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Cancers Jul 2022Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal...
Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.
PubMed: 35884617
DOI: 10.3390/cancers14143555 -
Journal of Personalized Medicine Jul 2021Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing... (Review)
Review
Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, , and pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.
PubMed: 34357128
DOI: 10.3390/jpm11070661 -
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 -
Cancer Reports (Hoboken, N.J.) Sep 2022Intracranial germinomas (GN) are rare cancers that primarily affect children, making them rarer still in adults. Standard treatment for this neoplasm includes...
BACKGROUND
Intracranial germinomas (GN) are rare cancers that primarily affect children, making them rarer still in adults. Standard treatment for this neoplasm includes neoadjuvant chemotherapy (NC) followed by radiotherapy (RT) or RT at a higher dose and larger field. These recommendations are based on studies focused mostly on children; it is currently unclear whether this treatment is applicable to adults.
CASE
We present a case of a 23-year-old adult male with no underlying pathologies, drug allergies, or family history of cancer, who presented for medical evaluation with blurred vision, diplopia, forgetfulness, and weight loss starting 3-4 months before the evaluation. Clinical examination indicated Parinaud's Syndrome. Magnetic resonance imaging (MRI) and computed tomography (CT) revealed a pineal tumor with ependymal dissemination in both lateral ventricles, which was causing obstructive hydrocephalus. The patient had surgery consisting of ventriculostomy, Holter shunt insertion, cisternal ventricular intubation, and cisterna magna anastomosis to improve ventricular drainage. Pathology confirmed pineal germinoma. Cerebrospinal fluid cytology and MRI of the axis were negative. Four cycles of NC were given to the patient (carboplatin, etoposide, and ifosfamide), with reduced dosage. Once a partial volumetric response was confirmed, whole-ventricular radiotherapy (WVR) was initiated with a total tumor bed dose of 45 Gy over 25 sessions in 5 weeks. Optimum clinical results were observed, and no short-term (<90 day) radiation toxicity was observed. The patient was able to resume his normal activities soon after treatment. Follow-ups over 2 years post-surgery indicated continued control of the lesion and absence of symptoms except for mild diplopia.
CONCLUSION
Although this is a case report, these data suggest that a reduced NC course and WVR may effectively treat adult GN. This protocol likely decreases the risk of undesirable NC and RT secondary effects, while providing excellent local control; however, using a narrower RT field is not recommended.
Topics: Adult; Brain Neoplasms; Child; Diplopia; Germinoma; Humans; Male; Pineal Gland; Pinealoma; Young Adult
PubMed: 35347869
DOI: 10.1002/cnr2.1611 -
Endocrinology, Diabetes & Metabolism... Feb 2019Intracranial germinomas are rare tumors affecting mostly patients at young age. Therefore, molecular data on its etiopathogenesis are scarce. We present a clinical case...
Intracranial germinomas are rare tumors affecting mostly patients at young age. Therefore, molecular data on its etiopathogenesis are scarce. We present a clinical case of a male patient of 25 years with an intracranial germinoma and a 16p11.2 microdeletion. His initial complaints were related to obesity, loss of facial hair and polydipsia. He also had a history of social-interaction difficulties during childhood. His blood tests were consistent with hypogonadotropic hypogonadism and secondary adrenal insufficiency, and he had been previously diagnosed with hypothyroidism. He also presented with polyuria and polydipsia and the water deprivation test confirmed the diagnosis of diabetes insipidus. His sellar magnetic resonance imaging (MRI) showed two lesions: one located in the pineal gland and other in the suprasellar region, both with characteristics suggestive of germinoma. Chromosomal microarray analysis was performed due to the association of obesity with social disability, and the result identified a 604 kb 16p11.2 microdeletion. The surgical biopsy confirmed the histological diagnosis of a germinoma. Pharmacological treatment with testosterone, hydrocortisone and desmopressin was started, and the patient underwent radiotherapy (40 Gy divided in 25 fractions). Three months after radiotherapy, a significant decrease in suprasellar and pineal lesions without improvement in pituitary hormonal deficiencies was observed. The patient is currently under follow-up. To the best of our knowledge, we describe the first germinoma in a patient with a 16p11.2 deletion syndrome, raising the question about the impact of this genetic alteration on tumorigenesis and highlighting the need of molecular analysis of germ cell tumors as only little is known about their genetic background. Learning points: Central nervous system germ cell tumors (CNSGTs) are rare intracranial tumors that affect mainly young male patients. They are typically located in the pineal and suprasellar regions and patients frequently present with symptoms of hypopituitarism. The molecular pathology of CNSGTs is unknown, but it has been associated with gain of function of the KIT gene, isochromosome 12p amplification and a low DNA methylation. Germinoma is a radiosensitive tumor whose diagnosis depends on imaging, tumor marker detection, surgical biopsy and cerebrospinal fluid cytology. 16p11.2 microdeletion syndrome is phenotypically characterized by developmental delay, intellectual disability and autism spectrum disorders. Seminoma, cholesteatoma, desmoid tumor, leiomyoma and Wilms tumor have been described in a few patients with 16p11.2 deletion. Bifocal germinoma was identified in this patient with a 16p11.2 microdeletion syndrome, which represents a putative new association not previously reported in the literature.
PubMed: 30738016
DOI: 10.1530/EDM-18-0149 -
JCO Global Oncology Apr 2023This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with...
PURPOSE
This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care.
PATIENTS AND METHODS
Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGβ levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease.
RESULTS
Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%.
CONCLUSION
The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.
Topics: Male; Humans; Child; Adolescent; Female; Prospective Studies; Brazil; Retrospective Studies; Brain Neoplasms; Germinoma; Biomarkers, Tumor
PubMed: 37075267
DOI: 10.1200/GO.22.00257 -
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 -
Neuro-ophthalmology (Aeolus Press) 2022Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary...
Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.
PubMed: 35859628
DOI: 10.1080/01658107.2022.2034890 -
Frontiers in Oncology 2022CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland.... (Review)
Review
CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in and and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.
PubMed: 36132131
DOI: 10.3389/fonc.2022.982608 -
Cureus Oct 2022Pineal gland tumours are reported rarely in Malayasia and early diagnosis and intervention promise a better prognosis for patients. We report a rare case of pineal gland...
Pineal gland tumours are reported rarely in Malayasia and early diagnosis and intervention promise a better prognosis for patients. We report a rare case of pineal gland tumour with drop metastases in the fourth ventricle in a 20-year-old young male with Parinaud syndrome. The patient, who had no underlying medical illnesses, presented with neurological symptoms and limb weakness associated with tremors and blurring of vision which worsened over a span of four months. The patient was having difficulty in ambulating with reduced power over the lower limbs with tremors as well as Parinaud syndrome indicated through the limitation of upward gaze, light-near dissociation of the pupils and convergence nystagmus. An MRI showed the presence of a pineal gland tumour with drop metastases in the fourth ventricle with calcification. The patient underwent an endoscopic third ventriculostomy and tumour biopsy. The biopsy indicated a pineal gland tumour with a germinoma subset and the patient was subjected to radiotherapy. Latency of diagnosis is an important prognostic factor as it reduces the survival rate for these patients hence the following discussion on the pineal gland tumour and its diagnostic dilemma.
PubMed: 36204259
DOI: 10.7759/cureus.29855