Extensive Extraneural Metastases of Cerebral Glioblastoma in a Pediatric Patient: An Extreme Case Report and Comprehensive Review of the Literature

<b><i>Introduction:</i></b> Extraneural metastases of glioblastoma are very rare clinical entities, especially in pediatric patients. Because of their rarity, they can be confused with other pathological processes. <b><i>Case Presentation:</i></b> We report a case of 16-year-old boy with extensive extraneural metastases of glioblastoma. Lung, liver, cervical lymph nodes, skin, and bone metastases were detected in the patient. <b><i>Conclusion:</i></b> We describe the presentation, evaluation, and diagnosis of this rare condition with regard to pertinent literature.

A case series of extraneural metastatic glioblastoma at Memorial Sloan Kettering Cancer Center

Background Extraneural metastasis of glioma is a rare event, often occurring in patients with advanced disease. Genomic alterations associated with extraneural glioma metastasis remain incompletely understood. Methods Ten patients at Memorial Sloan Kettering Cancer Center diagnosed with extraneural metastases of glioblastoma (9 patients) and gliosarcoma (1 patient) from 2003 to 2018 were included in our analysis. Patient characteristics, clinical course, and genomic alterations were evaluated. Results Patient age at diagnosis ranged from 14 to 73, with 7 men and 3 women in this group. The median overall survival from initial diagnosis and from diagnosis of extraneural metastasis was 19.6 months (range 11.2 to 57.5 months) and 5 months (range 1 to 16.1 months), respectively. The most common site of extraneural metastasis was bone, with other sites being lymph nodes, dura, liver, lung, and soft tissues. All patients received surgical resection and radiation, and 9 patients received temozolomide, with subsequent chemotherapy appropriate for individual cases. 1 patient had an Ommaya and then ventriculoperitoneal shunt placed, and 1 patient underwent craniectomy for cerebral edema associated with a brain abscess at the initial site of resection. Genomic analysis of primary tumors and metastatic sites revealed shared and private mutations with a preponderance of tumor suppressor gene alterations, illustrating clonal evolution in extraneural metastases. Conclusions Several risk factors emerged for extraneural metastasis of glioblastoma and gliosarcoma, including sarcomatous dedifferentiation, disruption of normal anatomic barriers during surgical resection, and tumor suppressor gene alterations. Next steps with this work include validation of these genomic markers of glioblastoma metastases in larger patient populations and the development of preclinical models. This work will lead to a better understanding of the molecular mechanisms of metastasis to develop targeted treatments for these patients.

EPEN-07. PATTERNS OF EXTRANEURAL METASTASES IN PEDIATRIC SUPRATENTORIAL EPENDYMOMA: CASE SERIES AND REVIEW OF THE LITERATURE

BACKGROUND Ependymomas account for 10% of all malignant pediatric intracranial tumors. Standard therapy includes maximal safe surgical resection followed by involved-field radiation. Up to 50% of localized pediatric ependymomas recur. Extraneural metastases at time of recurrence are rarely reported. OBJECTIVE To describe extraneural metastases of pediatric ependymomas. METHODS Retrospective review of patients’ medical records and literature review. RESULTS Three patients with history of locally recurrent, supratentorial ependymoma developed extraneural metastases: one in a cervical lymph node, one with a scalp nodule, and one with a dural lesion. Each extraneural recurrence had similar histologic and molecular features as the initial diagnosis. The cervical lymph node recurrence was treated with multimodal therapy; she is without disease four years later. The isolated scalp nodule occurred at the exit site of a subgaleal drain placed during prior resection. Following nodule resection, he developed additional scalp and lymph node disease and is receiving palliative care. The isolated dural recurrence occurred at the exit site of a ventriculoperitoneal shunt placed following a previous resection. She died of progressive disease 18 months after dural lesion resection. Reports of lymph node, scalp, and dural metastases of ependymomas are exceedingly rare, and outcomes are poor. CONCLUSIONS Extraneural manifestations of ependymoma are rare. Regional seeding from prior surgical procedures may play a role in metastatic spread. Extraneural metastases should be considered in children previously treated for ependymoma who develop local findings even in the absence of CNS relapse. Salvage therapy with curative intent should be considered using a multimodal approach.

Extraneural metastatic anaplastic ependymoma: a systematic review and a report of metastases to bilateral parotid glands

Background Anaplastic ependymoma with extraneural metastases is associated with a poor clinical outcome. Metastatic spread to the parotid gland is a rare clinical entity that requires multidisciplinary intervention. Herein, we present a systematic review of anaplastic ependymoma with extraneural metastases and report on a case with metastases to both parotid glands. Methods Electronic databases were searched from their inception to February 2019. Inclusion criteria included reports of anaplastic ependymoma with extraneural metastasis. Studies were excluded if the tumor grade was not reported. A case illustration is provided. Results The search yielded 15 cases of anaplastic ependymoma with extraneural metastases, including the present case. Mean age at diagnosis was 15 years. The initial tumor location was predominantly supratentorial (93.3%). All cases demonstrated leptomeningeal seeding before extraneural metastasis. Mean survival from initial diagnosis was 4.5 years. Metastasis to the parotid gland occurred in 2 cases, including the present case. We present a 17-year-old female patient who underwent gross total resection of a supratentorial, paraventricular anaplastic ependymoma followed by adjuvant external beam radiation therapy. The patient developed recurrent leptomeningeal seeding, treated with Gamma Knife radiosurgery over a 5-year period. She returned with a parotid mass and cervical lymphadenopathy and underwent parotidectomy and modified radical neck dissection. She continued to experience recurrences, including the left parotid gland, and was ultimately placed in hospice care. Conclusions Anaplastic ependymoma with extraneural metastasis is rare. A combination of repeated surgical resection, radiation therapy, and chemotherapy can be used to manage recurrent and metastatic disease, but outcomes remain poor.