br Case report A year old male presented to

Case report A 58-year-old male presented to the emergency room with sudden-onset aphasia. Neurological examination showed no significant focal neurological deficits other than aphasia. Brain magnetic resonance imaging (MRI) showed a nonenhanced TASIN-1 tumor in the left frontoparietal lobe (Fig. 1). The patient then underwent stereotactic biopsy for diagnosis. The histopathological report of the specimen was astrocytoma [World Health Organization (WHO) Grade II, Fig. 2, Table 1]. Debulking surgery under intraoperative monitoring was suggested, but the patient refused. We then arranged radiotherapy (60 Gy to the tumor bed and 54 Gy to the subclinical regions) as primary treatment. The follow-up brain MRI 3 months after the first biopsy showed a slight increase in the T2 high signal lesion in the left frontoparietal lobe, without significant tumor progression (Fig. 1). Headache, right-hand weakness, dysarthria, and intermittent aphasia developed 6 months after the first biopsy. The follow-up brain MRI showed an increase in tumor size on T2-weighted images, and a newly formed ring-enhanced area in the center of the tumor was noted on T1WI, without midline structure shifting (Fig. 1). The patient then underwent a second stereotactic biopsy on account of a suspicion of tumor progression, based on imaging findings. The second pathology report confirmed the diagnosis of the tumor as an anaplastic astrocytoma, with increased expression of TP53 and O-6-methylguanine-DNA methyltransferase (MGMT; WHO Grade III, Fig. 2, Table 1). We then administered chemotherapy with temozolomidel as a secondary treatment, and also arranged concomitant radiotherapy (50 Gy for the tumor bed and 25 Gy in the subclinical regions). However, symptoms of right-side limb weakness and dysarthria progressed 2 months after the second treatment. His follow-up brain MRI showed a progressive marginally enhanced lesion in the left temporo-parietal lobe with severe perifocal edema (Fig. 1). The differential diagnoses included radiation necrosis due to large dosage of radiotherapy and tumor progression. Because of the remarkable mass effect, craniotomy for tumor removal was performed. The pathology report of the specimen obtained in this operation revealed the diagnosis had changed to glioblastoma multiforme by the presence of pseudopalisading necrosis (WHO Grade IV, Fig. 2, Table 1). The patient did not respond well to temozolomide chemotherapy after craniotomy, and the disease continued to progress. He was kept under supportive hospice care, and died 18 months after the initial diagnosis.
Discussion Carcinogenesis due to radiotherapy in the treatment of benign brain tumor has been documented in many reports. Nishio et al reported 11 patients who underwent cranial irradiation and developed secondary tumors within a span of 13 years. Another possible effect of radiotherapy is radiation-induced malignant transformation of tumors, which can occur after radiation treatment for benign tumors, such as vestibular schwannoma and pituitary adenoma. The possible mechanism is that an insufficient number of cells are killed in the tumor and some of the surviving cells acquire mutations in genes, such as TP53, that can transform a benign tumor into a malignant one. In our case, the TP53 gene mutation rate increased from 40% in the first specimen to 60% in the second after treatment (Fig. 2). This was molecular biological evidence that the tumor in our patient showed a similar transformation process as malignant transformation in benign tumor after radiotherapy. According to the literature, there are two subtypes of glioblastoma: primary (de novo) and secondary. Secondary glioblastomas (5% of glioblastoma patients) develop through progression from low-grade diffuse astrocytoma or anaplastic astrocytoma. The specimens of secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations. In our patient, the histopathological diagnosis of astrocytoma in the first specimen and the expression of TP53 mutation in the glioblastoma specimen were consistent with the diagnosis of secondary glioblastoma, which implied that the tumor had developed from a lower grade tumor.