Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation.

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

Preoperative angiographic considerations and neurological outcome after surgical treatment of intradural spinal hemangioblastoma: a multicenter retrospective case series.

PURPOSE: Intradural spinal hemangioblastomas are rare highly hypervascularized benign neoplasms. Surgical resection remains the treatment of choice, with a significant risk of postoperative neurological deterioration. Due to the tumor infrequency, scientific evidence is scarce and limited to case reports and small case series. METHODS: We performed a retrospective multicenter study including five high-volume neurosurgical centers analyzing patients surgically treated for spinal hemangioblastomas between 2006 and 2021. We assessed clinical status, surgical data, preoperative angiograms, and embolization when available. Follow-up records were analyzed, and logistic regression performed to assess possible risk factors for neurological deterioration. RESULTS: We included 60 patients in Germany and Austria. Preoperative angiography was performed in 30% of the cases; 10% of the patients underwent preoperative embolization. Posterior tumor location and presence of a syrinx favored gross total tumor resection (93.8% vs. 83.3% and 97.1% vs. 84%). Preoperative embolization was not associated with postoperative worsening. The clinical outcome revealed a transient postoperative neurological deterioration in 38.3%, depending on symptom duration and preoperative modified McCormick grading, but patients recovered in most cases until follow-up. CONCLUSION: Spinal hemangioblastoma patients significantly benefit from early surgical treatment with only transient postoperative deterioration and complete recovery until follow-up. The performance of preoperative angiograms remains subject to center disparities.

Regional Spondylodiscitis Disparities: Impact on Pathogen Spectrum and Patients.

Background: Spondylodiscitis is an infectious disease affecting an intervertebral disc and the adjacent vertebral bodies and is often the complication of a distant focus of infection. This study aims to ascertain the regional and hospital-specific disparities in bacterial patterns and resistance profiles in spontaneous and iatrogenic spondylodiscitis and their implications for patient treatment. Methods: We enrolled patients from two German hospitals, specifically comparing a university hospital (UVH) with a peripheral non-university hospital (NUH). We documented patient demographics, laboratory results, and surgical interventions. Microbiological assessments, antibiotic regimens, treatment durations, and resistance profiles were recorded. Results: This study included 135 patients. Upon admission, 92.4% reported pain, with 16.2% also presenting neurological deficits. The primary microbial species identified in both the UVH and NUH cohorts were S. aureus (37.3% vs. 31.3%) and cog. neg. staphylococci (28.8% vs. 34.4%), respectively. Notably, a higher prevalence of resistant bacteria was noted in the UVH group (p < 0.001). Additionally, concomitant malignancies were significantly more prevalent in the UVH cohort. Conclusion: Significant regional variations exist in bacterial prevalence and resistance profiles. Consequently, treatment protocols need to consider these nuances and undergo regular critical evaluation. Moreover, patients with concurrent malignancies face an elevated risk of spondylodiscitis.

Cavernous Malformations and Hemangioblastomas of the Spinal Cord Show Distinct Differences in Clinical Course - A Retrospective Single-Center Analysis of 112 Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to analyze the clinical differences between the vascular pathologies and a benign tumor of the spinal cord in a perioperative situation. METHODS: We performed a retrospective analysis of patients who had undergone surgery for lesions in the spinal cord between 1984 and 2015. Patients were screened for CMs and HBs as the primary inclusion criteria. General patient information, surgical data, and disease-specific data were collected from the records. Cooper-Epstein scores for clinical symptoms were evaluated preoperatively, at discharge, and at the 6-month follow-up. RESULTS: A total of 112 patients were included, of which 46 had been diagnosed with CMs and 66 with HBs. Patients with CMs often demonstrated more preoperative neurological deterioration compared to those with HBs (P < .05); accordingly, in took longer to diagnose HBs. Complete resection was possible for 96.8% of all patients with CMs and 90% of those with HBs. At the 6-month follow-up, patients with HBs more often presented with persisting neurologic impairment of the upper extremities compared to the CM patients (P < .001). CONCLUSION: CMs and HBs of the spinal cord have similarities but also exhibit significant differences in neurological presentation and perioperative course. Surgical therapy is the treatment of choice for symptomatic lesions, and complete surgical resection is possible in the majority of cases for both entities. Neurologic outcomes are usually favorable, although patients with HBs retain neurologic deficits more often.

Comprehensive profiling of myxopapillary ependymomas identifies a distinct molecular subtype with relapsing disease.

BACKGROUND: Myxopapillary ependymoma (MPE) is a heterogeneous disease regarding histopathology and outcome. The underlying molecular biology is poorly understood, and markers that reliably predict the patients' clinical course are unknown. METHODS: We assembled a cohort of 185 tumors classified as MPE based on DNA methylation. Methylation patterns, copy number profiles, and MGMT promoter methylation were analyzed for all tumors, 106 tumors were evaluated histomorphologically, and RNA sequencing was performed for 37 cases. Based on methylation profiling, we defined two subtypes MPE-A and MPE-B, and explored associations with epidemiological, clinical, pathological, and molecular characteristics of these tumors. RESULTS: MPE-A occurred at a median age of 27 years and were enriched with tumors demonstrating papillary morphology and MGMT promoter hypermethylation. Half of these tumors could not be totally resected, and 85% relapsed within 10 years. Copy number alterations were more common in MPE-A. RNA sequencing revealed an enrichment for extracellular matrix and immune system-related signatures in MPE-A. MPE-B occurred at a median age of 45 years and included many tumors with a histological diagnosis of WHO grade II and tanycytic morphology. Patients within this subtype had a significantly better outcome with a relapse rate of 33% in 10 years (P = 3.4e-06). CONCLUSIONS: We unraveled the morphological and clinical heterogeneity of MPE by identifying two molecularly distinct subtypes. These subtypes significantly differed in progression-free survival and will likely need different protocols for surveillance and treatment.