRI. Histopathologically, the tumor showed the biphasic feature of the predominating micronodular neuropil‐like islands and the diffusely infiltrating glial component. In addition, the prominent blood vessels with perivascular hyalinization were observed. On cytogenetic study, loss of 4q, 5q, 11p and gain of 6p, 7, 8, 11q, 12p, 15q were found. The remaining tumor after subtotal resection progressed 7 months later, despite combined chemo‐ and radiotherapy. From the results, it seems that GTNI does not share pathologic or genetic features with conventional astrocytoma, suggesting a unique entity with aggressive behavior.     

Surgery for epilepsy in children with dysembryoplastic neuroepithelial tumor: clinical spectrum,seizure outcome,neuroradiology, and pathology

Introduction  Dysembryoplastic neuroepithelial tumors (DNTs) were first described by Daumas-Duport et al. in 1988 as a typically cortical tumor affecting young patients with long-standing, drug-resistant epilepsy. Methods  We reviewed the medical records of 29 patients with DNT between 1994 and 2007 at Hacettepe University Children’s Hospital retrospectively; age at the time of surgery, age at seizure onset, electroencephalography (EEG), MRI, medical treatment, surgical procedure, seizure outcome, and pathological findings were documented. Results  Male to female ratio was 15/14. Age at the time of evaluation ranged 4–24 years. Twenty-seven patients (93.1%) had complex partial seizures, one (3.44%) had simple partial seizures, and one patient had generalized seizures. Preop interictal EEG showed epileptiform discharges in 24 patients, while in five patients interictal EEG before surgery showed no epileptiform discharges. Pathologically, 24 of our patients were classified as complex type and five as simple type. MRI showed temporal lesion in 20 (68.9%) patients and nine patients had extratemporal DNT. We choose the type of surgery according to lesion and the epileptojenic zone. Finally, 27 patients had Engel Class IA and two patients had Engel Class IB outcome. Conclusion  Complete resection of the lesion with epileptojenic zone is important for seizure-free outcome. Timing of surgery, extent of surgery, and stopping antiepileptic drugs are still important factors.     

Usefulness of [11C]methionine PET in the diagnosis of dysembryoplastic neuroepithelial tumor with temporal lobe epilepsy

PURPOSE: We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). METHODS: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. RESULTS: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p = 0.045; L/C ratio, p = 0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p = 0.91) and L/C ratio (p = 0.38). CONCLUSIONS: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET.     

Papillary glioneuronal tumor with a high proliferative component and minigemistocytes in a child

Papillary glioneuronal tumor (PGNT) is a rare type of primary brain tumor. Although PGNT has traditionally been defined as a clinically indolent neoplasm, several cases with high proliferative activity and tumor recurrence have recently been reported. We report a case of PGNT in a 12‐year‐old boy who presented with epilepsy and harbored a 64 mm cystic tumor with a high proliferative component in the right temporal lobe. ¹¹C‐methionine positron emission tomography (PET) showed high uptake in the solid mass. Gross total resection of the tumor mass was achieved and the patient became seizure‐free without any neurological deficits. Histologically, the tumor contained two distinct areas of a vasocentric papilliform structure and a desmoplastic component. Minigemistocytic cells and small necrotic regions were observed adjacent to the pseudopapillae. Immunohistochemical analyses revealed both glial and neuronal differentiation. The Ki‐67 proliferation index was high (14%) in the area corresponding to the high uptake region in the ¹¹C‐methionine PET. No tumor recurrence was observed 20 months after surgery. High proliferative PGNTs are rare and to our knowledge this is only the third pediatric case of PGNT with atypical features reported in the literature. Hence, we here review the reported cases of PGNT and discuss the clinical, radiological and histological features of this malignancy.