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PubMed1992

The recurrence of primary intracranial germinomas. Special reference to germinoma with STGC (syncytiotrophoblastic giant cell).

Twenty three cases of primary intracranial germinomas including five cases of germinomas with syncytiotrophoblastic giant cells are studied and analyzed, with special reference to the recurrence under radiotherapy. The follow-up period for all cases was 7 months to 12 years (average: 5.8 years) with that for pure germinomas ranging from 8 months to 12 years (average: 5.7 years) and that for germinomas with syncytiotrophoblastic giant cells ranging from 7 months to 11 years (average: 6.3 years). Late recurrence was observed in three cases (3/23, 13%), developing outside of the initial irradiation field. With regard to recurrence, significant correlation to radiation fields was evident, while it was not to radiation doses. Furthermore, germinoma with syncytiotrophoblastic giant cells showed a more significant tendency to recur than pure germinoma. The radiotherapy of germinomas is discussed and the clinical features of germinoma with syncytiotrophoblastic giant cells are presented.

Adolescent↗
PubMed2003

Germinoma with syncytiotrophoblastic giant cells recurring 13 years after radiotherapy for a pineal germinoma--case report.

A 28-year-old man presented with progressive mental deterioration. Thirteen years earlier he had undergone radiation therapy for a pineal germinoma. Neuroimaging showed a homogeneously enhanced mass lesion along the ventricular wall. The cerebrospinal fluid (CSF) level of human chorionic gonadotropin (HCG) was high. Endoscopic biopsy revealed that the tumor was a two-cell pattern germinoma. The diagnosis was germinoma with syncytiotrophoblastic giant cells (STGC). He first received three cycles of chemotherapy with carboplatin and etoposide and then two cycles with ifosfamide, cisplatin, and etoposide. Subsequently, the tumor size decreased markedly and the CSF level of HCG returned to normal. However, he died 22 months after the recurrence. Histological verification and measurement of tumor markers are necessary for the optimum treatment of germ cell tumors. Adequate initial chemotherapy and long-term follow up are essential for patients with germinoma with STGC.

Adult↗
PubMed1990

Pineal germinoma with unilateral blindness. Seeding of germinoma cells in optic nerve sheath.

A 13-year-old boy presented with blindness and loss of the papillomacular bundle in the left eye, bilateral papilledema sparing the area of axonal loss, and Parinaud's syndrome. Computerized tomography (CT) revealed an enlarged kinked left optic nerve and enlarged optic canal as well as a tumor in the pineal area producing hydrocephalus. Magnetic resonance (MR) scans showed multiple spinal metastases. The histological diagnosis was germinoma. On completion of four courses of chemotherapy with cis-platin, vinblastine, and bleomycin, repeated CT of orbita and MR imaging of the spine demonstrated the disappearance of the tumor surrounding the left optic nerve and of the spinal metastases. This is believed to be the first case report of seeding of germinoma into the perioptic arachnoid space.

Adolescent↗
PubMed1997

Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy.

PURPOSE: The limited information in the literature suggests that intracranial germinoma with syncytiotrophoblastic giant cells (STGC) producing human chorionic gonadotropin (HCG) is associated with a higher recurrence rate compared with pure germinoma producing no HCG. To determine whether the poorer prognosis for germinoma with STGC is an inevitable finding, we retrospectively analyzed data for our patients. METHODS AND MATERIALS: Data were analyzed for 44 patients who had pretreatment examination of HCG titers in the serum and/or cerebrospinal fluid (CSF) and underwent radiotherapy between 1978 and 1993. The diagnosis of germinoma was made histologically in 19 patients and clinically in 25 according to the established criteria. The treatment volume was the primary tumor site in 9 patients, the cerebrospinal axis in 29, and other in 6. The median follow-up period was 90 months. RESULTS: Twenty (45%) of the 44 patients had elevated HCG titer. The abnormal HCG levels ranged from 4.9 to 189 mIU/ml (median: 18 mIU/ml) in serum and 8.2 to 660 mIU/ml (median: 26 mIU/ml) in CSF. No difference was found between the two groups in any patient or treatment characteristics including tumor size and incidence of CSF dissemination. The mean radiation dose to the primary tumor site was 46.4 Gy for pure germinoma and 47.5 Gy for germinoma with STGC. The 10-year survival and relapse-free survival rates were both 100% for the patients with germinoma with STGC and both 89% for those with pure germinoma. Among these patients, only two with pure germinoma developed recurrence. CONCLUSIONS: Our data suggest that the prognosis of intracranial germinoma with STGC treated with adequate radiation therapy does not differ from that of pure germinoma. Our current policy of delivering 40-45 Gy for tumors < 4 cm in diameter seems to be a reasonable treatment for germinoma with STGC.

Adolescent↗
PubMed2001

Impacts of elevated level of hCG in serum on clinical course and radiotherapy results in the histology-confirmed intracranial germinomas.

The prognosis of intracranial germinoma producing the human chorionic gonadotropin (hCG) is controversial due to limited information. We undertook a retrospective analysis to determine whether this type of tumor has similar clinical course and prognosis to hCG non-secreting germinoma. Thirty-one histologically confirmed intracranial germinoma patients who had pretreatment hCG examination in serum/CSF were treated with radiotherapy between 1980 and 1996. hCG level was measured by immunoradioassay of beta subunit of hCG. Six patients had elevated serum hCG levels and were defined as having hCG secreting germinoma. All except three patients received craniospinal axis irradiation. The follow-up ranged from 19-175 months with a median of 63 months. hCG secreting germinoma accounted for 19% of intracranial germinoma cases. Elevated hCG levels ranged from 39-260 IU/l in serum. No difference was found between hCG non-secreting germinoma and hCG secreting germinoma in terms of patient or treatment characteristics. There was no recurrence among the six hCG secreting germinoma patients. The 5-year overall and disease-free survival rates were 96% for patients with hCG non-secreting germinomas and 100% for the patients with hCG secreting germinomas. The survival difference was not significant (p = 0.59). Our results suggest that elevated level of hCG did not result in any differences in the clinical characteristics or survival after radical radiotherapy in histologically confirmed intracranial germinoma.

Adolescent↗
PubMed1999

[A clinical analysis of patients with primary intracranial germinomas: the relationship between proliferative potential and recurrence].

We analyzed clinically 30 germinomas (22 pure germinomas and 8 germinomas with syncytiotrophoblastic giant cell (STGC) and also investigated the proliferative potential of 18 germinomas immunohistochemically using MIB-1 monoclonal antibody in formalin-fixed paraffin-embedded sections. The majority of patients responded favorably and completely to the treatment. Seven patients (four had germinomas with STGC and the other three had pure germinomas) suffered recurrence after a complete response to radiotherapy and/or chemotherapy. The patients with germinomas with STGC experienced recurrence significantly more often than those with pure germinomas (P < 0.01). Three of the patients died. The MIB-1 indexes of the germinomas ranged from 18% to 80%. The average MIB-1 index of pure germinomas is 58.5 +/- 17.3%, that of germinomas with STGC is 45.3 +/- 17.1%. There was no significant difference between the two groups. The MIB-1 indexes of 3 recurrent cases were 64.3%, 51.9%, and 20.8%, respectively. There were no significant differences in the MIB-1 indexes between nonrecurrent cases and recurrent ones.

Adolescent↗
PubMed1998

Pineal germinomas with granulomatous inflammation. Report of two cases and review of the literature.

The authors report on two cases of pineal germinomas with granulomatous inflammation (granulomatous germinomas). Macroscopically, both tumors were relatively hard and grayish in color. Histological examination revealed a germinoma with multinucleated giant cells and Schaumann bodies in one case, and a germinoma with the background of acellular fibrillated matrix in the other. On immunohistochemical analysis, the granulomatous germinomas were shown to contain many macrophages, T- and B-lymphocytes, and glial fibrillary acid protein-positive cells infiltrating the specimens, compared to nongranulomatous germinomas. Analysis of Masson's trichrome staining tests showed that large areas of the granulomatous germinomas were occupied by a collagenous component; this was not the case in cases of nongranulomatous germinomas. Analysis of monoclonal anti-human Ki-67 results showed that the granulomatous germinomas had a lower score than nongranulomatous germinomas (p < 0.05, unpaired t-test), indicating that germinomas with granulomatous inflammation may have a better prognosis.

Journal Article↗
PubMed2006

Pure pineal germinomas: analysis of gender incidence.

OBJECTIVE: Pure pineal germinomas have been rarely reported in girls. Gender incidence and differences of pure pineal germinomas are not well known. The authors report a series of pure pineal germinoma and its gender characteristic is reviewed. METHODS AND RESULTS: Of a total of 50 germ cell tumors operated on between 1988 and 2004 we found 26 cases (median age at diagnosis, 12 years) of pineal germ cell tumors. Of these, 14 cases (male/female ratio: 13/1) were pure pineal germinomas, and 12 cases (male/female ratio: 12/0) were non-germinoma germ cell tumors. In pure pineal germinomas, the main clinical presentations were intracranial hypertension and cranial nerve dysfunction. Imaging studies disclosed a homogeneous type of tumor (n = 10) and associated hydrocephalus (n = 6). Cases were managed with biopsy and subsequent radiation therapy and chemotherapy. After a follow up of 10 years, pure germinoma cases have no neurological deficits and tumor recurrence. The literature on gender incidence of pure pineal germinomas is analyzed and possible causes are discussed. CONCLUSIONS: Although rare, pure pineal germinoma can be found in female subjects. On the basis of the literature review, the male/female ratio in cases of pure pineal germinoma is between 5:1 and 22:1 (mean 14:1). In our series, the male/female ratio was 13:1.

Adolescent↗
PubMed1988

Isoenzymes of alkaline phosphatase in germinoma cells.

Utilizing 18 germinomas, the characteristics of isoenzymes of alkaline phosphatase (ALP) in germinoma cells were examined by light and electron microscopic enzymohistochemical and immunohistochemical techniques and biochemical methods including inhibition tests, electrophoresis and electrosyneresis. ALP in germinoma cells was generally located on the cell surface. In a few germinoma cells, however, ALP was seen not only on the cell membrane but also in the endoplasmic reticulum. Enzymohistochemically as well as biochemically, ALP in germinoma cells was little sensitive to L-phenylalanine, moderately sensitive to L-homoarginine and somewhat resistant to heat in its inhibition tests. Immunohistochemical examinations and electrosyneresis showed the presence of the placental type of ALP in germinoma cells and biochemical analyses revealed that the heat-stable component of ALP in germinoma cells was consistent with the D-variant of the placental type of ALP. Therefore, germinoma cells possessed mixed isoenzymes of ALP, consisting mainly of the liver/bone type and a small amount of D-variant of the placental type on the cell surface. The prominent expression of ALP in germinoma cells may be due to the enhanced expression of gonadal genes active in the germinoma genome.

Adult↗
PubMed2006

Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy.

BACKGROUND: Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. OBJECTIVE: To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. MATERIALS AND METHODS: Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. RESULTS: Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. CONCLUSION: The association of a focal lesion in the basal ganglia of children with progressive hemiparesis, neuropsychiatric symptoms and ipsilateral cerebral and/or brain stem hemiatrophy should prompt the diagnosis of ectopic germinoma, avoiding delay in the diagnosis and further irreversible clinical deterioration, in a malignancy with an otherwise favorable prognosis. In these patients, hemiatrophy preceding or accompanying the imaging depiction of a basal ganglia mass lesion is thought to be caused by a paraneoplastic process.

Adolescent↗
PubMed2000

Usefulness of gallium-67 scintigraphy in neurohypophyseal germinoma.

The application of gallium-67 (67Ga) citrate has not been reported for the detection of an intracranial germinoma. The purpose of this report is to further evaluate the effectiveness of 67Ga scintigraphy in neurohypophyseal germinomas. 67Ga studies in five male patients with histologically verified intracranial pure germinomas were evaluated. Two germinomas were located in the neurohypophysis, two in the pineal region, and one in both the neurohypophysis and pineal region. The control group included 36 patients with histologically verified pituitary macro-adenomas. 67Ga study at the time of original diagnosis showed an abnormal accumulation in two neurohypophyseal germinomas, and negative accumulation in the other germinomas. In the two patients with neurohypophyseal germinomas, 67Ga study showed an abnormal accumulation in the intracranial tumour region in accordance with magnetic resonance (MR) findings. After postoperative irradiation or chemoradiotherapy, MR imaging and 67Ga studies revealed the complete disappearance of this tumour and no metastatic spread. In one of these two patients, a whole-body 67Ga study demonstrated multiple bone metastases one year later, and the reduction of these metastatic regions after chemotherapy. 67Ga study disclosed negative accumulation in all 36 pituitary macroadenomas. Although 67Ga uptake by neurohypophyseal germinomas may not be specific for this condition, this approach may provide some clues for diagnosing patients with neurohypophyseal germinomas.

Adolescent↗
PubMed2000

A comparative study of apoptosis and proliferation in germinoma and glioblastoma.

Intracranial germinoma has a relatively good prognosis when treated with radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis irrespective of these treatments. Cell proliferation and cell death are opposing processes in tumor growth, with tumor progression reflecting the balance between proliferating and apoptotic cells. We investigated cell proliferation and cell death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis, were studied by immunohistochemistry. Although germinomas showed strong MIB-1 immunostaining similar to that seen in glioblastomas, germinomas included significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1 labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher, statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P < 0.01). Furthermore, germinomas showed greater expression of BAX than did glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A comparison of these apoptotic-related proteins showed that immunoreactivity for BAX was relatively higher in germinomas than in glioblastomas (P < 0.01), corresponding well to numerous apoptotic cells identified in germinoma tissues. These findings may account for the prognostic difference between germinoma and glioblastoma in the face of a similar proliferation potential according to MIB-1 immunostaining. The balance between cell proliferation and death should be considered when predicting outcomes in patients with intracranial tumors.

Antigens, Nuclear↗
PubMed1989

Suprasellar germinomas in childhood. A reappraisal.

Germinomas in childhood may arise in both the suprasellar and pineal region, and outcome has been reported to be worse for suprasellar germinomas with a 5-year survival rate of 20% as compared to 60% for pineal germinoma. To determine the factors impacting on outcome, the results of a uniform treatment approach were evaluated and included primary surgical debulking (PSD) and systemic craniospinal axis radiation (CSRT) for suprasellar germinomas. Between 1976 and 1985 ten consecutive patients (seven females, three males) with the pathologically confirmed diagnosis of suprasellar germinoma were treated. Outcome was compared to four male patients with pineal germinoma treated over the same time period and series of patients reported in the literature. At diagnosis the mean age of patients with suprasellar germinoma was 13.9 years (range, 8.9 to 9.4 years). Symptoms were present for a mean of 18 months (range, 2 to 72 months) prior to diagnosis and included diabetes insipidus, anterior pituitary dysfunction, decreased vision, headache, vomiting, and diplopia. Staging studies, including myelography (n = 4) and cerebrospinal fluid cytology (n = 7), disclosed dissemination in only one child. Surgical treatment included biopsy in three cases, partial resection in five, and total resection in two; no permanent postsurgical complications were noted. The mean radiation therapy dose to the tumor site was 4953 cGy (range, 4400 to 5250 cGy) and to the spine 3354 cGy (range, 3000 to 4000 cGy). Patients were followed for a mean period of 5.1 years (range, 1.9 to 10.5 years). One patient with SG who did not receive treatment initially developed a pineal tumor after diagnosis; she was treated with PSD and CSRT and is asymptomatic 5 years later. All the remaining patients are alive and remain disease-free. Surgical resection and CSRT results in excellent disease control for children with suprasellar germinomas, and outcome is similar to those patients with pineal germinoma.

Adolescent↗
PubMed2003

Combined 201Tl and 67Ga brain SPECT in patients with suspected central nervous system lymphoma or germinoma: clinical and economic value.

BACKGROUND: Surgical resection is costly and an unfavorable prognostic factor for primary central nervous system (CNS) lymphoma and germinoma patients. OBJECTIVE: To assess the diagnostic and economic impact of combined 201Tl and 67Ga brain SPECT on the management of patients suspected of having CNS lymphoma or germinoma. METHODS: Sequential 201Tl and 67Ga brain SPECT was performed in 40 patients with cranial tumors to assess the diagnostic and economic impact of combined 201Tl and 67Ga SPECT on the management of patients suspected of having CNS lymphoma or germinoma. All intracranial masses were pathologically confirmed. The final diagnoses of a total of 47 foci were: 11 non-Hodgkin's lymphomas in 10 patients, 3 germinomas in 2 patients, 10 glioblastomas in 9 patients, 10 cerebral metastases in 8 patients, 13 meningiomas in 11 patients. Decision-tree sensitivity analysis for pretest probability regarding expected cost saving was performed for introduction of the combined study. RESULTS: All but one focus of CNS lymphomas or germinomas (92.9%, 13/14) exhibited more intense uptake of 67Ga than of 201Tl (p < 0.001). All foci of glioblastomas (10/10) and meningiomas (13/13), and 60% of metastatic foci (6/10) exhibited higher uptake of 201Tl than of 67Ga (p < 0.035). Expected cost saving in the 1% to 50% range of pretest probability of CNS lymphoma or germinoma would be from minus dollars 842US to plus dollars 2,047US per patient for introduction of the combined study, because of substitution of stereotactic biopsy for craniotomy. The pretest probability was the key factor for cost saving of the combined study. CONCLUSIONS: A 67Ga-positive and 201Tl-positive pattern with more intense uptake of 67Ga than 201Tl probably suggests CNS lymphoma or germinoma. This combination study appears to be cost-effective only in patients highly suspected of having CNS lymphoma or germinoma.

Adolescent↗
PubMed1997

Intracranial germinoma: the case for lower dose radiation therapy.

PURPOSE: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. METHODS AND MATERIALS: Between 1975 and 1995, 40 patients with the diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All patients received whole-brain (WB) RT (median dose: 32.4 Gy, range: 15-44.37 Gy) and a boost to the tumor volume (median total tumor volume dose: 52 Gy, range: 45-59.5 Gy). Thirty patients received RT to the spine (median dose: 26 Gy, range: 18.75-37.5 Gy). Four patients were treated with cisplatin-based chemotherapy and WB RT with a boost to the tumor volume (dose range: 51-54 Gy). A low-dose RT only group was defined as < or = 25.5 Gy to the WB (9 patients); < 50 Gy to the primary site (14 patients); and < 22 Gy to the spine (9 patients). Seventeen tumors were biopsy-proven germinoma, and 17 patients presented with multiple midline germinomas (MMG). Among 26 patients who had tumor markers measured, 27% had elevation of beta-human chorionic gonadotropin and by definition, no patient had an elevation of AFP. Twenty-four percent of 26 patients who had spine imaging or cerebral spinal fluid cytology had evidence of tumor seeding at diagnosis. The male to female ratio was 1.9:1. Median age at diagnosis was 14 years for male patients and 9.5 years for female patients (p = 0.02), (overall age ranges: 0.5-31 years). Median follow-up was 62 months (range: 3-226 months). Late effects of 29 patients with follow-up of > or = 20 months and adequate documentation in their medical records were analyzed. RESULTS: The 5-year actuarial rate of disease-free survival (DFS) and overall survival (OS) for biopsy-proven germinomas and presumed germinomas was 97%. No patient died of germinoma. There were no local failures regardless of the dose of RT, elevation of HCG tumor marker, or CSF dissemination at presentation. At presentation 22 patients had evidence of at least one endocrine abnormality. At follow-up there were no new patients diagnosed with an endocrine abnormality; however, 13 out of 22 patients had an increase in the number of endocrine deficiencies requiring hormone replacement. At presentation, 14 patients showed evidence of growth retardation. At follow-up there were no new cases of growth failure in the remaining patients. CONCLUSIONS: Germinomas are highly curable with RT alone. Lower doses of RT to the craniospinal axis without chemotherapy appear to produce equally effective DFS and OS as do higher doses of RT or combination chemotherapy and RT. Craniospinal RT may be indicated for patients with MMG or patients with evidence of spinal seeding. Long-term effects of growth retardation, and other endocrine deficiencies appear to be correlated with disease at presentation rather than solely with treatment.

Adolescent↗
PubMed1999

Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma.

OBJECTIVES: Some intracranial germinomas, which may contain syncytiotrophoblastic giant cells (STGCs), are associated with a mildly to moderately increased human chorionic gonadotropin (HCG) concentration in serum, and patients with such germinomas are thus treated more aggressively than those with "pure" germinoma. However, the patients with germinoma and detectable HCG in CSF but not in serum have been classified and treated similarly to those with "pure" germinomas. The outcome of these patients and the relevance of HCG in the CSF were analysed. METHODS: The outcomes of patients with germinoma and increased serum HCG concentration (n=7) were compared with those of patients having detectable HCG titre in the CSF but not in the serum (n=5). RESULTS: Both groups in our series received similar treatments and also showed similar recurrence rates. The 40% recurrence rate in the group with HCG only in CSF did not correspond to the rate typical for "pure" germinoma: these tumours would be expected to have a better outcome. An additional patient whose CSF HCG were raised without increased serum HCG at recurrence is presented. CONCLUSIONS: It is recommended that patients with an increased HCG concentration in CSF should be considered to have "HCG producing germinoma", and they should be treated and followed up accordingly.

Adolescent↗