Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.     

Pediatric central nervous system germ cell tumors: a review

Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or beta-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation. Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates >90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.     

Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors.

PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs). PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR. RESULTS: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC. CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.     

Keimzelltumoren bei Kindern und Jugendlichen

Germ cell tumors (GCT) in children and adolescents are heterogeneous and develop from totipotent primordial germ cells. Their clinical behaviour correlates with histologic differentiation and tumor biology and varies between benign and highly aggressive and metastatic tumors. Considering the low incidence and histologic heterogeneity of GCTs, it is necessary to obtain reference histopathologic evaluation. Histologic differentiation, clinical course and response to chemotherapy strongly correlate with production of the tumor markers AFP and β-HCG. Radiographic assessment has to consider areas of potential local spread and characteristic metastatic sites such as the lymph nodes for extracranial sites and the central nervous system for germ cell tumors of the brain. Therapy of malignant GCT follows a multimodal approach. Radiotherapy plays a major role as consolidation treatment in CNS GCTs. Local tumor control is of utmost importance. The prognosis of malignant GCTs is favourable if patients are treated according to current standards. The future aim is optimised therapy stratification based on clinical and molecular-biological parameters.     

Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990-1994

The Central Brain Tumor Registry of the United States (CBTRUS) obtained 5 years of incidence data (1990-1994)--including reports on all primary brain and CNS tumors--from 11 collaborating state cancer registries. Data were available for 20,765 tumors located in the brain, meninges, and other CNS sites, including the pituitary and pineal glands. The average annual incidence was estimated at 11.5 cases per 100,000 person-years. The higher incidence of tumors in male patients (12.1 per 100,000 person-years) than in female patients (11.0 per 100,000 person-years) was statistically significant (P < 0.05); the higher incidence in whites (11.6 per 100,000 person-years) compared with blacks (7.8 per 100,000 person-years) was statistically significant (P < 0.05). The most frequently reported histologies were meningiomas (24.0%) and glioblastomas (22.6%). Higher rates for glioblastomas, anaplastic astrocytomas, oligodendrogliomas, anaplastic oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas not otherwise specified, medulloblastomas, lymphomas, and germ cell tumors in male than in female patients were statistically significant (P < 0.05), with relative risks (RR) ranging from 1.3 to 3.4. Meningiomas were the only tumors with a significant excess in females (RR = 0.5). We noted higher occurrence rates in whites than in blacks for the following histologies: diffuse astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas NOS, medulloblastomas, nerve sheath tumors, hemangioblastomas, and germ cell tumors, with RRs ranging from 1.5 to 3.4. Racial differences in occurrence rates were not observed for predominately benign meningiomas or pituitary tumors. This study represents the largest compilation of data on primary brain and CNS tumors in the United States. Standard reporting definitions and practices must be universally adopted to improve the quality and use of cancer registry data.     

Germ cell tumors in children and adolescents in Finland: trends over 1969–2008

Purpose

Malignant germ cell tumors (GCTs) are a heterogeneous group of neoplasms putatively originating from the primordial germ cell. In adults, an increasing incidence of GCTs, particularly testicular tumors, has been reported in recent decades. However, population-based evidence in children and adolescents remains limited. We investigated the incidence of malignant GCTs diagnosed in childhood or adolescence, using population-based nationwide data from Finland.

Methods

We obtained information from the Finnish Cancer Registry on all malignant GCTs registered in 1969–2008 in children or adolescents aged 0–19 years. Data on tumor location, histology, stage, and survival were collected. Age-standardized incidence and survival rates were calculated.

Results

A total of 334 cases of malignant GCT were identified. Their proportion among all malignant tumors among 0- to 19-year-olds increased from 3 to 9.7 % in boys with time, but remained stable in girls (3 %). The overall incidence rate was 0.6 per 100,000 (0.8 in boys and 0.4 in girls), and differed significantly between the age groups. A significant increase in the incidence of testicular GCTs was seen in boys in the age group of 15–19 years.

Conclusions

Although malignant GCTs are rare, their relative frequency in children and adolescents has increased during recent decades, the change being mainly due to an increasing frequency of the testicular tumors among teenagers. The causes of the increase remain unknown, but environmental exposures are likely to be involved.     

Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003

BACKGROUND:

It is believed that gonadal and extragonadal germ cell tumors (GCTs) arise from primordial germ cells and may have similar etiopathogenesis. Unlike testicular GCTs, there has been limited comprehensive population‐based analysis of ovarian and extragonadal GCTs.

METHODS:

All malignant GCTs and all central nervous system (CNS) GCTs with benign and uncertain behavior that were registered in England in the age group 0 to 84 years from 1979 to 2003 were included in the current study. Incidence rates were calculated and adjusted to the world standard population.

RESULTS:

There were 33,364 GCTs (92.5% testes, 3.9% ovary, 3.2% extragonadal) in individuals aged 0 to 84 years. The CNS was the most common extragonadal site. An initial peak in incidence at ages 0 to 4 years of nongerminomas was observed at all sites except ovary. Second incidence peaks between ages 10 to 39 years that were more marked among males also were observed at all sites. The ages at these incidence peaks varied by site and were 10 to 14 years (CNS), 15 to 19 years (ovary), 25 to 29 years (other extragonadal sites), and 30 to 34 years (testes). A statistically significant increase in incidence over time was observed in germinomas (testes, CNS) and nongerminomas (testes, ovary).

CONCLUSIONS:

The age‐incidence patterns observed suggested a common initiation of GCTs in embryonic/fetal life with variable rates of tumor progression as a result of subsequent events that may be site specific. The authors concluded that future genetic studies should consider GCTs from all sites to enable a better understanding of their etiology. Cancer 2012. © 2012 American Cancer Society.     

Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas

Background

Pediatric and young adult central nervous system (CNS) germinomas have favorable cure rates. However, long-term follow-up data are limited because of the rarity of this tumor. We report the long-term overall survival (OS) and causes of late mortality for these patients.

Methods

Data between 1973 and 2005 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Kaplan Meier survival analysis was performed on 5-year survivors of childhood CNS germinomatous germ cell tumors (GGCTs) and nongerminomatous germ cell tumors (NGGCTs). Standardized mortality ratios (SMRs) were calculated using US population data to compare observed versus expected all-cause death and death from stroke. Cumulative incidence was calculated using a competing risk model.

Results

Four hundred five GGCTs and 94 NGGCTs cases were eligible. OS at 20 and 30 years for GGCTs was 84.1% and 61.9%, respectively, and was 86.7% for NGGCTs at both time points. Five-year survivors of GGCTs and NGGCTs experienced a 10-fold increase in mortality risk compared with their peers (SMR, 10.41; 95% confidence interval [CI], 7.71–13.76 vs SMR, 10.39;95% CI, 4.83–19.73, respectively). Five-year survivors GGCTs also experienced a nearly 59-fold increase in risk of death from stroke (SMR, 58.93; 95% CI, 18.72–142.10). At 25 years, the cumulative incidence of death due to cancer and subsequent malignancy was 16% and 6.0%, respectively.

Conclusion

Although CNS germinomas have favorable cure rates, late recurrences, subsequent malignancies, and stroke significantly affect long-term survival. Close attention to long-term follow-up with assessment of stroke risk factors is recommended.     

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BackgroundThe Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed.MethodsA questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan.ResultsFifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them.ConclusionAll patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.     

Descriptive epidemiology of vestibular schwannomas

Vestibular schwannomas, commonly termed acoustic neuromas, arise from the vestibular branch of the eighth cranial nerve (acoustic nerve) and are benign, slow-growing brain tumors that negatively impact patient quality of life. They are thought to account for the majority of intracranial nerve sheath tumors. To describe incidence rate patterns and trends of primary nerve sheath tumors of the brain/CNS and the subset of vestibular schwannomas in two population-based incidence registries, data were obtained from 11 Central Brain Tumor Registry of the United States (CBTRUS) collaborating state registries and the Los Angeles County Cancer Surveillance Program (LACCSP) (1975-1998). Average annual incidence rates were tabulated by age, gender, race, year, and region and were age-adjusted to the year 2000 U.S. standard population. Multiplicative Poisson regression models were used to compare trends in primary nerve sheath tumors of the brain/CNS overall and in subgroups, including vestibular schwannomas, controlling for age, gender, race, microscopic confirmation, and region. Joinpoint regression analysis was used to identify any sharp changes in incidence over time. The overall incidence of primary nerve sheath tumors of the brain/CNS was 1.1 per 100,000 person-years (CBTRUS, 1995-1999 and LACCSP, 1995-1998). The incidence of vestibular schwannomas was similar for both data sets: 0.6 per 100,000 person-years (CBTRUS, 1995-1999) and 0.8 per 100,000 person-years (LACCSP, 1995-1998). Moreover, the incidence of primary nerve sheath tumors of the brain/CNS overall (CBTRUS, 1985-1999 and LACCSP, 1975-1998) and of vestibular schwannomas (CBTRUS, 1992-1999 and LACCSP, 1992-1998) increased over time. However, the incidence of benign schwannomas in sites other than the acoustic nerve either decreased (CBTRUS, 1992-1999) or experienced no significant change (LACCSP, 1992-1998). While improvements in diagnosis and reporting may explain some of these trends, further consideration of potential etiologic factors may be warranted.     

Incidence of intracranial germ cell tumors by race in the United States, 1992–2010

Little is known about the etiology of intracranial germ cell tumors (iGCTs), although international incidence data suggest that the highest incidence rates occur in Asian countries. In this analysis, we used 1992–2010 data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program to determine whether rates of iGCT were also high in Asian/Pacific Islanders living in the United States. Frequencies, incidence rates and survival rates were evaluated for the entire cohort and for demographic subgroups based on sex, age category (0–9 and 10–29 years), race (white, black, and Asian/Pacific Islander), and tumor location (pineal gland vs. other) as sample size permitted. Analyses were conducted using SEER*Stat 8.1.2. We observed a significantly higher incidence rate of iGCT in Asian/Pacific Islanders compared with whites (RR = 2.05, 95 % CI 1.57–2.64, RR = 3.04, 95 % CI 1.75–5.12 for males and females, respectively) in the 10–29 year age group. This difference was observed for tumors located both in the pineal gland and for tumors in other locations. Five-year relative survival differed by demographic and tumor characteristics, although these differences were not observed in comparisons limited to cases treated with radiation. Increased incidence rates of iGCT in individuals of Asian descent in the SEER registry are in agreement with data from the International Agency for Research on Cancer, where Japan and Singapore were among the countries with highest incidence. The increased incidence in individuals of Asian ancestry in the United States suggests that underlying genetic susceptibility may play a role in the etiology of iGCT.     

Trends in childhood brain tumor incidence, 1973–2009

In the mid-1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due. We used Surveillance, Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site. The incidence of CBT remained stable from 1987 to 2009 [annual percent change (APC) = 0.10; 95 % confidence intervals (CI) ?0.39 to 0.61] with an AAIR for all CBT of 3.32 (95 % CI 3.22–3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983–1986), when the incidence of CBT increased by 53 % (APC = 14.06; 95 % CI 4.05–25.0). From 1983 to 1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981 to 2009, suggesting a change from a more general to more specific classification. After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.     

Epidemiology of germ cell tumors in Asia of pineal region tumor

A higher incidence of pineal region tumors in Asian countries compared to Western countries has been reported. In the Brain Tumor Registry of Japan (BTRJ), there were 38,273 primary brain tumors except those of unknown histology (1123 cases) registered in the period between 1984 and 1993, in which 807 pineal region tumors with 104 unknown histology were registered in BTRJ. Of these pineal region tumors, germ cell tumors had the highest frequency, 70.3%, followed by pineal parenchymal tumors, 12.0%; pineocytoma in 7.8% and pineoblastoma in 4.2%. Limited to germ cell tumors, germinoma was 68.0%, then teratoma including malignant teratoma, had the second high frequency, 14.7% in pineal region. While, data reported by Allaire et al. and Edwards et al. revealed that the incidence of germinoma was 88.6%, 52.4% of germ cell tumors in pineal region in France and in USA, respectively. Although number of cases is very small, it is suggested that the percentage of germinoma in germ cell tumors in the pineal region might be almost the same in Western countries as in Asian countries, and the occurrence of germ cell tumors in the pineal region was much higher than those in Asia. Age and gender distribution of pineal region tumors indicated that germ cell tumors and pineocytoma showed a high incidence in males and in children. Most of malignant pineal region tumors other than germinomas showed poor prognosis, but recent progress in surgical techniques and effective chemotherapy will improve the prognosis.     

Editor's choice: Years of potential life lost for brain and CNS tumors relative to other cancers in adults in the United States, 2010

Background

Years of potential life lost (YPLL) complement incidence and survival rates by measuring how much a patient''s life is likely to be shortened by his or her cancer. In this study, we examine the impact of death due to brain and other central nervous system (CNS) tumors compared to other common cancers in adults by investigating the YPLL of adults in the United States.

Methods

Mortality and life table data were obtained from the Centers for Disease Control and Prevention''s National Center for Health Statistics Vital Statistics Data for 2010. The study population included individuals aged 20 years or older at death who died from one of the selected cancers. YPLL was calculated by taking an individual''s age at death and finding the corresponding expected remaining years of life using life table data.

Results

The cancers with the greatest mean YPLL were other malignant CNS tumors (20.65), malignant brain tumors (19.93), and pancreatic cancer (15.13) for males and malignant brain tumors (20.31), breast cancer (18.78), and other malignant CNS tumors (18.36) for females. For both sexes, non-Hispanic whites had the lowest YPLL, followed by non-Hispanic blacks, and Hispanics.

Conclusion

Malignant brain and other CNS tumors have the greatest mean YPLL, thereby reflecting their short survival time post diagnosis. These findings will hopefully motivate more research into mitigating the impact of these debilitating tumors.     

Trends in the incidence of testicular germ cell tumors in the United States

BACKGROUND: Recent reports have suggested that the increasing rates of testicular germ cell tumors in some populations have begun to plateau. This study was conducted to examine whether rates among white men in the United States have begun to stabilize and whether rates among black men in the United States have remained low. METHODS: Testicular germ cell tumor incidence data from in the Surveillance, Epidemiology, and End Results Program were analyzed for the years 1973-1998. Trends were examined separately for seminoma and nonseminoma. Using age-period-cohort analyses with 5-year age intervals and 5-year calendar-period intervals, changes in the slope of the trends in birth-cohort and calendar-period effects were examined. RESULTS: Among white men, rates of seminoma continued to increase, but the rate of increase steadily declined throughout the 26-year time span. Nonseminoma rates among whites increased more slowly during the first three time intervals, then plateaued in the final interval. Rates of both seminoma and nonseminoma in black men fluctuated throughout the first three time intervals. In the final interval, the rates of seminoma increased almost 100%, whereas the rates of nonseminoma increased more modestly. Age-period-cohort modeling of the incidence data in white men found that, whereas the dominant effect was that of birth cohort, there also was a period effect. CONCLUSIONS: Among white men in the United States, the incidence of testicular germ cell tumors varied by histology, with a continuing increase in risk only for seminoma. Among black men in the United States, the surprising increases seen between 1988 and 1998 were likely to be a calendar-period effect.     

The detection of p53 gene mutation using a microdissection technique in primary intracranial germ cell tumors

Using a microdissection technique, the contribution of the p53 mutation to tumorigenesis and prognosis in each histological subtype of the intracranial germ cell tumors (GCTs) was evaluated. Nineteen patients had primary intracranial GCTs, including 4 germinomas (GEs), 4 teratomas (TEs), 1 mixed tumor of GE and TE, and 10 mixed GCTs containing non-germinomatous malignant germ cell tumors (NG-MGCTs). After microdissection of specific subtypes, genomic DNA was screened for mutations in exons 5-8 of the p53 gene, using the dideoxyfingerprinting (ddF) followed by direct DNA sequencing. The direct sequencing revealed a total of six mutations in PCR products derived from the five cases (26%) which showed mobility shifts in ddF. Among the six mutations detected, four were missense mutations and two were silent. Missense mutations of the p53 gene tended to occur more frequently in the NG-MGCT component than in the GE or TE components (3/15 vs. 1/12 vs. 0/13). The incidence of missense mutations was not different between the survivors (3/13) and the deceased (1/6). This study suggests the possible role of the p53 gene in the tumori-genesis of NG-MGCT. However, p53 gene mutation did not correlate with the prognosis of NG-MGCT.     

Brain and other central nervous system tumor statistics, 2021

Brain and other central nervous system (CNS) tumors are among the most fatal cancers and account for substantial morbidity and mortality in the United States. Population-based data from the Central Brain Tumor Registry of the United States (a combined data set of the National Program of Cancer Registries [NPCR] and Surveillance, Epidemiology, and End Results [SEER] registries), NPCR, National Vital Statistics System and SEER program were analyzed to assess the contemporary burden of malignant and nonmalignant brain and other CNS tumors (hereafter brain) by histology, anatomic site, age, sex, and race/ethnicity. Malignant brain tumor incidence rates declined by 0.8% annually from 2008 to 2017 for all ages combined but increased 0.5% to 0.7% per year among children and adolescents. Malignant brain tumor incidence is highest in males and non-Hispanic White individuals, whereas the rates for nonmalignant tumors are highest in females and non-Hispanic Black individuals. Five-year relative survival for all malignant brain tumors combined increased between 1975 to 1977 and 2009 to 2015 from 23% to 36%, with larger gains among younger age groups. Less improvement among older age groups largely reflects a higher burden of glioblastoma, for which there have been few major advances in prevention, early detection, and treatment the past 4 decades. Specifically, 5-year glioblastoma survival only increased from 4% to 7% during the same time period. In addition, important survival disparities by race/ethnicity remain for childhood tumors, with the largest Black-White disparities for diffuse astrocytomas (75% vs 86% for patients diagnosed during 2009-2015) and embryonal tumors (59% vs 67%). Increased resources for the collection and reporting of timely consistent data are critical for advancing research to elucidate the causes of sex, age, and racial/ethnic differences in brain tumor occurrence, especially for rarer subtypes and among understudied populations.     

Elevated levels and distinct patterns of expression of A-type cyclins and their associated cyclin-dependent kinases in male germ cell tumors

Aberrant expression of several key regulators controlling the G1/S phase of the cell cycle has been implicated in human male germ cell tumorigenesis. Given the critical role of cyclin A2 at both the G1/S and G2/M transitions and the essential role for cyclin A1 in male germ cell development, our present study focused on the involvement of the A-type cyclins in the transformation and progression of male germ cell tumors (GCTs). The expression of the A-type cyclins and their catalytic partners Cdk1 and Cdk2 was examined in all types and stages of human male GCTs, including carcinoma in situ(CIS), seminoma and non-seminoma GCTs, along with normal testis samples. Elevated levels of cyclin A2, Cdk1 and Cdk2 were detected in the majority of GCTs and were correlated with the invasiveness of the tumors (p < 0.05). Cyclin A1 expression was virtually undetectable in CIS and seminoma, but was aberrantly expressed in all non-seminomatous GCTs. Cyclin A2 expression was strongly correlated with that of its catalytic partners Cdk1 and Cdk2 in all types of testicular tumors examined (p < 0.05), whereas a strong correlation between cyclin A1 and Cdk1 or Cdk2 was only seen in non-seminomatous GCTs (p < 0.05). Histone kinase activities of cyclin A1/Cdks and cyclin A2/Cdks were found to be elevated in tumors. Our data suggest that aberrant expression of A-type cyclins and their Cdks is a significant factor in male germ cell tumorigenesis. The abundant ectopic expression of cyclin A1 in non-seminomatous GCTs and its absence in CIS and seminomas is likely linked to the tumor transformation and progression and may be relevant to clinical prognosis.     

The incidences of malignant gonadal and extragonadal germ cell tumors in males and females: a population-based study covering over 40?years in Finland

Purpose

Germ cell tumors (GCTs) comprise a heterogeneous group of tumors derived from primordial germ cells. The incidence of malignant testicular GCTs has increased in recent decades, but little is known about possible changes in malignant female GCTs. Population-based data covering all malignant GCTs in both sexes remain limited.

Methods

All cases of malignant GCTs in 1969–2008 were collected from the Finnish Cancer Registry and their age-adjusted annual incidences calculated.

Results

The overall incidence of malignant GCTs was 2.56 per 100,000 person-years in males and 0.34 per 100,000 in females. The incidence of gonadal GCTs increased from 2.27 to 8.36 per 100,000 in males between 15 and 44?years of age. Moreover, the incidence of all histological subtypes of gonadal GCTs increased in males. In females, the only increase was seen in the incidence of ovarian non-dysgerminoma (from 0.07 to 0.29/100,000). The incidence of extragonadal GCTs did not change during the study period, being 0.18 and 0.10 per 100,000 in males and females, respectively.

Conclusions

The incidence of gonadal GCTs in males increased significantly during the 40-year study period, whereas in females, no such change was observed. There were significant gender differences regarding the distribution of histological subtypes and patients’ ages. However, the incidence of extragonadal GCTs remained low in both sexes. The differences in the incidences of gonadal GCTs derived from the same population suggest that the risk factors of these malignancies differ between the two sexes.