Childs Nerv Syst (2003) 19:778–781 DOI 10.1007/s00381-003-0807-0 Norihito Shimamura Ken-ichiroh Asano Kazumi Ogane Akinori Yagihashi Hiroki Ohkuma Shigeharu Suzuki Received: 19 February 2003 Published online: 13 September 2003 © Springer-Verlag 2003 N. Shimamura (✉) · K.-i. Asano K. Ogane · A. Yagihashi · H. Ohkuma S. Suzuki Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaihu-chou, 036–8562 Hirosaki, Japan e-mail: shimab@cc.hirosaki-u.ac.jp Tel.: +81-172-395115 Fax: +81-172-395116 C A S E R E P O RT A case of definitely congenital glioblastoma manifested by intratumoral hemorrhage Abstract Background: A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. Methods: Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. Results: Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival. Keywords Adjuvant chemotherapy · Congenital glioblastoma · Hemosiderin intensity · Intratumoral hemorrhage · Magnetic resonance imaging · Radical removal Introduction Case report The reported incidence of congenital primary central nervous system tumors is 1.1–3.4 per million live births [2, 5], and glioblastoma has been found to account for 3.1–8.9% of congenital brain tumors [1, 12, 18]. Solitare and Krigman defined congenital brain tumor in three categories: definitely congenital—present or producing symptoms at birth; probably congenital—present or producing symptoms within the first week of life; and possibly congenital—present or producing symptoms within the first few months of life [15]. Only 16 cases of definitely congenital glioblastoma have been reported in the English literature [1, 3, 4, 9, 10, 12, 14, 16, 18, 19]. We experienced a case of definitely congenital left-sided supratentorial glioblastoma in a female neonate. We achieved a relatively long survival period of 27 months for this patient. This female infant was born of a 43-year-old mother at 40 weeks and 2 days of gestational age. During the gestational period, the obstetric gynecologist who had attended the mother in private practice had not recognized the presence of a brain tumor in the fetus on ultrasound examination. The baby was delivered by vacuum extraction owing to fetal distress. At the time of birth, her weight was 3,100 g, her head circumference was 34.0 cm, and her Apgar scores were 8 at 1 min and 9 at 5 min. The day after birth, her crying and feeding became weak. At 4 days of age, she developed a high fever and bulging of the anterior fontanel. The pediatrician obtained a brain CT (Fig. 1) and MRI (Fig. 2), which revealed a huge, left-sided brain tumor and intratumoral hemorrhage. The tumor was 48 mm¥48 mm¥40 mm in size. It occupied a region from the left para-hippocampal gyrus to the parietal lobe and parts of the other lobes. Ring-like hemosiderin intensities were seen on both T1- and T2-weighted images, indicating that the intratumoral hemorrhage had occurred a few weeks previously, during the prenatal period. The tumor was partially enhanced with gadolinium contrast-enhanced medium. When the baby was 10 days old her weight had decreased to 2,916 g and her head circumference was 35.3 cm. There were no thoracic or abdominal deformities. The Moro reflex in the right arm was slightly weak, and 779 Fig. 1 Plain computed tomography image taken when the patient was 4 days of age. Huge, round, heterogeneous, high-density mass and perifocal edema were detected. Midline structures were not conspicuously shifted despite the huge tumor size Fig. 2a–c Magnetic resonance imaging. a Plain T1-weighted image; b gadolinium-enhanced T1-weighted image with the tumor slightly enhanced; c T2weighted image showing environmental brain edema Fig. 3 Several typical pathological findings were seen on staining, including pleomorphic astrocytic tumor cells, pseudopalisading necrosis, and microvascular proliferation. (HE, ¥200) palmar grasping was also weak on the right side. We waited until the baby had gained some weight before performing surgery. When she was 22 days of age we performed total surgical removal of the brain tumor, which was soft and necrotic and easily extractable. She had no additional neurological deficit after the operation. Hematoxylin-eosin staining revealed the presence of pleomorphic astrocytic tumor cells, hypervascularity, tumor cell mitosis, microvascular proliferation and pseudopalisading necrosis (Fig. 3). Immunohistochemical studies were negative for synaptophysin and AFP, and positive for vimentin, S-100, and NSE. GFAP was partially and variably positive. MIB-1 index was 21.4%. Pathological examination yielded the diagnosis of glioblastoma. Postoperative adjuvant chemotherapy was performed in our pediatric department and involved the following courses of treatment: five courses of vincristine, etoposide, and carboplatin; three courses of isophosphamide, cisplatin, and etoposide; and three courses of ACNU, vincristine, and prednisolone. Surgical tumor removal was performed four times during this patient's lifetime. The interval between the first and second of these operations was 12 months. The patient was able to stand by herself at 18 months 780 of age. Owing to recurrence and dissemination of the tumor, whole-brain irradiation with a dose of 54 Gy was administered during her 2nd year of life. Tumor recurrence and emaciation led to the baby’s death 27 months after her birth. Discussion Conventionally, congenital brain tumor has been divided into three categories defined as definitely, probably, and possibly congenital, according to Solitare and Krigman [6] and Jellinger and Sunder-Plassmann [14]. According to these authors' definitions, the tumor in our case was definitely congenital, because symptomatic distress occurred immediately after delivery. Including our patient, only 17 cases of definitely congenital glioblastoma have been reported in the English literature [1, 3, 4, 9, 10, 12, 14, 16, 18, 19], and MRI findings of congenital glioblastoma in 7 of these cases [1, 3, 9, 10, 14, 16]. Tumor hemorrhage similar to that in our case was reported in detail in these imaging studies of the central nervous system. The onset of tumor hemorrhage can be dated by MRI, so that more precise identification of a congenital brain tumor is possible. There is a consensus in the literature that the more primitive the tumor is the more likely it is to bleed. The incidence of hemorrhage from tumors of neuroepithelial tissue was 8.1% in one study [17]. Astrocytomas hemorrhaged in only 7% of pediatric patients [8], whereas in glioblastoma cases hemorrhage occurred in 13.3% of patients aged 14 years and under [17]. The pathological diagnosis in our case was glioblastoma even though the GFAP was partially and variably positive, because in this case there was no biphasic tissue pattern with areas displaying the gliomatous or mesenchymal tissue that is essential for the diagnosis of glio- sarcoma and large portions of a glioblastoma can lack GFAP expression [7, 11]. Many reports have described the survival of glioblastoma cases as short, with death occurring within several months [9, 10, 16, 19]. In a review of eight cases of congenital glioblastoma in 1987, surgery was mostly not performed and the survival periods were no more than 2 months [4]. In a review of 24 cases of congenital glioblastoma multiforme in 2001, the survival periods reported were relatively long, with an average survival after treatment of 32.8 months [19]. When radical removal is performed at the first operation the surgeon is counting on the plasticity of infant cerebral function, and the radical surgery was the key point in the long survival [13, 20]. The long survival in our own case was also achieved by aggressive tumor removal at the first operation, plus chemotherapy and hyperalimentation. Intensive therapy made it possible to prolong the survival of this patient with congenital glioblastoma in whom the central nervous system was highly plastic. Conclusion We achieved long-term survival in a neonate with a definitely congenital glioblastoma. Total surgical removal and adjuvant chemotherapy were important elements of her treatment, as in noncongenital pediatric cases. 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