Primary Intracranial Germ Cell Tumors: A Study with an Integrated Clinicopathological Approach.

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.

Primary midbrain germinomas: Report of a rare case with an updated review of the literature.

Intracranial germinomas are most commonly extra-axial germ cell tumors that are predominantly found in the pineal and suprasellar regions. Primary intra-axial midbrain germinomas are extremely rare, with only eight reported cases. Here we present a 30-year-old man who presented with severe neurological deficits, with an MRI that showed a heterogeneously enhancing mass with ill-defined margins in the midbrain, and with surrounding vasogenic edema extending to the thalamus. The presumptive preoperative differential diagnosis included glial tumors and lymphoma. The patient underwent a right paramedian suboccipital craniotomy and biopsy obtained through the supracerebellar infratentorial transcollicular approach. The histopathological diagnosis was reported as pure germinoma. After patient discharge, he received chemotherapy with carboplatin and etoposide, followed by radiotherapy. Follow-up MRI at up to 26 months showed no contrast-enhancing lesions but a mild T2 FLAIR hyperintensity adjacent to the resection cavity. Differential diagnosis of midbrain lesions can be challenging and should include glial tumors, primary central nervous system lymphoma, germ cell tumors, and metastasis. Accurate diagnosis requires adequate tissue sampling. In this report, we present a very rare case of a primary intra-axial germinoma of the midbrain which is biopsied via a transcollicular approach. This report is also unique as it provides the first surgical video of an open biopsy and the microscopic appearance of an intra-axial primary midbrain germinoma via a transcollicular approach.

Differentiation between germinoma and other pineal region tumors using diffusion-and susceptibility-weighted MRI.

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.

Intracranial germinoma in the lateral ventricle with polydipsia and polyuria: a case report and literature review.

Central nervous system germ cell tumors (CNSGCTs) are rare neoplasms which usually develop in the midline structures. They are occasionally involved in off-midline structures of the brain. Here, we report an extremely rare case of an intracranial germinoma in the lateral ventricle. The patient was a 10-year-old boy with a 1-year history of polydipsia and polyuria. Brain magnetic resonance imaging (MRI) showed a relatively homogeneously enhancing lesion in the lateral ventricle, and the posterior pituitary gland was not hyperintense on T1-weighted imaging. Subependymoma was suspected, and tumor removal operation was performed; however, because the intraoperative pathological investigation revealed germinoma, we could only perform partial removal of the tumor. Postoperative histology also confirmed germinoma. Then, the patient received chemotherapy, followed by radiation therapy. MRI showed no recurrence for 6 years after treatment. Intracranial germinoma in the lateral ventricle is extremely rare. The diagnosis is occasionally challenging, especially when the tumors are located in atypical locations. This paper presents a literature review of previously described CNSGCTs of the lateral ventricle to improve awareness of CNSGCTs in atypical locations. We also consider the relationship between imaging findings and clinical manifestations.

A comprehensive machine-learning model applied to MRI to classify germinomas of the pineal region.

BACKGROUND: Pineal region tumors (PRTs) are highly histologically heterogeneous. Germinoma is the most common PRT and is treatable with radiotherapy and chemotherapy. A non-invasive system that helps identify germinoma in the pineal region could reduce lab exams and traumatic therapies. METHODS: In this retrospective study, 122 patients with histologically confirmed PRTs and pre-operative multi-modal MR images were included. Radiomics features were extracted from different ROIs and image sequences separately. A computational framework that combines a few classification and feature selection algorithms were used to predict histology with radiomics features and demographics. We systemically benchmarked performance of models with feature matrices from all possible combinations of ROIs and image sequences. The Area under the ROC Curve (AUC) was then used to evaluate model performance. RESULTS: Models with demographics and radiomics features outperform radiomics-only or demographics-only models. The best demographical-radiomics model reached the highest AUC of 0.88 (CI95%: 0.81-0.96). Through the comprehensive evaluation of possible sequence combinations in the differential diagnosis of pineal tumor, T1 and T2 emerged as the most informative sequences for the task. There is imbalanced usage of feature classes as we analyze their proportion in all models. CONCLUSIONS: The demographical-radiomics model can accurately and efficiently identify germinomas in the pineal region. The preference for MRI sequences, radiomics feature classes, features selection and classification algorithms provide a valuable reference for future attempts at developing classifiers on medical images.

Pediatric pineal region masses: a single-center experience over 25 years.

PURPOSE: Pineal region tumors (PRT) represent less than 1% of brain neoplasms. The rare and heterogeneous nature of these tumors is reflected in the variety of treatment modalities employed. METHODS: A single-center retrospective review of all pediatric patients with pineal region tumors between November 1996 and June 2021 was performed. Fifty-six cases of pineal tumors were reviewed for age and symptoms upon presentation, diagnostic methods, imaging characteristics, histological classification, treatment modalities, recurrence, and mortality rates. RESULTS: The average age at diagnosis was 11.3 years. The majority of patients were male (82.1%) and Caucasian (73.2%). The most common presenting symptoms were headache (n = 38, 67.9%) and visual problems (n = 34, 60.7%). Hydrocephalus was present in 49 patients (87.5%). Germinoma (n = 20, 35.7%) and non-germinomatous germ cell tumor (NGGCT) (n = 17, 30.4%) were the most common tumors. Chemotherapy was employed for 54 patients (96.4%), radiation for 49 (87.5%), and surgical resection for 14 (25.0%). The average duration of treatment was 5.9 months. Progression-free survival was 74.4% at 5 years and 72.0% at 10 years. Overall survival was 85.7% at 5 years and 77.1% at 10 years. CONCLUSION: Treatment of pineal region tumors must be targeted to each patient based on presentation, subtype, presence of hydrocephalus, and extent of disease. Upfront surgical resection is usually not indicated. As advances in oncological care proceed, treatment modalities may continue to improve in efficacy.

A GIANT GERMINOMA MIMICS HIGH-GRADE GLIOMA: A RARE FORM OF THALAMIC REGION TUMOR.

A fourteen-year-old boy initially presented with weakness in the right extremity, worsening in the last three months with stiffness and convulsions in his right extremity. Magnetic resonance imaging of the brain revealed an intra-axial tumor measuring 8.3x7.3x6.8 cm, leading to obstructive hydrocephalus. The patient's condition suddenly worsened with decreased consciousness, and then emergency surgery was performed for tumor resection and external ventricular drainage before switching to a ventriculoperitoneal shunt on the fifth day after surgery. Histopathological examination revealed a germinoma, which is rare in the thalamic region. The patient responded well to radiation therapy after surgery. Ectopic GCT may be difficult to differentiate on radiological examination alone. The current case was initially diagnosed as a high-grade glioma based on radiological findings. A definite diagnosis can be made only after a histopathological examination, which requires a tissue sample. Therefore, many tumors are surgically excised for biopsy purposes A good preoperative examination is very important to determine the approach to patient management. Furthermore, radiotherapy is mandatory for germinoma because of its radiosensitivity.

Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission.

OBJECTIVE: To evaluate the pathomechanism of the recurrence of intracranial germinoma after complete response and to confirm the association of the initial magnetic resonance imaging and therapeutic factors with recurrence. METHODS: This study included patients who were followed up for ≥5 years and who were treated in our hospital from 1980 to 2021. Those with germinoma and germinoma with syncytiotrophoblastic giant cells were diagnosed pathologically. Data were categorizedbased on "gender," "single region," "intraventricular dissemination at the initial diagnosis," "hydrocephalus," "types of radiation therapy (RT)," and "chemotherapy." Fisher's exact probability test was used to assess differences between the no recurrence and recurrence groups. RESULTS: Among 43 patients, 34 had no recurrence, 5 had delayed recurrence (≥60 months), and 4 had early recurrence (<60 months). Follow-up periods were 143.5 (60-380), 198 (88-222), and 132.5 (75-291) months for the no recurrence, delayed recurrence, and early recurrence groups, respectively. Five patients with delayed recurrence showed 3 intracranial lesions and 2 spinal lesions. Four patients with early recurrence showed 3 intracranial lesions and 1 spinal lesion. Differences in delayed recurrences (focal RT vs. RT including whole-ventricle system; P = 0.0491) were significant in Fisher's exact test. CONCLUSIONS: RT including the whole-ventricle system reduces delayed craniospinal relapses including dissemination, local, and distant recurrences even ≥5 years after complete response in patients with primary central nervous system germinoma.

Diencephalic syndrome in a female child due to intracranial germinoma: a case report.

INTRODUCTION: Diencephalic syndrome (DS) is a rare syndrome with failure to thrive (FTT) as the primary manifestation, which is often associated with astrocytoma or glioma and rarely caused by germinoma. To our knowledge, there are no reports of female patients presenting with DS secondary to germinoma. CASE REPORT: we report a case (an 11-year-old girl) of diencephalic syndrome presenting with FTT. She was diagnosed with severe malnutrition in the local hospital two years before admission and still did not show normal development after long-term nutritional support. Finally, after ruling out increased metabolism, inadequate caloric intake, and nutrient absorption, intracranial MRI showed a space-occupying lesion in the suprasellar cisterna-hypothalamus area. After excluding other causes of FTT, a biopsy was performed for pathological examination and demonstrated a germinoma. An excellent therapeutic effect was achieved during the three-month follow-up after radiotherapy. CONCLUSION: This case reminds us that intracranial tumors should be considered an indispensable etiology for patients with suspicious FTT, and early diagnosis and intervention may achieve a good prognosis.

Pineal germinoma in a young adult: A case report.

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.

Diagnostic radiation-induced regression of a metastatic primary intracranial germinoma: a case report.

Pineal region germinomas are sensitive to radiotherapy. Standard neurosurgical management involves obtaining a tissue biopsy and to relieve the often accompanying obstructive hydrocephalus. We present a patient with a suspected hyper-radiosensitive metastatic primary intracranial germinoma where computed tomography scanning resulted in tumor regression before radiotherapy could be administered.

Unusual presentation of epilepsy of germinoma located in the frontal-lobe: case report and literature review.

Germinoma is rare in peripheral lobar locations in the brain, with only 10 cases of primary frontal lobe germinoma having been reported in the previous literature. Epilepsy is a rare manifestation of germinomas. We describe an unusual case of a primary frontal germinoma in a 21-year-old man who presented with epilepsy. A presumptive diagnosis of abscess or cystic glioma was made, and then, we performed microsurgery under magnetic resonance imaging (MRI) neuronavigation guidance. Postoperative histopathologic examination identified the tumour as a rare germinoma. Subsequently, adjuvant radiotherapy and chemotherapy programmes were adopted in the present case, and there were no recurrence and postoperative seizure symptoms observed in the follow-up 6 months after operation.

[Lesion of optic nerves and chiasm following bifocal germinoma recurrence]. / Porazhenie zritel'nykh nervov i khiazmy kak proyavlenie retsidiva bifokal'noi germinomy.

The authors report a patient with recurrent bifocal germinoma of the optical nerves and chiasm after previous combined treatment. The tumor resulted progressive visual acuity loss despite subsequent therapy (glucocorticoid therapy, chemo- and radiotherapy). Differential diagnosis between tumor progression and consequences of radiotherapy was complicated by MRI negative pattern. Subsequent development of the process, signs of anterior visual pathway damage and tumor spread throughout the ventricular system and subarachnoid spaces according to neuroimaging data indicated recurrence of disease.

Germinoma en un paciente con emaciación y retraso de crecimiento. A propósito de un caso / Germinoma in a patient with emaciation and growth retardation. Case report

Los tumores del sistema nervioso central representan la segunda enfermedad oncológica más habitual en niños y adolescentes. Entre los tumores intracraneales, los de células germinales son infrecuentes. Los síntomas que desencadenan son cefalea, náuseas, vómitos, déficits hormonales, alteraciones visuales, pérdida de peso, pobre crecimiento y pubertad precoz. Menos frecuentemente, producen trastornos del movimiento o psiquiátricos. Algunos de estos tumores pueden ser asintomáticos un largo período, lo que desencadena un diagnóstico tardío.Se presenta a una paciente femenina de 14 años con pérdida de peso y falla del crecimiento, con diagnóstico erróneo de trastorno de la conducta alimentaria. Tras estudios pertinentes, se arribó al diagnóstico de germinoma del sistema nervioso central. Al ser esta patología infrecuente y de presentación variable, requiere alto sentido de alerta por parte de la familia involucrada y del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento

Central nervous system tumors are the second most frequent oncological disease among children and teenagers. Among the intracranial tumors, the germ cells ones are infrequent. The symptoms they cause are headaches, nausea and vomiting, hormonal deficits, visual disturbances, weight loss, poor growth and early puberty. Less frequently, they produce movement or psychiatric disorders. Some of these tumors can be asymptomatic for a long period leading to a late diagnosis.The case of a 14-year-old female patient is presented. She showed weight loss and growth failure, with wrong diagnosis of eating disorder. After proper study methods, we arrived to central nervous system germinoma diagnosis. Because this pathology is rare and has a variable form of presentation, it requires that the family involved and the health team to be alert, to avoid delays in diagnosis and treatment.