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Year : 2006  |  Volume : 1  |  Issue : 2  |  Page : 63-65

Glioblastoma multiforme occurring in a child with acute lymphoblastic leukemia

Postgraduate Institute of Neurological Surgery, Dr. Achanta Lakshmipathi Neurosurgical Centre, VHS Hospital, Chennai, India

Correspondence Address:
Nigel Peter Symss
Postgraduate Institute of Neurological Surgery, Dr. Achanta Lakshmipathi Neurosurgical Centre, VHS Hospital, Taramani, Chennai - 600 113
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1745.27456

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A three and a half year old boy was diagnosed to have acute lymphoblastic leukemia in September 2002 and was treated with induction chemotherapy. He also received prophylactic cranial irradiation (12 Gy) and intrathecal methotrexate. In November 2005, at the age of 7 years, he developed right focal seizures and was diagnosed to have a glioblastoma in the left parietooccipital region while the leukemia was in remission. The possibilities are the glioma may have been radiation- and / or chemotherapy-induced.

Keywords: Glioblastoma multiforme, leukemia, methotrexate, radiotherapy.

How to cite this article:
Symss NP, Pande A, Chakravarthy MV, Ramamurthi R. Glioblastoma multiforme occurring in a child with acute lymphoblastic leukemia. J Pediatr Neurosci 2006;1:63-5

How to cite this URL:
Symss NP, Pande A, Chakravarthy MV, Ramamurthi R. Glioblastoma multiforme occurring in a child with acute lymphoblastic leukemia. J Pediatr Neurosci [serial online] 2006 [cited 2023 May 30];1:63-5. Available from: https://www.pediatricneurosciences.com/text.asp?2006/1/2/63/27456

   Introduction Top

Radiation therapy is an established cause of secondary neoplasia in the central nervous system.[1],[2],[3],[4] Both benign and malignant tumors can develop after cranial irradiation, in the form of meningiomas[5],[6],[7] and sarcomas.[8],[9],[10] Reports of glial neoplasms after radiation therapy have been documented less frequently.

The management of children with acute lymphoblastic leukemia (ALL) includes an effective combination of induction chemotherapy and with this therapy patients were noted to experience prolonged hematological remission. However, induction chemotherapy did not prevent the development of central nervous system leukemia. Hence intrathecal methotrexate, either alone or in combination with cranial or craniospinal irradiation, is effective in preventing the initial CNS leukemia in most patients, thereby increasing survival of children with ALL.

We report a patient who developed a glioblastoma in the left parietooccipital region 4 years after prophylactic cranial irradiation and methotrexate for ALL.

   Case Report Top

A 3-year-old boy, the youngest of three siblings, born of a nonconsanguineous marriage was admitted to a cancer hospital in Sept 2002 and diagnosed to have acute ALL. He was admitted with history of multiple episodes of high grade fever, listlessness and pain in both the knee joints, causing difficulty in walking. He had no prior illness. He had no bleeding diathesis, no family history of cancer or hereditary disease. Hematological examination and bone marrow aspirate confirmed the diagnosis of acute ALL. He was treated with six cycles of induction chemotherapy with prednisolone, L. asparaginase , danorubicin and vincristine. He also received twelve doses of intrathecal methotrexate during that period along with prophylactic cranial irradiation to the whole brain from December 2002 to January 2003 (a total dose of 12 Gy in 30 sittings). He completed chemotherapy in January '05 and continues to be in remission. He was referred to us from the cancer hospital in November '05 with history of one episode of right focal seizures involving the face and upper limb. There was no history suggestive of raised intracranial pressure. On neurological examination, his fundus was normal and he had no deficits. CT scan of the brain, plain and contrast study, showed an ill-defined mixed-density lesion, heterogeneously enhancing with contrast in the left parietooccipital region, with perilesional edema and mass effect [Figure - 1]. He underwent a stereotactic biopsy of the lesion [Figure - 2]. Histologically the lesion was highly cellular and vascular with endothelial proliferation with increased mitotic activity, suggestive of a glioblastoma multiforme.

   Discussion Top

The apparent induction of a second malignant neoplasm following antineoplastic treatment is well known. In establishing a causal relationship between therapeutic irradiation and the development of a secondary tumor, significant histological differences must be apparent to reduce the possibility that the latter tumor evolved from its predecessor. Criteria identifying a neoplasm as radiation induced have been proposed by Fajardo.[10] Principal among these are that the induced tumor should occur in the previously irradiated field, that it should appear after a latent period and that it should differ from the initially treated neoplasm. The possible etiological factors in the induction of the GBM in our patient are radiation or chemotherapy or a combination of both. Radiation therapy is an established cause of secondary neoplasia in the CNS. Benign tumors like meningiomas and malignant tumors like sarcomas can develop after cranial irradiation and have been reported in the literature. Meningiomas have a relatively long latency period, whereas sarcomas develop after a shorter latency. Modan et al.[11] have reviewed 11,000 children who received radiotherapy for tinea capitis. These children received between 350 and 400 rads, with a calculated dose of 140 rads to the brain. The results confirmed that there was a significantly higher risk of developing head and neck tumors after radiotherapy. The idea that radiation might play a causal role in the formation of malignant glial tumors was first suggested in 1958 by Kent and Pickering, who reported the appearance of a GBM in a monkey following thermal neutron irradiation to its whole head.[12] Only a few cases of radiation-induced gliomas in humans have been reported.[13],[14],[16],[17] The radiation dosage ranged from 400 to 6,000 rads with an average latent period of 9 (range 1-26) years. Jones,[18] in 1960, reported a patient who developed a right hemispheric astrocytoma 10 years following treatment with 4,000 rads of radiation therapy for an angioblastic meningioma. Robinson[4] reported two cases of malignant astrocytoma after cranial irradiation. Corey et al,[19] in 1985, reported a 13-year-old girl who developed an anaplastic astrocytoma of the cerebellum 7 years after irradiation of the CNS and prophylactic chemotherapy for ALL. This was the first reported case of a glioma in a child who received CNS irradiation for leukemia. It has been suggested that the presence of gliotic brain tissue increases the probability of induction of gliomas by radiation as compared with other irradiated brain tissue.[20],[21]

The role of radiation as a carcinogenic agent has been well established; however, the exact mechanism of radiation-induced carcinogenesis remains unknown. Radiation-induced neoplasia appear to arise through mutagenic capacity and chromosomal aberration and the mechanisms leading to neoplastic transformation is a multistage (multihit kinetics) process rather than a single one-hit process.[22],[23] The other possible causative factor in the induction of the tumor in our patient could be the combination of cranial irradiation with intrathecal methotrexate.[24] The administration of methotrexate along with cranial irradiation with 200 cGy or more may result in leukoencephalopathy with multiple necrotic areas with or without gliosis disseminated throughout the cerebral white matter.[20] However, there is no evidence in man or experimental animals to suggest that intrathecal methotrexate, when given alone, is carcinogenic or that it enhances the carcinogenic effect of radiation.

The other rare possibility is that the lesion may have occurred 'spontaneously,' but considering the low incidence of GBM in children, this is unlikely. Also, the other possibility of predisposition to neural crest and neuroectodermal tumors seen in association with Von Recklinghausen's disease was ruled out as there was no family history and stigmata of Von Recklinghausen's disease.

Statistical and clinical analyses suggest that a genetic predisposition to multiple neoplasms, the synergistic action of cranial irradiation and intrathecal methotrexate and the prolonged exposure to methotrexate could be etiological factors in inducing these second tumors.

   References Top

1.Liwnicz BH, Berger TS, Liwnicz RG, Aron BS. Radiation-associated intracranial gliomas: A report of four cases and analysis of post radiation tumors of the central nervous system. Neurosurg 1985;17:436-45.  Back to cited text no. 1    
2.Saeneger EL, Silverman FN, Sterling TD, Turner ME. Neoplasia following therapeutic irradiation for benign conditions in childhood. Radiology 1960;74:889-904.  Back to cited text no. 2    
3.Marus G, Levin CV, Rutherford GS. Malignant glioma following radiotherapy for unrelated primary tumors. Cancer 1986;58:886-94.  Back to cited text no. 3    
4.Robinson RG. A second brain tumour and irradiation. J Neurol Neurosurg Psychiatr 1978;41:1005-12.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Bogdanowicz WM, Sachs E Jr. The possible role of radiation in oncogenesis of meningioma. Surg Neurol 1974;2:379-83.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Iacono RP, Apuzzo ML, Davis RL, Tsai FY. Multiple meningiomas following radiation therapy for medulloblastoma: Case report. J Neurosurg 1981;55:282-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Sridhar K, Ramamurthi B. Intracranial meningioma subsequent to radiation for a pituitary tumour: Case report. Neurosurgery 1989;25:643-5.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Ahmad K, Fayos JV. Pituitary fibrosarcoma secondary to radiation therapy. Cancer 1978;42:107-10.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Arlen M, Higinbotham NL, Huvos AG, Marcove RC, Miller T, Shah IC. Radiation-induced sarcoma of bone. Cancer 1971;28:1087-99.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Fajardo LF. Pathology of Radiation Injury. Masson: New York; 1982. p. 252-5.  Back to cited text no. 10    
11.Modan B, Baidatz D, Mart H, Steinitz R, Levin SG. Radiation induced head and neck tumors. Lancet 1974;1:277-9.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Kent SP, Pickering JE. Neoplasms in monkeys (Macaca mulatta): Spontaneous and irradiation induced. Cancer 1958;11:138-47.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Chung CK, Stryker JA, Cruse R, Vannuci R, Towfighi J. Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with a lymphocytic leukemia. Cancer 1981;47:2563-6.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Robinson RG. A second brain tumour and irradiation. J Neurol Neurosurg Psychiatr 1978;41:1005-12.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Preissig SH, Bohmfalk GL, Reichel GW, Smith MT. Anaplastic astrocytoma following radiation for glomas jugular tumour. Cancer 1979;43:2243-7.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Mazumdar DP, Desai K, Goel A. Gliomblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic. Neurol India 1999;47:142-4.  Back to cited text no. 16    
17.Shah KC, Rajshekar V. Glioblastoma multiforme in a child with acute lymphoblastic leukemia. Neurol India 2004;52:375-7.  Back to cited text no. 17    
18.Jones A. Supervoltage X-ray therapy of intracranial tumors. Ann R Coll Surg Engl 1960;27:310-54.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Raffel C, Michael S, Edwards B, Davis RL, Ablin AR. Postirradiation cerebellar glioma. J Neurosurg 1985;62:300-3.  Back to cited text no. 19    
20.Peylan RN, Poplack DG, Pizzo PA, Adornato BT, Di Chiro G. Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of central nervous system with radiation and intrathecal chemotherapy. N Engl J Med 1978;298:815-8.  Back to cited text no. 20    
21.Sogg RL, Donaldson SS, Yorke CH. Malignant astrocytoma following radiotherapy of a carniopharyngioma. J Neurosurg 1978;48:622-7.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]
22.Furth J, Lorenz E. Carcinogenesis by ionizing radiation. In : Radiation Biology. Hollaender A, (editor). Mc Graw Hill: New York; 1954. p. 1145-201.  Back to cited text no. 22    
23.Glucksmann A, Lamerton LF, Mayneord WV. Carcinogenic effects of radiation. In : Cancer. Raven RW (editor). Butter worth Press: London; 1957. p. 477-539.  Back to cited text no. 23    
24.Inati A, Sallen SE, Cassady JR, Bryan SH, Clavell LA, Belli JA, et al . Efficacy and morbidity of CNS prophylaxis in childhood ALL: Eight years experience with cranial irradiation and intrathecal methotrexate. Blood 1971;61:297-303.  Back to cited text no. 24    


[Figure - 1], [Figure - 2]

This article has been cited by
1 Radiation-Induced Glioblastoma Multiforme in a Remitted Acute Lymphocytic Leukemia Patient
Daewon Joh, Bong Jin Park, Young Jin Lim
Journal of Korean Neurosurgical Society. 2011; 50(3): 235
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