Leptomeningeal metastases in glioma: The Memorial Sloan Kettering Cancer Center experience.

OBJECTIVE: To perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics. METHODS: We conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes. RESULTS: One hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8-67.7) months, astrocytoma 6.5 (0.1-28.5) months, and glioblastoma 3.8 (0.1-32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival. CONCLUSION: Patients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.

Endoscopic diagnosis of an MRI-occult, low-grade glioma with ependymal dissemination.

A 21-year-old man presented with triventricular hydrocephalus due to a tectal mass. He underwent an endoscopic third ventriculostomy, and multiple nodules were identified at the floor of the third ventricle intraoperatively. Surgical pathology of one of these lesions demonstrated that the tissue represented a low-grade astrocytoma. The case highlights the existing potential of neuroendoscopy to reveal neuroimaging-occult lesions, in spite of the significant advances of MRI. Furthermore, the combination of the age of the patient, the nonenhancing MRI appearance, and the multifocality of the lesions constitutes a rare and interesting neoplastic presentation within the brain. The constellation of findings likely represents dissemination of a low-grade tectal glioma via the CSF compartment.

Brain gliomas presenting with symptoms of spinal cord metastasis.

Three patients with brain gliomas (aged 41, 37, and 43 years) presented spinal cord symptoms as first neurological presentation (two cases) or at anaplastic progression (one case). Histologically, two cases were anaplastic (WHO III) astrocytomas and one anaplastic (WHO III) oligodendroglioma. The spinal surgery consisted of partial tumor resection in two cases with localized spinal cord metastasis, and tumor biopsy in another with diffuse spreading to the conus and cauda. Spinal irradiation was performed in one case. The time interval between the spinal surgery and the appearance of brain symptoms was very short (1 month or less). Two patients underwent brain surgery (tumor resection in one and stereotactic biopsy in another). The survival time was very short (2 and 3 months) in the two patients with anaplastic astrocytoma, whereas the patient with anaplastic oligodendroglioma survived 1 year after the spinal surgery. Brain gliomas may exceptionally present with symptoms of a spinal cord metastasis. The magnetic resonance imaging finding of a spinal cord enhancing lesion, particularly if associated with root enhancement, should suggest the presence of a brain glioma. In cases with a localized spinal lesion, an early spinal surgery is advised for both diagnosis and decompression of the nervous structures. However, the clinical outcome is poor and the survival time is short.

Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult.

We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process.

Pediatric spinal pilomyxoid astrocytoma.

Pediatric spinal pilomyxoid astrocytoma (PMA) is an extremely rare tumor that merits recognition as a specific, unique entity. The authors present the case of an intramedullary PMA in the thoracic spinal cord of an 11-year-old boy who presented with back pain, scoliosis, and multiple lung nodules. The patient underwent T5-11 laminoplasty and near-total resection of the spinal tumor. The final pathological diagnosis was WHO Grade II PMA. The patient did well for 14 months until the tumor progressed both clinically and radiographically. A literature review focusing on the clinical characteristics, histology, and treatment of PMAs provides a better understanding of these rare lesions. Because of the small number of cases optimal treatment guidelines have not been established, but gross-total resection and adjuvant chemotherapy with alkylating agents appear to confer a better long-term prognosis. Pediatric patients with PMAs can remain recurrence free at least 5 years after surgery, although these tumors may disseminate or dedifferentiate into more malignant gliomas. Recognition of intramedullary PMA as a unique entity in children is vital to the development of specific surgical and adjuvant treatment regimens.

Mortality is higher in patients with leptomeningeal metastasis in spinal cord tumors.

UNLABELLED: Spinal cord tumors are a rare neoplasm of the central nervous system (CNS). The occurrence of metastases is related to poor prognosis. The authors analyzed one series of metastasis cases and their associated mortality. METHODS: Clinical characteristics were studied in six patients with intramedullary tumors with metastases in a series of 71 surgical cases. RESULTS: Five patients had ependymomas of which two were WHO grade III. The patient with astrocytoma had a grade II histopathological classification. Two patients required shunts for hydrocephalus. The survival curve showed a higher mortality than the general group of patients with no metastases in the CNS (p<0.0001). CONCLUSION: Mortality is elevated in patients with metastasis and greater than in patients with only primary lesions. The ependymomas, regardless of their degree of anaplasia, are more likely to cause metastasis than spinal cord astrocytomas.

Mortality is higher in patients with leptomeningeal metastasis in spinal cord tumors / Mortalidade é mais elevada na disseminação metastática leptomeníngea em tumores da medula espinhal

Spinal cord tumors are a rare neoplasm of the central nervous system (CNS). The occurrence of metastases is related to poor prognosis. The authors analyzed one series of metastasis cases and their associated mortality. METHODS: Clinical characteristics were studied in six patients with intramedullary tumors with metastases in a series of 71 surgical cases. RESULTS: Five patients had ependymomas of which two were WHO grade III. The patient with astrocytoma had a grade II histopathological classification. Two patients required shunts for hydrocephalus. The survival curve showed a higher mortality than the general group of patients with no metastases in the CNS (p<0.0001). CONCLUSION: Mortality is elevated in patients with metastasis and greater than in patients with only primary lesions. The ependymomas, regardless of their degree of anaplasia, are more likely to cause metastasis than spinal cord astrocytomas.

Tumores da medula espinhal são neoplasias raras do sistema nervoso central (SNC). A ocorrência de metástases é relacionada a pior prognóstico. Os autores analisaram uma série de casos de metástases e a mortalidade relacionada. MÉTODO: Foram estudadas as características clínicas em seis pacientes com metástases tumorais numa série de 71 casos operados. RESULTADOS: Cinco pacientes tinham ependimomas e dois dos quais foram grau III pela classificação da OMS. O paciente portador de astrocitoma tinha classificação histopatológica de grau II. Dois pacientes necessitaram de derivação devido à hidrocefalia. A curva de sobrevivência mostrou mortalidade mais elevada no grupo de pacientes com disseminação pelo SNC (p<0,0001). CONCLUSÃO: A mortalidade, além de elevada em pacientes com metástases, é maior do que em pacientes apenas com lesão primária. Os ependimomas, independentemente do seu grau de anaplasia, costumam causar mais metástases do que os astrocitomas medulares.

Rim and flame signs: postgadolinium MRI findings specific for non-CNS intramedullary spinal cord metastases.

BACKGROUND AND PURPOSE: No highly specific MR imaging features distinguishing ISCMs from primary cord masses have been described. Our purpose was to retrospectively compare peripheral enhancement features on postgadolinium MR imaging of ISCMs with primary intramedullary cord masses. MATERIALS AND METHODS: A consecutive group of patients with firmly diagnosed ISCM (45 patients with 64 ISCMs) and a comparison group with consecutive pathologically proved primary intramedullary spinal cord masses (64 patients with 64 primary spinal cord masses: ependymoma, astrocytoma, hemangioblastoma, ganglioglioma, and cavernous malformation) were included. MR images were evaluated for 2 specific signs on postgadolinium images: a "rim" sign (more intense thin rim of peripheral enhancement around an enhancing lesion) and "flame" sign (ill-defined flame-shaped region of enhancement at the superior/inferior lesion margins). The frequency of rim and/or flame signs in ISCMs and primary cord masses was compared (χ2 test). For ISCMs, the maximal dimension of the enhancing lesion was correlated with the presence of rim or flame signs (t test). RESULTS: Rim and flame signs, alone and in combination, were seen more frequently in ISCMs than in primary cord masses (P<.0001 for each). Specificity and sensitivity, respectively, for diagnosing ISCMs among spinal cord masses on a per-patient basis were the following: rim sign, 97%, 47%; flame sign, 97%, 40%; at least 1 sign, 94%, 60%; and both signs concurrently, 100%, 27%. In the ISCM group, the presence of either a rim or flame sign correlated with a larger measured maximum enhancing lesion size (P=.0065 and P=.0012, respectively). CONCLUSIONS: The rim and flame signs are common in and specific for ISCM and are rare in primary spinal cord masses.

Analysis of NADP+-dependent isocitrate dehydrogenase-1/2 gene mutations in pediatric brain tumors: report of a secondary anaplastic astrocytoma carrying the IDH1 mutation.

Somatic mutations of the isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (p.R132H), have been reported for WHO grade II and III diffuse gliomas and secondary glioblastomas. We investigated IDH1/2 mutations in a retrospective series of 165 pediatric brain tumors, including atypical teratoid/rhabdoid tumors (AT/RT) and choroid plexus tumors, which had not previously been investigated. Mutation analysis was performed by use of pyrosequencing and, additionally, data were validated for a cohort of 70 gliomas from among the series by use of the arrayed primer extension technique. We identified one tumor which harbored mutation of IDH1 at codon 132 and no alteration was identified in the matched-germline DNA. No IDH2 mutations were detected. Most noteworthy, the IDH1 mutant tumor was an anaplastic astrocytoma involving the cortex in the left frontal lobe which appeared seven years after radiation treatment for an extensive sellar/suprasellar craniopharyngioma. This anaplastic astrocytoma was regarded as secondary to radiation treatment because it seemed to originate within the irradiation field that received a dose varying from a maximum of 30.6 Gy of 4 MV X-rays down to very few Gy of lower-energy scattered radiation. In this work our observations agree with those in previous reports showing the rarity of IDH1/2 mutations in childhood tumors. The interesting identification of an IDH1 mutation in a radiation-induced secondary malignant glioma raises the likelihood that these types of tumor may develop IDH1/2 mutations. Thus, caution is needed when dealing with these tumors, and further genetic analysis is warranted.

A spinal cord astrocytoma and its concurrent osteoblastic metastases at the time of the initial diagnosis: a case report and literature review.

Bone metastasis from a spinal cord astrocytoma has been reported only twice in the English medical literature. It is generally known that bone metastasis is found after the initial diagnosis with/without intervening surgery rather than being found at the time of the diagnosis of astrocytoma. The purpose of this article is to report for the first time a case of concurrent bone metastasis from a spinal cord astrocytoma at the time of diagnosing the spinal cord astrocytoma.

Ifosfamide, carboplatin and etoposide in recurrent malignant glioma.

After failure of temozolomide, there is no established standard salvage chemotherapy for patients with recurrent glioblastoma (GBM). Two phase II trials combining ifosfamide, carboplatin and etoposide chemotherapy (ICE) showed favorable results. We therefore applied the ICE protocol to 13 patients (10 GBM, 3 anaplastic astrocytomas). Partial or complete remissions were not observed. None of the 13 patients survived progression-free for 6 months. Our retrospective analysis suggests that the ICE regimen is not effective in patients with recurrent high-grade glioma if applied at second or third relapse.

Diencephalic juvenile pilomyxoid astrocytoma with leptomeningeal dissemination.

Pilomyxoid astrocytoma (PMA) is a recently described neoplasm. PMA shares few features with pilocytic astrocytoma (PA), the most common central nervous system (CNS) tumor in the pediatric population, yet displays histological differences. Previous studies have shown that PMAs have more aggressive biological behavior as compared to PA. These findings suggest that PMA may be a unique and distinct neoplasm. We report a pilomyxoid astrocytoma of the hypothalamic-chiasmatic region with leptomeningeal dissemination in a 3-month old infant. This case report discusses the histological, clinical, and radiographic characteristics of PMA. In addition, the current treatment options and research potential involving this disease are also briefly described.