Germinoma with involvement of midline and off-midline intracranial structures.
09 Feb 2014-Case reports in endocrinology (Hindawi Publishing Corporation)-Vol. 2014, pp 936937-936937
TL;DR: Germinoma must be considered in patients with insipidus diabetes with a sellar mass with thickening of pituitary stalk; and ectopic germinomamust be suspected in patientsWith slowly progressive hemiparesis with cerebral hemiatrophy, even with a rare condition, colocalization of midline and off-midline germinomas must be suspected.
Abstract: Germinomas are malignant intracranial germ tumors, usually found in suprasellar regions. Less than 10% are localized in off-middle structures, and synchronous involvement of both structures has only exceptionally been published. A case of an 18-year-old male patient with progressive right-sided hemiparesis and panhypopituitarism was reviewed. Brain MRI showed a solid mass involving pituitary and hypothalamus with thickening of pituitary stalk, high intensity lesions on T2-weighted imaging in left internal capsule, caudate nucleus, globus pallidus, and mild atrophy of the left internal capsule and cerebral peduncle. Nonadenomatous lesions were considered in the differential diagnosis. Alfa-fetoprotein (AFP) levels were negative in both serum and cerebrospinal fluid (CSF), while β-human chorionic gonadotrophin (β-HCG) levels were slightly increased in CSF. A transsphenoidal biopsy identified a germinoma. Four cycles of chemotherapy with bleomicine, etoposide, and cysplatin were given, followed by radiotherapy, but patients died due to a recidiva. Conclusion. Germinoma must be considered in patients with insipidus diabetes with a sellar mass with thickening of pituitary stalk; and ectopic germinoma must be suspected in patients with slowly progressive hemiparesis with cerebral hemiatrophy. Even with a rare condition, colocalization of midline and off-midline germinoma must be suspected in the presence of these typical signs of both localizations.
Citations
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TL;DR: Assessment of the susceptibility-weighted imaging (SWI) or T2* gradient echo (GRE) features of intracranial GCT may potentially assist in differentiating pure germinomas from NGGCT and in the characterization of basal ganglia involvement.
Abstract: The role of T2*-based MR imaging in intracranial germ cell tumors (GCTs) has not been fully elucidated. The aim of this study was to evaluate the susceptibility-weighted imaging (SWI) or T2* gradient echo (GRE) features of germinomas and non-germinomatous germ cell tumors (NGGCTs) in midline and off-midline locations. We retrospectively evaluated all consecutive pediatric patients referred to our institution between 2005 and 2016, for newly diagnosed, treatment-naive intracranial GCT, who underwent MRI, including T2*-based MR imaging (T2* GRE sequences or SWI). Standard pre- and post-contrast T1- and T2-weighted imaging characteristics along with T2*-based MR imaging features of all lesions were evaluated. Diagnosis was performed in accordance with the SIOP CNS GCT protocol criteria. Twenty-four subjects met the inclusion criteria (17 males and 7 females). There were 17 patients with germinomas, including 5 basal ganglia primaries, and 7 patients with secreting NGGCT. All off-midline germinomas presented with SWI or GRE hypointensity; among midline GCT, all NGGCTs showed SWI or GRE hypointensity whereas all but one pure germinoma were isointense or hyperintense to normal parenchyma. A significant difference emerged on T2*-based MR imaging among midline germinomas, NGGCTs, and off-midline germinomas (p < 0.001). Assessment of the SWI or GRE characteristics of intracranial GCT may potentially assist in differentiating pure germinomas from NGGCT and in the characterization of basal ganglia involvement. T2*-based MR imaging is recommended in case of suspected intracranial GCT.
24 citations
Cites background from "Germinoma with involvement of midli..."
...Review of the literature demonstrated that three additional cases of concomitant involvement of the suprasellar compartment and basal ganglia turned out to be all pure germinomas [9, 25, 26]....
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TL;DR: It is found that children with bifocal tumors likely need a wider radiation field, especially if they have a high-risk tumor type, high- risk appearance on MRI, or tumors spread throughout the nervous system.
Abstract: Suprasellar germ cell tumors (S-GCTs) are rare, presenting in either solitary or multifocal fashion. In this study, we retrospectively examine 22 solitary S-GCTs and 20 bifocal germ cell tumors (GCTs) over a 30-year period and demonstrate clinical, radiographic, and prognostic differences between the two groups with therapeutic implications. Compared to S-GCTs, bifocal tumors were almost exclusively male, exhibited higher rate of metastasis, and had worse rates of progression free and overall survival trending toward significance. We also introduce a novel magnetic resonance (MR) imaging classification of suprasellar GCT into five types: a IIIrd ventricle floor tumor extending dorsally with or without an identifiable pituitary stalk (Type Ia, Ib), ventrally (Type III), in both directions (Type II), small lesions at the IIIrd ventricle floor extending to the stalk (Type IV), and tumor localized in the stalk (Type V). S-GCTs almost uniformly presented as Type I-III, while most bifocal GCTs were Type IV with a larger pineal mass. These differences are significant as bifocal GCTs representing concurrent primaries or subependymal extension may be treated with whole ventricle radiation, while cerebrospinal fluid (CSF)-borne metastases warrant craniospinal irradiation (CSI). Although further study is necessary, we recommend CSI for bifocal GCTs exhibiting high-risk features such as metastasis or non-germinomatous germ cell tumor histology.
16 citations
TL;DR: Determining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma and the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart, implying that the location of the Germinoma might need to be considered when β- HCG is used as a marker to predict metastasis.
Abstract: Background
Beta (β)-human chorionic gonadotropin (β-HCG) is used to confirm the diagnosis and plan treatment of intracranial germinomas. However, the cutoff values of serum β-HCG in diagnosis of intracranial germinomas reported in the literature are inconsistent. To establish an appropriate cutoff value of serum β-HCG for diagnosis of intracranial germinomas, we retrospectively reviewed the records of intracranial tumor patients who received serum β-HCG and α-fetoprotein (AFP) tests for diagnostic purposes at our hospital from 2005 to 2014.
Methods
A total of 93 intracranial germinomas and 289 intracranial non-germ cell tumors were included in this study. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of 3 cutoffs (0.1, 0.4, and 0.5 mIU/mL) for diagnosing intracranial germinomas. The serum β-HCG level of intracranial germinoma patients was further analyzed to investigate the effect of metastasis status and tumor location on serum β-HCG level.
Results
The area under the ROC curve was 0.81 (P < .001), suggesting β-HCG is an effective marker. Of the 3 cutoff values, 0.1 mIU/mL possessed a highest sensitivity (66.67%) and good specificity (91%). Although there was no β-HCG level difference between metastatic and non-metastatic intracranial germinoma patients, the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart (P < .05), implying that the location of the germinoma might need to be considered when β-HCG is used as a marker to predict metastasis.
Conclusions
Determining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma.
13 citations
Cites background from "Germinoma with involvement of midli..."
...Intracranial germinomas commonly originate in the midline, including the pineal and neurohypophyseal regions [8]....
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TL;DR: Suprasellar germinomas are highly curable lesions when diagnosed early, but the association of chemotherapy and radiotherapy allows reduce adverse effects and shows great results.
11 citations
20 May 2019
TL;DR: The reported case shows an unusual coexistence of germinoma with prominent inflammation in the brain and highlights the importance of brain biopsy in such complex cases.
Abstract: The authors report a case of a germinoma of the brain in the child with symptoms restricted to central nervous system. Ten-year-old girl presented initially with sight deterioration, learning difficulties, abnormal behavior, polydipsia, and polyuria. Brain magnetic resonance examination revealed T2 hyperintensity of the corpus callosum, anterior commissure, and caudate nuclei. Brain biopsy revealed extensive macrophage infiltration. Given these results and positive antinuclear antibodies in the blood, immunosuppressive and immunomodulatory treatment was implemented but it was not effective. The patient developed progressive quadriparesis, sleep disturbances, and dementia. Second brain biopsy was performed and it revealed germinoma cells. Chemotherapy was administered, but the girl died due to disseminated intravascular coagulation syndrome. The reported case shows an unusual coexistence of germinoma with prominent inflammation in the brain and highlights the importance of brain biopsy in such complex cases.
7 citations
Cites background from "Germinoma with involvement of midli..."
...On the other hand, lymphocytic reaction seen in germinomas is thought to be protective and reduction in lymphocytic infiltration with for example steroids might induce tumor growth.(14) It cannot be excluded that such phenomenon was at least partly associated with the deterioration of the clinical status of our patient after immunomodulatory agents....
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References
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TL;DR: Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum and treatment and prognosis differ greatly between groups.
Abstract: Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or beta-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation. Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates >90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.
338 citations
TL;DR: Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.
Abstract: PURPOSERadiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided.PATIENTS AND METHODSPatients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide.RESULTSSeventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months...
333 citations
"Germinoma with involvement of midli..." refers methods in this paper
...This last approach was tested by the International Central Nervous System Germ Cell Tumor Study Group, reporting a high rate of complete response but with a high rate of relapse [17]....
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TL;DR: Investigation of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors found disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients.
Abstract: PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-β)–secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients wit...
155 citations
TL;DR: The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiated treatment of central nervous system germ cell tumors.
Abstract: Background
The treatment of central nervous system (CNS) germ cell tumors (GCT) remains controversial. The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiation.
Methods
Between January 2001 and December 2004 newly diagnosed patients with CNS GCT were treated with one of two risk-tailored chemotherapy regimens. Twenty-five patients aged 4 months to 24.5 years were stratified: Regimen A consisted of 4–6 cycles of carboplatin/etoposide alternating with cyclophosphamide/etoposide for low risk (LR) localized germinoma with normal cerebrospinal fluid (CSF) and serum tumor markers. Regimen B consisted of 4–6 cycles of carboplatin/cyclophosphamide/etoposide for intermediate-risk (IR) germinoma with positive human chorionic gonadotrophin-beta (HCGβ) and/or CSF HCGβ 50 mIU/ml.
Results
Eleven patients were classified as LR, 2 IR, and 12 HR. Seventeen (68%) patients achieved complete radiographic and marker responses after two courses and 19 (76%) after four courses of chemotherapy. Eleven patients relapsed at a mean of 30.8 months; eight of them subsequently received irradiation. The 6-year event free and overall survival for the 25 patients was 45.6% and 75.3%, respectively.
Conclusion
These intensive chemotherapy regimens proved less effective than irradiation containing regimens. Our results indicate that, at the present time, standard treatment for CNS GCT continues to include irradiation either alone or combined with chemotherapy for pure germinomas and with chemotherapy for those with MMGCT. Pediatr Blood Cancer 2010;54:377–383. © 2009 Wiley-Liss, Inc.
122 citations
TL;DR: An excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma is identified, and ventricular field radiation appears a logical alternative to decrease the incidence of such relapses.
Abstract: Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.
117 citations
"Germinoma with involvement of midli..." refers background in this paper
...In an attempt to reduce themorbidity of CSI, cooperative groups had investigated the feasibility of a sequential treatment of chemotherapy followed by focal irradiation [15, 16] or even chemotherapy alone....
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