Clinical features, radiologic findings, and treatment of pediatric germ cell tumors involving the basal ganglia and thalamus: a retrospective series of 15 cases at a single center

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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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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Molecular tumor profiling (MTP) of poorly differentiated neoplasms (PDN) of unknown primary site.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11080 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11080-11080 ◽

Cited By ~ 2

Author(s):

F Anthony Greco ◽

David R. Spigel ◽

John D. Hainsworth

Keyword(s):

Germ Cell ◽

Clinical Features ◽

Germ Cell Tumors ◽

Unknown Primary ◽

Genetic Profiling ◽

Genetic Sequencing ◽

Pathologic Evaluation ◽

Appropriate Therapy ◽

Chromosomal Changes ◽

Specific Tissue

11080 Background: The inability to definitively determine the lineage of neoplasms is less common with modern immunohistochemistry (IHC) and genetic profiling. Nonetheless some PDN defy lineage classification by extensive standard pathologic evaluation. The advent of MTP may provide a new method of improving the diagnosis of these challenging cancers. Methods: A total of 30 of 751 (4%) patients (pts) seen from 2000 – 2012 with cancer of unknown primary (CUP) had PDN without a definitive lineage determined by IHC (median 18 IHC stains, range 9 – 51). From 2008 – 2012 the 30 biopsies had MTP (RT-PCR mRNA CancerTYPE ID, bioTheranostics, Inc.). Additional IHC, genetic sequencing, fluorescent in situ hybridization for specific chromosomal changes and repeat biopsies were performed when feasible to support the MTP diagnosis, and clinical features correlated. Results: MTP lineage diagnoses were made in 25 of 30 (83%), including 10 carcinomas (3 germ cell, 2 neuroendocrine, 5 others), 5 melanomas, 8 sarcomas (3 peritoneal mesothelioma, 1 PNET) and 2 hematopoietic neoplasms (1 lymphoma, 1 chloroma). Additional IHC, genetic testing [BRAF, i(12)p] or repeat biopsies confirmed the MTP diagnoses in 11 of 15 tumors, and the clinical features were consistent with the MTP diagnoses in the majority of patients. Conclusions: This MTP assay can frequently provide a diagnosis for CUP pts and PDN without a definitive lineage defined by extensive IHC. The earlier application of MTP will likely provide an expedited diagnosis, and for some neoplasms is the only test capable of defining lineage and a more specific diagnosis. Appropriate therapy, particularly for pts with germ cell tumors, melanoma, and lymphoma depends on a specific tissue of origin diagnosis.

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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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