Nobuo Ono

Recurrence of primary intracranial germinomas after complete response with radiotherapy: recurrence patterns and therapy.

Nine germinoma patients are described who developed a recurrence after a complete response to radiation without adjuvant chemotherapy. Extraembryonic tumors producing alpha-fetoprotein and human chorionic gonadotropin were excluded from this study. Four patterns of recurrence are described with respect to mechanism and appropriate treatment. Type I germinoma recurrence, characterized by intracranial recurrence caused by an inadequate initial irradiation field was treated by total craniospinal irradiation. Type II recurrence, characterized by a benign teratoma caused by late growth of the teratoma component was treated by surgery alone. All patients with these patterns of recurrence are still alive. Type III local recurrence is characterized by human chorionic gonadotropin- or alpha-fetoprotein-producing tumors of extraembryonic origin. This pattern of recurrence should be treated by chemotherapy or radiosurgery, because all these patients died. Type IV germinoma recurrence consists of extraneural metastasis without evidence of intracranial recurrence. Two of these patients were treated with chemotherapy. In summary, four patients died after recurrence, whereas the remaining five patients survived. The classification of germinoma recurrence patterns should facilitate the selection of the most appropriate treatment. However, it has been difficult to identify the precise histopathology by biopsy or partial resection alone. Furthermore, chemotherapy is indicated in treating germinomas that have a ventriculoperitoneal shunt because of the risk of extraneural metastases.

Diagnosis of germinal neoplasm in the thalamus and basal ganglia

Germinal neoplasms originating in the thalamus and basal ganglia were histologically verified by stereotactic biopsies in five cases and by other methods in three cases. Immunoperoxidase staining was performed on the tumors using antibodies against human chorionic gonadotropin and placental alkaline phosphatase. The presence of human chorionic gonadotropin was demonstrated in one germinoma and two mixed tumors, but not in three germinomas. Placental alkaline phosphatase was demonstrated to be present in four germinomas and one mixed tumor. Stereotactic biopsy specimens can be studied immunohistochemically, and the placental isoenzyme of alkaline phosphatase appears to be a new tumor marker for germinoma.

Recurrence of Primary Intracranial Germinomas after Complete Response with Radiotherapy

ABSTRACTNINE GERMINOMA PATIENTS are described who developed a recurrence after a complete response to radiation without adjuvant chemotherapy. Extraembryonic tumors producing α-fetoprotein and human chorionic gonadotropin were excluded from this study. Four patterns of recurrence are described with

Analysis of hemangiopericytic meningiomas by immunohistochemistry, electron microscopy and cell culture.

Intracranial hemangiopericytic meningiomas (HM) from seven patients were examined by immunostaining, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and cell culture. Positive staining for Factor VIII-related antigen was restricted to capillary endothelial cells. There was no reaction with anti-glial fibrillary acidic protein (GFAP) serum or anti-S-100 protein serum. In these neoplasms TEM displayed extracellular basement membrane-like material (BMLM), cytoplasmic intermediate filaments (IF) associated with a dense body, dilated rough-surfaced endoplasmic reticulum containing BMLM, a small area of interdigitation of cell membranes, and a unique intercellular punctate or linear density. By SEM these tumors had intercellular shell-like or reticular structures and irregularly branched capillaries which were compressed by ellipsoidal- or carrot-shaped tumor cells. Short-term monolayer culture showed rapid and vigorous growth of tumor cells, and the formation of pseudolumens but not of whorls. The TEM of cultured cells also showed cytoplasmic IF associated with the dense body. By SEM the cultured cells were flat and had a discoid nucleus with conspicuous nucleolar hillocks. Our results show that HM are mainly poorly specialized mesenchyme-related tumors of the meninges; some possess a potential for aggressive growth and some for differentiation into smooth muscle cells. Further study is needed to determine their histogenesis.

Large dose fraction radiotherapy in the treatment of glioblastoma

SummaryTwenty-four adults with glioblastoma multiforme (astrocytoma, grade 4) underwent postoperative large dose fraction radiotherapy (LDFR; 5 Gy twice weekly) with Linac X-rays. The outcome in this group was compared with that of 26 patients who received conventional fractionated radiotherapy (CFR; 2 Gy 5 times weekly). The time, dose, and fractionation (TDF) factor was about 100 in both groups. The survival rates following LDFR and CFR were, respectively, 63% vs 65% at 1 year; 36% vs 8% at 2 years; 17% vs 4% at 3 years; and 4% vs 0% at 5 years. Although the survival curve for LDFR was superior to that for CFR, the difference was not statistically significant. Autopsies of nine LDFR and 13 CFR patients showed no residual tumor in one case and no cases, respectively; small residual tumor in three cases in each group; extensive coagulation necrosis of the tumor and surrounding brain tissue in one LDFR and four CFR patients; tumor proliferation in three LDFR and four CFR cases; and mixed glioblastoma and fibrosarcoma in one LDFR and two CFR patients. These results suggest that maximum tumor removal followed by LDFR may offer a better prognosis for patients with glioblastoma than that offered by surgery plus CFR.

Germ cell tumor in the basal ganglia: Immunohistochemical demonstration of α-fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen

A case of germ cell tumor in the basal ganglia and its vicinity was successfully treated surgically and by radiation. alpha-Fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen were found in the tumor tissue, using the immunoperoxidase method. The presence of three immunohistochemically demonstrated tumor markers in a single germ cell tumor is extremely unusual. These results strongly suggest a cell differentiation or transformation in germ cell tumors.

A suprasellar embryonal carcinoma producing alpha-fetoprotein and human chorionic gonadotropin; treated with combined chemotherapy followed by radiotherapy

A case of primary suprasellar embryonal carcinoma that produced alpha-fetoprotein and human chorionic gonadotropin in a 12-year-old girl is reported. Partial removal of the tumor and cis-platinum-based combined chemotherapy followed by local radiotherapy resulted in a definite regression of the tumor and improvement from clinical signs and symptoms. After these treatments, the concentrations of alpha-fetoprotein and human chorionic gonadotropin in both serum and cerebrospinal fluid decreased to undetectable levels. Serum basic fetoprotein, another tumor marker, can be a tool for evaluating the clinical course following postoperative chemotherapy.

Pathobiology of intracranial germ-cell tumors: immunochemical, immunohistochemical, and electron microscopic investigations.

SummaryIn an attempt to clarify the pathobiology of intracranial germ-cell tumors, we studied 56 patients with these tumors, both clinically and pathologically. Our evaluations included immunochemical, immunohistochemical, and electron microscopic observations. Thirty tumors originated in the pineal region, ten in the suprasellar region, nine in the basal ganglia, and two in other regions. Five had double sites of origin. Histologically, there were 39 germinomas, six teratomas, four embryonal carcinomas, two choriocarcinomas and five mixed tumors. Among tumors tested immunochemically, serum carcinoembryonic antigen (CEA) was positive in 3.4%, serum alpha-fetoprotein (AFP) in 25.8%, and serum human chorionic gonadotropin (HCG) in 32.1%. In CSF, CEA was positive in 14.3%, AFP in 26.3%, and HCG in 75%. One third of germinomas were positive for serum HCG, and 88.9% for CSF HCG. One half of teratomas were positive for CEA of CSF. In immunohistochemical testing, the positive rates for CEA, AFP, HCG, and placental alkaline phosphatase (PLAP) were 26.9%, 11.5%, 24.1%, and 55.6%, respectively. Most teratomas were positive for CEA and the reactions were prominant in gland-like structures. HCG-positive syncytial cells were found in three germinomas and two embryonal carcinomas as well as in choriocarcinomas. The majority of germinomas were positive for PLAP and the reactive sites were tumor cell membranes and cytoplasm. On electron microscopy, germinomas were least differentiated, followed in order by embryonal carcinomas, choriocarcinomas, and teratomas. Further clinical and pathological studies will be necessary for a better understanding of the biology of these tumors.

A comparison of children with suprasellar germ cell tumors and craniopharyngiomas: Final height, weight, endocrine, and visual sequelae after treatment

BACKGROUND Although treatment results of craniopharyngiomas and germ cell tumors in children have been reported extensively, the relationship between various posttreatment sequelae and the nature of the tumor is not well understood. METHODS From 1968-94, 47 children with 23 suprasellar germ cell tumors and 24 craniopharyngiomas were treated at Gunma University Hospital, Japan. Forty survivors were assessed with regard to Karnofsky scores, visual scores, final height, final weight, and other endocrine sequelae as long-term functional prognostic indicators. RESULTS Kaplan-Meier life-table estimates and Karnofsky scores were not significantly different between the two histologic groups. The visual function of survivors did not differ significantly at diagnosis. However, the final visual function following treatment in the germ cell tumor group was better than in the craniopharyngioma group (p < 0.05). Antidiuretic hormone secretion was significantly impaired at diagnosis in the germ cell tumor group (p < 0.0001). However, there was only a marginally significant difference in posttreatment persistent diabetes insipidus. Craniopharyngioma children were shorter and more obese at diagnosis (p < 0.02), and became much more obese than germinoma children with the same hormone therapy (p < 0.003), although the height difference became insignificant following growth hormone treatment. CONCLUSIONS Children with craniopharyngiomas tended to have more visual disturbances, increased dwarfism and obesity, and less diabetes insipidus than patients with germ cell tumors despite adequate therapy. The method of quantifying visual function may in itself be useful.

Basal interhemispheric supra- and/or infrachiasmal approaches via superomedial orbitotomy for hypothalamic lesions: preservation of hypothalamo-pituitary functions in combination treatment with radiosurgery

Abstract Although several approaches to the hypothalamus have been used, none is able to give full views of the hypothalamus. The risk of permanent morbidity for hypothalamo-pituitary functions is still high, especially in patients with cranio-pharyngioma. Basal interhemispheric supra-chiasmal or infra-chiasmal approaches via superomedial orbitotomy were developed for better visualization of the hypothalamus. Operative techniques and results, including combination treatment with radiosurgery, are reported. Twelve patients with tumors compressing the hypothalamus upward or extending into the III ventricle, or both, were operated on: 3 tumors were removed totally, 6 tumors subtotally and 3 tumors partially. Six patients received radiosurgery for residual tumor. Four patients with hypopituitarism preoperatively required oral corticosteroids and thyroid hormones postoperatively. The basal interhemispheric approach via superomedial orbitotomy is useful for better visualization of the hypothalamus and preservation of hypothalamo-pituitary functions.