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.

MYCN immunohistochemistry as surrogate marker for MYCN-amplified spinal ependymomas.

MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.

Pediatric spinal ependymoma with chromothripsis of chromosome 6: a case report and review of the literature.

BACKGROUND: Ependymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20-40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes. CASE PRESENTATION: We present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis of the harvested spinal ependymoma tumor sample revealed a 46,XX,-6,+7,-22,+mar[16]/46,XX[4] karyotype. Subsequent OncoScan microarray analysis of the formalin-fixed paraffin-embedded tumor sample confirmed + 7, -22 and clarified that the marker chromosome represents chromothripsis of the entire chromosome 6 with more than 100 breakpoints. Fluorescent in situ hybridization and microarray analysis showed no evidence of MYCN amplification. The final integrated pathology diagnosis was spinal ependymoma (central nervous system World Health Organization grade 2 with no MYCN amplification. CONCLUSION: This case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.

Resection of an Intradural Intramedullary C7-T1 Tumor: Technical Nuances and Complication Management.

Primary spinal cord tumors are relatively rare, comprising approximately 4%-16% of all tumors originating from the central nervous system. These tumors are anatomically separable into 2 broad categories: intradural intramedullary and intradural extramedullary. Intramedullary tumors are composed predominantly of gliomas (infiltrative astrocytoma) and ependymomas.1-4 The primary treatment approach for these tumors is surgical resection, aiming to preserve neurologic function.5-9 In Video 1, the authors showcase a step-by-step approach for microsurgical resection of a primary spinal ependymoma, with emphasis on microsurgical technique and utility of adjunct equipment, such as intraoperative ultrasound and neuromonitoring.10,11 The patient consented to the procedure.

Supratentorial extra-ventricular ependymoma as a mass lesion in a child: report and literature review.

Supratentorial extra-ventricular ependymoma (SEE) are extremely rare in pediatric population and have varied presentation based on size, location, epicentre and compression on neurovascular structure. The authors report a 7-year-old girl presenting with seizure, who had a lobar SEE on MRI scan, successfully treated by microsurgical resection and adjuvant therapy.

Lateral-type posterior fossa ependymomas in pediatric patients: a national collaborative study.

PURPOSE: To review a multicentric series of lateral-type posterior fossa ependymomas operated in the last ten years and to analyze the factors related to clinical evolution and tumor survival. METHODS: Descriptive, retrospective study. Active members of the Spanish Society of Pediatric Neurosurgery were invited to participate in this multicentric study. Clinical and radiological data were incorporated to an open database. The role of histologic grade, grade of resection, postoperative morbidities, and clinical follow-up was evaluated through bivariate associations (chi-square), Kaplan-Meier's curves (log-rank test), and multivariate analysis (binary logistic regression). RESULTS: Fourteen centers entered the study, and 25 cases with a minimum follow-up of 6 months were included. There were 13 boys and 12 girls with a mean age close to 3 years. Mean tumor volume at diagnosis was over 60 cc. A complete resection was achieved in 8 patients and a near-total resection in 5 cases. Fifteen tumors were diagnosed as ependymoma grade 2 and ten as ependymoma grade 3. Major morbidity occurred postoperatively in 14 patients but was resolved in twelve within 6 months. There were six cases of death and 11 cases of tumor progression along the observation period. Mean follow-up was 44.8 months. Major morbidity was significantly associated with histologic grade but not with the degree of resection. Overall and progression-free survival were significantly associated with complete surgical resection. At the last follow-up, 16 patients carried a normal life, and three displayed a mild restriction according to Lansky's scale. CONCLUSIONS: Lateral-type posterior fossa ependymomas constitute a specific pathologic and clinical tumor subtype with bad prognosis. Gross total resection is the goal of surgical treatment, for it significantly improves prognosis with no additional morbidity. Neurological deficits associated to lower cranial nerve dysfunction are common, but most are transient. Deeper genetic characterization of these tumors may identify risk factors that guide new treatments and stratification of adjuvant therapies.

What Factors Predict the Development of Neurologic Deficits Following Resection of Intramedullary Spinal Cord Tumors: A Multi-Center Study.

BACKGROUND: Intramedullary spinal cord tumors are challenging to resect, and their postoperative neurological outcomes are often difficult to predict, with few studies assessing this outcome. METHODS: We reviewed the medical records of all patients surgically treated for Intramedullary spinal cord tumors at our multisite tertiary care institution (Mayo Clinic Arizona, Mayo Clinic Florida, Mayo Clinic Rochester) between June 2002 and May 2020. Variables that were significant in the univariate analyses were included in a multivariate logistic regression. "MissForest" operating on the Random Forest algorithm, was used for data imputation, and K-prototype was used for data clustering. Heatmaps were added to show correlations between postoperative neurological deficit and all other included variables. Shapley Additive exPlanations were implemented to understand each feature's importance. RESULTS: Our query resulted in 315 patients, with 160 meeting the inclusion criteria. There were 53 patients with astrocytoma, 66 with ependymoma, and 41 with hemangioblastoma. The mean age (standard deviation) was 42.3 (17.5), and 48.1% of patients were women (n = 77/160). Multivariate analysis revealed that pathologic grade >3 (OR = 1.55; CI = [0.67, 3.58], P = 0.046 predicted a new neurological deficit. Random Forest algorithm (supervised machine learning) found age, use of neuromonitoring, histology of the tumor, performing a midline myelotomy, and tumor location to be the most important predictors of new postoperative neurological deficits. CONCLUSIONS: Tumor grade/histology, age, use of neuromonitoring, and myelotomy type appeared to be most predictive of postoperative neurological deficits. These results can be used to better inform patients of perioperative risk.

Imaging features to distinguish posterior fossa ependymoma subgroups.

OBJECTIVES: Posterior fossa ependymoma group A (EPN_PFA) and group B (EPN_PFB) can be distinguished by their DNA methylation and give rise to different prognoses. We compared the MRI characteristics of EPN_PFA and EPN_PFB at presentation. METHODS: Preoperative imaging of 68 patients with posterior fossa ependymoma from two centers was reviewed by three independent readers, blinded for histomolecular grouping. Location, tumor extension, tumor volume, hydrocephalus, calcifications, tissue component, enhancement or diffusion signal, and histopathological data (cellular density, calcifications, necrosis, mitoses, vascularization, and microvascular proliferation) were compared between the groups. Categorical data were compared between groups using Fisher's exact tests, and quantitative data using Mann-Whitney tests. We performed a Benjamini-Hochberg correction of the p values to account for multiple tests. RESULTS: Fifty-six patients were categorized as EPN_PFA and 12 as EPN_PFB, with median ages of 2 and 20 years, respectively (p = 0.0008). The median EPN_PFA tumoral volume was larger (57 vs 29 cm3, p = 0.003), with more pronounced hydrocephalus (p = 0.002). EPN_PFA showed an exclusive central position within the 4th ventricle in 61% of patients vs 92% for EPN_PFB (p = 0.01). Intratumor calcifications were found in 93% of EPN_PFA vs 40% of EPN_PFB (p = 0.001). Invasion of the posterior fossa foramina was mostly found for EPN_PFA, particularly the foramina of Luschka (p = 0.0008). EPN_PFA showed whole and homogeneous tumor enhancement in 5% vs 75% of EPN_PFB (p = 0.0008). All mainly cystic tumors were EPN_PFB (p = 0.002). The minimal and maximal relative ADC was slightly lower in EPN_PFA (p = 0.02 and p = 0.01, respectively). CONCLUSION: Morphological characteristics from imaging differ between posterior fossa ependymoma subtypes and may help to distinguish them preoperatively. CLINICAL RELEVANCE STATEMENT: This study provides a tool to differentiate between group A and group B ependymomas, which will ultimately allow the therapeutic strategy to be adapted in the early stages of patient management. KEY POINTS: • Posterior fossa ependymoma subtypes often have different imaging characteristics. • Posterior fossa ependymomas group A are commonly median or lateral tissular calcified masses, with incomplete enhancement, affecting young children and responsible for pronounced hydrocephalus and invasion of the posterior fossa foramina. • Posterior fossa ependymomas group B are commonly median non-calcified masses of adolescents and adults, predominantly cystic, and minimally invasive, with total and homogeneous enhancement.

When a dermatopathologist encounters the ultra-rare: A case series of superficial soft tissue/cutaneous myxopapillary ependymomas.

Myxopapillary ependymoma (MPE) is an uncommon variant of ependymoma, almost exclusively seen in conus medullaris or filum terminale. MPE can be diagnostically challenging, especially when arising extra-axially. Here we report 5 cases of superficial soft tissue/cutaneous MPE, identified across three tertiary institutions. All patients were female and three of them (3/5, 60%) were children (median age 11 years, range 6-58 years). The tumors presented as slow-growing masses of the sacrococcygeal subcutaneous soft tissues, occasionally identified after minor trauma and clinically favored to be pilonidal sinuses. Imaging showed no neuraxis connection. Macroscopically, tumors were well-circumscribed, lobulated, and solid and microscopically they exhibited typical histopathology of MPE, at least focally. Two of the tumors (2/5, 40%) showed predominantly solid or trabecular architecture with greater cellular pleomorphism, scattered giant cells, and increased mitotic activity. All tumors (5/5, 100%) showed strong diffuse immunohistochemical expression of GFAP. One tumor clustered at the category "ependymoma, myxopapillary" by methylome analysis. Two patients (2/5, 40%) had local recurrence at 8 and 30 months after the initial surgery. No patients developed metastases during the follow-up period (median 60 months, range 6-116 months). Since a subset of extra-axial MPEs behaves more aggressively, timely and accurate diagnosis is of paramount importance.

RFX2 promotes tumor cell stemness through epigenetic regulation of PAF1 in spinal ependymoma.

PURPOSE: Spinal ependymoma (SE) is a rare tumor that is most commonly low-grade and tends to recur when complete tumor resection is not feasible. We investigated the molecular mechanism induces stem cell features in SE. METHODS: Immunohistochemical staining was conducted to analyze the expression of RFX2 in tumor tissues of SE patients at different stages. The expression of tumor stemness markers (Netsin and CD133) was analyzed using western blot analysis and IF, and the efficiency of sphere formation in SE cells was analyzed. The biological activities of SE cells were analyzed by EdU proliferation assay, TUNEL, wound healing, and Transwell assays. The regulatory relationship of RFX2 on PAF1 was verified by ChIP-qPCR and the dual-luciferase assay. SE cells were injected into the spinal cord of nude mice for in vivo assays. RESULTS: RFX2 was higher in the tumor tissues of SE-III patients than in the tumor tissues of SE-I patients. RFX2 knockdown reduced the expression of tumor stemness markers in SE cells and inhibited the sphere formation efficiency. Moreover, RFX2 knockdown ameliorated the malignant progression of SE in nude mice, as manifested by prolonged survival and alleviated SE tumor infiltration. RFX2 bound to the PAF1 promoter to induce its transcription. Overexpression of PAF1 overturned the effects of RFX2 knockdown on stem cell features and biological activities of SE cells, thereby reducing survival in mice. CONCLUSIONS: RFX2 activates PAF1 transcription, which promotes tumor stemness of SE cells and leads to the malignant progression of SE.

C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B Fusion Negative Anaplastic Ependymoma with Lipogenic Differentiation.

Lipogenic differentiation in ependymoma is an infrequent occurrence with very few reported cases. The grading was done solely based on the histomorphology and molecular subtyping was not described in such ependymomas. New molecular classification divided ependymomas in nine different subgroups, of which supratentorial location tumor usually exhibits C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins. A 46-year-old female presented with headache and right-sided parapresis. Radilogy revealed a large intraxial left parietooccipital mass lesion, which histologically and immuohistochemically confirmed as anaplastic ependymoma with extensive lipogenic changes. The ependymal origin of the tumor was corroborated by the immunohistochemistry and ultrastructural studies. Molecular studies for C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins were negative. This is the first documentation of fusion negative supratentorial anaplastic ependymoma with lipogenic differentiation. This novel finding needs further reinforcement by similar studies to identify its impact on the disease outcome.

Sacral ependymoma presents 20 years after initial posterior fossa lesion.

Posterior fossa ependymomas (PFEs) are designated histologically as low-grade neoplasms. Despite being characterised as benign, cases of metastasis have been reported only a few times with the patients concurrently diagnosed with the primary tumour. Interval drop metastasis or spontaneous second distal tumours are extremely rare and, in most cases, are diagnosed within a few months of primary tumour resection. Here, we report a patient with a grade 2 paediatric PFE exhibiting a 20-year interval to a second sacral ependymoma. The patient was initially diagnosed with a PFE at the age of 10 years and underwent tumour resection and postoperative radiotherapy. In their late 20s, the patient presented with basilar artery occlusion complicated by life-threatening epistaxis. Post-thrombolysis, the patient presented with a large sacral grade 1 myxopapillary ependymoma with cauda equina syndrome-like symptoms. Here, we present a rare case of two ependymomas with a 20-year interval in the same patient with compounding comorbidities.

Neurologic outcomes for adult spinal cord ependymomas stratified by tumor location: a retrospective cohort study and 2-year outlook.

Determine whether craniocaudal spinal cord tumor location affects long-term neurologic outcomes in adults diagnosed with spinal ependymomas (SE). A retrospective cohort analysis of patients aged ≥ 18 years who underwent surgical resection for SE over a ten-year period was conducted. Tumor location was classified as cervical, thoracic, or lumbar/conus. Primary endpoints were post-operative McCormick Neurologic Scale (MNS) scores at < 3 days, 6 weeks, 1 year, and 2 years. One-way ANOVA was performed to detect significant differences in MNS scores between tumor locations. Twenty-eight patients were identified. The average age was 44.2 ± 15.4 years. Sixteen were male, and 13 were female. There were 10 cervical-predominant SEs, 13 thoracic-predominant SEs, and 5 lumbar/conus-predominant SEs. No significant differences were observed in pre-operative MNS scores between tumor locations (p = 0.73). One-way ANOVA testing demonstrated statistically significant differences in post-operative MNS scores between tumor locations at < 3 days (p = 0.03), 6 weeks (p = 0.009), and 1 year (p = 0.003); however, no significant difference was observed between post-operative MNS scores at 2 years (p = 0.13). The mean MNS score for patients with thoracic SEs were higher at all follow-up time points. Tumors arising in the thoracic SE are associated with worse post-operative neurologic outcomes in comparison to SEs arising in other spinal regions. This is likely multifactorial in etiology, owing to both anatomical differences including spinal cord volume as well as variations in tumor characteristics. No significant differences in 2-year MNS scores were observed, suggesting that patients ultimately recover from neurological insult sustained at the time of surgery.

The evolution of spinal cord surgery: history, people, instruments, and results.

INTRODUCTION: Spinal cord surgery has and always will be a challenging operation with satisfying results, but also with potentially devastating results. Over the last century, there has been an evolution in the way we perceive and conduct spinal cord surgery. The phenomenal evolution in technology from the very first x-ray pictures helps to localize the spinal pathology through the use of high-resolution MRI and ultrasonography that allows for high precision surgery with relatively minimal exposure. METHODS: The advancements in the surgical technique and the utilization of neuromonitoring allow for maximal safe resection of these delicate and intricate tumors. We also are beginning to understand the biology of spinal cord tumors and vascular lesions, as in the recent 2021 WHO classification which identifies specific entities such as spinal ependymomas, MYCN-amplified, as separate entity from the other subtypes of ependymomas. Surgeons have also accepted the importance of maximal safe resection for most of the spinal cord pathologies rather than just performing biopsy and adjuvant treatment. CONCLUSION: There have been significant advances since the first resection of an intramedullary tumor including diagnosis, imaging, and surgical technique for children. These advances have improved the prognosis and outcome in these children.

A Pediatric Case of Extraneural Subcutaneous Metastasis of Ependymoma.

Ependymoma is the third most common brain tumor in children. Extracranial metastases of ependymomas are uncommon. A 21-month-old Japanese boy was diagnosed to be brain dead due to a posterior fossa (PF) brain tumor. Surgical resection of the tumor was not performed. Twenty-seven months later, he developed a truncal subcutaneous tumor, which was pathologically diagnosed as PF ependymoma group A. We observed the intracranial recurrence of the brain tumor, an invasion to the left orbit, and a neoplasm in his liver before he died. This case suggests that PF ependymoma group A can metastasize extracranially to various organs.

Mapping pediatric brain tumors to their origins in the developing cerebellum.

BACKGROUND: Distinguishing the cellular origins of childhood brain tumors is key for understanding tumor initiation and identifying lineage-restricted, tumor-specific therapeutic targets. Previous strategies to map the cell-of-origin typically involved comparing human tumors to murine embryonal tissues, which is potentially limited due to species-specific differences. The aim of this study was to unravel the cellular origins of the 3 most common pediatric brain tumors, ependymoma, pilocytic astrocytoma, and medulloblastoma, using a developing human cerebellar atlas. METHODS: We used a single-nucleus atlas of the normal developing human cerebellum consisting of 176 645 cells as a reference for an in-depth comparison to 4416 bulk and single-cell transcriptome tumor datasets, using gene set variation analysis, correlation, and single-cell matching techniques. RESULTS: We find that the astroglial cerebellar lineage is potentially the origin for posterior fossa ependymomas. We propose that infratentorial pilocytic astrocytomas originate from the oligodendrocyte lineage and MHC II genes are specifically enriched in these tumors. We confirm that SHH and Group 3/4 medulloblastomas originate from the granule cell and unipolar brush cell lineages. Radiation-induced gliomas stem from cerebellar glial lineages and demonstrate distinct origins from the primary medulloblastoma. We identify tumor genes that are expressed in the cerebellar lineage of origin, and genes that are tumor specific; both gene sets represent promising therapeutic targets for future study. CONCLUSION: Based on our results, individual cells within a tumor may resemble different cell types along a restricted developmental lineage. Therefore, we suggest that tumors can arise from multiple cellular states along the cerebellar "lineage of origin."

Review and update on pediatric ependymoma.

Since our last Special Annual Issue dedicated to the topic of ependymoma in 2009, critical advancements have been made in the understanding of this disease which is largely confined to childhood. In the era of molecular profiling, the prior classification of ependymoma based on histology has become largely irrelevant, with multiple new subtypes of this disease now being described in the newest 2021 WHO CNS Tumor Classification System. Despite our advancements in understanding the underlying biology of these tumors, the mainstays of treatment-gross total surgical resection followed by confocal radiation therapy-have continued to yield the best treatment results across multiple studies and centers. Here, we provide an update on our understanding of the advancements made in tumor biology, surgical, and oncologic management of this disease. As we move into an era of more personalized medicine, it is critical to reflect on our historical understanding of different disease entities, to better understand the future directions of our treatments.

Ependymomas in Children and Adults.

Ependymomas account for approximately 5% of all CNS tumors in adults and around 10% in the pediatric population. Contrary to traditional theories supporting that ependymomas arise from ependymal cells, recent studies propose radial glial cells as the cells of origin. In adults, half of the ependymomas arise in the spinal cord, whereas in the pediatric population, almost 90% of ependymomas are located intracranially. Most of the ependymomas are usually low-grade tumors except anaplastic variants and some cases of RELA-fusion-positive ependymomas, a molecular variant consisting the most recent addition to the 2016 World Health Organization (WHO) classification. Of note, the recently described molecular classification of ependymomas into nine distinct subgroups appears to be of greater clinical utility and prognostic value compared to the traditional histopathological classification, and parts of it are expected to be adopted by the WHO in the near future. Clinical manifestations depend on the location of the tumor with infratentorial ependymomas presenting with acute hydrocephalus. Gross total resection should be the goal of treatment. The prognostic factors of patients with ependymomas include age, grade, and location of the tumor, with children with intracranial, anaplastic ependymomas having the worst prognosis. In general, the 5-year overall survival of patients with ependymomas is around 60-70%.

A clinicopathological analysis of supratentorial ependymoma, ZFTA fusion-positive: utility of immunohistochemical detection of CDKN2A alterations and characteristics of the immune microenvironment.

EPN-ZFTA is a rare brain tumor where prognostic factors remain unclear and no effective immunotherapy or chemotherapy is currently available. Therefore, this study investigated its clinicopathological features, evaluated the utility of MTAP and p16 IHC as surrogate markers of CDKN2A alterations, and characterized the immune microenvironment of EPN-ZFTA. Thirty surgically removed brain tumors, including 10 EPN-ZFTA, were subjected to IHC. MLPA was performed for CDKN2A HD in 20 ependymal tumors, including EPN-ZFTA. The 5-years OS and PFS of EPN-ZFTA were 90% and 60%, respectively. CDKN2A HD was detected in two cases of EPN-ZFTA; these cases were immunohistochemically negative for both MTAP and p16 and recurred earlier after surgery. As for the immune microenvironment of EPN-ZFTA, B7-H3, but not PD-L1, was positive in all cases of EPN-ZFTA; Iba-1-positive or CD204-positive macrophages were large, while infiltrating lymphocytes were small, in number in EPN-ZFTA. Collectively, these results indicate the potential of MTAP and p16 IHC as useful surrogate markers of CDKN2A HD in EPN-ZFTA, and tumor-associated macrophages, including the M2 type, may contribute to its immune microenvironment. Furthermore, the expression of B7-H3 in EPN-ZFTA may indicate the usefulness of B7-H3 as a target of immune checkpoint chemotherapy for EPN-ZFTA via B7-H3 pathway.

Conventional and Advanced Imaging of Spinal Cord Tumors.

Spinal cord tumors are best identified by conventional MR imaging with contrast. Most intramedullary spinal cord tumors have characteristic MR imaging features that allow an accurate preoperative diagnosis. The spinal cord tumors reviewed in this article include the most common tumors, ependymomas and astrocytomas, as well as the less common tumors such as hemangioblastomas and metastases. Rare tumors such as primary CNS lymphoma and melanocytic tumors are also described. Advanced imaging techqniques of more common intramedullary tumors are also reviewed.