CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Subependymomas of the fourth ventricle: To operate or not to operate?

BACKGROUND: There is a paucity of literature regarding the clinical characteristics and management of subependymomas of the fourth ventricle due to their rarity. Here, we describe the operative and non-operative management and outcomes of patients with such tumors. METHODS: This retrospective single-institution case series was gathered after Institutional Review Board (IRB) approval. Patients diagnosed with a subependymoma of the fourth ventricle between 1993 and 2021 were identified. Clinical, radiology and pathology reports along with magnetic resonance imaging (MRI) images were reviewed. RESULTS: Patients identified (n = 20), showed a male predominance (n = 14). They underwent surgery (n = 9) with resection and histopathological confirmation of subependymoma or were followed with imaging surveillance (n = 11). The median age at diagnosis was 51.5 years. Median tumor volume for the operative cohort was 8.64 cm3 and median length of follow-up was 65.8 months. Median tumor volume for the non-operative cohort was 0.96 cm3 and median length of follow-up was 78 months. No tumor recurrence post-resection was noted in the operative group, and no tumor growth from baseline was noted in the non-operative group. Most patients (89 %) in the operative group had symptoms at diagnosis, all of which improved post-resection. No patients were symptomatic in the non-operative group. CONCLUSIONS: Surgical resection is safe and is associated with alleviation of presenting symptoms in patients with large tumors. Observation and routine surveillance are warranted for smaller, asymptomatic tumors.

Intramedullary Subependymoma Of Lower Thoracic Cord.

Spinal subependymoma (SSE) is a rare intramedullary, benign tumour. Surgical excision isthe preferred approach. However, the interwoven pattern of neural tissue within the tumour dictates the extent of resection. Where gross total resection is linked with possible neurological deficits, subtotal resection or close observation may support better functional outcomes. The evidence for the management of SSE is based mostly on case reports. Herein, we review the existing literature regarding treatment options and clinical outcomes of spinal subependymoma.

Tumors of Choroid Plexus and Other Ventricular Tumors.

Tumors arising inside the ventricular system are rare but represent a difficult diagnostic and therapeutic challenge. They usually are diagnosed when reaching a big volume and tend to affect young children. There is a wide broad of differential diagnoses with significant variability in anatomical aspects and tumor type. Differential diagnosis in tumor type includes choroid plexus tumors (papillomas and carcinomas), ependymomas, subependymomas, subependymal giant cell astrocytomas (SEGAs), central neurocytomas, meningiomas, and metastases. Choroid plexus tumors, ependymomas of the posterior fossa, and SEGAs are more likely to appear in childhood, whereas subependymomas, central neurocytomas, intraventricular meningiomas, and metastases are more frequent in adults. This chapter is predominantly focused on choroid plexus tumors and radiological and histological differential diagnosis. Treatment is discussed in the light of the modern acquisition in genetics and epigenetics of brain tumors.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas.

OBJECTIVE: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the "ribbon sign." METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The "ribbon sign" was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 10 patients with IMSC subependymomas. The ribbon sign was demonstrated on 9 (90%) patients with histologically proven subependymomas. Other tumor types did not display the ribbon sign. CONCLUSION: The ribbon sign is a potentially distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumors. Recognition of the ribbon sign should prompt clinicians to consider a diagnosis of subependymoma, aiding the neurosurgeon in planning the surgical approach and adjusting the surgical outcome expectation. Consequently, the risks and benefits of gross-versus subtotal resection for palliative debulking should be carefully considered and discussed with patients.

Epigenetic Alteration of H3K27me3 as a Possible Oncogenic Mechanism of Central Neurocytoma.

Central neurocytoma (CN) is a low-grade neuronal tumor that mainly arises from the lateral ventricle (LV). This tumor remains poorly understood in the sense that no driver gene aberrations have been identified thus far. We investigated immunomarkers in fetal and adult brains and 45 supratentorial periventricular tumors to characterize the biomarkers, cell of origin, and tumorigenesis of CN. All CNs occurred in the LV. A minority involved the third ventricle, but none involved the fourth ventricle. As expected, next-generation sequencing performed using a brain-tumor-targeted gene panel in 7 CNs and whole exome sequencing in 5 CNs showed no driver mutations. Immunohistochemically, CNs were robustly positive for FGFR3 (100%), SSTR2 (92%), TTF-1 (Nkx2.1) (88%), GLUT-1 (84%), and L1CAM (76%), in addition to the well-known markers of CN, synaptophysin (100%) and NeuN (96%). TTF-1 was also positive in subependymal giant cell astrocytomas (100%, 5/5) and the pituicyte tumor family, including pituicytoma and spindle cell oncocytoma (100%, 5/5). Interestingly, 1 case of LV subependymoma (20%, 1/5) was positive for TTF-1, but all LV ependymomas were negative (0/5 positive). Because TTF-1-positive cells were detected in the medial ganglionic eminence around the foramen of Monro of the fetal brain and in the subventricular zone of the LV of the adult brain, CN may arise from subventricular TTF-1-positive cells undergoing neuronal differentiation. H3K27me3 loss was observed in all CNs and one case (20%) of LV subependymoma, suggesting that chromatin remodeling complexes or epigenetic alterations may be involved in the tumorigenesis of all CNs and some ST-subependymomas. Further studies are required to determine the exact tumorigenic mechanism of CN.

Third Ventricular Subependymomas: Clinical Features and Outcomes Over Two Decades.

BACKGROUND: Subependymomas are uncommon, benign slow-growing neoplasms of the central nervous system preferentially arising within the fourth and lateral ventricles. Third ventricle involvement has been described rarely. The aim of this study is to provide the first systematic review of third ventricular subependymomas (TVSE) by analyzing all reported cases over 2 decades and describing a case example. METHODS: MEDLINE and Embase databases were searched for the 20 years ending January 1, 2022, using relevant MeSH and non-MeSH terms, including "subependymoma" and "third ventricle." Methodology followed PRISMA guidelines. RESULTS: Of 804 identified studies, 131 met inclusion eligibility. The literature yielded 17 patients with TVSE plus our example (18 total). Of these patients, 83% (15/18) presented in adulthood (average age, 42 ± 19 years), of whom 73% were women. The pediatric cohort age was 5 ± 1 years, 67% (4/6) of whom were girls. The most common presenting symptom in both cohorts was headache (80%), followed by memory disturbances and vomitus. In adults, symptomatic tumors were approached by open craniotomy in all but 1 case, most using a transcallosal approach. Gross total resection was obtained in 73%. A ventriculoperitoneal shunt was inserted in 2/15 adult and 4/6 pediatric patients. Overall, both cohorts showed symptomatic improvement without disease recurrence. One patient died perioperatively. CONCLUSIONS: Subependymomas should be considered in the differential diagnosis of third ventricular tumors. The clinical presentation of TVSE mainly parallels hydrocephalus symptoms and, hence, awareness is of vital importance for timely treatment. The surgical goal should be gross total resection, which can be curative and offers greatest clinical improvement across the population.

Possible association of trichorhinophalangeal syndrome I and intracranial subependymoma.

Trichorhinophalangeal syndromes (TRPSs) are rare hereditary syndromes with autosomal dominant inheritance. Patients exhibit abnormalities including bulbous pear-shaped nose, broad columella, and long and flat philtrum, fine, sparse, brittle, slow-growing scalp hair, skeletal abnormalities, and short stature. Three families; age at subependymoma surgery, pathogenic TRPS1(NM_014112.5) variant, and subependymoma number are described.

A Case of Cerebellar Intraparenchymal Subependymoma with Next-Generation Sequencing Analysis.

Subependymomas are rare, intraventricular glial tumors histologically characterized by clusters of small uniform cells distributed in an abundant fibrillary matrix. These tumors can arise in the parenchyma of the cerebrum, cerebellum, or spinal cord. Herein, we report an extremely rare case of cerebellar intraparenchymal subependymoma in a 62-year-old woman. The patient presented with dizziness for several years, and brain magnetic resonance imaging revealed a well-defined solid mass in the right cerebellum, upon which a stereotactic biopsy was performed. Histologically, the tumor showed a distinctive multinodular pattern with unevenly distributed glial cells and an abundant fibrillary matrix. Next-generation sequencing analysis showed balanced genomes without genetic alterations, including single-nucleotide variants, small insertions, deletions, or copy number alterations. Follow-up magnetic resonance imaging revealed that the size of the mass has not changed; the patient has not received any surgical treatments since the pathologic diagnosis and is living healthily.

Survival of patients and risk factors for subependymoma: a population-based study.

OBJECTIVE: Given the paucity of data on the subependymoma, we aimed to evaluate its risk factors from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We collected survival and clinical information on patients with subependymoma diagnosed between 1975 and 2016 from the SEER database and screened them according to inclusion and exclusion criteria. Then, univariate and multivariate Cox regression analyses were used to identify significant prognostic factors, and nomograms were constructed to visualize the results. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were used to assess the predictive ability of the nomogram. We divided the patient scores into two groups according to the high- and low-risk groups and constructed a survival curve using Kaplan-Meier analysis. RESULTS: A total of 731 patients were initially enrolled, including 511 (69.9%) males and 220 (30.1%) females. After screening, a total of 581 patientswere further evaluated by statistical analysis. The 5- and 10-year survival estimates were 92.0% and 81.9%, respectively. Sex (male, p=0.018; HR=2.3547, 95% CI=1.158-4.788) and age (≥56 years, p<0.001; HR=5.640, 95% CI= 3.139-10.133) were identified as independent prognostic factors for overall survival. The nomogram contained 4 prognostic factors. The C-index was 0.741, and the ROC and calibration curves also indicated the good predictability of the nomogram. CONCLUSION: In this large cohort, a significant association was noted between age/sex and outcome, which could serve an important role for patient education. Even though a significant association was not found between the extent of resection and outcome, the effect of surgery on prognosis should be further explored.Abbreviations: AUC: area under the curve; CI: confidence interval; C-index: concordance index; CNS: central nervous system; GTR: gross total resection; HR: hazard ratio; NOS: not specific; OS: overall survival; PTR: partial resection; ROC: receiver operating characteristic; SEER: Surveillance, Epidemiology, and End Results; STR: subtotal resection; WHO: World Health Organization.

Imaging characteristics of 4th ventricle subependymoma.

PURPOSE: Subependymomas located within the 4th ventricle are rare, and the literature describing imaging characteristics is sparse. Here, we describe the clinical and radiological characteristics of 29 patients with 4th ventricle subependymoma. METHODS: This is a retrospective multi-center study performed after Institutional Review Board (IRB) approval. Patients diagnosed with suspected 4th ventricle subependymoma were identified. A review of clinical, radiology, and pathology reports along with magnetic resonance imaging (MRI) images was performed. RESULTS: Twenty-nine patients, including 6 females, were identified. Eighteen patients underwent surgery with histopathological confirmation of subependymoma. The median age at diagnosis was 52 years. Median tumor volume for the operative cohort was 9.87 cm3, while for the non-operative cohort, it was 0.96 cm3. Thirteen patients in the operative group exhibited symptoms at diagnosis. For the total cohort, the majority of subependymomas (n = 22) were isointense on T1, hyperintense (n = 22) on T2, and enhanced (n = 24). All tumors were located just below the body of the 4th ventricle, terminating near the level of the obex. Fourteen cases demonstrated extension of tumor into foramen of Magendie or Luschka. CONCLUSION: To the best of our knowledge, this is the largest collection of 4th ventricular subependymomas with imaging findings reported to date. All patients in this cohort had tumors originating between the bottom of the body of the 4th ventricle and the obex. This uniform and specific site of origin aids with imaging diagnosis and may infer possible theories of origin.

Tumor characteristics and surgical outcomes of intracranial subependymomas: a systematic review and meta-analysis.

OBJECTIVE: The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. METHODS: A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. RESULTS: Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). CONCLUSIONS: Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

Sincronía de diferentes tumores radioinducidos en superviviente de leucemia linfoblástica aguda / Different radioinducid tumors synchrony in an acute lymphoblastic leukemia survivor

La aparición de tumores craneales inducidos por radiación en pacientes pediátricos tratados de enfermedades hematológicas como la leucemia/linfoma linfoblástico T (T-ALL/LBL) es un fenómeno conocido que puede incluir lesiones de diferentes grados de malignidad y precisar tratamiento neuroquirúrgico. Presentamos el caso de un varón de 38 años remitido a nuestro servicio por la aparición brusca de diplopía con hemiparesia izquierda progresiva de 6 meses de evolución y caídas frecuentes. Tras realización de pruebas de imagen, se objetivan distintas lesiones intraaxiales y extraaxiales con diferente comportamiento radiológico decidiéndose un abordaje quirúrgico único para su exéresis. La anatomía patológica confirma cuatro variantes histológicas: meningioma (grado 1 y 2 [atípico]), subependimoma y cavernoma. Discutimos el papel teratogénico y efectos biológicos de las radiaciones ionizantes (AU)

The cranial radiation-induced tumors appearance in pediatric patients treated for hematological diseases such as leukemia/T-lymphoblastic lymphoma (T-ALL/LBL) is a known phenomenon that may include lesions of different malignant degrees and require neurosurgical treatment. We present the case of a 38-year-old man referred to our department for a sudden diplopia with 6-month progressive left hemiparesis and frequent falls. After imaging tests, different intra and extraxial lesions with different radiological behavior were observed, performing a single surgical approach for their resection. The pathological anatomy confirms four histological variants: meningioma (grade 1 and 2 [atypical]), subependymoma, and cavernoma. We discuss the teratogenic role of ionizing radiation (AU)

A case of chronic dysaesthesia in the torso and upper limbs: lessons from a cervical spinal cord subependymoma.

INTRODUCTION: Subependymomas are slow growing WHO grade 1 tumours, typically attached to the ventricular wall of the fourth or lateral ventricles. Spinal subependymomas are rarer still and experience of their biological characteristics remains limited. CASE PRESENTATION: A 29-year-old lady presented with chronic attacks of itchy dysaesthesia involving the left hand, neck and trunk, and associated with ipsilateral leg spasms. Recent symptomatic change involved occasional limping and left sided facial numbness but no pain. MRI showed an intradural mass surrounding most of the cervical spinal cord, which appeared scalloped extrinsically, rather than diffusely expanded, by a seemingly extramedullary lesion. At operation, the cord appeared expanded, with no clear margin or distinction between tumour and cord tissue; and the tumour was found to be intramedullary with an exophytic component, rather than extramedullary. Moderate reduction of the left abductor pollicis brevis evoked potential led to a pause in surgery. There was transient hand weakness postoperatively with full recovery, and no radiological change in the tumour morphology for a further 6 years. DISCUSSION: An intramedullary tumour such as a spinal cord subependymoma can be mistaken radiologically for an extramedullary tumour, such as an epidermoid. If a subependymoma is suspected, given its indolent course and long-term survival, caution in the extent of surgical resection is advisable in order to avoid surgical morbidity.

Spinal cord subependymoma mimicking syringomyelia in a child: a case report.

Spinal cord subependymomas (SCSEs) in children are extremely rare, and no reports distinguishing SCSEs from syringomyelia have been published. We report a case of a 10-year-old boy who presented with torticollis, scoliosis, as well as pain that had begun in the posterior portion of the neck and progressed to the right shoulder and upper arm. Magnetic resonance imaging showed an intramedullary cyst-like lesion with the same signal intensity as that of cerebrospinal fluid. Idiopathic syringomyelia with scoliosis was first suspected, and a syrinx-subarachnoid space shunt was performed. After surgery, the lesion was slightly smaller; however, 2 years after surgery, it had re-grown, causing excruciating pain but no other symptoms. A second surgery was performed, and gross total resection was achieved. Pathological evaluation revealed SCSE. SCSE needs to be considered as a differential diagnosis for spinal centric cyst-like lesions in children.

A rare case of intraparenchymal subependymoma in a child.

Subependymoma is a slow-growing, exophytic, intraventricular glial neoplasm that commonly arises in the ventricular system. However, a report found that the frequency of intracerebral subependymoma was 0.4% in 1000 routine autopsies. To the best of our knowledge, only seven cases of intracerebral subependymoma have been reported. We report a rare case of intracerebral subependymoma in a child. An 11-year-old girl with generalized tonic-clonic seizures visited the emergency room and had an intraparenchymal tumor on the left frontal lobe on magnetic resonance imaging (MRI). Craniotomy with gross total removal was performed without any perioperative morbidities. The tumor was finally histopathologically diagnosed as a subependymoma.