Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment

Object Intracranial germ cell tumors (GCTs) originating in the basal ganglia are rare. The authors investigated factors related to the diagnosis of these lesions as well as outcome in order to help decrease the time to diagnosis and improve treatment efficacy. Methods The authors reviewed the clinical features of 142 cases of intracranial GCT in their institute. Fourteen cases of basal ganglia GCT were identified. The symptoms, neuroimaging findings, delay between symptom onset and diagnosis or treatment, initial and further treatment, and outcome were investigated. Results Major symptoms were motor weakness and precocious puberty. Gadolinium-enhanced T1-weighted MR images showed enhancement in 8 of 11 patients examined, but only slight hyperintensity without enhancement in 2 patients. Ipsilateral peduncle and hemispheric atrophy were found in 3 and 4 patients, respectively. Cases of basal ganglia GCT were characterized by a longer delay from the initial neuroimaging examination to diagnosis compared with GCT in other regions. Five patients had aggravated hemiparesis in the extremities due to the delay in diagnosis. Despite good response to the initial therapy, 5 patients experienced recurrence; 2 of these 5 had malignant GCTs, and 3 had been treated only with chemotherapy or radiochemotherapy with insufficient radiation dose and field. Finally, the 2 patients with malignant GCTs died of the disease, and 1 died of aspiration pneumonia due to dissemination around the brainstem. Conclusions Early diagnosis requires MR imaging with administration of contrast medium in young patients presenting with motor weakness and/or precocious puberty. Serial neuroimaging studies should be performed if any tiny lesion is detected in the basal ganglia. Since insufficient treatment resulted in early recurrence, radiation therapy with adequate dose and field is essential.

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GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

Neuro-Oncology ◽

10.1093/neuonc/noaa222.235 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii330-iii331

Author(s):

Hirokazu Takami ◽

Koichi Ichimura ◽

Kohei Fukuoka ◽

Akitake Mukasa ◽

Nobuhito Saito ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Basal Ganglia ◽

Pineal Gland ◽

Germ Cell ◽

Prognostic Significance ◽

Germ Cell Tumors ◽

Molecular Data ◽

Molecular Heterogeneity ◽

Intracranial Germ Cell Tumor

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

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CTNI-63. PROGNOSTIC FACTORS IN PATIENTS WITH BASAL GANGLIA GERM-CELL TUMORS: A RETROSPECTIVE ANALYSIS OF THE SINGLE CHINESE INSTITUTE EXPERIENCE FROM 2009 TO 2019

Neuro-Oncology ◽

10.1093/neuonc/noaa215.229 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii57-ii57

Author(s):

Qingjun Hu ◽

Juan Li ◽

Mingyao Lai ◽

Cheng Zhou ◽

Zhaoming Zhou ◽

...

Keyword(s):

Survival Rate ◽

Basal Ganglia ◽

Germ Cell ◽

Retrospective Analysis ◽

Surgical Resection ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Course Of Disease ◽

Free Survival

Abstract OBJECTIVE To evaluate the clinical factors related to the prognosis of basal ganglia germ cell tumors. METHODS A retrospective analysis of 52 cases of the basal ganglia germ cell tumors treated from January 2009 to January 2019 in the department of oncology of Guangdong Sanjiu Brain Hospital. The median age: 12 years (range: 5–32), The median course of disease: 11.7 months (range: 1–54). Thirteen cases were diagnosed by biopsy and 39 cases were diagnosed by elevated tumor markers. There were 31 patients (59.6%) diagnosed with germinomas and 21 patients (40.4%) with non-germ germ cell tumors. Univariate and multivariate survival analysis was performed. RESULTS To October 15, 2019, the median follow-up time was 30.4 months (range 2–124 months). The 5-year survival rate was 85%, and the 5-year progression-free survival rate was 84%. Multivariate analysis found whether serum AFP was greater than 100mIU / ml, (with HR: 11.441,95% CI: 2.09–47.66, P = 0.005),the degree of surgical resection(with HR 5.323 (1.19–23.812), P = 0.029), PD as the effect of radiotherapy (HR: 16.53, (1.19–23.81), P = 0.001) were independent prognostic factor affecting survival. CONCLUSION The pathological type, degree of surgical resection, and response to initial treatment can all affect survival.

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Klinefelter syndrome and germ cell tumors: review of the literature

International Journal of Pediatric Endocrinology ◽

10.1186/s13633-020-00088-0 ◽

2020 ◽

Vol 2020 (1) ◽

Author(s):

Kimberley Bonouvrie ◽

Jutte van der Werff ten Bosch ◽

Machiel van den Akker

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Klinefelter Syndrome ◽

Case Reports ◽

Age Groups ◽

Germ Cell Tumors ◽

Young Patients ◽

Cell Tumor ◽

Healthy Population ◽

Extragonadal Germ Cell Tumors

Abstract Objective The most common presentation of Klinefelter syndrome (KS) is infertility and features of hypogonadism. Currently no consensus exists on the risk of malignancy in this syndrome. Several case reports show an incidence of extragonadal germ cells tumors (eGCT) of 1.5 per 1000 KS patients (OR 50 against healthy population). Malignant germ cell tumors are rare in children. They account for 3% of all children cancers. Young patients with a germ cell tumor are not routinely tested for Klinefelter syndrome. This can therefore result in underdiagnosing. Literature data suggest a correlation between eGCT and KS. To the best of our knowledge there is no precise description of the primary locations of germ cell tumors in KS patients. The purpose of this study is to evaluate age groups and primary locations of extragonadal germ cell tumors in Klinefelter patients. With this data we investigate whether it is necessary to perform a cytogenetic analysis for KS in every eGCT patient. Study design This study is based on case report publications in PubMed/Medline published until march 2020 that described “Klinefelter Syndrome (MeSH) AND/OR extragonadal germ cell tumors”. Publications were included when patients age, location and histology of the germ cell tumor was known. Two double blinded reviewers selected the studies.Results: 141 KS patients with eGCTs were identified. Mean age at presentation was 17.3 years (StDev + − 10.2). In contrast to the extragonadal germ cell tumors in adults, most eGCT in children were mediastinal or in the central nervous system (respectively 90/141; 64% and 23/141; 16% of all tumors). Distribution of histologic subtypes showed that the largest fraction represented a teratoma, mixed-type-non-seminomateus GCT and germinoma, respectively 34/141; 24%, 26/141; 18% and 20/141; 14% of all tumors. Conclusion These data suggest a correlation between primary extragonadal germ cell tumors and Klinefelter syndrome. There appears to be an indication for screening on KS in young patients with an eGCT in the mediastinum. A low threshold for radiologic examinations should be considered to discover eGCT. We emphasize the need for genetic analysis in all cases of a male with a mediastinal germ cell tumor for the underdiagnosed Klinefelter syndrome.

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Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium

Neuro-Oncology ◽

10.1093/neuonc/noz139 ◽

2019 ◽

Vol 21 (12) ◽

pp. 1565-1577 ◽

Cited By ~ 1

Author(s):

Hirokazu Takami ◽

Kohei Fukuoka ◽

Shintaro Fukushima ◽

Taishi Nakamura ◽

Akitake Mukasa ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Basal Ganglia ◽

Pineal Gland ◽

Germ Cell ◽

Prognostic Significance ◽

Germ Cell Tumors ◽

Molecular Data ◽

Molecular Heterogeneity ◽

Intracranial Germ Cell Tumor

Abstract Background We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

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RARE-14. STRUCTURAL BRAIN PLASTICITY OF THE GRAY MATTER IN PATIENTS WITH BASAL GANGLIA GERM CELL TUMORS: A VBM STUDY

Neuro-Oncology ◽

10.1093/neuonc/noz175.937 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi224-vi224

Author(s):

Yanong Li

Keyword(s):

Basal Ganglia ◽

Germ Cell ◽

Gray Matter ◽

Gray Matter Volume ◽

Germ Cell Tumors ◽

T Test ◽

Whole Brain ◽

Volume Increase ◽

Matter Volume ◽

Significant Difference

Abstract OBJECTIVE To assess the whole brain structural plasticity in case of unilateral basal ganglia germ cell tumors (BGGCTs). METHODS To detect changes in gray matter volume of the whole brain from structural Magnetic Resonance Imaging (MRI), we used voxel-based morphometry (VBM) in a sample of 41 patients with BGGCTs invading the left basal ganglia (BasalG_L group; n = 22) or the right basal ganglia (BasalG_R group; n = 19) and a sample of 16 patients with GCTs arising in pineal or suprasellar regions, comparing these groups with 16 age-matched normal controls (NCs) by two-sample t test after that. RESULTS To left BGGCTs patients, the regions of whole brain VBM analysis emphasized a large cluster of voxels with gray matter volume increase in left para hippocampal (k = 529 voxels, T=4.18, p< 0.01) and decrease in left thalamus (k = 527 voxels, T=-4.88, p< 0.01). At the same time, the cluster of voxels with gray matter volume increase in right middle cingulate cortex (rMCC) (k = 172 voxels, T=3.96, p< 0.01), and decrease in right inferior frontal gyrus (rIFG), pars opercular (k = 495 voxels, T= -4.29, p< 0.01) in right BGGCTs patients. Furthermore, gray matter volume showed no significant difference between groups of patients with GCTs arising in pineal or suprasellar regions and NCs by two-sample t test. And the results were corrected by family-wise-error correction. CONCLUSIONS The revealed results demonstrate that slow-growing but destructive lesion of the BGGCTs markedly and asymmetrically atrophies the gray matter volume in specific brain regions and shows compensatory plasticity in each side of cerebral hemisphere. Our findings direct focus on the whole cerebral adaptation that perhaps be a physiologic basis for the high level of functional compensation and partially explain the relationships between gray matter remodeling and cognitive disturbances observed in patients with BGGCTs.

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Bilateral Germ Cell Tumors Involving the Basal Ganglia and Thalamus

Neurosurgery ◽

10.1227/00006123-198904000-00015 ◽

1989 ◽

Vol 24 (4) ◽

pp. 579-583 ◽

Cited By ~ 12

Author(s):

Tatsuya Kobayashi ◽

Jun Yoshida ◽

Yoshihisa Kida

Keyword(s):

Basal Ganglia ◽

Germ Cell ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Early Stage ◽

Germ Cell Tumors ◽

Biological Behavior ◽

Computed Tomographic ◽

Normal Limits ◽

Extrapyramidal Signs

ABSTRACT Two cases of a human chorionic gonadotropin-producing germ cell tumor originating bilaterally in the basal ganglia and thalamus are reported. The biological behavior and clinical characteristics were similar to those of unilateral germinomas involving the basal ganglia and thalamus. Common clinical features were slowly progressive unilateral pyramidal signs and bilateral and/or unilateral extrapyramidal signs which occurred either concomitantly or sequentially. Bilateral symmetrical lesions were demonstrated by computed tomography and/or magnetic resonance imaging at an early stage of illness. Serum and cerebrospinal fluid human chorionic gonadotropin levels were elevated (116 and 141 mIU/ml, respectively) but decreased and remained within normal limits after radiation therapy alone. Radiosensitivity was confirmed by repeated computed tomographic scans and tumor marker measurements. Multiple concomitant germ cell tumors is a rare, but interesting lesion, especially considering its pathogenesis and oncogenesis.

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Germ Cell Tumors of the Basal Ganglia and Thalamus

Pediatric Neurosurgery ◽

10.1159/000120716 ◽

1993 ◽

Vol 19 (3) ◽

pp. 121-126 ◽

Cited By ~ 15

Author(s):

Masaharu Yasue ◽

Hideaki Tanaka ◽

Masato Nakajima ◽

Masami Kamio ◽

Norio Nakamura ◽

...

Keyword(s):

Basal Ganglia ◽

Germ Cell ◽

Germ Cell Tumors

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Clinical interpretation of residual uptake in 11C-methionine positron emission tomography after treatment of basal ganglia germ cell tumors: report of 3 cases

Journal of Neurosurgery Pediatrics ◽

10.3171/2015.3.peds14458 ◽

2015 ◽

Vol 16 (4) ◽

pp. 367-371

Author(s):

Kohei Fukuoka ◽

Takaaki Yanagisawa ◽

Yuko Watanabe ◽

Tomonari Suzuki ◽

Masao Matsutani ◽

...

Keyword(s):

Basal Ganglia ◽

Germ Cell ◽

Germ Cell Tumors ◽

Treatment Strategies ◽

Standardized Uptake Value ◽

Progression Free Survival ◽

Additional Treatment ◽

Free Survival ◽

Posterior Limb ◽

Met Pet

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.

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