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Keiji Sano and Masao Matsutani

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Ryo Nishikawa and Masao Matsutani

Primary intracranial germ cell tumors (GCTs) comprise 3.1% of all brain tumors and 13.6% of those in patients younger than 15 years of age in Japan. They are classified into five basic histological types: germinoma, teratoma, choriocarcinoma, yolk sac tumor, and embryonal carcinoma; or into mixed tumor types when they consist of two or more components. Radiation therapy with or without chemotherapy has proven effective in the treatment of germinoma, whereas there is a poor prognosis for choriocarcinoma, yolk sac tumor, embryonal carcinoma, and mixed tumors having components of the group of malignant intracranial GCTs. The underlying mechanisms for such different responses to radio- and chemotherapies of intracranial GCTs remain unknown.

In this study, the authors analyzed the expression of p53 and p21WAF1/Cip1 proteins by immunohistochemical analysis in 35 intracranial GCTs. Expression of p53 protein was observed in 33 (94%) of 35 intracranial GCTs. Expression of p21WAF1/Cip1 was detected in seven (20%) of 35 intracranial GCTs. None of the 15 germinomas was immunoreactive for p21WAF1/Cip1 protein, whereas in a group of malignant intracranial GCTs, four (80%) of five cases showed immunoreactivity for p21WAF1/Cip1 protein. Analysis of the data suggests that overexpression of p21WAF1/Cip1 in intracranial GCTs may correlate with decreased sensitivity to radio- and chemotherapy and suggest a poor prognosis.

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Tomokatsu Hori, Hideo Terao, Tsuneyoshi Eguchi and Masao Matsutani

✓ A case of a huge, rapidly enlarging, intraoral carotid aneurysm, presenting with dysphagia and dyspnea, was successfully treated by a combination of extracranial-intracranial bypass and internal carotid artery ligation. This case is unusual in that a tendency to bleed was observed for about 3 weeks after the operation. This is thought to be related to a consumption coagulopathy associated with the aneurysm.

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Hideo Terao, Tomokatsu Hori, Masao Matsutani and Riki Okeda

✓ Two cases of cryptic vascular malformation that were not demonstrated by cerebral angiography were detected by computerized tomography. One of these patients had a cavernous angioma in the fourth ventricle with recurrent subarachnoid hemorrhages, and the other harbored a small arteriovenous malformation and intracerebral hematoma. The usefulness and limitations of computerized tomography in the identification of cryptic vascular malformations are discussed.

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Taichi Tachikawa, Jun-ichi Adachi, Ryo Nishikawa and Masao Matsutani

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Takamitsu Fujimaki, Masao Matsutani, Akio Asai, Takeshi Kohno and Morio Koike

✓ A case of cerebral venous thrombosis due to polycythemia secondary to adaptation to a high altitude is reported. A 27-year-old previously healthy man developed severe neurological symptoms after climbing 8511m. Computerized tomography and cerebral angiography suggested hemorrhagic infarction or intratumoral hemorrhage, and a craniotomy was performed. Pathological examination confirmed the diagnosis of hemorrhagic infarction secondary to cortical venous thrombosis. The etiology and incidence of cerebral venous thrombosis secondary to polycythemia are discussed.

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Masao Matsutani, Keiji Sano, Kintomo Takakura, Takamitsu Fujimaki, Osamu Nakamura, Nobuaki Funata and Terukazu Seto

✓ The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy.

The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone.

From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

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Chifumi Kitanaka, Masao Matsutani, Shigeo Sora, Sachiko Kitanaka, Ayako Tanae and Itsuro Hibi

✓ Although precocious puberty is common in boys with human chorionic gonadotropin (hCG)-secreting brain tumors, it is extremely rare in girls. The authors describe a 6-year-old girl with an hCG-secreting suprasellar immature teratoma who presented with diabetes insipidus, increased intracranial pressure, and precocious puberty. On admission, breast budding was observed. The serum hCG level was 1230 mIU/ml. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) remained below detectable levels, even after gonadotropin-releasing hormone stimulation. Serum estrogen and androgen were moderately elevated. After chemotherapy, breast budding disappeared with normalization of serum hCG.

It has been believed that hCG does not produce precocious puberty in girls in the absence of FSH, and this has been used as an explanation for the rarity of precocious puberty in girls with hCG-secreting brain tumors. However, it has also been reported that hCG has not only LH activity but also intrinsic, although weak, FSH-like activity. In the present case, this FSH-like activity was considered to have played a role in the development of precocious puberty. It is speculated that a very high level of serum hCG can produce precocious puberty in girls. The rarity of intracranial germ-cell tumors with a high potential of hCG secretion may be one of the reasons why hCG-induced precocious puberty is uncommon in girls.

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Kohei Fukuoka, Takaaki Yanagisawa, Tomonari Suzuki, Kenji Wakiya, Masao Matsutani, Atsushi Sasaki and Ryo Nishikawa

Congenital intracranial immature teratomas carry a dismal prognosis, and the usefulness of chemotherapy for these tumors has not been elucidated. The authors report on the successful management of a case of congenital intracranial immature teratoma by using neoadjuvant chemotherapy and surgery after the failure of an initial attempt at resection.

The patient was an infant who had begun vomiting frequently at the age of 12 days and had been admitted to a hospital at the age of 18 days with continued vomiting, increased head circumference, and disturbance of consciousness. A CT scan of the brain revealed a large mass in his posterior fossa and hydrocephalus. Surgery was performed on an emergent basis, but only minor tumor resection could be performed due to massive intraoperative hemorrhage. The histopathological diagnosis was immature teratoma. Postoperatively, the infant was in critical condition due to severe postoperative complications, and when he was transferred to the authors' institution 43 days after birth, his respiratory condition was still unstable because of lower cranial nerve palsy. Chemotherapy with carboplatin and etoposide resulted in moderate shrinkage of the tumor. Further chemotherapy led to improvement in the patient's general condition and weight gain, which allowed for a second attempt at resection. During this second surgery, which was performed when the child was 8 months of age, after 8 courses of chemotherapy, the tumor was completely resected with little bleeding. Histological findings from the second operation were consistent with mature teratoma.

This case indicates that upfront chemotherapy may be effective for the initial management of such cases. Although the objective response to the treatment was modest, chemotherapy reduced the hemorrhagic nature of the tumor, facilitated improvement of the patient's general condition, and allowed for successful resection.

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Kohei Fukuoka, Takaaki Yanagisawa, Yuko Watanabe, Tomonari Suzuki, Masao Matsutani, Ichiei Kuji and Ryo Nishikawa

Although 11C-methionine (MET)-PET has been used to diagnose intracranial germ cell tumors (GCTs) arising in the basal ganglia, whether this imaging technique is useful in assessing treatment response and residual tumor is still unclear. The authors report 3 cases of basal ganglia GCTs in which the residual MET uptake at the end of treatment did not develop into a relapse, even without additional treatment. Case 1 is a 22-year-old man who had a second relapse of a left basal ganglia germinoma with diffuse dissemination on the walls of both of his lateral ventricles. MET-PET revealed high MET accumulation around tumors and their surroundings (maximum standardized uptake value [SUVmax] 3.3). After all treatments, MET-PET demonstrated mild tracer accumulation in both basal ganglia (SUVmax 2.2). Progression-free survival was 56 months from the second relapse without any further treatment. Case 2 is a 17-year-old boy with a left basal ganglia germinoma that showed increased MET uptake (SUVmax 4.2). After treatment, MET-PET revealed residual MET uptake (SUVmax 2.4) along the left posterior limb of the internal capsule. Progression-free survival was 52 months from the start of treatment. Case 3 is a 7-year-old boy with a left basal ganglia choriocarcinoma with increased tumor MET uptake (SUVmax 2.5). A minor enhanced mass remained on MRI after treatment with residual MET accumulation (SUVmax 1.4). Progression-free survival was 44 months. Treatment strategies based on MET uptake on PET should be carefully designed in patients with basal ganglia GCTs to avoid overtreatment and complications.