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Neuro-oncology Advances 2023Germinomas are sensitive to radiation and chemotherapy, and their management distinctly differs from other kinds of pineal region tumors. The aim of this study was to...
BACKGROUND
Germinomas are sensitive to radiation and chemotherapy, and their management distinctly differs from other kinds of pineal region tumors. The aim of this study was to construct a prediction model based on clinical features and preoperative magnetic resonance (MR) manifestations to achieve noninvasive diagnosis of germinomas in pineal region.
METHODS
A total of 126 patients with pineal region tumors were enrolled, including 36 germinomas, 53 nongerminomatous germ cell tumors (NGGCTs), and 37 pineal parenchymal tumors (PPTs). They were divided into a training cohort ( = 90) and a validation cohort ( = 36). Features were extracted from clinical records and conventional MR images. Multivariate analysis was performed to screen for independent predictors to differentiate germ cell tumors (GCTs) and PPTs, germinomas, and NGGCTs, respectively. From this, a 2-step nomogram model was established, with model 1 for discriminating GCTs from PPTs and model 2 for identifying germinomas in GCTs. The model was tested in a validation cohort.
RESULTS
Both model 1 and model 2 yielded good predictive efficacy, with c-indexes of 0.967 and 0.896 for the diagnosis of GCT and germinoma, respectively. Calibration curve, decision curve, and clinical impact curve analysis further confirmed their predictive accuracy and clinical usefulness. The validation cohort achieved areas under the receiver operating curves of 0.885 and 0.926, respectively.
CONCLUSIONS
The 2-step model in this study can noninvasively differentiate GCTs from PPTs and further identify germinomas, thus holding potential to facilitate treatment decision-making for pineal region tumors.
PubMed: 37706201
DOI: 10.1093/noajnl/vdad094 -
BMC Pediatrics Sep 2023Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors... (Review)
Review
BACKGROUND
Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors (NGGCTs) is often accompanied by elevated tumor markers. Occult extracranial metastases or recurrences with negative markers are often difficult to detect in time, resulting in a very poor prognosis.
CASE PRESENTATION
A 12-year-old boy was admitted to our institution with dizziness, headache, vomiting, and sleepiness. Magnetic resonance imaging (MRI) showed a pineal mass, accompanied by a significant increase in serum alpha-fetoprotein (AFP). The patient subsequently underwent total removal of the tumor. Pathology revealed that the tumor was a mixed GCT, consisting of mature teratoma, germinoma, and yolk sac tumor. Intracranial GCT achieved complete remission after intensive adjuvant chemotherapy and radiotherapy. Regular follow-up MRI revealed no recurrence of the intracranial tumor and continued monitoring of tumor markers revealed no abnormalities. Eight months later, the patient was readmitted due to progressive abdominal pain. Imaging and physical examination revealed abdominal occupation and lymphatic mass in the neck. He received salvage chemotherapy, anti-PD-1 immunotherapy, and palliative chemotherapy, but still developed multiple organ dysfunction syndromes (MODS) due to tumor progression and eventually died after one month.
CONCLUSIONS
This profound case suggests that intracranial NGGCTs may develop occult extracranial malignancy, which can be very severe at the time of clinical symptoms and has an extremely poor prognosis. Therefore, in addition to tumor marker monitoring, regular follow-up with extracranial imaging may be warranted to detect extracranial tumors as early as possible, although perhaps not as frequently as with neuroimaging.
Topics: Male; Humans; Child; Neoplasms, Germ Cell and Embryonal; Teratoma; Brain Neoplasms; Dermoid Cyst; Biomarkers, Tumor
PubMed: 37679697
DOI: 10.1186/s12887-023-04213-9 -
Cureus Jul 2023Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches...
Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches for three months, a 13-year-old boy was diagnosed with depression due to exhibiting reduced speech, hypersomnia, and psychomotor slowing for three weeks. It was preceded by headache for three months. Examination revealed visual acuity of 6/6 bilaterally, convergence-retraction nystagmus worst on upgaze, limited bilateral ocular motility in upgaze, and light-near dissociation on pupil examination, all of which point towards Parinaud's syndrome. However, there was no lid retraction to suggest Collier's sign. Fundus examination revealed papilledema. Magnetic resonance imaging showed a large pineal mass extending to both thalami, dilated ventricles due to obstructive hydrocephalus, and cerebral edema. An urgent external ventricular drain was inserted, and biopsy revealed pineal gland germinoma. Chemotherapy and radiotherapy resulted in adequate tumor shrinkage. This case report highlights that subacute behavioral changes may mask a potentially life-threatening intracranial tumor, especially when associated with abnormal eye movement.
PubMed: 37637548
DOI: 10.7759/cureus.42497 -
Acta Endocrinologica (Bucharest,... 2023Intracranial germ cell tumors (GCTs) include two categories: germinoma and non germinoma. The pineal gland and suprasellar are the most common site of involvement. The...
Intracranial germ cell tumors (GCTs) include two categories: germinoma and non germinoma. The pineal gland and suprasellar are the most common site of involvement. The patient is a 14-year-old boy who presented with paralysis of upward gaze, polyuria, polydipsia and diplopia. Examination of vertical eye movements was impaired. Puberty then progressed to stage 3 of Marshall - Tanner and had stopped. In laboratory studies, the patient had anterior hypopituitarism and diabetes insipidus (DI). In pituitary and hypothalamic MRIs, a mass-like enlargement of the pituitary stalk and pineal region was seen, but due to the small size of the lesions, stereotactic biopsy was not possible. During this time, the patient developed recurrent attacks of hydrocephalus. Serum and CSF β-subunit of Human chorionic gonadotropin levels were negative. Treatment was not started because different lesions could cause disease in this area. After one year, a biopsy was performed and the germ cell tumor was diagnosed. Chemotherapy was started and after treatment the vision disorder and diplopia disappeared, but DI and pituitary dysfunction remained. Treatment of intracranial germinoma is multidisciplinary. GCTs are very sensitive to radiation therapy. They are treated with combination of chemotherapy, radiotherapy, surgery, endocrine therapy and have a good prognosis.
PubMed: 37601706
DOI: 10.4183/aeb.2023.99 -
Folia Neuropathologica 2023BCOR 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...
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 -
World Neurosurgery: X Oct 2023Surgical approaches for tissue diagnosis of pineal tumors have been associated with morbidity and mortality. The classification of images by machine learning (ML) may...
INTRODUCTION
Surgical approaches for tissue diagnosis of pineal tumors have been associated with morbidity and mortality. The classification of images by machine learning (ML) may assist physicians in determining the extent of resection and treatment plans for a specific patient. Therefore, the present study aimed to evaluate the diagnostic performances of the ML-based models for distinguishing between pure and non-germinoma of the pineal area. In addition, the secondary objective was to compare diagnostic performances among feature extraction methods.
METHODS
This is a retrospective cohort study of patients diagnosed with pineal tumors. We used the RGB feature extraction, histogram of oriented gradients (HOG), and local binary pattern methods from magnetic resonance imaging (MRI) scans; therefore, we trained an ML model from various algorithms to classify pineal germinoma. Diagnostic performances were calculated from a test dataset with several diagnostic indices.
RESULTS
MRI scans from 38 patients with pineal tumors were collected and extracted features. As a result, the k-nearest neighbors (KNN) algorithm with HOG had the highest sensitivity of 0.81 (95% CI 0.78-0.84), while the random forest (RF) algorithm with HOG had the highest sensitivity of 0.82 (95% CI 0.79-0.85). Moreover, the KNN model with HOG had the highest AUC, at 0.845. Additionally, the AUCs of the artificial neural network and RF algorithms with HOG were 0.770 and 0.713, respectively.
CONCLUSIONS
The classification of images using ML is a viable way for developing a diagnostic tool to differentiate between germinoma and non-germinoma that will aid neurosurgeons in treatment planning in the future.
PubMed: 37456691
DOI: 10.1016/j.wnsx.2023.100231 -
Advances in Experimental Medicine and... 2023Primary central nervous system germ cell tumors (CNS GCTs) are part of the GCTs in children and adults. This tumor entity presents with geographic variation, age, and...
Primary central nervous system germ cell tumors (CNS GCTs) are part of the GCTs in children and adults. This tumor entity presents with geographic variation, age, and sex predilection. There are two age peaks of incidence distribution at the first few months of life and in adolescence. CNS GCTs are heterogeneous in histopathological subtypes, locations, and tumor marker (AFP, β-hCG) secretions. In the WHO CNS tumor classification, GCTS are classified as germinoma and nongerminomatous GCT (NGGCT) with different subtypes (including teratoma). Excluding mature teratoma, the remaining NGGCTs are malignant (NGMGCT). In teratoma, growing teratoma syndrome and teratoma with somatic-type malignancy should be highlighted. The common intracranial locations are pineal region, neurohypophysis (NH), bifocal pineal-NH, basal ganglia, and cerebral ventricle. Above 50% of intracranial GCTs (IGCTs) present obstructive hydrocephalus. Spinal tumors are rare. Age, locations, hydrocephalus, and serum/CSF titer of β-hCG correlate with clinical manifestations. Delayed diagnosis is common in tumors arising in neurohypophysis, bifocal, and basal ganglia resulting in the increasing of physical dysfunction and hormonal deficits. Staging work-up includes CSF cytology for tumor cells and contrast-enhanced MRI of brain and spine for macroscopic metastasis before treatment commences. The therapeutic approach of CNS GCTs integrates locations, histopathology, staging, tumor marker level, and therapeutic classification. Treatment strategies include surgical biopsy/excision, chemotherapy, radiotherapy (single or combination). Secreting tumors with consistent imaging may not require histopathological diagnosis. Primary germinomas are highly radiosensitive and the therapeutic aim is to maintain high survival rate using optimal radiotherapy regimen with/without chemotherapy combination. Primary NGNGCTs are less radiosensitive. The therapeutic aim is to increase survival utilizing more intensive chemotherapy and radiotherapy. The negative prognostic factors are residue disease at the end of treatment and serum or CSF AFP level >1000 ng/mL at diagnosis. In refractory or recurrent NMGGCTs, besides high-dose chemotherapy, new therapy is necessary. Molecular profiling and analysis help for translational research. Survivors of pediatric brain tumors frequently experience cancer-related cognitive dysfunction, physical disability, pituitary hormone deficiency, and other CNS complications after cranial radiotherapy. Continuous surveillance and assessment may lead to improvements in treatment protocols, transdisciplinary interventions, after-treatment rehabilitation, and quality of life.
Topics: Child; Adult; Adolescent; Humans; alpha-Fetoproteins; Spinal Neoplasms; Quality of Life; Neoplasms, Germ Cell and Embryonal; Brain Neoplasms; Germinoma; Teratoma; Spinal Cord Neoplasms; Brain; Retrospective Studies
PubMed: 37452948
DOI: 10.1007/978-3-031-23705-8_16 -
Advances in Experimental Medicine and... 2023Pineal region tumors fall into five broad categories: benign pineal region tumors, glial tumors, papillary tumors, pineal parenchymal tumors, and germ cell tumors....
Pineal region tumors fall into five broad categories: benign pineal region tumors, glial tumors, papillary tumors, pineal parenchymal tumors, and germ cell tumors. Genetic and transcriptional studies have identified key chromosomal alterations in germinomas (RUNDC3A, ASAH1, LPL) and in pineocytomas/pineoblastomas (DROSHA/DICER1, RB1). Pineal region tumors generally present with symptoms of hydrocephalus including nausea, vomiting, papilledema, and the classical Parinaud's triad of upgaze paralysis, convergence-retraction nystagmus, and light-near pupillary dissociation. Workup requires neuroimaging and tissue diagnosis via biopsy. In germinoma cases, diagnosis may be made based on serum or CSF studies for alpha-fetoprotein or beta-HCG making the preferred treatment radiosurgery, thereby preventing the need for unnecessary surgeries. Treatment generally involves three steps: CSF diversion in cases of hydrocephalus, biopsy through endoscopic or stereotactic methods, and open surgical resection. Multiple surgical approaches are possible for approach to the pineal region. The original approach to the pineal region was the interhemispheric transcallosal first described by Dandy. The most common approach is the supracerebellar infratentorial approach as it utilizes a natural anatomic corridor for access to the pineal region. The paramedian or lateral supracerebellar infratentorial approach is another improvement that uses a similar anatomic corridor but allows for preservation of midline bridging veins; this minimizes the chance for brainstem or cerebellar venous infarction. Determination of the optimal approach relies on tumor characteristics, namely location of deep venous structures to the tumor along with the lateral eccentricity of the tumor. The immediate post-operative period is important as hemorrhage or swelling can cause obstructive hydrocephalus and lead to rapid deterioration. Adjuvant therapy, whether chemotherapy or radiation, is based on tumor pathology. Improvements within pineal surgery will require improved technology for access to the pineal region along with targeted therapies that can effectively treat and prevent recurrence of malignant pineal region tumors.
Topics: Humans; Pinealoma; Pineal Gland; Brain Neoplasms; Glioma; Hydrocephalus; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37452938
DOI: 10.1007/978-3-031-23705-8_6 -
Neurology India 2023Primary intracranial germ cell tumors (ICGCTs) are rare and are histologically classified as germinomas and non-germinomatous with distinctive prognostic and therapeutic...
BACKGROUND AND OBJECTIVE
Primary intracranial germ cell tumors (ICGCTs) are rare and are histologically classified as germinomas and non-germinomatous with distinctive prognostic and therapeutic implications. ICGCTs, essentially due to the inherent difficulty of surgical access, pose different challenges and management connotations than their extracranial counterparts. This is a retrospective analysis of histologically verified ICGCTs, which was undertaken to evaluate various clinicopathological features and their implications on patient management.
MATERIALS AND METHODS
Eighty-eight histologically diagnosed cases (over 14 years) of ICGCT at our institute formed the study cohort and were classified into germinoma and non-germinomatous germ cell tumors (NGGCTs). Additionally, germinomas were further subdivided on the basis of 1) tumor marker (TM) levels, as germinoma with normal TM, mildly elevated TM, and markedly elevated TM and 2) radiology features, as germinomas with typical radiology and atypical radiological features.
RESULTS
ICGCT with age ≤6 years (P = 0.049), elevated TM (P = 0.047), and NGGCT histology (P < 0.001) showed significantly worse outcomes. Furthermore, germinomas with markedly elevated TM and certain atypical radiological features showed prognosis akin to NGGCT.
CONCLUSIONS
Analysis of our largest single cancer center Indian patient cohort of ICGCT shows that inclusion of age ≤6 years, raised TM, and certain radiological features may assist clinicians in overcoming the limitations of surgical sampling, with better prognostication of histologically diagnosed germinomas.
Topics: Humans; Child; Brain Neoplasms; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Germinoma; Prognosis
PubMed: 37322747
DOI: 10.4103/0028-3886.378644