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(a) May-Giemsa staining of the CSF sediment showing atypical cells, (b, c) Immunocytochemistry of the CSF sediment showing atypical cells (white arrowheads) with enlarged hyperchromatic delicate irregular nuclei that are positive for Olig2, (b) and negative for LCA (c), The surrounding lymphocytes (black arrowheads) are positive for LCA, (c) and negative for Olig2 (b) (100 × objective), (d, e) Paraffin sections of the biopsy of the intracranial lesion. H and E staining, (d) and Olig2 immunostaining, (e) Scale bars = 50 μm
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Radiation-induced glioma arising in the spinal cord is extremely rare. We report a case of radiation-induced spinal cord glioblastoma with cerebrospinal fluid (CSF) dissemination 10 years after radiotherapy for T-cell lymphoblastic lymphoma.
A 32-year-old male with a history of T-cell lymphoblastic lymphoma presented with progressive gait disturban...
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... With reference to that reported case, therapeutic radiation might be useful in preventing remnant tumor from regrowth in our case. However, evidence level was quite low for the efficacy of radiation therapy, and there remain concerns about radiation-induced injury or tumor in the future [8,9]. Therefore, performance of radiation should be carefully decided in consideration of the risks and benefits of this adjuvant therapy. ...
Gliofibroma is a rare tumor that develops in the brain and spinal cord. Due to the rarity of its nature, its pathophysiology and appropriate treatment remain elusive. We report a case of intramedullary spinal cord gliofibroma that was surgically treated multiple times. This report is of great significance because this is the first case of recurrence of this tumor.
A 32-year-old woman complained of gait disturbance and was referred to our institution. At the age of 13 years, she was diagnosed with intramedullary gliofibroma and underwent gross total resection (GTR) in another hospital. Based on imaging findings, tumor recurrence was suspected at the level of cervical spinal cord, and surgery was performed. However, the resection volume was limited to 50% because the boundary between the tumor and spinal cord tissue was unclear and intraoperative neuromonitoring alerted paralysis. At 1 year postoperatively, the second surgery was performed to try to resect the residual tumor, but subtotal resection was achieved at most. At 2 years after the final surgery, no tumor recurrence was observed, and neurologic function was maintained to gait with cane.
Although complete resection is desirable for this rare tumor at the initial surgery, there is a possibility to recur even after GTR with long-term follow-up. During surgical treatment for tumor recurrence, fair adhesion to the spinal cord is expected, and reoperation and/or adjuvant therapy might be considered in the future if the tumor regrows and triggers neurological deterioration.
... The majority of spinal cord RIGs occur after radiation treatment of non-neurologic head and neck tumors or the mediastinal radiation performed for hematologic malignancies. [10][11][12][13][14][15] The majority of RIG secondary to treatment of medulloblastoma occur at the site of the primary pathology or at other intracranial locations. [9,[16][17][18][19] There is one case of a cervical spinal cord anaplastic astrocytoma that occurred 17 years after craniospinal radiation for a cerebellar medulloblastoma. ...
Medulloblastomas are one of the most common malignant pediatric brain tumors. Therapy has evolved into multimodality treatments consisting of surgery, radiation, and adjuvant chemotherapy. While craniospinal radiation remains standard for patients older than 3 years of age, it is not free of side effects and long-term complications. The development of malignant gliomas following therapy is a well-documented phenomenon. However, the majority of these radiation-induced glioblastomas (RIG) are intracranial, and intraspinal lesions are rare. The patient is a 22-year-old female with a history of a posterior fossa medulloblastoma diagnosed 8 years prior for which she underwent surgical resection followed by adjuvant chemotherapy and craniospinal radiation. Surveillance imaging showed no evidence of recurrence or new lesions for the following 5 years. She presented with nausea and vomiting and imaging revealing a new intramedullary cervical spinal cord lesion. She then developed acute quadriplegia several days after presentation. She underwent a cervical laminectomy and resection of this lesion, which was initially diagnosed as recurrent medulloblastoma before genomic analysis ultimately revealed it to be a RIG. Spinal RIGs that occur secondary to treatment for an intracranial neoplasm are exceedingly rare. The majority of spinal cord RIGs have been reported secondary to treatment for tumors outside of the neuroaxis, while the majority of RIGs secondary to treatment for intracranial tumors remain intracranial. Nevertheless, RIGs are associated with a short clinical history, aggressive progression, and poor outcome.
... 3 For those that arise in the spinal cord, there have only been four previously reported cases, and neither have been in the conus medullaris nor have come from a history of brachytherapy for cervical cancer. [3][4][5][6] Because of the long latency for diagnosing radiation-induced tumours, it is of importance to keep these in mind in patients presenting with tumours distant from but still within the previous irradiation field. 7 ...
... [9][10][11][12] We included only in this review, those four studies in which a specific diagnosis of radiation-induced glioblastoma was made and treated as such. [3][4][5][6] Clifton 4 in 1980 originally reported a case of a 21-year-old man who initially underwent radiation for a mediastinal Hodgkin's lymphoma and developed radiation-induced glioblastoma in the cervicothoracic region after 6 years. There was worsening neurological symptomatology over 4 months. ...
... The most recent report of radiation-induced spinal cord glioblastoma was by Kikkawa and colleagues 6 . They described a case of a 21-year-old man with T-cell lymphoblastic lymphoma who underwent irradiation of the mediastinal region. ...
Radiation-induced spinal glioblastoma is an extremely rare disease with only four previously published reports in the literature. We report the fifth case, a 69-year-old woman who previously underwent treatment with brachytherapy for cervical cancer, and thereafter presented with neurologic deficits from a conus medullaris tumour. Biopsy and histopathology confirm glioblastoma, not otherwise specified. Treatment of spinal glioblastoma consists of surgery, either biopsy or excision and chemoradiation. However, results are still unsatisfactory and prognosis remains poor.
... Among the secondary tumors of the central nervous system, a few cases of intracerebral glioblastomas in previously irradiated tissue have been reported [1][2][3], though they are considerably less frequent than secondary meningiomas [4,5]. A tumor must fulfil several criteria to be considered of radiation-induced etiology [2,6,7]: It must develop in a previous radiation field with an interval of several years between the tumors clinical presentation and the original radiotherapy; and be confirmed as histologically distinct from the tumor for which the radiotherapy was originally given. ...
... Secondary malignancy following curative treatment for a Hodgkin's lymphoma is well-recognized in the literature [8,9]. We have found nine cases of spinal cord glioblastomas which were possibly secondary to radiotherapy [3,7,[10][11][12][13][14][15][16], of which the radiotherapy had been indicated for lymphatic disease in five [7,10,11,13,14]. All patients were male, aged less than 50 years old [7,10,11,13,14] with a presentation interval following radiotherapy of three to nine years (Table 1). ...
... Secondary malignancy following curative treatment for a Hodgkin's lymphoma is well-recognized in the literature [8,9]. We have found nine cases of spinal cord glioblastomas which were possibly secondary to radiotherapy [3,7,[10][11][12][13][14][15][16], of which the radiotherapy had been indicated for lymphatic disease in five [7,10,11,13,14]. All patients were male, aged less than 50 years old [7,10,11,13,14] with a presentation interval following radiotherapy of three to nine years (Table 1). ...
Purpose: Reports of a glioblastoma arising in a previously irradiated field are rare in the literature, even more so in the conus medullaris of the spinal cord. Method: Case report and review of the literature reporting other radiation-induced intra-medullary glioblastomas. Results: We report a case of glioblastoma of the conus, which subsequently metastasized to the brain, arising in a 45 years old man, nine years after treatment for Hodgkin's lymphoma, which had included the administration of 41 Gy to the brain and spinal cord. Conclusion: Despite a well-conducted treatment by several lines of chemotherapy, the pronostic of radiationinduced glioblastoma is poor especially since these patients often cannot benefit from a re-irradiation due to the maximum dose supported by the spinal cord. Implications of cancer survivors: Associations are now established between therapeutic exposures and specific complications but considerable inter-individual variability is observed for a given therapeutic exposure. In this context, identification of genetic susceptibilities for specific treatment-associated late effect is a very promising future approach. Improvement in our knowledge on genetic susceptibilities may help define more personalized primary therapies that weigh treatment efficacy with the risk of late complications.
By conducting a systemic search of the PubMed database, we performed a comprehensive literature review to characterize secondary gliomas following radiotherapy treatment and to determine the most appropriate treatment strategy. Our analysis included 296 cases of radiation-induced gliomas. The primary lesion was characterized as a hematological malignancy in 104 cases (35.1 %), pituitary adenoma in 35 (11.8 %), craniopharyngioma in 19 (6.4 %), medulloblastoma in 38 (12.8 %), germ cell tumor in 13 (4.3 %), low-grade glioma in 28 (9.4 %), cancer/sarcoma in 12 (4.0 %), scalp region disease in 15 (5.0 %), meningioma/schwannoma in 13 (4.3 %), metastatic brain tumor in 5 (1.6 %), and other types (e.g., arteriovenous malformations and angiomas) in 14 (4.7 %). The average age of onset for primary lesions was 16.0 ± 15.8 years, and the average radiation dose delivered to the primary lesion was 37.6 ± 20.0 Gy. Secondary gliomas could be divided into grade I (1), grade II (32), grade III (88), and grade IV (173) tumors. The median overall survival for all glioma cases was 11 months (95 % confidence interval [CI], 9–12), with a 2-year survival rate of 20.2 %. On multivariate analysis, combined modality treatment and the latency period from the radiotherapy treatment to the glioma diagnosis were variables associated with the overall survival of patients with grade III/IV secondary gliomas. For patients treated with cranial radiotherapy, the risk of secondary glioma incidence warrants a longer follow-up period beyond the standard time frame typically designated for determining the risk of primary tumor relapse. Moreover, combination therapy is a potential treatment option for radiation-induced gliomas.
Accounting for less than 0.2% of all glioblastomas, high grade gliomas of the spinal cord are very rare. Here, we discuss our approach to managing patients with high grade spinal cord glioma and review the literature on the subject. Six patients with high grade spinal cord gliomas who presented to our institution between 1990 and 2015 were reviewed. Each patient underwent subtotal surgical resection, with a subset receiving adjuvant chemotherapy and radiation. Our primary outcomes of interest were pre-operative and post-operative functional status. One year survival rate was 100%. All patients had stable or improved American Spine Injury Association score immediately after surgery, which was maintained at 3. months in 83.3% of patients. Karnofsky Performance Status (KPS) was stable at 3. month follow up in 50% of patients, but all had decreased KPS 1. year after surgery. A subset of patients received post-operative radiation and chemotherapy with 0% tumor recurrence rate at 3. months. We assessed the molecular profiles of tumors from two patients in our series and found that each had mutations in TP53, but had wildtype BRAF, IDH-1, and MGMT. Taken together, our data show that patients with high grade spinal cord gliomas have an excellent survival at 1. year, but with some decline in functional status within this period. Further studies are needed to elucidate the natural history of the disease and to explore the role of adjuvant targeted molecular therapies.
Malignant gliomas are known uncommon risks of brain irradiation, referred to as radiation-induced malignant gliomas (RIMGs). In this study, we have illustrated 4 cases of RIMG that occurred at our institution and performed the largest comprehensive review of the literature to better characterize RIMGs.
Patients were identified through the Pubmed database. Pearson's R linear correlation test was used to evaluate the correlation between radiotherapy (RT) dose and age with latency period. Student's t test was used to evaluate differences between latency periods for original tumor lesions. A nBed analysis was performed to indicate the minimum and maximum radiation threshold for neoplasia. A Kaplan-Meir analysis was used to illustrate the overall survival curves.
A total of 172 cases from the Pubmed database and 4 cases occurring at our institution were included in the analysis. The median amount of RT dose administered was 35.6 Gy, with most common dosage ranges 21-30 Gy (31%) and 41-50 Gy (21.5%). Median latency period was 9 years until diagnosis of RIMG, and occurred within 15 years in 82% of the patients. There was no correlation between the age of the patient at which RT treatment was administered (R(2)=.00081) or amount of RT (R(2)=.00005) and latency period for the RIMG. The mean BED for neoplasia of a RIMG was 63.3 Gy. The median survival of patients with a RIMG has improved over time (p=.004), with the median survival of 9 months prior to 2007 and 11.5 months post 2007.
The risk of a RIMG appears to hold for all age groups, histologies, and RT dosages. Even as risk remains low, patients should be aware of RIMG as a possible complication.
Copyright © 2014 Elsevier Inc. All rights reserved.
