Authors: Didier Frappaz, Girish Dhall, Matthew J Murray...

The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.

Topics: Adolescent; Brain Neoplasms; Consensus; Germinoma; Humans; Male; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Testicular Neoplasms; Young Adult

PubMed: 34724065
DOI: 10.1093/neuonc/noab252

Authors: Ute Bartels, Arzu Onar-Thomas, Sunita K Patel...

BACKGROUND

The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate.

METHODS

Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim.

RESULTS

One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment.

CONCLUSIONS

While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Child; Child, Preschool; Etoposide; Germinoma; Humans; Pineal Gland; Prospective Studies; Young Adult

PubMed: 34850169
DOI: 10.1093/neuonc/noab270

Authors: Daniel J Minter, Megan Richie, Priya Kumthekar...

Topics: Brain; Central Nervous System Neoplasms; Diabetes Insipidus; Diagnosis, Differential; Germinoma; Humans; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms; Young Adult

PubMed: 33789016
DOI: 10.1056/NEJMcps2028560

Authors: Warinthorn Phuttharak, Mix Wannasarnmetha, Peerawit Lueangingkasut...

PURPOSE

To evaluate the effectiveness of diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) for differentiation between germinoma and other pineal region tumors.

METHOD

This retrospective study consisted of 72 patients with pathologically proven pineal region tumors between January 2010 and August 2020. Tumors were classified as germinomas (40), non-germinomatous germ cell tumors (11) (NGGCT), pineal parenchymal tumors (10) (PPT), and other types of tumors (11). Visual scale score, ADC values and SWI intratumoral susceptibility signal (ITSS) score were analyzed and compared to histopathology data.

RESULTS

The mean apparent diffusion coefficient (ADCmean) and minimum apparent diffusion coefficient (ADCmin) ratio of germinoma were significantly lower than NGGCT. ADCmean or ADCmin cut-off ratio of ≤ 1.48 or ≤ 1.32 allowed for discrimination between germinoma and NGGCT with sensitivity and specificity of 100 % and 63.6 %. An ADCmin cut-off ratio of ≥ 0.93 allowed for discrimination between germinoma and PPT with sensitivity and specificity of 60 % and 80.0 %. ADCmin cut-off ratio of ≤ 1.15 allowed for discrimination of germinoma from other types of tumors with sensitivity and specificity of 87.5 % and 54.5 %.

CONCLUSIONS

ADC ratio can differentiate germinoma from other types of pineal region tumors. Our initial results suggest that ITSS score was not significantly correlated with specific histology subtype.

Topics: Humans; Pinealoma; Retrospective Studies; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Germinoma; Neoplasms, Germ Cell and Embryonal; Cell Differentiation; Brain Neoplasms; Pineal Gland

PubMed: 36584565
DOI: 10.1016/j.ejrad.2022.110663

Review

Authors: Diana S Osorio, Jeffrey C Allen

The following is a general overview of the management of CNS germinomas. Over the last 35 years, CNS germinomas have become one of the pediatric brain tumors with the best outcomes with a greater than 85% overall survival over 5 years. This is in part due to the fact that germinomas are very responsive to chemotherapy and radiation. Some of the major challenges going forward will be to find ways to minimize the adverse effects of our treatments particularly with regard to radiation and to improve the quality of life of patients who develop neurologic, neurocognitive and/or endocrine deficiencies.

Topics: Brain Neoplasms; Germinoma; Humans

PubMed: 26118663
DOI: 10.2217/cns.15.13

Authors: Joanna Trubicka, Maria Łastowska, Agnieszka Karkucińska-Więckowska...

BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain tumours investigated. Immunohistochemical detection of BCOR expression may therefore serve as a potential diagnostic marker. Nevertheless, in rare paediatric glioma cases recurrent EP300-BCOR fusions were detected, which resulted in strong BCOR immunopositivity. We have therefore examined other, not analysed so far, types of central nervous system (CNS) tumours, pineoblastoma and germinoma, to assess a potential involvement of BCOR in these tumours. Levels of BCOR RNA expression were investigated by NanoString nCounter system analysis in a series of altogether 66 high grade paediatric tumours, including four pineoblastoma cases. Immunohistological detection of BCOR was performed in eight pineoblastoma, five germinoma and four atypical teratoid rhabdoid tumours (ATRTs), all located in the pineal region. We detected BCOR expression in all pineoblastomas, at the RNA and protein levels, but not in germinomas and ATRTs. Further analysis of pineoblastoma samples did not reveal the presence of either BCOR internal tandem duplication or BCOR fusion involvement. Positive immunohistological BCOR nuclear reaction in pineoblastoma may therefore differentiate this type of tumour from other high grade tumours located in the pineal region.

Topics: Humans; Child; Pinealoma; Brain Neoplasms; Germinoma; RNA; Rhabdoid Tumor; Pineal Gland; Proto-Oncogene Proteins; Repressor Proteins

PubMed: 37587886
DOI: 10.5114/fn.2023.129377

Review

Authors: Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore...

PURPOSE OF REVIEW

Intracranial germinomas constitute a rare brain tumor entity of unknown etiology, characterized by unique histopathology and molecular biology. In this manuscript, we review the literature focusing on the epidemiology, histopathology with molecular biology, clinical presentation with emphasis on tumor location, diagnostic workup, and current treatment strategies with related clinical outcomes of intracranial germinomas.

RECENT FINDINGS

Although the optimal treatment strategy remains a matter of debate, intracranial germinomas respond well to radiotherapy, chemotherapy, or a combination of both and are characterized by very high cure and survival rates. It is well-known that early discrimination of germinomas from other intracranial neoplasms facilitates the timely initiation of appropriate treatment, thereby contributing to the reduction of morbidity as well as mortality. Ongoing research will need to be directed towards discovering and refining reliable parameters for early diagnosis and evaluation of prognosis in patients with intracranial germinomas.

Topics: Humans; Germinoma; Brain Neoplasms; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Survival Rate

PubMed: 37036624
DOI: 10.1007/s11912-023-01416-2

Authors: Lixuan Huang, Jiangnian Gong, Daqin Feng...

Intracranial germ cell tumors (GCTs) are rare neoplasms with a peak incidence in adolescents. Germinoma is the most common histological subtype of intracranial GCTs. Its symptoms include intracranial hypertension, visual field defects, and hormonal disorders, affecting the physical health of adolescents. Germinoma is sensitive to chemo-radiotherapy, and most patients do not require neurosurgical resection. Therefore, improving the accuracy of germinoma diagnosis helps to avoid unnecessary surgery. At present, the application of artificial intelligence (AI) in medical imaging has improved the accuracy of disease diagnosis. However, few studies focused on the AI model to diagnosis germinoma and there are no publicly available imaging datasets for germinoma. This study aimed to create a comprehensive dataset for germinoma using magnetic resonance imaging/computed tomography findings with clinical and radiomic data to train and validate AI models. Featuring 65 pathologically confirmed germinomas, the dataset included axial T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, T1-weighted imaging, T1-weighted imaging with contrast enhancement, diffusion-weighted MR imaging, CT images, clinical data, and morphological and radiomic-based features obtained by segmentation.

Topics: Humans; Germinoma; Magnetic Resonance Imaging; Adolescent; Tomography, X-Ray Computed; Brain Neoplasms; Male; Artificial Intelligence; Female; Child; Radiomics

PubMed: 39984475
DOI: 10.1038/s41597-025-04596-7

Authors: Serdar Şahin, Ozan Başkurt, Nil Çomunoğlu...

Topics: Humans; Autoimmune Hypophysitis; Hypopituitarism; Germinoma; Diagnostic Errors

PubMed: 37227236
DOI: 10.4274/balkanmedj.galenos.2023.2023-3-60

Authors: S A Seligman

Topics: Adolescent; Adult; Child; Child, Preschool; Dysgerminoma; Female; Humans; Hypogonadism; Infant; Infant, Newborn; Middle Aged; Ovarian Neoplasms

PubMed: 6043689
DOI: 10.1136/pgmj.43.500.400