A systematic review of extraneural meningioma metastasis: timing, evolution and outlook.

PURPOSE: Extraneural meningioma metastasis is a rare occurrence and may pose a clinical challenge due to its unclear prognosis. In this systematic review, we analyze patient demographics, clinical characteristics, management strategies, and outcomes. METHODS: PubMed, EMBASE, Scopus, Cochrane, and Web of Science databases were searched from inception to February 23, 2024 for cases of metastatic meningioma according to PRISMA guidelines. Descriptive statistics, Mann-Whitney U test, Fisher's exact tests, Kaplan-Meier curves, and log-rank tests were used for selected analyses. RESULTS: A total of 288 patients (52% male) were included with an average age of 49 years at meningioma diagnosis. Tumors were distributed across WHO grade 1 (38%), 2 (36%), and 3 (26%). Most patients experienced intracranial recurrence (79%) and mean time to first metastasis was approximately 8 years. No change in WHO grade between primary and metastasis was observed for most cases (65%). Treatment of the initial metastasis was most often with surgery (43%), chemotherapy (20%), or no treatment (14%). Half of the patients were alive (50%) with an average follow-up of 3 years following metastasis. Overall median survival was 36 months for the entire cohort. This differed significantly between WHO grade 1 versus 2/3 meningioma primaries (168 vs. 15 months, p < 0.005). CONCLUSION: Metastatic meningioma appears to be associated with more positive prognosis than other brain tumor types with extra-neural metastasis or metastasis in general. This is particularly true for cases arising from a WHO grade 1 meningioma.

Anaplastic oligodendroglioma metastasizing to the bone marrow: a unique case report and literature review.

Oligodendrogliomas are a rare type of primary brain tumor. They are genetically defined as diffuse gliomas carrying mutation in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2) and codeletion of chromosomes 1p and 19q. The WHO grading system distinguishes two histopathologic grades of ODs: grade II (low-grade) and grade III (anaplastic oligodendroglioma or AO). These tumors rarely metastasize outside of central nervous system with only few cases reported in the literature. Here we present a case of an AO, which metastasized to the bone marrow and other sites within a year of diagnosis despite aggressive treatment measures. Our patient eventually succumbed to his disease, raising many questions about this rare condition, its natural course and optimal management strategy.

A case of molecularly profiled extraneural medulloblastoma metastases in a child.

BACKGROUND: Extraneural metastases are relatively rare manifestations of medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group three MYCN-amplified medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options. CONCLUSION: To the best of our knowledge, this is the first molecularly characterized report of extraneural metastases of medulloblastoma in a child.

Cervical Lymph Node Metastasis From Medulloblastoma in a Young Adult: Case Report and Literature Review.

Medulloblastoma, an embryonal tumor located in the posterior fossa of the brain, originates from the neuro-epidermal layer of the cerebellum. It is the most prevalent malignant tumor in children, while it is rare in adults and predominantly affects males. Multimodal therapeutic interventions, such as surgery, radiotherapy, and chemotherapy, have substantially enhanced the prognosis of this condition. Extraneural metastases are infrequent. We present a case of medulloblastoma relapse with nodal metastasis in a 28-year-old adult.

Pediatric H3K27M­mutant diffuse midline glioma with vertebral metastasis: A case report and literature review.

H3K27M-mutant diffuse midline glioma (DMG) is a type of high-grade glial tumor, which occurs in the midline structure and develops mostly in children. Extraneural metastases (ENM) are exceedingly rare in patients with H3K27M-mutant DMG. A 9-year-old male patient presented with a headache, nausea and vomiting. Following magnetic resonance imaging and immunohistochemical molecular testing examination, the patient was diagnosed with H3K27M-mutant DMG and received chemoradiotherapy plus five cycles of chemotherapy with temozolomide intermittently as an adjuvant therapy. The treatment resulted in a slight reduction of the tumor volume. However, 2 months later, the patient was admitted to hospital with complaints of drooping of the mouth, and waist and back pain. Magnetic resonance imaging and positron-emission tomography-computed tomography revealed an unusual presentation with multiple vertebral metastases and craniospinal leptomeningeal dissemination. Following discussion between the members of a multidisciplinary medical team, the patient underwent one cycle of chemotherapy with cyclophosphamide, vincristine and cisplatin. However, the condition did not improve and the patient died 4 weeks after the diagnosis of ENM. The mechanisms underlying the development of these rare metastases remain unclear. The present case report provides insights into the clinical characteristics and potential metastasis mechanisms of this aggressive disease and may help to elucidate new pathways for the management of ENM.

Medulloblastoma with Subcutaneous Spread: A Rare Entity.

Medulloblastoma is the most common malignant pediatric brain tumor. Histological subclassification and adjuvant therapy have improved prognostication and outcome. Extraneural metastasis remains a poor prognostic factor and subcutaneous seeding is rarely encountered and reported in the pediatric population. We report a 3-year-old child who rapidly presented with subcutaneous seeding a month following gross total resection of his tumor.

Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

Cervical Lymph Node Metastases from Central Nervous System Tumors: A Systematic Review.

Introduction: Lymph node metastasis (LNM) from primary tumors of the central nervous system (CNS) is an infrequent condition, and classically it was thought that CNS tumors could not spread via the lymphatic route. Recent discoveries about this route of dissemination make its knowledge necessary for surgeons and pathologists to avoid delays in diagnosis and unnecessary treatments. The aim of this paper is to review the literature and to discuss the relevant pathogenetic mechanism and the cytologic features along with recommendations for surgical treatment of these cervical LNM. Materials and Methods: Using PRISMA guidelines, we conducted a systematic review of the literature published from 1944 to 2021, updating the comprehensive review published in 2010 by our group. Results: Our review includes data of 143 articles obtaining 174 patients with LNM from a primary CNS tumor. The mean age of the patients was 31.9 years (range, 0.1-87) and there were 61 females (35.1%) and 103 males (59.2%), and in 10 cases (5.7%) the gender was not specified. The more frequent sites of distant metastasis were bones (23%), lungs (11.5%) and non-cervical lymph nodes (11%). Conclusion: Cervical LNM from CNS tumors is infrequent. Pathologic diagnosis can be obtained by fine-needle aspiration cytology in most cases, giving surgeons the option to plan the appropriate surgical treatment. Given the poor prognosis of these cases, the most conservative possible cervical dissection is usually the treatment of choice.

Diffuse midline glioma metastasis to the peritoneal cavity via ventriculo-peritoneal shunt: Case report and review of literature.

Extraneural dissemination of primary intracranial tumours to the peritoneal cavity via ventriculoperitoneal shunts is rare, with medulloblastoma and germ-cell tumours most common and gliomas seldom implicated. This report is the first described case of a diffuse midline glioma H3 K27M-mutant disseminating to the peritoneal cavity via a shunt. A four-year-old female presented with a large solid-cystic lesion centred on the suprasellar cistern, histologically revealed to be diffuse midline glioma H3 K27M-mutant. The patient received multiple courses of radiotherapy to the primary lesion and metachronous spinal metastases, and underwent bilateral ventriculoperitoneal shunts. She presented fourteen months following diagnosis with acute hydrocephalus and massive ascites revealed to be due to histologically confirmed intra-abdominal glioma metastasis secondary to shunting. Bilateral ventriculoatrial shunts along with targeted abdominal radiotherapy and repeated ascitic drainage were performed. The patient died one month later. A literature review demonstrated that intra-abdominal glioma metastasis is an extremely rare complication of cerebrospinal fluid diversion predominantly affecting paediatric patients with high-grade lesions within the first year after diagnosis and portends poor prognosis. Predisposition to metastasis is likely associated with tumour proximity to cerebrospinal fluid spaces and tumour biology. Contraindicating shunting in the presence of an intracranial tumour cannot be endorsed but rather shunt-related metastasis should be an acknowledged risk, and not-to-be-forgotten presentation.

Extracranial Metastases of a Cerebral Glioblastoma: A Case Report and Review of the Literature.

The glioblastoma, a malignant human brain tumor, is known for its devastating intracranial progress and its dismal prognosis. Whereas treatment and research are most prominently focused on the primary tumor lesion, in recent years evidence has accumulated that points to the rare occurrence of extracranial glioblastoma metastases. We here present a case of a female patient with a known glioblastoma who was detected to harbor multiple metastases in the bones, lung, pleura, liver, mesentery, and the subcutaneous soft tissue. Pathogenetically, these metastatic lesions developed most probably after a local progression of the left temporal glioblastoma through the skull base, thus getting access to the systemic lymphatics. Similar cases of extensive glioblastoma metastization, their putative underlying mechanisms, and implications for clinical care are discussed.

A systematic review of shunt-related extraneural metastases of primary central nervous system tumors.

Extraneural metastasis (ENM) of primary central nervous system (CNS) tumors is an uncommon occurrence. Case reports and case series describe ENM after shunting, but this phenomenon has not been well characterized. In this review we aim to better understand the risk factors and clinical implications of ENM associated with shunting. A literature search of cases of ENM related to shunt placement in patients with primary CNS tumors reported through January 2018 was performed using PubMed and Google Scholar. We identified 106 cases of ENM of primary CNS tumors related to shunt placement. The three most common tumor histologies resulting in ENM were germinoma (24%), medulloblastoma (21%), and glioblastoma (11%). Of the patients with ENM, 48% had leptomeningeal spread and 37% had brain or spinal cord metastasis. Mean survival time from shunt placement was 13 months. Ventriculoatrial-shunted cases had higher rates of widespread metastasis and shorter average survival time from shunt placement (2 months) than the average of all types of shunts. Given the known association with ENM, careful consideration should be given to shunt placement in patients with primary CNS tumors, especially germinomas, medulloblastomas, and glioblastomas. Appropriate surveillance should be instituted after shunt placement, and leptomeningeal or neural metastasis should prompt the consideration of potential ENM. When considering distal shunt options, our review suggests that ventriculoatrial shunts should be avoided if possible. For truly obstructive pathologies, the risk of ENM is a further indication to consider other treatment options such as endoscopic third ventriculostomy rather than shunt placement.

Extensive Therapies for Extraneural Metastases from Glioblastoma, as Confirmed with the OncoScan Assay.

BACKGROUND: The diagnosis of extraneural metastasis from glioblastoma is usually based on the histopathology and immunohistochemical staining of a tumor specimen. Information regarding the molecular features of glioblastoma and optimal treatment strategies for extraneural metastasis is limited. CASE DESCRIPTION: A 58-year-old woman with a glioblastoma located in the left temporal lobe underwent resection followed by radiotherapy plus concomitant and adjuvant temozolomide. Ipsilateral cervical lymph node tumors were treated 29 months later with supraomohyoid neck dissection and temozolomide. The diagnosis of lymph node metastases from glioblastoma was confirmed with an OncoScan assay and pathologic analysis. The brain and lymph node tumors had identical genotypes: C228T-mutated TERT promoter, wild-type IDH1, wild-type IDH2, wild-type TP53, EGFR amplification, and unmethylated MGMT promoter. Subsequently, multiple bone metastases were detected and treated with CyberKnife radiosurgery. Widespread extraneural metastases were detected 49 months after the initial diagnosis, and the patient underwent chemotherapy with cisplatin and semustine. There was no evidence of intracranial relapse until death, which occurred 5 months after chemotherapy. CONCLUSIONS: Similar to carcinomas, glioblastomas can spread via the lymphatic route. Extensive therapies for extraneural metastases from glioblastoma can alleviate discomfort and prolong survival, especially in patients without intracranial relapse.

Intracranial Hemangiopericytomas : A Retrospective Study of 15 Patients with a Special Review of Recurrence.

OBJECTIVE: Although surgical resection is used to treat meningeal hemangiopericytoma (MHPC), there is a high risk of subsequent recurrence. This study investigated factors associated with treatment outcomes and recurrence in patients who had undergone surgical resection of intracranial MHPC. METHODS: Fifteen patients underwent surgical treatments performed by one senior neurosurgeon between 1997 and 2013. Clinical data, radiologic images, surgical outcomes, recurrence, and other relevant characteristics were reviewed and analyzed. RESULTS: Fifteen patients were included in the analysis, 12 (80%) of whom had tumors in the supratentorial region, and 3 (20%) of whom had tumors in the infratentorial region. Complete resection was achieved in all 15 patients, and 3 (20%) patients were administered radiosurgery and conventional radiotherapy after surgery as adjuvant radiotherapy. Three patients developed recurrence, 2 of whom had not received adjuvant radiotherapy. In 1 of the patients who had not received adjuvant radiotherapy, recurrence developed at the original tumor site, 81 months after surgery. The other 2 recurrences occurred at other sites, 78 and 41 months after surgery. The 5- and 10-year overall survival rates were 88.3%, while the 5- and 10-year recurrence-free survival rates were 83% and 52%, respectively. Additionally the mean Ki-67 index differed significantly between patients who did and did not develop recurrence (43% vs. 14%; p=0.001). CONCLUSION: Because of the high risk of MHPC recurrence, MHPC tumors should be completely resected, whenever feasible. However, even when complete resection is achieved, adjuvant radiotherapy might be necessary to prevent recurrence.

A case of early extraneural medulloblastoma metastases in a young adult.

Extraneural metastases are a relatively rare manifestation of the primary brain tumors, and a major part of the cases has been associated with initial medulloblastoma. Herein, we present the case of a young female adult diagnosed and operated for medulloblastoma. The patient developed extraneural metastases in the first postoperative year. The condition exhibited an aggressive course of development, and the applied treatment approaches were unable to halt its progression. A short literature review identifies the predictive factors determining both prognosis and treatability of the condition; the current limitations and future perspectives of the treatment options are discussed.

Extraneural metastasis of glioblastoma multiforme presenting as an unusual neck mass.

Glioblastoma multiforme (GBM) is the most aggressive intracranial tumor and it commonly spreads by direct extension and infiltration into the adjacent brain tissue and along the white matter tract. The metastatic spread of GBM outside of the central nervous system (CNS) is rare. The possible mechanisms of extraneural metastasis of the GBM have been suggested. They include the lymphatic spread, the venous invasion and the direct invasion through dura and bone. We experienced a 46-year-old man who had extraneural metastasis of the GBM on his left neck. The patient was treated with surgery for 5 times, radiotherapy and chemotherapy. He had survived 6 years since first diagnosed. Although the exact mechanism of the extraneural metastasis is not well understood, this present case shows the possibility of extraneural metastasis of the GBM, especially in patients with long survival.