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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.67 no.3a São Paulo Sept. 2009 



Anaplastic astrocytoma post radiotherapy of pineal germinoma


Astrocitoma anaplástico após radioterapia de germinoma da pineal



Victor García-NavarroI; Martha Lilia Tena-SuckII; Miguel A. CelisIII; Rosalba VegaII; Daniel RembaoII; Citlaltepetl SalinasII

IService of Neurosurgery, National Institute of Neurology and Neurosurgery Mexico City
IIDepartment of Neuropathology, National Institute of Neurology and Neurosurgery Mexico City
IIIService of Radiosurgery, National Institute of Neurology and Neurosurgery Mexico City



Intracranial germ cell tumors (GCTs), especially pineal tumors have attracted the special attention of neuropathologists and neurosurgeons because of their unique growth sites, characteristic subtypes with different histology, and high incidence in Japan and other Asian countries1. They are usually arise in midline structures, including the pineal or suprasellar regions, more commonly seen in pediatric patients than in adults2,3. Radiosurgery is increasingly being used to treat pineal region tumors, either as an additional therapy after conventional treatments, the potential for late effects makes the treatment controversial2.

Radiation-induced intracranial neoplasms are uncommon but well described and include gliomas, meningiomas, and sarcomas4-6.

Germinoma developing an anaplastic astrocytoma is a rare event of radiation-induced intracranial tumors.



A 46-year-old female, at the age of 38 yr, presented signs of intracranial hypertension, and visual disturbances. MRI-imaging showed a pineal tumor (Fig 1A). The intraoperative smear showed round cells with vesicular and prominent nucleoli and clear, glycogen-rich cytoplasm (Fig 1B). The tumor was excised and the histopathology showed a germinoma (Fig 1C), and was immunopositive to fosphatase alcalin placentary (FAP), and glial acidic fibrillary protein (GAFP) was negative (Fig 1D). She had received radiation therapy with 50Gy.

Five years later, she presented headaches, memory loss, depression and complex partial seizures. MRI-imaging disclosed ring-like enhanced mass lesion in the left cerebellar lobe (Fig 2A). Tumor biopsy was performed through a suboccipital approach. The tumor was partially excised (80%) The histological diagnosis showed a grade I fibrillary astrocytoma (Fig 2B). It was GFAP+, P53- and MIB-1Li of 6.4%. The patient received post-operative chemotherapy and radiotherapy (RT), at total dose of 40Gy. She received a 6-week course of chemotherapy (lovustine, CCNU). During the next 3 years remained clinically and radiographically stable. However, she presented seizure activity, and imaging studies were consistent with tumor recurrence. She showed frontal cephalea, psychotic depression, amaurosis, right hemiplegia, and cerebellum syndrome. MRI-images disclosed enhanced mass lesion in the right temporal lobe corresponding to the previous irradiated field (Fig 2C), Right temporal lobectomy were performed. Histological showed astrocytoma grade III (Fig 2D), was GAFP+ (Fig 2E), P53+ and MIB-1Li was 43% (Table), with features of radiation effects (Fig 2F). The postoperative course was eventfully and died. An autopsy was not performed.



Total removal of pineal tumors is the therapy of choice2. Subtotal resection, atypical histological features, and high cell proliferation rates correlate with recurrence1-3. Radiotherapy has shown to be effective and has been given for pituitary tumor, astrocytoma, pinealoma, craniopharyngioma, glioblastoma and metastasic carcinoma2.

The clinical features and long-term outcome with delayed cerebral radiation necrosis (DCRN) are described4,5, produces a distinctive clinical picture, and remains a poorly recognized complication of cranial irradiation6.

Cerebral vascular disease has been reported as a long-term complication of cranial radiotherapy too7. The mean latency to onset of the first neurological symptoms are 22 months (range 6-40 months), and mean duration of follow-up is 86 months (range 60-126). Patients with germinona may die after radiotherapy at a mean of 84 months (range 62-983,4).

The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed8. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The precise clinical features that correlate irradiation and oncogenesis are not completely defined, but some authors have suggested that tumors are radiation-induced when they are histologically different from the treated ones, and arise in greater frequency in irradiated patients than among normal, and tend to occur in younger people with an unusual aggressiveness7.

The criteria for radiation-induced tumor have been established by Cahan et al8. A tumor location within irradiated area, no evidence of tumor prior to radiotherapy, a long latency period between radiation and tumor occurrence, and histological verification of the primary tumor must be pathologically different from the primary tumor and present at the time of irradiation and there must be no genetic predisposition for second tumor8.

The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors1-3. However, the immunohistochemistry remains still very helpful in differential diagnosis1.

Henson JW et al.9, reported that some primary human astrocytomas increase expression of p53 and p21 and decrease proliferation in response to RT. However, the small size of the series argues for further studies of radiation-induced molecular changes in primary human astrocytoma tissue.

In summary, we present a 46 years-old female who received radiotherapy of pineal germinoma. 5 year later she presented a second tumor an astrocytoma grade I, in cerebellum, received radiotherapy and 3 years later, presented a third different tumor, an anaplastic astrocytoma in the temporal lobe, associated to cerebral radio necrosis. Although radiation-induced neoplasia followed by radiotherapy is diagnosed.



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9. Henson JW, Hobbs W, Chakravarti A, Louis DN. Alterations in p53, p21, and MIB-1 labeling index in primary human astrocytomas following radiation therapy. J Neurooncol 2005;74:151-154.         [ Links ]



Received 17 February 2009, received in final form 4 June 2009. Accepted 11 June 2009.



Dra. Martha Tena-Suck - Departamento de Neuropatología / Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" - Av. Insurgentes Sur, 3788 Col. La fama, Delegación Tlalpan - C.P. 14269 México DF - México. E-mail:

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