Clinical presentation and extent of resection impacts progression-free survival in spinal ependymomas.

PURPOSE: Primary treatment of spinal ependymomas involves surgical resection, however recurrence ranges between 50 and 70%. While the association of survival outcomes with lesion extent of resection (EOR) has been studied, existing analyses are limited by small samples and archaic data resulting in an inhomogeneous population. We investigated the relationship between EOR and survival outcomes, chiefly overall survival (OS) and progression-free survival (PFS), in a large contemporary cohort of spinal ependymoma patients. METHODS: Adult patients diagnosed with a spinal ependymoma from 2006 to 2021 were identified from an institutional registry. Patients undergoing primary surgical resection at our institution, ≥ 1 routine follow-up MRI, and pathologic diagnosis of ependymoma were included. Records were reviewed for demographic information, EOR, lesion characteristics, and pre-/post-operative neurologic symptoms. EOR was divided into 2 classifications: gross total resection (GTR) and subtotal resection (STR). Log-rank test was used to compare OS and PFS between patient groups. RESULTS: Sixty-nine patients satisfied inclusion criteria, with 79.7% benefitting from GTR. The population was 56.2% male with average age of 45.7 years, and median follow-up duration of 58 months. Cox multivariate model demonstrated significant improvement in PFS when a GTR was attained (p <.001). Independently ambulatory patients prior to surgery had superior PFS (p <.001) and OS (p =.05). In univariate analyses, patients with a syrinx had improved PFS (p =.03) and were more likely to benefit from GTR (p =.01). Alternatively, OS was not affected by EOR (p =.78). CONCLUSIONS: In this large, contemporary series of adult spinal ependymoma patients, we demonstrated improvements in PFS when GTR was achieved.

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.

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.

Cauda equina neuroendocrine tumor: a report of three cases and review of the literature with focus on differential diagnosis and postoperative management.

INTRODUCTION: Cauda equina neuroendocrine tumors (CENETs), previously described as cauda equina paragangliomas (PGLs) are rare and well-vascularized benign entities which can be often misdiagnosed with other intradural tumors more common in this anatomical site, such as ependymomas and neurinomas. We describe three cases of CENETs observed at our institution with particular focus on differential diagnosis and postoperative management. Since the lack of guidelines, we performed a literature review to identify factors that can predict recurrence and influence postoperative decision making. CASE REPORT AND LITERATURE REVIEW: We report on three patients, two of them presenting with a clinical history of lower back pain and sciatica. In all cases magnetic resonance imaging (MRI) of the lumbosacral spine with and without Gd-DTPA revealed an intradural lesion with strong contrast enhancement, first described as atypical ependymoma or schwannoma. A complete tumor resection was achieved in all cases, the histopathological diagnosis classified the tumors as CENETs. In our literature review, a total of 688 articles were screened and 162 patients were included. Patients demographic data, clinical symptoms, resection and recurrence were recorded. DISCUSSION: Differential diagnosis between CENETs and other more common tumors affecting cauda equina region, such as ependymomas or schwannomas (neurinomas), is still very challenging. Due to the lack of specific clinical or radiological characteristics, a correct preoperative diagnosis is almost impossible. With this paper we want to point out that CENETs must be considered in the differential diagnosis, most of all in case of entities with atypical radiological features. According to the literature, tumor recurrence after gross total resection is unlikely, while a long-term follow-up is recommended in case of subtotal resection or local aggressive behavior.

Technical aspects of fourth ventricle ependymomas in adults: how I do it.

BACKGROUND: Ependymomas in the fourth ventricle in adults are rare entity. Surgical treatment of adult ependymomas is the only treatment modality since no other effective alternative is available. Radical resection often means cure but it is hindered by the nature and location of the lesion. METHODS: Technical aspects of the fourth ventricle ependymoma surgery in adults are discussed. Anatomy of the area is provided with the step-by-step surgical algorithm. CONCLUSION: Radical resection of low-grade ependymoma with a detailed understanding of the anatomy in this area is vital considering the high effectiveness of the treatment and its excellent prognosis.

Outcomes following management of relapsed pediatric posterior fossa ependymoma in the molecular era.

PURPOSE: The overall survival and prognostic factors for children with multiply recurrent posterior fossa ependymoma are not well understood. We aimed to assess prognostic factors associated with survival for relapsed pediatric posterior fossa ependymoma. METHODS: An institutional database was queried for children with a primary diagnosis of posterior fossa ependymoma from 2000 to 2019. Kaplan-Meier survival analysis and Cox-proportional hazard regression were used to assess the relationship between treatment factors and overall survival. RESULTS: There were 60 patients identified; molecular subtype was available for 56, of which 49 (87.5%) were PF-A and 7 (12.5%) were PF-B. Relapse occurred in 29 patients (48%) at a mean time of 24 months following primary resection. Median 50% survival was 12.3 years for all patients and 3.3 years following diagnosis of first relapsed disease. GTR was associated with significantly improved survival following primary resection (HR 0.373, 95% CI 0.14-0.96). Presence of recurrent disease was significantly associated with worse survival (p < 0.0001). At recurrent disease diagnosis, disseminated disease was a negative prognostic factor (HR 11.0 95% CI 2.7-44) while GTR at first relapse was associated with improved survival HR 0.215 (95% CI: 0.048-0.96, p = 0.044). Beyond first relapse, the impact of GTR was not significant on survival, though surgery compared to no surgery was favorable with HR 0.155 (95% CI: 0.04-0.59). CONCLUSIONS: Disseminated disease at recurrence and extent of resection for first relapsed disease were important prognostic factors. Surgery compared to no surgery was associated with improved survival for the multiply recurrent ependymoma cohort.

Efficacy of the pedicle trapezius muscle flap for the multisurgical removal of pediatric posterior fossa anaplastic ependymoma.

OBJECTIVE: Exceedingly refractory, pediatric anaplastic ependymoma in many cases requires multisurgical removal. The high risk of poor wound healing and CSF leakage especially at the posterior fossa make this tumor difficult to treat. CASE: A 9-year-old girl has had 4th ventricular anaplastic ependymoma since the age of 3. She experienced tumor removal 8 times including 4 posterior fossa craniotomies because tumors were disseminated not only to the posterior fossa but also to the cerebral hemispheres. She also underwent a dermal graft using a free flap. She experienced CSF leaks and meningitis frequently because the wound healing was poor. We performed a dermal flap closure using a pedicle trapezius muscle flap with a plastic surgeon when we performed the 5th tumor removal. RESULT: We achieved complete wound closure in spite of broad deficiencies in subcutaneous and epidermal tissues. After that, recurrences of posterior fossa tumors presented within a short term, and tumor removal via an incision of a pedicle trapezius muscle flap was performed without recurrence of CSF leaks and meningitis. DISCUSSION AND CONCLUSION: For the first time, we are able to report on the efficacy of using the pedicle trapezius muscle flap for multisurgical removal of pediatric posterior fossa anaplastic ependymoma. The muscle flap was found to be effective because of the multiple surgeries expected, and the pedicle trapezius muscle flap was found to be resilient to multiple surgical procedures. Although advantageous, the dorsal scapular artery which is required for flap creation is actually difficult to harvest. Compared to a flee flap, the pedicle trapezius muscle flap maintains vascular supply. Furthermore, this technique has the possibility of being applied to defective dura mater closure that cannot be watertight due to multiple surgeries. However, it is very important to inform the patient's family not only about the improved efficacy of surgery, but also to raise awareness on consequential cosmetic issues.

Current management in the treatment of intramedullary ependymomas in children.

PURPOSE: Current management of pediatric intramedullary ependymoma is extrapolated from adult series since large studies in children are unavailable. This has led us to share our experience with this rare tumor and compare it to the literature and to review and highlight important aspects of current management and point out inconsistencies. METHODS: This is a retrospective analysis of patients with intramedullary ependymoma managed at our institution between 2004 and 2021. RESULTS: During the study period, 5 patients were treated for intramedullary ependymoma. Cases of myxopapillary ependymoma were excluded. The mean age of our cohort was 11.2 years. We identified 4 cases of grade II ependymoma and 1 case of grade III ependymoma. Gross tumor removal (GTR) was achieved in two patients (40%) of patients. One patient was treated with radiotherapy for recurrence and two patients received chemotherapy. There were no cases of recurrence among patients treated with GTR, but in all patients treated with STR. Eighty percent of patients either improved or stayed stable neurologically. During follow-up (mean 73 months), 2 patients died of disease. CONCLUSION: GTR and tumor grade remain the key prognostic factor of long-term tumor-free survival. Many questions prevail regarding outcomes, correct use of adjuvant therapy, and prognostic factors.

A unique case of intracranial collision tumor composed of ganglioglioma WHO gr I and supratentorial ependymoma WHO gr III: case-based literature review.

PURPOSE: Intracranial collision tumor is a rare entity that represents the coexistence of two histopathological different tumor types in the same area without histological admixture or an intermediate cell population zone. So far, several cases of collision tumors with ganglioglioma as its component have been reported in the literature, while supratentorial ependymoma has never been reported as a collision tumor component. We are presenting a unique case of collision tumor in patient without previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis. METHODS AND RESULTS: A 17-year-old male with no previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis was presented to our clinic with grand mal seizure. Brain magnetic resonance imaging with gadolinium contrast was done revealing a contrast-enhancing lesion of right frontal lobe closely related to dura, surrounded by perifocal edema. The patient underwent a gross total tumor resection. Histological examination revealed collision tumor with two distinct components: ganglioglioma and supratentorial ependymoma. CONCLUSION: To our best knowledge, no previous reports of collision tumor composed of ganglioglioma and supratentorial ependymoma in a single patient have been reported. We believe that this report could significantly contribute to further surgical practice as well as to treatment decision for these types of collision tumors.

Placement of EVD in pediatric posterior fossa tumors: safe and efficient or old-fashioned? The Vienna experience.

PURPOSE: The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity. METHODS: This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022. RESULTS: Of the 100 patients with posterior fossa tumors, 80 patients (80%) had radiological signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients, the EVD was inserted at a mean of 2.25 days prior to the tumor resection; 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11, and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas, and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61 ± 3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35 ± 3.8 (range 0-16 days). EVD-associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at 6 months after surgery was necessary in 13 patients (13%), including two VP shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p < 0.001). In patients with metastatic disease, 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p = 0.001). CONCLUSION: The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.

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.

Clinical management and prognosis of spinal myxopapillary ependymoma: a single-institution cohort of 72 patients.

PURPOSE: Myxopapillary ependymoma (MPE) was classified as grade 2 tumor in the 2021 World Health Organization central nervous system classification because of its high recurrence probability. This study aimed to investigate predictive factors and management of tumor recurrence. METHODS: Seventy-two patients with spinal MPE underwent initial surgical treatment at our hospital between 2011 and 2021. Kaplan-Meier curves and Cox regression were used to analyze the correlation between clinical variables and progression-free survival (PFS). RESULTS: The median age at diagnosis was 33.5 years (range 8-60 years). Twenty-one patients (29.2%) had preoperative spinal drop metastases. Gross total resection (GTR) was performed in 37 patients (51.4%). The median follow-up was 7.2 years, and the follow-up rate was 88.9% (64 of 72 cases). Twelve of the 64 patients (18.9%) relapsed, and preoperative drop metastasis occurred in 7 patients (58.3%). The estimated 5-year and 10-year PFS rates were 82% and 77%, respectively. Univariate analysis showed that GTR was associated with improved PFS (hazard ratio [HR] 0.149, p = 0.014), while preoperative drop metastasis (HR 3.648, p = 0.027) and tumor involvement sacrococcygeal region (HR 7.563, p = 0.003) were associated with tumor recurrence. Adjuvant radiotherapy (RT) was significantly associated with improved PFS in patients with preoperative drop metastasis (p = 0.039). CONCLUSION: Complete surgical resection under the premise of protecting neurological function is an important factor in reducing spinal MPE recurrence. Adjuvant RT is recommended when the tumor invades the capsule with preoperative drop metastasis or adhesion to the nerve and cannot reach GTR.

Combined telovelar posterolateral (far lateral) approach for the resection of a large posterior fossa ependymoma: how I do it.

BACKGROUND: Ependymomas are glial cell tumors whose recommended treatment, according to the recent European guidelines, is surgical. Patient outcomes, in terms of progression-free survival and overall survival, are strongly related to the extent of resection. However, in some cases, critical locations and/or large dimensions could make a gross total resection challenging. In this article, we describe the surgical anatomy and technique of a combined telovelar-posterolateral approach for the resection of a giant posterior fossa ependymoma. METHODS: A 24-year-old patient who presented to our institution complaining of a 3-month history of headache, vertigo, and imbalance. Preoperative MRI scans showed a large mass within the fourth ventricle, extending towards the left cerebellopontine angle and perimedullary space through the homolateral Luschka foramen. Surgical treatment was proposed with the aims of releasing the preoperative symptoms, obtaining the tumor's histopathological and molecular definition, and preventing any future neurological deterioration. The patient gave his written consent for surgery and consented to the publication of his images. A combined telovelar-posterolateral approach was then performed to maximize the tumor's exposure and resection. Surgical technique and anatomical exposure have been extensively described, and a 2-dimensional operative video has been included. RESULTS: The postoperative MRI scan demonstrated an almost complete resection of the lesion, with only a millimetric tumor remnant infiltrating the uppermost portion of the inferior medullary velum. Histo-molecular analysis revealed a grade 2 ependymoma. The patient was discharged home neurologically intact. CONCLUSIONS: The combined telovelar-posterolateral approach allowed to achieve a near total resection of a giant multicompartimental mass within the posterior fossa in a single surgical stage.

Posterior fossa ependymoma with preoperative cerebrospinal metastases: a case report with literature review.

BACKGROUND: Adult posterior fossa ependymomas (PF-EPN) with preoperative cerebrospinal metastases are extremely rare. Only 3 cases have been reported in previous literature. CASE PRESENTATION: A case of a 32-year-old male patient complained of headaches for three months. Pure tone audiometry showed a slight decrease in bilateral hearing. Auditory evoked potential indicated that the hearing on the left was slightly weaker than that on the right. Magnetic resonance imaging (MRI) revealed a primary tumor arising within the fourth ventricle and metastasizing to bilateral cerebellopontine angle (CPA), the third ventricle, the left lateral ventricle, T1, L1-2 and L5. A gross total resection (GTR) was performed on the lesion located in the left CPA. The histological examination showed a papillary ependymoma (WHO grade II). Immunohistochemical staining for H3K27me3 showed that nuclear positivity in more than 80% of cells. No NF2 mutation was observed. No progression was found during a 24-month follow-up. CONCLUSIONS: Our data indicate that preoperative multiple metastases in adult PF-EPN are extremely rare. This kind of disease usually has a low WHO grade and a favorable prognosis. GTR should be achieved when feasible and patients need a long-term follow-up with MRI.

Fahr's disease associated with anaplastic ependymoma: a case report and review of the literature.

Fahr's disease, also known as familial idiopathic basal ganglia calcification or bilateral strio-pallido-dentate calcinosis, is a rare entity characterized by abnormal vascular calcium depositionin the thalamus, basal ganglia, cerebral cortex and the dentate nuclei of the cerebellum. Intracranial ependymomas comprise approximately 2% to 9% of all neuroepithelial tumors. It is reported that supratentorial ependymoma constitute 30% to 50% of all intracranial ependymal tumors. Among supratentorial ependymomas, approximately 50% of them are located extraventricular and demonstrate no relationship with the ventricularsystem.The association of brain tumor with Fahr's disease is a rare entity and has been reported several times before. Whereas, to best our knowledge, the association of Fahr's disease and supratentorial anaplastic ependymoma is described in the present study for the first time.

Giant intradural extramedullary spinal ependymoma, a rare arachnoiditis-mimicking condition: case report and literature review.

BACKGROUND AND IMPORTANCE: Ependymomas are tumours arising from the ependymal cells lining the ventricles and the central canal of the spinal cord. They represent the most common intramedullary spinal cord tumour in adults and are very rarely encountered in an extramedullary location. Only 40 cases of intradural extramedullary (IDEM) ependymomas have been reported, all of which were diagnosed pre-operatively as IDEM ependymomas on contrast-enhanced MRI. CLINICAL PRESENTATION: We report a 23-year old male presenting with rapidly worsening signs and symptoms of spinal cord disease. A spinal MRI demonstrated a posterior multi-cystic dilatation extended between T1 and T12. Post-contrast sequences showed peri-medullar leptomeningeal enhancement and the diagnosis of spinal arachnoiditis was made. The patient underwent surgery and the spinal cord appeared circumferentially wrapped by an irregular soft tissue. The tissue was sub-totally removed and the pathological diagnosis was ependymoma WHO grade II. The patient experienced an excellent neurological recovery and no further treatments were administered. A small residue is now stable at 2.5 years follow-up. CONCLUSIONS: Giant IDEM ependymomas are rare entities and pre-operative diagnosis can be challenging in some cases. Surgery represents the main treatment option being resolutive in most cases.

Mobile cauda equina ependymoma, case report and literature review.

The aim of this study was to describe a very rare presentation of ependymoma that can derive from intraoperative complications for surgeons and increased morbidity for the patients. Multiple cases of mobile cauda equina tumors leading to inadequate approach have been reported in the literature, however, the reports of ependymoma histology are very rare. This report describes the third adult case in recent years and a retrospective review of cases reported in the literature until today. We show the clinical and radiographic presentation of a 79 years old patient that presented a mobile cauda equina tumor in the preoperative image, who went to surgery for resection and arthrodesis, obtaining in post-operative histology the diagnostic of ependymoma. The preoperative image shows the migration of the tumor avoiding the wrong approach. The patient went to surgery for laminectomy, pedicular screw arthrodesis L1-S1, and tumor removal, obtaining a complete resection and confirmed histology diagnostic of ependymoma, unfortunately, the patient died five days after by a cardiac arrest. The recent literature reports only four cases of mobile ependymoma, two of them in pediatrics patients and just only two adult cases, which means this is the third adult case of an ependymoma. Mobile cauda equina ependymoma is a very rare neoplasm presentation but is an entity that can lead to mistakes in the approach and may be useful for the neurosurgeons who day per day treat this pathology beware of this possibility.

[Laser fluorescence spectroscopy in surgical treatment of intramedullary tumors: experience of the Burdenko Neurosurgery Center]. / Primenenie lazernoi fluorestsentnoi spektroskopii pri khirurgicheskom lechenii intramedullyarnykh opukholei: opyt FGAU «NMITs neirokhirurgii im. akad. N.N. Burdenko¼.

One of the important problems in microsurgical resection of intramedullary spinal cord tumors is excessive surgical aggression and subsequent neurological impairment. Laser fluorescence spectroscopy with electrophysiological monitoring provides high-quality resection of intramedullary tumors with monitoring of spinal cord structures in real time. This approach increases safety and quality of resection. OBJECTIVE: To analyze efficacy of fluorescence navigation technique and laser fluorescence spectroscopy in surgical treatment of various spinal cord tumors. MATERIAL AND METHODS: There were more than 1000 patients with intramedullary spinal cord tumors between 2001 and 2022. Intraoperative fluorescence navigation with laser spectroscopy was used in 47 cases. All patients underwent examination before and after surgery. We analyzed somatic, neurological and functional status (McCormick scale). MRI of the spinal cord and intraoperative fluorescence spectroscopy (OPMI Pentero 900 microscope with a fluorescent module, Carl Zeiss, Germany) were performed. To induce visible fluorescence, we used 5-ALA-Alasens (NIOPIK, Russia). Laser spectroscopy was carried out on a LESA-01-BIOSPEC analyzer (Biospec JSC, Russia). Morphological analysis of intramedullary spinal cord tumors was carried out in the laboratory of neuromorphology of the Burdenko Neurosurgery Center. RESULTS: In our sample, fluorescence navigation and laser fluorescence spectroscopy were used only in surgical treatment of intramedullary tumors. Laser fluorescence spectroscopy was valuable to identify fragments of intramedullary ependymoma and astrocytoma in 86% of cases, visual fluorescence - only in 81% of cases. Advisability of this technique for low-grade astrocytomas is unclear and requires further study. CONCLUSION: Visual fluorescence combined with laser spectroscopy is a promising method for intraoperative imaging of tumor remnants. This approach can improve safety, quality and results of surgical treatment.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Impact of tumor-associated syrinx on outcomes following resection of primary ependymomas of the spinal cord.

PURPOSE: To interrogate the association of tumor-associated syrinxes with postoperative neurological and oncological outcomes in patients surgically treated for WHO grade 2 spinal ependymomas. METHODS: Adults treated for primary spinal intramedullary ependymomas between 2000 and 2020 were identified and data were gathered on preoperative neurological exam, radiographic characteristics, operative details, and postoperative neurological outcome. Neurological status was graded on the modified McCormick Scale (MMS). Neurological worsening immediately postoperatively and at last follow-up were defined by ≥ 1 MMS grade deterioration. Decision-tree analyses were also performed to identify independent predictors of new neurological deficits. RESULTS: Seventy patients were identified; mean age 45.4 ± 12.7; 60% male. Forty-eight patients (68.6%) had tumor-associated syrinxes, were more common among males (68.8%) and cervical lesions (68.8 vs. 31.8%; P = 0.005). Postoperatively patients with syrinxes had better MMS (P = 0.035) and were less likely to require a gait aid (39.6 vs. 81.8; P = 0.002). This latter difference persisted to last follow-up (22.9 vs. 59.1%; P = 0.006). On decision-tree analysis the strongest predictors of long-term neurological worsening were advanced age (≥ 63 years) and worse baseline neurological function. Worsened neurological status in the immediate postoperative period was best predicted by thoracic localization, the presence of a hemosiderin cap, and longer craniocaudal extension. CONCLUSION: For spinal ependymomas, tumor-associated syrinxes may portend decreased risk for immediate postoperative neurologic deficits but do not predict long-term neurological outcomes (MMS) or odds of successful gross total resection. Thoracic localization appears to best predict new immediate postoperative deficits, and worse baseline neurological function and advanced age best predict long-term deficits.