Original Article

Free Access

Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006

Corresponding Author

Jenny N. Poynter PhD

[email protected]

Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota

Fax: (612) 624-7147

Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, 420 Delaware Street SE MMC 715, Minneapolis, MN 55455===Search for more papers by this author

James F. Amatruda MD, PhD,

James F. Amatruda MD, PhD

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas

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Julie A. Ross PhD,

Julie A. Ross PhD

Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota

Search for more papers by this author

Jenny N. Poynter PhD,

Corresponding Author

Jenny N. Poynter PhD

[email protected]

Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota

Fax: (612) 624-7147

Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, 420 Delaware Street SE MMC 715, Minneapolis, MN 55455===Search for more papers by this author

James F. Amatruda MD, PhD,

James F. Amatruda MD, PhD

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas

Search for more papers by this author

Julie A. Ross PhD,

Julie A. Ross PhD

Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota

Search for more papers by this author

First published: 01 July 2010

https://doi.org/10.1002/cncr.25454

Citations: 102

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Abstract

BACKGROUND:

Pediatric germ cell tumors (GCTs) are rare and heterogeneous tumors with uncertain etiology. In the current study, data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program were used to evaluate trends in incidence and survival of GCTs in boys and girls ages ≤19 years. To the authors' knowledge, few studies to date have evaluated trends in pediatric GCTs. Results from these analyses may provide clues to the etiology of GCTs.

METHODS:

Frequencies, incidence rates, and 5-year relative survival rates stratified by sex were evaluated overall and by demographic subgroups based on age (birth to 9 years and 10-19 years), race (white, black, and other), and ethnicity (non-Hispanic and Hispanic) as sample size permitted.

RESULTS:

In whites, the incidence of GCTs was lower for females than males in the 10-year to 19-year age group (rate ratio [RR], 0.47; 95% confidence interval [95% CI], 0.42-0.53), whereas the rates were similar in the age group for birth to 9 years. In contrast, incidence rates were higher in black females than in black males in both age groups (RR, 2.01 [95%CI, 1.08-3.84] in those ages birth to 9 years; RR, 3.30 [95% CI, 2.13-5.28] in those ages 10-19 years). The incidence of ovarian GCT was significantly higher in Hispanic compared with non-Hispanic girls in the groups aged 10 to 19 years. Incidence rates increased during the study period in boys ages 10 to 19 years (annual percentage change [APC], 1.2; 95% CI, 0.4-2.1) and girls ages birth to 9 years (APC, 1.9; 95% CI, 0.3-2.5).

CONCLUSIONS:

The incidence of pediatric GCTs in the United States appears to be increasing only in certain subgroups, suggesting that the etiology is not completely overlapping in all age groups. Differences in incidence patterns by race and ethnicity merit further investigation. Cancer 2010. © 2010 American Cancer Society.

Pediatric germ cell tumors (GCTs) are rare and heterogeneous tumors hypothesized to occur as a result of events in utero,1, 2 although the etiology is largely unknown. GCTs are grouped together due to their presumed common cell of origin, the primordial germ cell (PGC). During normal fetal development, PGCs originate in the embryonic yolk sac and then migrate to the gonads.3 GCTs typically occur in the testes or ovaries; however, extragonadal GCTs can occur and have been hypothesized to result from abnormal germ cell migration during development.4 GCTs are grouped into 2 broad classes: seminomas, comprised of the seminomas of the testes and dysgerminomas of the ovaries; and nonseminomas, comprised of yolk sac tumors, teratomas, embryonal carcinomas, and choriocarcinomas.5 Teratomas are comprised of tissues from all 3 germ layers (ectoderm, mesoderm, and endoderm) and are the most common GCTs in the ovary and extragonadal locations. Yolk sac tumors (endodermal sinus tumors) are the most common malignant GCTs in the testes of infants and young boys.5

The increasing incidence of testicular cancer in adults has been well documented.6-12 This increase is believed to be the result of a birth cohort effect, which supports a role for prenatal exposures in the etiology of this malignancy.6, 10, 11 In contrast, no clear trend in incidence has been observed in studies of pediatric testicular GCT, with several studies suggesting an increase in incidence,9, 12, 13 whereas others have observed no significant change in incidence.14-16 Survival is favorable for boys with GCTs,17 which can be attributed to the effectiveness of platinum-based chemotherapy in patients with these tumors.18-20

Trends in incidence of GCTs in girls have not been studied extensively. Several recent analyses using data from the Surveillance, Epidemiology, and End Results (SEER) Program21 of the National Cancer Institute (NCI) have evaluated ovarian GCTs in both the pediatric and adult populations.22-25 These data suggest that the incidence of ovarian GCTs has not changed significantly.22 Similar to testicular GCTs, the survival rate is very high for ovarian GCTs.22-24

In recent publications from our group,17, 26 we reported on incidence (1992-2004) and 5-year survival trends (1975-1999) for pediatric cancers, including GCTs overall, using data from the SEER program.21 In this analysis, we evaluated GCTs in considerably more detail in a larger dataset with longer follow-up (1975-2006). Specifically, we have evaluated frequencies, incidence, and survival by tumor location and histology, which may provide clues to the etiology of these tumors.

MATERIALS AND METHODS

Using data from NCI's SEER program,21 we analyzed the incidence and survival of pediatric and adolescent GCTs in boys and girls overall and by tumor location and histologic subtype as previously described.17, 26 We used data from the SEER 9 registries, which actively collect information regarding demographics, tumor site, and morphology, stage at diagnosis, and vital status from 9 cancer registries in 5 states (Connecticut, Hawaii, Iowa, New Mexico, and Utah) and 4 metropolitan areas (Atlanta, Detroit, San Francisco-Oakland, and Seattle-Puget Sound).27 The SEER 9 registries represent approximately 9% of the US population27 with an estimated case ascertainment rate of 98%.28 We included first malignancies diagnosed between 1975 and 2006 among individuals aged ≤19 years. Moreover, data from the SEER 13 registries (SEER 9 registries plus Los Angeles, San Jose-Monterey, Rural Georgia, and the Alaskan Native Tumor Registry) were used to evaluate incidence and survival by ethnicity (non-Hispanic vs Hispanic).

The third edition of the International Classification of Disease for Oncology,29 histology and topology codes included in the third edition of the International Classification of Childhood Cancer (ICCC)30 categories Xb. (malignant extracranial and extragonadal GCTs) and Xc. (malignant gonadal GCTs) were used to classify GCTs. In this analysis, we included only those GCTs coded as malignant in the SEER database. For analyses by tumor location, we stratified the tumors into gonadal (topography codes C56.9, and C62.0-C62.9) and extragonadal (topography codes C00.0-C55.9, C57.0-C61.9, C63.0-C69.9, C73.9-C75.0, C75.4-C76.8, and C80.9). The following histology categories were evaluated: germinoma (ICCC 9060-9065), malignant teratoma (9080-9084), embryonal carcinoma (9070-9072), yolk sac tumor (9071), choriocarcinoma (9100, 9103, and 9104), and mixed GCT (9085, 9101, 9102, and 9105).

This analysis used existing data with no personal identifiers; therefore, the study was exempt from review by the University of Minnesota Institutional Review Board.

Statistical Analysis

Frequencies and age-adjusted incidence rates were calculated using SEER*STAT software31; incidence rates are reported as the number of cases per 1,000,000 person-years of follow-up. The US 2000 standard population was used in direct age standardization. Rate ratios (RR) were used to compare incidence rates in demographic subgroups. Trends in incidence rates were evaluated using the weighted least-squares regression in Joinpoint (Joinpoint Regression Program Version 3.3.1; Statistical Research and Applications Branch, National Cancer Institute, Bethesda, MD).32, 33 The average annual percentage changes (APCs) and corresponding 95% confidence intervals (95% CIs) were calculated using calendar year as the independent variable and the natural logarithm of the age-adjusted incidence rate as the dependent variable. Joinpoints, which are points in time at which a trend changes, were not permitted. The APC was considered significant if the 95% CI did not include 0.

The life tables method in SEER*Stat31, 34 was used to calculate 5-year relative survival rates and corresponding standard errors for five 5-year diagnostic cohorts (1976-1980, 1981-1985, 1986-1990, 1991-1995, and 1996-2000). SEER follow-up rates into 2006 were high for both males and females ages birth to 19 years (94% and 93%, respectively).27 Relative survival rates are ratios of observed-to-expected survival and are reported as percentages. The expected rates were based on data from the National Center for Health Statistics and take into account differences in distributions of age, sex, race, and year of diagnosis. Relative rates were adjusted if they exceeded 100%, increased over time, or involved heterogeneity in withdrawal (exact method). We used Z tests to compare relative survival rates across cohorts.35

All analyses were stratified by sex. Incidence and survival were evaluated for the entire cohort and for demographic subgroups based on age (birth to 9 years and 10-19 years), race (white, black, and other [includes American Indian/Alaskan Native and Asian/Pacific Islander]), and ethnicity (non-Hispanic and Hispanic) as sample size permitted.

RESULTS

Incidence

Malignant GCTs were recorded in the SEER registry in 1140 boys and 970 girls from 1975 through 2006. Incidence peaks were observed before the age of 1 year and from ages 15 to 19 years in both boys and girls (Fig. 1). Gonadal and extragonadal tumors were equally represented in boys diagnosed before age 4 years, whereas the majority of tumors diagnosed after age 10 years were located in the testes (Fig. 1 Top). In girls, the tumors diagnosed before age 4 years were comprised almost exclusively of extragonadal tumors, whereas the majority of tumors diagnosed after age 10 years were mainly located in the ovaries (Fig. 1 Bottom).

Details are in the caption following the image — **Figure 1**
Open in figure viewer PowerPoint

Incidence of pediatric germ cell tumors (GCTs) is shown by tumor location in (*Top*) boys and (*Bottom*) girls in the Surveillance, Epidemiology, and End Results (SEER) registry, 1975 through 2006.

In infants and young children, teratomas and yolk sac tumors were the most common tumor type in both boys and girls (data not shown). Tumors with nonseminoma histology (teratoma, embryonal carcinoma, and mixed GCTs) were the most common histologic subtypes in boys diagnosed after the age of 10 years. Germinomas and teratomas were the most common tumor types diagnosed in adolescent girls.

There were no statistically significant differences in the incidence of GCTs overall in boys or girls diagnosed before age 10 years by race; however, differences were observed by tumor location (Table 1). The incidence of gonadal tumors was higher in boys in the other race category than in white boys ages birth to 9 years (RR, 2.16; 95% CI, 1.31-3.44). In adolescent boys, the incidence was highest for whites and lowest for blacks, both overall and for gonadal GCTs (Table 1). This difference was noted for most histologic subtypes as well. In contrast, for adolescent girls, the incidence was significantly higher in blacks than in whites for GCTs overall. The incidence of gonadal GCTs was significantly higher in girls in the other race category than in whites (RR, 1.48; 95% CI, 1.10-1.95), and the incidence of extragonadal GCTs was significantly higher in blacks than in whites (RR, 2.44; 95% CI, 1.41-4.08). The incidence of teratomas was significantly higher in both blacks and the other race category than whites for girls in this age category (RR, 1.57 [95% CI, 1.03-2.44] and RR, 1.68 [95% CI 1.03-2.68], respectively).

Table 1. Frequency and Incidence Rates of Pediatric GCTs by Race, Ethnicity, and Age Group in Girls and Boys in the NCI SEER Registry, Overall and by Tumor Location

	Boys						Girls
	Overall		Gonadal		Extragonadal		Overall		Gonadal		Extragonadal
	No.a (%)	Incidence Rate	No.a (%)	Incidence Rate	No.a (%)	Incidence Rate	No.a (%)	Incidence Rate	No.a (%)	Incidence Rate	No.a (%)	Incidence Rate
Age Group: Birth to 9 Years
Raceb
White	149 (76)	3.3	83 (73)	1.8	66 (81)	1.4	141 (75)	3.3	41 (84)	1.0	100 (71)	2.3
Black	17 (9)	2.1	7 (6)	0.9	10 (12)	1.2	33 (17)	4.2	5 (10)	0.6	28 (20)	3.5
American Indian/Alaskan Native, Asian/Pacific Islander	29 (15)	4.8	24 (21)	4.0c	5 (6)	0.8	15 (8)	2.7	3 (6)	0.6	12 (9)	2.1
Ethnicityd
Non-Hispanic	114 (67)	3.6	58 (62)	1.8	56 (73)	1.8	126 (74)	4.2	35 (66)	1.2	91 (71)	3.0
Hispanic	56 (33)	4.3	35 (38)	2.7	21 (27)	1.6	45 (26)	3.8	18 (34)	1.7	27 (21)	2.1
Age Group: 10-19 Years
Raceb
White	853 (91)	18.6	787 (92)	17.1	66 (78)	1.4	384 (72)	8.8	331 (72)	7.6	53 (69)	1.2
Black	27 (3)	3.6c	23 (3)	3.1c	4 (5)	0.5c	89 (17)	11.8c	67 (15)	8.9	22 (29)	2.9c
American Indian/Alaskan Native, Asian/Pacific Islander	58 (6)	10.8c	43 (5)	7.8c	15 (18)	2.7	62 (12)	11.6	60 (13)	11.2c	2 (3)	0.4
Ethnicityd
Non-Hispanic	542 (72)	17.7	501 (72)	16.4	41 (73)	1.3	277 (69)	9.2	250 (70)	8.3	27 (64)	0.9
Hispanic	209 (28)	20.8	194 (28)	19.3	15 (27)	1.5	124 (31)	13.2e	109 (30)	11.5e	15 (36)	1.6

GCTs indicates germ cell tumors; NCI, National Cancer Institute; SEER, Surveillance, Epidemiology, and End Results.
a Number of cases in the SEER registry, 1975 through 2006.
b Incidence data from the SEER 9 Registries, 1975 through 2006.
c Rate was significantly different than rate in white patients.
d Incidence data from the SEER 13 Registries, 1992 through 2006.
e Rate was significantly different than rate in non-Hispanic patients.

Differences were also observed in the incidence of GCTs in males and females in different racial groups. In whites, the incidence of GCTs was lower for females than males in the patients ages 10 to 19 years (RR, 0.47; 95% CI, 0.42-0.53), whereas the incidence was similar in patients ages birth to 9 years (RR, 1.01; 95% CI, 0.80-1.29). In contrast, incidence rates were higher in black females than in black males in both age groups (RR, 2.01 [95%CI, 1.08-3.84] in patients ages birth to 9 years and RR, 3.30 [95% CI, 2.13-5.28] in patients ages 10-19 years). In the other race category, no significant differences in incidence were observed by sex in either age group (RR, 0.56 [95% CI, 0.28-1.08] for patients ages birth to 9 years; RR, 1.11 [95% CI, 0.76-1.61] for patients ages 10- to 19 years).

There were no significant differences noted in the incidence of GCTs overall, by tumor location, or by tumor histology in non-Hispanic versus Hispanic boys and girls ages birth to 9 years. Similarly, no significant differences in incidence were observed based on ethnicity in boys ages 10 to 19 years, overall, or by tumor location (Table 1). We did observe a higher incidence of mixed GCTs in Hispanic boys than in non-Hispanic boys in this age group (RR, 1.39; 95% CI, 1.09-1.76). The incidence of GCTs overall was higher in girls ages 10 to 19 years with Hispanic ethnicity, and this difference was due to the increased incidence of gonadal GCTs in this subgroup (RR, 1.39; 95% CI, 1.10-1.75).

Incidence Trends

Trends in incidence of GCTs during the period 1975 through 2006 are shown in Figure 2. There was no evidence for an increase in the incidence of GCTs in boys ages birth to 9 years (APC, −0.3; 95% CI, −1.9 to 1.5). In contrast, we observed a statistically significant increase in incidence during the study period in boys ages 10 to 19 years (APC, 1.2; 95% CI, 0.4-2.1). In girls, the data suggest that the incidence of GCTs increased in those ages birth to 9 years (APC, 1.9; 95% CI, 0.3-2.5), whereas no increase was noted in girls ages 10 to 19 years (APC, −0.1; 95% CI, −0.8 to 0.7). These findings should be interpreted with caution, because all subgroups included <10 cases in several years. The small sample size did not permit the evaluation of incidence trends by tumor location, tumor histology, or race/ethnicity.

Survival Rates

The 5-year relative survival rates for GCTs overall were high in all age groups. For example, in the diagnostic period between 1996 and 2000, the 5-year relative survival was 94.1 (95% CI, 75.8-98.7) in boys ages birth to 9 years, 94.5 (95% CI, 89.0-97.2) in boys ages 10 to 19 years, 89.3 (95% CI, 69.2-96.6) in girls ages birth to 9 years, and 97.7 (95% CI, 90.5-99.5) in girls ages 10 to 19 years. The 5-year relative survival rates differed by tumor location, with more favorable survival noted for gonadal tumors compared with extragonadal tumors (Fig. 3). Significant improvements in survival from gonadal GCTs were observed in all diagnostic periods compared with the period between 1976 through 1980 in boys ages 10 to 19 years, and survival was higher for extragonadal tumors in this age group for 1996 through 2000 compared with 1976 through 1980 and 1986 through 1990. For females, survival improved significantly for the period 1996 through 2000 compared with 1976 through 1980. The difference in survival between gonadal and extragonadal tumors was more pronounced in boys than girls and decreased in more recent diagnostic periods. Survival was significantly higher for extragonadal tumors during the 1996 through 2000 diagnostic period compared with 1976 through 1980 and 1981 through 1985 in boys ages birth to 9 years (P <.05). Survival was especially poor for extragonadal tumors during the 1976 through 1980 diagnostic period in adolescent boys and girls, with marked improvement noted over time. The small sample size precludes analysis of survival by tumor histology and race/ethnicity.

DISCUSSION

We have evaluated the incidence and survival of pediatric and adolescent GCTs during the period 1975 through 2006 using data from the SEER Program. This relatively large dataset has allowed us to evaluate incidence overall in boys and girls, and also for subgroups based on tumor location and histology. No significant differences in incidence rates by race or ethnicity were observed in children diagnosed between birth and 9 years of age; however, statistically significant differences were observed in the older age group. Moreover, incidence rates increased significantly during the study period for boys in the group ages 10 to 19 years and girls in the group ages birth to 9 years.

The distribution of tumors by location differed in the pediatric and adolescent age groups, with extragonadal tumors comprising a larger percentage of tumors diagnosed in children before the age of 4 years than children diagnosed after age 10 years. Previous reports have estimated that 40% to 55% of pediatric GCTs are found in extragonadal locations,36-40 whereas only 5% to 10% of GCTs diagnosed in adults are found in extragonadal locations.3, 41 This difference is hypothesized to be due to differences in the maturity of the germ cells that give rise to the tumors in these age groups.4 Pediatric GCTs likely originate from a PGC that underwent immediate reprogramming to become a pluripotent embryonic germ cell, whereas GCTs occurring in adolescents and young adults most likely originate from more mature PGCs,42 which may be unable to survive outside of the normal niches of the ovary and testis or specialized sites such as the thymus, in the case of mediastinal GCTs.

The incidence of GCTs was similar in boys and girls in the group of patients ages birth to 9 years, whereas the incidence was much higher in boys in the group ages 10 to 19 years. This finding is believed to be due to the more limited number of germ cells in females in the mature ovaries.43, 44 Incidence patterns differed by tumor location in boys and girls. Several factors may contribute to these differences. The higher rate of gonadal GCTs reported in young boys may reflect a more permissive environment in the immature testis than in the immature ovary. Another factor may be physiologic differences between the sexes: in females, germ cells undergo a prenatal meiotic arrest that persists until puberty, whereas in males, mitotic proliferation of germ cells resumes shortly after birth and continues throughout childhood.45 Yet another factor may be the lower number of germ cells in young girls, as a result of apoptosis of germ cells during development. In this context, it is particularly interesting that, when germ cell apoptosis is inhibited in a mouse model, a population of ectopic germ cells with delayed maturation can be identified in the sacral/tail region specifically in female mice.46 If a similar phenomenon occurs in humans, it may be that germ cells escaping developmental apoptosis go on to form sacrococcygeal tumors, particularly in girls.

The increase in the incidence of testicular GCTs in young adults during the past half century has been well documented in the literature.6-12 These data from the SEER program support other reports that GCTs are increasing in adolescent males; however, to our knowledge, there is no corresponding increase in incidence in the younger pediatric male age group. In contrast, we observed increasing incidence of GCTs in girls in the pediatric age group (ages birth to 9 years) but no corresponding increase in adolescent girls (ages 10-19 years). These data suggest that differing etiologic factors are involved in GCTs in different age groups and by sex.

Evidence suggests that at least some risk factors, such as cryptorchidism,47, 48 overlap for pediatric and adult testicular GCTs; however, the distinct clinical3, 19, 49, 50 and genetic profiles51-53 of pediatric and adult GCTs provide support for distinct etiologies. Several mechanisms have been hypothesized for the increase in testicular GCTs in males, with much attention focused on exposure to estrogens and environmental hormone disruptors54; however, the exact mechanism is not clear. Epidemiologic studies have evaluated the role of in-utero hormone exposure in both adult testicular GCT1, 2, 55, 56 and in pediatric GCTs,40, 57, 58 with conflicting results. Endocrine disrupting agents, including persistent organochlorine pesticides (POPs)59-61 and polychlorinated biphenyls,59, 62 have also been investigated in epidemiologic studies of adult testicular GCT, with evidence suggesting that POPs60 may be associated with increased risk. Data from in vitro and in vivo studies provide evidence that exposure to estrogens and endocrine disruptors may influence germ cell apoptosis63-66 and stimulate cell proliferation.67, 68 Exposure to these chemicals has increased over time and could be responsible for the observed increase in incidence. Further investigation will be required to draw definitive conclusions regarding the role of these agents in risk of GCTs, especially in girls.

We observed different patterns of GCT incidence by race and ethnicity in males and females. In the adolescent age group, the incidence was significantly higher in white males than in males in the other race groups. This higher incidence of testicular GCT in adult white males has been well documented in the literature.10, 69, 70 In contrast, incidence rates were found to be significantly lower in white females in the adolescent age category compared with females in the other race categories. In addition, a higher incidence of gonadal GCTs was observed in Hispanic females in the group ages 10 to 19 years. Previous studies have also reported differences in GCT incidence by race and ethnicity. A recent study of Southeast Asian children in California reported a higher incidence of GCTs in Asians compared with non-Hispanic whites.71 Previous reports have reported a higher incidence of GCTs in Hispanic children in the United States,72-74 and 1 of these studies found that the increased incidence was confined mainly to gonadal GCTs and reached statistical significance only in females.74 Any explanations for these differing incidence patterns would be purely speculative; however, it is possible that genetic factors or differences in hormone levels may play a role.

The 5-year relative survival rates are very high for pediatric GCTs, mainly due to the effectiveness of platinum-based chemotherapy.18-20 Although survival rates were high overall, differences were observed in survival rates by tumor location, with more favorable survival noted in tumors located in the gonads than in extragonadal locations. This finding is supported by numerous publications demonstrating lower survival rates in patients with pediatric GCTs diagnosed in extragonadal locations.38, 75, 76 Differing survival rates based on extragonadal location have also been reported38, 77; unfortunately, the number of cases in this analysis was not sufficient to stratify by extragonadal location. The higher survival rate reported in gonadal compared with extragonadal tumors has been hypothesized to be due to more complete tumor excision in tumors located in the gonads.19 Other potential explanations for the higher survival rate noted in patients with gonadal GCTs include differences in sensitivity to chemotherapy and induction of apoptosis.

The SEER dataset has many strengths, including a high rate of case ascertainment and high quality data. However, several limitations must also be considered. The SEER 9 registries provide population-based ascertainment of cancer cases for approximately 9% of the US population. Differences in demographic characteristics78 and cancer incidence rates79 may exist in the 91% of the population not covered by the SEER 9 registries. Teratomas in children are frequently considered benign, and misreporting of these tumors is a possibility. Clinical and diagnostic practices have changed during the long time period of case ascertainment for this analysis (1975-2006), which may have influenced our results. Improved imaging and diagnosis would most likely lead to an increasing incidence over time. Because we observed increasing incidence rates in some subgroups, this is unlikely to completely explain the increases observed herein. The large number of tests we conducted leads to the possibility that some findings may be due to chance. The small numbers in some analyses, particularly for analyses of tumor histology, is also a limitation of this analysis, because unstable estimates caused by small cells could lead to spurious findings.

In summary, this analysis of the SEER data suggests that the incidence of GCTs may be increasing in young girls (ages birth to 9 years) in addition to the well-documented increase in adolescent males (ages 10-19 years). This analysis also highlights differences in incidence patterns in racial and ethnic subgroups. These findings should be explored further because they may shed light on the etiology of this poorly understood group of tumors.

CONFLICT OF INTEREST DISCLOSURES

Supported by the Children's Cancer Research Fund, Minneapolis, Minnesota.

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Citing Literature

Volume116, Issue20

15 October 2010

Pages 4882-4891

Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006