The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network.

PURPOSE: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

Myxopapillary ependymoma of the posterior mediastinum

A left paravertebral mass discovered incidentally on routine examination in a 39-year-old woman is described. Computerized tomography studies revealed a 7 × 6 cm, well circumscribed, noncalcified soft tissue mass with lobular borders abutting the left inferior pulmonary vein and descending aorta. It was not possible to determine the exact anatomic location of the mass based on the imaging studies as both peripheral lung tumors and posterior mediastinal lesions may exhibit the imaging findings described here. At thoracotomy, the mass was seen to be well circumscribed, focally attached to the pleura but without involvement of lung parenchyma, and situated in the left posterior mediastinum. On histological examination, the lesion showed the classical features of myxopapillary ependymoma. Immunohistochemical studies confirmed this impression by demonstrating strong positivity of the tumor cells for S-100 protein, glial fibrillary acidic protein, and CD99 and negative staining with other differentiation markers. A review of the literature with a discussion of the histologic and radiologic differential diagnosis of these lesions is presented. © 2006 Elsevier Inc. All rights reserved.

The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network

PURPOSE: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network.

BACKGROUND Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy. METHODS The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months. RESULTS Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis. CONCLUSIONS In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.

The Rare Cancer Network: achievements from 1993 to 2012.

The Rare Cancer Network (RCN), founded in 1993, performs research involving rare tumors that are not common enough to be the focus of prospective study. Over 55 studies have either been completed or are in progress.The aim of the paper is to present an overview of the 30 studies done through the RCN to date, organized by disease site. Five studies focus on breast pathology, including sarcoma, lymphoma, phyllodes tumor, adenoid cystic carcinoma, and ductal carcinoma in situ in young women. Three studies on prostate cancer address prostatic small cell carcinoma and adenocarcinoma of young and elderly patients. Six studies on head and neck cancers include orbital and intraocular lymphoma, mucosal melanoma, pediatric nasopharyngeal carcinoma, olfactory neuroblastoma, and mucosa-associated lymphoid tissue lymphoma of the salivary glands. There were 4 central nervous system studies on patients with cerebellar glioblastoma multiforme, atypical and malignant meningioma, spinal epidural lymphoma and myxopapillary ependymoma. Outside of these disease sites, there is a wide variety of other studies on tumors ranging from uterine leiomyosarcoma to giant cell tumors of the bone. The studies done by the RCN represent a wide range of rare pathologies that were previously only studied in small series or case reports. With further growth of the RCN and collaboration between members our ability to analyze rare tumors will increase and result in better understanding of their behavior and ultimately help direct research that may improve patient outcomes.

Malignant glioma after ependymoma: an unusual secondary malignancy

Purpose : Secondary malignancies (SM) are a known long-­‐term problem in children surviving brain tumors. We report on two unusual cases of SM observed after treatment of ependymoma. Case reports : 1. The first case is a female survivor of a low-­‐grade ependymoma (Grade II). She had been treated at the age of 3 months with surgery and chemotherapy. A relapse of the primary tumor happened two years later, which was completely removed and treated with local radiotherapy to the posterior fossa. Fifteen years after the first cancer, she developed a pontine glioma near the location of the previous radiotherapy. 2. The second case is a femal survivor of an ependymoma (Grade III) which was removed and irradiated when she was 4 years old. The child developed a pontine glioma near the location of the previous radiotherapy ten years after the diagnosis of the first cancer. Further extension of the disease showed after biopsy PNET-­‐ like features. Both patients passed away. Discussion and Conclusion : Second malignant neoplasia is a rare phenomenon and this risk should not overshadow the great success in treating cancer of childhood. Among the studied risk factors, young age and radiotherapy are well established. The reported patients were followed annually to ensure their remission and both developed symptoms and an unusual unreported secondary cancer a few months after the annual monitoring that was considered as normal. This issue highlights the complexity of monitoring cancer survivors and raises the question of the best way for their long-­‐term follow-­‐up.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study.

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

Bevacizumab for recurrent ependymoma.

BACKGROUND: Ependymoma is a rare type of glioma, representing 5% of all CNS malignancies. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence, ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. METHODS: In this Institutional Review Board-approved study, we retrospectively analyzed the records of 8 adult patients treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria), median time to progression (TTP), and median overall survival (OS; Kaplan-Meier method). RESULTS: There were 4 men and 4 women with a median age of 40 years (range, 20-65). Prior treatment included surgery (n = 8), RT (8), temozolomide (5), and carboplatin (4). Bevacizumab (5-15 mg/kg every 2-3 weeks) was administered alone (2) or concurrently with cytotoxic chemotherapy including irinotecan (3), carboplatin (2), or temozolomide (1). Six patients achieved a partial response (75%) and 1 remained stable for over 8 months. Median TTP was 6.4 months (95% confidence interval 1.4-7.4) and median OS was 9.4 months (95% confidence interval 7.0-not reached), with a median follow-up of 5.2 months among 5 surviving patients (63%). CONCLUSIONS: The radiographic response rate to bevacizumab-containing regimens is high. A prospective study is warranted.

Purely cortical anaplastic ependymoma

Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma.

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma"

By analogy to gliosarcoma, the term "ependymosarcoma" has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial-sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical - yet not frankly anaplastic - features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to "ependymosarcoma".

Oncocytic ependymoma: a new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells

Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as "dot-like" staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of "zipper-like" intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

Ependymoma of conus medullaris presenting as subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) due to spinal ependymoma is very rare. We report a 37 year old man who presented with typical clinical signs of SAH. Lumbar puncture confirmed SAH but cerebral angiography was negative, and further diagnostic work-up revealed an ependymoma of the conus medullaris as the source of the haemorrhage. A comprehensive review of the literature was conducted. Only 17 patients with spontaneous SAH due to a spinal ependymoma have been reported since 1958. However, in cases of SAH and negative diagnostic findings for cerebral aneurysms or malformations, this aetiology should be considered and work-up of the spinal axis completed.