Management of pediatric craniopharyngiomas has become increasingly conservative in recent years in recognition of the unfavorable outcome after extensive surgery²⁾. Adjuvant radiotherapy (RT) after subtotal resection has become the mainstay of management. Modern RT continues to have significant adverse effects especially in the pediatric population of craniopharyngiomas, where it is mainly palliative for this benign lesion in a population with an otherwise long life expectancy¹⁾. Radiation induced tumors (RIT) are rare and high grade gliomas are even more uncommon¹⁾. In children who undergo RT for craniopharyngiomas secondary gliomas have been reported although extremely rarely¹⁾. We report a child who was diagnosed as a craniopharyngioma at the age of 2 years and later underwent radiotherapy. She presented with a glioblastoma multiforme (GBM) 10 years later.

A 12-year-old child was brought to our casualty services with features of raised intracranial pressure and left hemiparesis of grade 4. Magnetic resonance imaging (MRI) of the brain revealed an enhancing lesion in the right temporal region with central necrosis and post-contrast enhancement. The lesion measured 6.9×5.0×5.7 cm with mass effect and midline shift (Fig. 1E, F). There was a small calcified remnant in the sellar region. A working diagnosis of a high grade glioma was made and the child underwent an emergency craniotomy and decompression of the lesion. The post-operative period was unremarkable. She had previously undergone a ventriculo-peritoneal shunt and decompression of a recurrent suprasellar craniopharyngioma at our institute 4 years prior (Fig. 1C, D). She had an earlier diagnosis of suprasellar craniopharyngioma and had been operated at another institute 10 years prior to presentation. She had undergone a second surgery, within two years of diagnosis, for a residual/recurrent lesion. Fig. 1A and B demonstrate the lesion prior to the second surgery. She was then subjected to adjuvant conventional fractionated RT of 55 Gy with bilateral opposed ports with an anterior field, following which she was asymptomatic for 6 years.

Post operative MRI revealed complete decompression of the lesion (Fig. 1G, H). The histopathology revealed a GBM (Fig. 2). She was treated with temazolamide chemotherapy by an oncologist and succumbed to the tumor a year after surgery.

Cahan et al.¹⁾ described four criteria for the diagnosis of RIT : 1) the tumor must originate within the field of previous irradiation; 2) the latency between the RT and RIT should be sufficiently long; 3) the histological characteristics must differ from the primary lesion which was irradiated; and 4) the patient must not harbor any pathological conditions favoring the development of tumors such as neurofibromatosis. The case in discussion did conform to these criteria.

The commonest RIT tumors are sarcomas and meningiomas but gliomas have been rarely reported¹⁾. Fifteen cases have been earlier reported in literature¹⁾. The average age of patient at the time of irradiation was 12.5 years¹⁾. The present patient was much younger at the time of RT. An average of 55 Gy has been recommended which was the same dose received by this child¹⁾. Temporal lobe is the commonest area to be localized by the secondary glioma as it does come in the field of irradiation¹⁾. Of these 15 patients only 6 were GBMs and only 4 occurred in children¹⁾. This patient is the 5th case of RT induced GBM for a craniopharyngioma.

No correlation is documented between the dosage of RT and the latency or grade of the secondary tumors¹⁾. The histology has varied from low grade gliomas (usually adult patients) to GBM¹⁾. The pediatric population appears more prone for the higher grade of RT induced malignancies¹⁾. There have been no demonstrable differences in the histopathology or molecular markers between RT induced GBM and the spontaneous types¹⁾. High grade gliomas, post RT, occur more often in the pediatric population as compared to adults¹⁾. The latency period for the secondary pediatric GBMs is about 9 years¹⁾. Our patient presented after 10 years.

Although ionizing radiation inducing gliomas in primates has been proven conclusively^5), such an association appears circumstantial based on the criteria outlined above. The actual etiological association between the RT and the occurrence of gliomas may never be substantiated at a molecular level and thus "radiation associated tumors" has been suggested as an alternative to RIT¹⁾. The incidence of the secondary gliomas is so small in comparison to the actual number of irradiated patients that the etiological proof is at best speculative³⁾. Further research into radiation induced neuronal damage may shed light on the molecular pathogenesis of this entity.

The "do-no-harm" management for pediatric craniopharyngiomas has become popular^2,4) and reports have highlighted the individualization of therapy for craniopharyngiomas to avoid RT induced adverse effects such as neurocognitive and neuroendocrine disturbance, optic neuropathy, radiation induced vasculopathy and RIT^2,4).

Rare instances such as this case report should not deter RT being used as an adjuvant therapy especially since the benefits of RT in halting the progression of pediatric craniopharyngiomas is well documented^3,4).

Stereotactic radiosurgery (SRS) has become a popular alternative to conventional fractionated RT in recent times⁷⁾. Although a recent report of c-knife 60Co radiosurgery-induced glioblastoma has been reported^8), SRS still appears to be a safer alternative smaller irradiated fields and the less radiation dose to the surrounding normal tissue¹⁾. Other modern modifications such as 3D conformal RT, intensity modulated RT and stereotactic RT (SRT) appear to be promising³⁾.

Recent reports have also indicated a possible role of alkylating chemotherapeutic agents in the management of radiation induced gliomas⁶⁾. This patient did receive a course of temazolamide.

This case does stir up the debate whether adjuvant RT is warranted in benign lesions such as craniopharyngiomas, which although does appear to arrest the disease in many cases, but may be associated with the deadly complication of radiation induced malignancy. Newer modalities such as SRS or SRT may prove to be a better alternative to conventional RT.