Primary Intracranial Germ Cell Tumors Research Articles

Treatment Course and Outcomes of Intracranial Teratomas in Pediatric Patients: A Retrospective 15-Year Case Series Study

Introduction: There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution. Methods: Authors reviewed a comprehensive pathology database at Stanford’s Lucile Packard Children’s Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed. Results: Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities. Discussion/Conclusion: We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

OCT3/4 is a potential immunohistochemical biomarker for diagnosis and prognosis of primary intracranial germ cell tumors: a systematic review and meta-analysis.

Intracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs. Meta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs. Nine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results. This study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis.

Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience

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. 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. 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%. 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.

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

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. 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. 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. 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.

GCT-05. Multi-institutional analysis of treatment modalities in metastatic germinoma in children

Abstract BACKGROUND: Primary intracranial germ cell tumors (GCTs) are rare heterogeneous tumors, with germinoma accounting for two-thirds of cases. Neoadjuvant chemotherapy with response-based reduced radiotherapy dose and field has become the standard management of localized CNS germinomas, however, treatment of primary metastatic disease has remained controversial. Furthermore, there is limited published research on the use of neoadjuvant chemotherapy in primary metastatic germinoma. METHODS: We performed a retrospective multi-institutional data collection and analysis of patients diagnosed with metastatic germinoma since 2000 to assess the overall survival (OS) and event-free survival (EFS) of the different treatment modalities administered. RESULTS: We identified 78 patients with germinoma, in two tertiary care centers, of which nine patients (11.5%; eight males) had metastatic disease. The median age at presentation was 13.3 years. All patients had a biopsy at presentation confirming the diagnosis. Three patients had positive CSF cytology (M1). Six patients received craniospinal irradiation (CSI) with boost to primary and metastatic sites, of which five patients received total CSI dose of 24 Gy, while the dose was unknown for one patient. One patient required one cycle of chemotherapy prior to CSI due to worsening visual changes, which subsequently resolved. One patient received two cycles followed by whole ventricular irradiation (WVI) of 23.4 Gy with a boost to the primary bed. One patient received WVI without neoadjuvant chemotherapy. One patient developed anoxic brain injury and only received chemotherapy. He died of recurrent progressive disease 15 months post-diagnosis. The median follow-up time was 77.5 months (range 15-130.5 months), with an OS of 88.9%. Further multi-institutional data collection and analysis is underway and will be presented at the meeting. CONCLUSION: We anticipate our results may elucidate the role of neoadjuvant chemotherapy in the treatment of metastatic germinoma, and whether when combined with lower CSI doses did not compromise EFS/OS.

Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: A rare case of hypopituitarism

Germinomas represent the most frequent tumor type in the pineal region and the synchronous involvement in the suprasellar region, known as bifocal disease, is increasingly recognized. Synchronous primary intracranial germ cell tumors are rare. Among all germ cell tumors, only 5–10% are found as synchronous lesions in pineal and suprasellar regions. They are also known by the entity “double mid-line atypical teratoma.” An adolescent male with phenotypic features of delayed puberty presents with features of hypopituitarism and raised intracranial tension. He was subsequently treated with hormonal replacement and diagnosed as a case of bifocal intracranial germinoma. Interestingly, he was lacking features of diabetes insipidus, which is a conspicuous feature in other reported cases. He was treated further with ventricular shunting followed by cranio spinal irradiation. The complex nature of endocrinological manifestations in bifocal intracranial germinoma will enriches our knowledge toward a potentially curable neuroendocrinological situation.

A pragmatic diagnostic approach to primary intracranial germ cell tumors and their treatment outcomes.

Background:Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity.Methods:Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs).Results:At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas.Conclusion:A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

GERM-04. PRIMARY INTRACRANIAL GERM CELL TUMORS ARE MORE PREVALENT AMONG PEDIATRIC PATIENTS OF ASIAN/PACIFIC ISLANDER RACE/ETHNICITY IN THE UNITED STATES

IntroductionPrimary intracranial germ cell tumors (GCTs) appear to be more prevalent among pediatric patients in eastern Asia than in the U.S. Herein we use cancer registry data to evaluate whether GCT prevalence differs by race/ethnicity among U.S. pediatric patients. MethodsPediatric patients (age≤14) presenting between 2004–2017 with a primary intracranial GCT were identified by ICD-O-3 histological and topographical coding from the National Cancer Database (comprising >70% of cancers newly-diagnosed cancers in the U.S.), and categorized by NICHD age stages. Patients’ age, sex, race/ethnicity, and overall survival, and tumor location and size were evaluated. Results889 pediatric patients with primary intracranial GCTs were identified, which were overwhelmingly male (64.8%) and pure germinomas (64.0%). Non-germinomatous (24.5%) and mixed (11.5%) tumor types were in the minority. Overall, primary GCTs comprised 4.9% of intracranial tumors in pediatric males and 2.9% of intracranial tumors in pediatric females. Asian/Pacific Islander pediatric patients in the U.S. had a notably higher prevalence of GCTs: among Asian/Pacific Islander males, 10.6% of all brain tumors were GCTs, compared to only 4.5% in White non-Hispanic patients, 2.8% in Black non-Hispanic patients, and 6.0% in Hispanic patients. Despite the much lower prevalence of GCTs among female patients overall, this predominance also persisted for Asian/Pacific Islander females, among whom 7.5% of brain tumors were GCTs, compared to only 2.5% in White non-Hispanic patients, 2.4% in Black non-Hispanic patients, and 4.1% in Hispanic patients. Overall, 9.4% of pediatric primary intracranial GCTs occurred in patients of Asian/Pacific Islander race/ethnicity, in contrast to 4.0% of diffuse astrocytic/oligodendroglial tumors, 2.8% of other astrocytic tumors, or 4.6% of embryonal tumors. ConclusionsPrimary intracranial GCTs affect a substantially larger proportion of both male and female pediatric patients of Asian/Pacific Islander race/ethnicity in the United States.

NQPC-02 Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study

Purpose: In the present study, we performed a retrospective review of patients receiving carboplatin based chemotherapy followed by radiotherapy for newly diagnosed primary intracranial germ cell tumors. In order to identify an optimal germ cell tumor treatment strategy, we evaluated treatment outcomes and toxicity and compliance.Methodology: This study included 110 consecutive patients with newly diagnosed primary intracranial germ cell tumors. The drug doses and administration schedule of carboplatin-etoposide (CARB-VP) were as follows: carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 on days 1 to 3). Ifosfamide-carboplatin-etoposide (ICE) treatment comprised ifosfamide (1500 mg/m2 daily for 3 days), carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 daily for 3 days). Patients with germinomatous germ cell tumors (pure germinoma or germinoma with STGC) basically receive three cycles of CARB-VP and a total dose of 30Gy whole ventricular radiotherapy. We delivered combination therapy consisting of combined ICE chemotherapy and craniospinal irradiation followed by the complete resection of the residual tumor for nongerminomatous malignant germ cell tumors.Results: The median follow-up time was 11.0 years (range, 0.5–37.8 years). The 5-year total survival rates of germinomatous and nongerminomatous germ cell tumors were 97.2% and 66.7%, respectively. The 10-year and 20-year total survival rates of germinomatous germ cell tumors were 95.7% and 90.0%, respectively. Adverse events related to carboplatin based chemotherapy are not detected. Furthermore, no treatment-related deaths were observed.Conclusions: Our treatment with surgery, carboplatin based chemotherapy followed by radiotherapy is effective in treating primary intracranial germ cell tumors, especially in germinomatous group.

Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study.

The current study aimed to evaluate the treatment outcomes and toxicities of patients with intracranial germ cell tumors (GCTs). This study retrospectively included 110 consecutive patients (70 patients in the germinomatous group and 40 patients in the nongerminomatous GCT [NGGCT] groups) receiving surgery, platinum-based chemotherapy, and radiotherapy for newly diagnosed primary intracranial GCTs. In the authors' protocol, patients with GCTs were further divided into the following four groups: the germinomatous group and the NGGCT groups (mature teratoma, intermediate prognosis, or poor prognosis). The median overall survival (OS) and progression-free survival (PFS) rates of the patients in the germinomatous group were significantly higher than those in the NGGCT group (p < 0.001). The 5-, 10-, and 20-year OS rates in the germinomatous group were 97.1%, 95.7%, and 93.2%, respectively, with a median follow-up of 11.0 years. On the contrary, the 5-, 10-, and 20-year OS rates in the NGGCT group were 67.3%, 63.4%, and 55.4%, respectively. The 5-, 10-, and 20-year PFS rates were 91.4%, 86.6%, and 86.6%, respectively, in the germinomatous group, whereas those of the NGGCT group were approximately 67.4%, 60.2%, and 53.5%, respectively. Based on the four types of classification in our study, the 5-, 10-, and 20-year OS rates in the NGGCT intermediate prognosis group were 78.9%, 71.8%, and 53.8%, respectively. On the contrary, the 3- and 5-year OS rates in the NGGCT poor prognosis group were 42.9% and 34.3%, respectively. Moreover, toxicities with the treatment of intracranial GCTs were found to be tolerable in the present study population. The multivariate survival models for OS in the NGGCT intermediate prognosis and poor prognosis groups demonstrated that only the alpha-fetoprotein status was significantly associated with worsened OS (HR 3.88, 95% CI 1.29-11.66; p = 0.02). The authors found that platinum-based chemotherapy and radiotherapy result in favorable survival outcomes in patients with germinomatous GCTs. Clinical outcomes were still unfavorable in the NGGCT intermediate prognosis and poor prognosis groups; therefore, a new protocol that increases the survival rate of patients belonging in both groups should be considered.

Primary intracranial germ cell tumors in children 36-year experience of a single center.

Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%-3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT. All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively. We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12-228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors. Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries.

Treatment and survival of primary intracranial germ cell tumors: a population-based study using SEER database.

Primary intracranial germ cell tumors are rare neoplasms derived from gonadal cells. They are categorized as germinoma, non-germinomatous germ cell tumor (NGCCT), or teratoma, with the latter two sparking controversy regarding the role of different treatment strategies. We provide the largest multicenter analysis of treatment outcomes for iGCTs to date. The Surveillance, Epidemiology, and End Result (SEER) database were used to record patient demographics, tumor, and treatment characteristics. Cox proportional hazards model and multiple comparisons for the Logrank test with Sidak correction was applied to compare the different treatment regimens and survival. 1043 iGCT cases were divided into three cohorts of Germinoma, Malignant Teratoma (MT), and NGGCT. The mean age was 17.7years for germinoma, 9.5years for MT, and 14.4years for NGGCT groups. Males comprised 77% of overall patient population. For Germinomas, both biopsy (hazard ratio [HR] = 4.6) and resection (HR = 14.1) had significantly worse survival outcomes compared to solo radiation therapy, with no difference between radiation and chemotherapy. For MT, no treatment combination had significantly different survival outcomes compared to resection alone. For NGGCTs, resection + chemotherapy + radiotherapy (HR = 0.012) and resection + chemotherapy (HR = 0.0049) had significantly better survival compared to resection alone. In germinomas, radiotherapy alone had superior survival outcomes compared to biopsy and resection, but no change in survival when compared to chemotherapy alone. Addition of radiotherapy or chemotherapy did not improve survival in MTs when compared to resection alone. Adding chemotherapy in NGGCT patients undergoing resection improved survival compared to resection alone.

RTHP-31. EMERGENCY RADIOTHERAPY IN INTRACRANIAL GERM CELL TUMORS (GCTS) PATIENTS WITH KPS≤ 40: ARETROSPECTIVE ANALYSIS OF 27 CASES

Abstract OBJECTIVES To evaluate the potential role of emergency radiotherapy in intracranial germ cell tumors GCTs) patients with KPS ≤ 40. METHODS A total of 27 primary intracranial germ cell tumors (GCTs) patients with KPS ≤ 40 between Jan 2007 and Dec 2018 were retrospectively evaluated. The median age at initial diagnosis was 15 years (range, 528 years). Among those, 11 patients were germinoma and 16 patients were nonseminomatous germ-cell tumors (NGGCTs). There were 9 solitary pineal, 5 suprasellar, 3 basal ganglia and 10 multifocal and disseminated tumors. All patients received emergency radiotherapy (2 Gy/fx/d). Prior to radiotherapy, 11 patients were manifested with hydrocephalus, 10 with hypopituitarism and 5 with intracranial tumo apoplexy. RESULTS The average follow up time was 44.4 months. The 5 year progression free survival rate and overall survival rate were 29.6% and 33.3%. The median overall survival time was 38 months. In particular, the median intracranial hypertension symptoms relief time was 2 days. The median KPS following radiotherapy was 80 comparing to 30 prior to radiotherapy (P &lt; 0.05). A significant improvement on KPS of 46.7±27.3 was observed in this study. CONCLUSION Emergency radiotherapy is implicated as a promising intervention for GCTs patients with elevated intracranial pressure (ICP). These advantages can be interpreted as direct cell killing effect and fast tumor shrinkage by ionizing radiation. However, to substantiate our findings, further investigations were highly warranted.

Surgical Role in Management of Intracranial Germ Cell Tumors in Pediatric Age Group

Introduction: Primary intracranial germ cell tumors (ICGCTs) are rare, histologically diverse, and diagnostically challenging tumors that are usually localized in the pineal and suprasellar regions of the brain. Advanced neurosurgical techniques such as neuroendoscopy and frameless stereotactic biopsy have made diagnosis of newly discovered cases of ICGCTs easier and safer. Material and methods: Seventeen patients with intracranial germ cell tumors operated upon between 2008 to 2012 at the Children's Cancer Hospital Egypt, were retrospectively reviewed and analyzed regarding the surgical decision, clinical outcome and surgical complications. Results: There were 9 cases of germinoma (53%), and 8 cases of non-germinomatous germ cell tumors (47%). Nine cases were in the pineal region, six in the suprasellar, and two in the thalamic region. Ten cases were operated upon initially by open surgery and frozen section with subtotal resection and seven cases were biopsied either endoscopically (3 cases) or by frameless guided stereotaxic (4 cases). Accurate pathology was achieved in all biopsied cases without major complications. In the germinoma group, the 4-year overall survival and progression free survival rate were 75% for both at a median follow up period of 26 (range 1 -50) months. For the non-germinomatous germ cell tumors group, the 4-year OS and PFS rates were 36.5% and 31.2% at a median follow up period of 11 (range 2-54) months, respectively. Conclusion: In cases of intracranial germ cell tumors with negative tumor markers the role of surgery is important in the establishment of proper histopathological diagnosis. However, in Non Germinomatous Germ Cell Tumors, further investigations should be done regarding the extent of resection owing to the poor long-term outcome.

GERM-02. IMMUNOHISTOCHEMICAL EVALUATION FOR THE PATHOGENESIS OF INTRACRANIAL GERM CELL TUMORS: EXPRESSION OF PLURIPOTENCY AND CELL DIFFERENTIATION MARKERS

Abstract INTRODUCTION: Primary intracranial germ cell tumors (iGCT) are rare neoplasms that occur in children and adolescents. This study examined both the pathogenesis and the origin of these tumors, as it has been hypothesized that they originate from a totipotent primordial germ cell. MATERIALS AND METHODS: We applied recent knowledge from gonadal germ cell tumors and analyzed expression of a wide panel of stem cell-related proteins(C-KIT, OCT-3/4 (POU5F1), NANOG, SOX2, CD30 and PLAP). Expression shown by immunohistochemistry was analyzed in 12 children and young adults with iGCT, contributing to a careful description of these unusual tumors and adding to the understanding of pathogenesis. RESULTS: Immunohistochemistry showed 5/5 positive in Oct3/4, 5/5 in NANOG, 9/9 in C-KIT and 1/5 in SOX2. All cases that showed positive staining in Oct3/4 or NANOG indicated that the tumors contained germinoma or embryonal carcinoma component. Immunohistochemistry revealed that stem cell related proteins were highly expressed in iGCT, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. CONCLUSION: The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumors strongly suggests that these tumors are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells. In addition, these data can be applied to stratify iGCT for treatment strategy in order to provide good survival rate and good functional outcome.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

The combination of a bifocal germinoma and arteriovenous malformations of the brain in children. Clinical observation and review of the literature

Primary intracranial germ cell tumors are rare heterogeneous group of neoplasms presented several histological types with different biological profile and response to therapy. Pure germinomas make up no more than 5 % of malignant tumors of the central nervous system in children, bifocal germinomas account for only 5–10 % of all germinomas. Radiotherapy and chemotherapy are usually used in intracranial germ cell tumors. The choice of initial therapy options is dependent on the histological variants of tumors, and the prevalence of the process (M-stage). Vascular malformations of the brain is rare in childhood, in a large proportion of cases, which is a random finding and can significantly affect the treatment policy in the presence of a brain disease (eg, neoplasia). We present a rare case of a combination of clinical bifocal germinomas and arteriovenous malformations of the brain in a boy 13 years old

Treatment of primary intracranial germ cell tumors: Single center experience with 42 clinically diagnosed cases.

Background and ObjectivePrimary intracranial germ cell tumors (GCTs) are a class of heterogeneous tumors. Surgery can quickly relieve tumor compression and provide histological diagnosis. It is very difficult to treat some patients who are unable to be pathologically diagnosed. We aimed to analyze clinically diagnosed GCTs patients.MethodsPatients clinically diagnosed as primary intracranial GCTs were included in this study.ResultsFrom 2002 to 2015, 42 patients clinically diagnosed with primary intracranial GCTs received chemotherapy and/or radiotherapy. Patients were assigned to diagnostic chemotherapy group (25 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 85.8%, 75.0% and 63.6%, respectively. There were no statistically significant difference (p value = 0.44). Patients were assigned to the group (30 cases) with secretory tumors and the group (12 cases) with non-secretory tumors based on their levels of tumor makers. The 5- year survival rates were 80.7% and 68.6%, respectively. There were no statistically significant difference (p value = 0.49).The major adverse reactions were grade III - IV bone marrow suppression with an incidence of 35.2% and grade II- III nausea/vomiting with an incidence of 45.8%.ConclusionSurgical removal of tumor or biopsy is recognized as the most accurate method to determine the pathological property of tumor. But for some patients who can not be pathologically diagnosed, they can receive comprehensive treatments such as chemotherapy combined with radiotherapy, and some of them can still have good responses.

Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature.

Primary intracranial germ cell tumors are rare, representing less than 5% of all central nervous system tumors. Overall, the majority of germ cell tumors are germinomas and approximately one-third are non-germinomatous germ cell tumors (NGGCT), which include teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or mixed malignant germ cell tumor. Germ cell tumors may secrete detectable levels of proteins into the blood and/or cerebrospinal fluid, and these proteins can be used for diagnostic purposes or to monitor tumor recurrence. Germinomas have long been known to be highly curable with radiation therapy alone. However, many late effects of whole brain or craniospinal irradiation have been well documented. Strategies have been developed to reduce the dose and volume of radiation therapy, often in combination with chemotherapy. In contrast, patients with NGGCT have a poorer prognosis, with about 60% cured with multimodality chemoradiation. There are no standard approaches for relapsed germ cell tumors. Options may be limited by prior treatment. Radiation therapy has been utilized alone or in combination with chemotherapy or high-dose chemotherapy and transplant. We discuss two cases and review options for frameless radiosurgery or fractionated radiotherapy.

Primary intracranial germ cell tumors: A single institution experience from a South Indian tertiary cancer center

Background: Intracranial germ cell tumors (ICGCTs) are rare tumors seen in the pineal and suprasellar regions. The World Health Organization has classified ICGCTs into germinoma and nongerminomatous GCT (NGGCT). Germinoma is radiosensitive and has excellent survival rate. Patients with NGGCTs are less sensitive to radiotherapy and have less favorable outcome. Objective: This retrospective observational study was carried out to determine the clinical features, treatment, and outcome of patients diagnosed as ICGCT from June 2006 to June 2014.Materials and Methods: Patients' medical records were reviewed for information regarding age, gender, presenting features, treatment instituted, complications, and treatment outcome. Results: Seven patients with ICGCT were studied. Their age ranged from 4 to 24 years, with median age being 13 years. All of them were male. Four patients had germinoma and three had mixed NGGCT. Four patients had pineal region mass, two patients had suprasellar mass, and one patient had bifocal disease with both pineal and suprasellar involvements. Following surgical debulking or ventriculoperitoneal shunt, patients received radiation and chemotherapy. One patient of germinoma and another patient of NGGCT died due to febrile neutropenia/sepsis. The overall survival was 4 years for patients with both germinoma and NGGCT. Conclusions: ICGCTs are rare tumors seen in the second decade of life, with male preponderance. With judicious use of chemotherapy and radiotherapy, germinoma has excellent survival outcome. The outcome of NGGCT can be improved with multimodality treatment.