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Chin Med J (Taipei) 1997;60:259-64.
Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Background. Primary intracranial germ-cell tumors (GCTs) account for about 11.1% of all primary brain tumors of children in Taiwan. Because these tumors commonly involve the hypothalamus-pituitary gland regions and their biochemical secreting character, patients frequently display neuroendocrinological symptoms and signs. Endocrinopathy, if present, often occurs prior to other neurological or radiological manifes-tations. This article reviews experience here, with present results comparing them with previous reports.
Methods. Twelve children who were diagnosed with primary intracranial germ-cell tumors between 1983 to 1995 were studied retrospectively. Their clinical presentations, laboratory results and treatment modalities as well as the current status were collected for presentation here.
Results. There were seven boys and five girls. The age distribution was from 5 to 15 years old. The most common symptom was increased intracranial pressure (9/12), followed by diabetes insipidus (8/12), vision deficit (8/12) and sexual precocity in 3 boys. In 11 patients the tumors arose from the suprasellar or pineal regions. In two patients the tumors arose synchronously in the suprasellar and pineal regions. Pure germinoma was found in six patients. Only one had an elevated tumor marker. These six patients all received radiation with or without operation therapy, and all are still alive . Six patients, each wih a non-germinomatous malignant germ-cell tumor, had a poorer prognosis. Although they received aggressive treatment, including operation, radiation and chemotherapy, three patients died, with a mean survival period of 3.3 years.
Conclusions. In cases of diabetes insipidus in children or sexual precocity in boys, a thorough investigation for intracranial germ-cell tumors is recommended. The treatment and outcome are different for germinomas and non-germinomatous malignant germ-cell tumors. A thorough pathological diagnosis is recommended for planning of treatment protocol in order to improve prognosis.
[Chin Med J (Taipei) 1997;60:259-64.]
Keywords: germ-cell tumor, intracranial, mixed germ-cell tumor, germinoma, diabetes insipidus (DI)
Received: September 8, 1995.
Accepted: July 25, 1997.
Address reprint requests to: Ing-Jing Lin, Department of Pediatrics, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Kang Road, Taichung, Taiwan, R.O.C.
The incidence of primary intracranial germ-cell tumors has marked geographical variations. A higher incidence has been reported in the East series [1-4]These tumors account for 11.1% of all primary central nervous system neoplasms of children in Taiwan [5].
Tumors of germ-cell derivation comprise five interelated neoplasms which demonstrate an order of increasing malignant behavior: germinoma, teratoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor) and choriocarcinoma. Intracranial germ-cell tumors frequently display both neurological symptoms and signs (raised intracranial pressure, vision deficit, seizure and consciousness change) and endocrinological symptoms and signs (diabetes insipidus, precocious puberty and delay in pubertal development). More interestingly, endocri-nological symptoms and signs often occur earlier than other neurological or radiological finding. This article reviews experience here and the results from use of several management methods.
During the 12-year period from 1983 to 1995, 12 children with primary intracranial germ-cell tumors, who were diagnosed or treated at Taichung Veteran General Hospital, were studied retrospectively. All clinical presentations, laboratory data, pathological reports and treatment procedures, as well as current status, were collected and analyzed. Germ-cell tumor was confirmed by pathological study in 10 patients. In the remaining two, the diagnoses were based on neuroimage findings and elevated titers of serum tumor markers. Neurological symptoms and signs were defined by clinically related symptoms and neurological finding. Precocity was diagnosed by physical examination and elevated sex steroid. Diabetes insipidus was defined by polyuria, polydipsia, hypernatremia and hypotonic urine.
Twelve children with primary intracranial germ-cell tumors were enrolled in this study group (Table 1). Seven were males and five were females. The age distribution was from 5 to 15 years old. The most frequent symptoms and signs were raised intracranial pressure (9/12), followed by diabetes insipidus (8/12) and vision deficit (8/12). In 11 patients, the tumors arose from the suprasellar and/or pineal regions: 3 in the pineal region; 6 in suprasellar and/or sellar area (Figure 1); 2 had tumors in both the pineal and suprasellar regions (Figure 2). Only one tumor arose in the left basal ganglion.
The clinical symptoms and signs were significantly related to the site of the tumor (Table 2). Patients with pineal tumor all presented with increased intracranial pressure, followed by vision deficit. No endocrinological manifestation could be found. In patients with suprasellar and/or sellar tumors, diabetes insipidus was the most frequent symptom, followed by increased intracranial pressure, vision deficit and precocity. All patients with germinoma had normal serum titers of tumor markers, except for one who had an elevated serum titer of beta-human chorionic gonadotropin. In contrast, in patients with non-germinomatous tumors, the tumor markers were all elevated. It is consistent with the previous report [2]. Eight of 12 patients underwent computerized tomography (CT). The tumors were typically hyperdense, frequently contained calcium and enhanced brightly with administration of contrast medium. Nine patients had magnetic resonance imaging (MRI) (Figures 1,2,3). MRI showed these intracranial germ-cell tumors in much better detail than CT. Postoperative myelography was not available. Three patients had cytological examination of cerebral spinal fluid (CSF), and all were negative for malignant cells. All of the patients with germinomas received surgery and/or radiation treatment. They are all alive. The longest post operative survival period to date is 12 years. In patients with non-germinomatous malignant germ-cell tumors, the prognosis was not good, despite aggressive treatment. Three patients have died, with a mean survival period of 3.3 years. Five patients with hydrocephalus had ventriculo-peritoneal shunts inserted. Four of these five patients remain alive. In two paitents, the ventriculo-peritoneal shunt was removed.
Although a previous report showed the male-to-female ratio of patients with primary germ-cell tumors is 2.24:1, and the peak incidence of age in both sexes is 10 to 12 years old [3], no obvious age distribution was found here. It is probably because of the small number of patients.
Pineal tumors typically obstruct the third ventricle, cause hydrocephalus and raised intracranial pressure. In patients with suprasellar germ-cell tumors, the common triad of signs are diabetes insipidus, vision deficit and hypopituitarism [6]. When a neuroendocrine disturbance is present, it often occurs prior to other neurological and radiological findings. For example, patient 8 suffered from diabetes insipidus for three years before radiological examination detected the tumor.
MRI had more advantages than CT in demonstrating the intracranial germ-cell tumors. It shows various tissue characters in mixed germ-cell tumors and can find very small suprasellar germinomas. Besides, it can also prevent children from radiation exposure. Howevere there is a limitation to neuroradiological examinaiton. Sometimes, the first MRI dose not show the tumor, although the patient has had diabetes insipidus for a while as in case 8 (Figure 3A, 3B). Longitudinal neuroimaging study is necessary for this condition (Figure 3B).
Three patients had precocity and all were male. Elevated serum titer of beta-human chorionic gonadotropin is associated with precocity only in boys, and not in girls. Mixed germ-cell tumors were found in 3 of 12 (25%) patients in our study. This was a higher percentage than the previous result 6/51 (11 %) [5]. This could be because larger tumor specimens were collected by surgery, rather than stereotatic biopsy, for diagnosis.
In germ-cell tumor, it has been well established that increased a-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta-HCG) levels in serum correlates with tumors with components that secrete these markers [5-7]. An increased serum titer of AFP levels have been seen in endodermal sinus tumor, embryonal carcinoma and immature teratoma. Elevation of beat-HCG serum titer is related to choriocarcinoma, germinoma or other germ-cell tumors which contain syncytiotrophoblast giant cells. This is consistent with the present series. Serum titers of AFP and beta-HCG assist the differential diagnosis of germinoma or other non-germinomatous malignant germ-cell tumors. These markers also work as a guideline to prediction of results of treatment or recurrence for non-germinomatous germ-cell tumors.
According to the previous reports [3], the five-year survival rates were 73.2% in germinoma and 33.3% for non-germinomatous germ-cell tumors. All of the patients here with germinoma are alive now; but three of the six patients with non-germinomatous germ-cell tumors have died. Their mean survival time was 3.3 years. The prognosis of intracranial germ-cell tumor relies on the histological diagnosis and the treatment modality of the disease. To improve the survival of the patients with non-germinomatous germ-cell tumors, chemotherapy was added to the conventional surgery and radiation therapy. An event-free survival rate of 86% two years after treatment was reported in patients receiving surgery, irradiation and 400 mg/m2 cisplatin chemotherapy [8]. Long term prognosis should be investigated in patients with non-germinomatous germ-cell tumors. In conclusion, intracranial germ-cell tumors are significant brain tumors in Taiwan. In cases of childhood diabetes insipidus or sexual precocity in boys, thorough investigation for intracranial germ-cell tumors is recommended. If the initial neuroimaging study is negative, logitudinal follow-up study is mandatory. To plan for appropriate treatment for better results, accurate pathological diagnosis with large specimens is recommended for management of intracranial germ-cell tumors.
Copyright: 1997, Chinese Medical Association (Taipei)