Trends in Incidence and Survival of Pediatric
and Adolescent Patients With Germ Cell
Tumors in the United States, 1975 to 2006
Jenny N. Poynter, PhD1,2; James F. Amatruda, MD, PhD3; and Julie A. Ross, PhD1,2
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 investi-
gation. Cancer 2010;116:4882–91. V
C 2010 American Cancer Society.
KEYWORDS: pediatric cancer, germ cell tumors, Surveillance, Epidemiology and End Results (SEER), incidence.
Pediatric germ cell tumors (GCTs) are rare and heterogeneous tumors hypothesized to occur as a result of events in
utero,1,2although 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.3GCTs 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.4GCTs are grouped into
2 broad classes: seminomas, comprised of the seminomas of the testes and dysgerminomas of the ovaries; and nonsemino-
mas, comprised of yolk sac tumors, teratomas, embryonal carcinomas, and choriocarcinomas.5Teratomas 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 infantsand youngboys.5
The increasing incidence of testicular cancer in adults has been well documented.6-12This 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,9,12,13whereas others have observed no significant change in incidence.14-16Survival
is favorable for boys with GCTs,17which can be attributed to the effectiveness of platinum-based chemotherapy in
DOI: 10.1002/cncr.25454, Received: March 11, 2009; Revised: April 28, 2010; Accepted: May 3, 2010, Published online July 1, 2010 in Wiley Online Library
Corresponding author: Jenny N. Poynter, PhD, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, 420 Delaware Street SE MMC
715, Minneapolis, MN 55455; Fax: (612) 624-7147; email@example.com
1Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota;2Masonic Cancer Center,
University of Minnesota, Minneapolis, Minnesota;3Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
October 15, 2010
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) Program21of the National Cancer Institute
(NCI) have evaluated ovarian GCTs in both the pediatric
and adult populations.22-25These data suggest that the
incidence of ovarian GCTs has not changed signifi-
cantly.22Similar to testicular GCTs, the survival rate is
In recent publications from our group,17,26we
reported on incidence (1992-2004) and 5-year survival
trends (1975-1999) for pediatric cancers, including
GCTs overall, using data from the SEER program.21In
this analysis, we evaluated GCTs in considerably more
detail in a larger dataset with longer follow-up (1975-
2006). Specifically, we have evaluated frequencies, inci-
dence, and survival by tumor location and histology,
which mayprovidecluesto theetiologyofthesetumors.
MATERIALS AND METHODS
Using data from NCI’s SEER program,21we 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.17,26We 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).27The SEER 9 registries represent approxi-
mately 9% of the US population27with an estimated case
ascertainment rate of 98%.28We included first malignan-
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
The third edition of the International Classification
of Disease for Oncology,29histology and topology codes
included in the third edition of the International Classi-
fication of Childhood Cancer (ICCC)30categories 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 (topogra-
phy 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
This analysis used existing data with no personal
identifiers; therefore, the study was exempt from review
by the University of Minnesota Institutional Review
Frequencies and age-adjusted incidence rates were calcu-
lated 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 (Join-
point Regression Program Version 3.3.1; Statistical
Research and Applications Branch, National Cancer
Institute, Bethesda, MD).32,33
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
The life tables method in SEER*Stat31,34was used
to calculate 5-year relative survival rates and correspond-
ing 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).27Relative 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 hetero-
geneity in withdrawal (exact method). We used Z tests to
All analyses were stratified by sex. Incidence and
survival were evaluated for the entire cohort and for
The average annual
Incidence and Survival in Pediatric GCTs/Poynter et al
October 15, 2010
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
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
locatedin theovaries(Fig.1 Bottom).
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 nonsemi-
noma 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
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 inci-
dence was highest for whites and lowest for blacks, both
overall and for gonadal GCTs (Table 1). This difference
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-
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
Figure 1. 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.
October 15, 2010
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 differ-
ences 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 ages10- to19years).
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
withHispanic ethnicity, and this differencewas due to the
increased incidence of gonadal GCTs in this subgroup
Trends in incidence of GCTs during the period 1975
through 2006 are shown in Figure 2. There was no evi-
dence 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
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
OverallGonadal ExtragonadalOverallGonadal Extragonadal
Age Group: Birth to 9 Years
149 (76) 3.3
29 (15) 4.8
83 (73) 1.8
24 (21) 4.0c
66 (81) 1.4
10 (12) 1.2
141 (75) 3.3
33 (17) 4.2
41 (84) 1.0
5 (10) 0.6
100 (71) 2.3
28 (20) 3.5
0.82.7 0.6 2.1
114 (67) 3.6
56 (33) 4.3
58 (62) 1.8
35 (38) 2.7
56 (73) 1.8
21 (27) 1.6
126 (74) 4.2
45 (26) 3.8
35 (66) 1.2
18 (34) 1.7
91 (71) 3.0
27 (21) 2.1
Age Group: 10-19 Years
853 (91) 18.6
787 (92) 17.1
66 (78) 1.4
15 (18) 2.7
384 (72) 8.8
89 (17) 11.8c
62 (12) 11.6
331 (72) 7.6
67 (15) 8.9
60 (13) 11.2c
53 (69) 1.2
22 (29) 2.9c
542 (72) 17.7
209 (28) 20.8
501 (72) 16.4
194 (28) 19.3
41 (73) 1.3
15 (27) 1.5
277 (69) 9.2
124 (31) 13.2e
250 (70) 8.3
109 (30) 11.5e
27 (64) 0.9
15 (36) 1.6
GCTs indicates germ cell tumors; NCI, National Cancer Institute; SEER, Surveillance, Epidemiology, and End Results.
aNumber of cases in the SEER registry, 1975 through 2006.
bIncidence data from the SEER 9 Registries, 1975 through 2006.
cRate was significantly different than rate in white patients.
dIncidence data from the SEER 13 Registries, 1992 through 2006.
eRate was significantly different than rate in non-Hispanic patients.
Incidence and Survival in Pediatric GCTs/Poynter et al
October 15, 2010
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 loca-
The 5-year relative survival rates for GCTs overall were
high in all age groups. For example, in the diagnostic pe-
riod between 1996 and 2000, the 5-year relative survival
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 loca-
tion, 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,
Figure 2. Incidence trends in pediatric germ cell tumors are
shown in (Top) boys and (Bottom) girls by age group (1975-
Figure 3. The 5-year relative survival rates for (Top) boys and
(Bottom) girls for 5-year diagnostic periods are shown by
age group and tumor location.
October 15, 2010
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 diag-
nostic period in adolescent boys and girls, with marked
improvement noted over time. The small sample size pre-
cludes analysis of survival by tumor histology and race/
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 inci-
dence rates by race or ethnicity were observed in children
diagnosed between birth and 9 years of age; however, stat-
istically significant differences were observed in the older
age group. Moreover, incidence rates increased signifi-
cantly during the study period for boys in the group ages
10to19years andgirls inthe groupages birthto9 years.
The distribution of tumors by location differed in
tumors comprising a larger percentage of tumors diag-
nosed in children before the age of 4 years than children
diagnosed after age 10 years. Previous reports have esti-
mated that 40% to 55% of pediatric GCTs are found in
extragonadal locations,36-40whereas only 5% to 10% of
GCTs diagnosed in adults are found in extragonadal
locations.3,41This 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.4Pediatric 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 thecaseofmediastinalGCTs.
The incidence of GCTs was similar in boys and girls
in the group of patients ages birth to 9 years, whereas the
incidencewas muchhigher in boys in the group ages 10to
19 years. This finding is believed to be due to the more
limited number of germ cells in females in the mature
ovaries.43,44Incidence 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
factormaybe physiologicdifferencesbetween thesexes:in
females, germ cells undergo a prenatal meiotic arrest that
persists until puberty, whereas in males, mitotic proli-
feration of germ cells resumes shortly after birth and
continues throughout childhood.45Yet 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 ectopicgermcells withdelayedmaturationcan be iden-
tified 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
formsacrococcygealtumors,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.6-12These 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 inci-
dence in the younger pediatric male age group. In con-
trast, 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,47,48overlap for pediatric and
adult testicular GCTs; however, the distinct clini-
cal3,19,49,50and genetic profiles51-53of 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,40,57,58with conflicting results.
organochlorine pesticides (POPs)59-61and polychlori-
nated biphenyls,59,62have also been investigated in
Incidence and Survival in Pediatric GCTs/Poynter et al
October 15, 2010
epidemiologic studies of adult testicular GCT, with evi-
dence suggesting that POPs60may be associated with
increased risk. Data from in vitro and in vivo studies
provideevidencethatexposuretoestrogens and endocrine
disruptors may influence germ cell apoptosis63-66and
stimulate cell proliferation.67,68Exposure to these chemi-
cals 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 roleofthese agentsin riskofGCTs,especiallyingirls.
We observed different patterns of GCT incidence
by race and ethnicity in males and females. In the adoles-
cent 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.10,69,70In con-
trast, 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 His-
panic 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,72-74and
1 of these studies found that the increased incidence was
confined mainly to gonadal GCTs and reached statistical
significance only in females.74Any explanations for these
differing incidence patterns would be purely speculative;
however, it is possible that genetic factors or differences in
The 5-year relative survival rates are very high for
pediatric GCTs, mainly due to the effectiveness of
platinum-based chemotherapy.18-20Although 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 extragona-
dal locations.38,75,76Differing survival rates based on
extragonadal location have also been reported38,77; un-
fortunately, the number of cases in this analysis was not
sufficient to stratify by extragonadal location. The higher
survival rate reported in gonadal compared with extrago-
nadal tumors has been hypothesized to be due to more
complete tumor excision in tumors located in the
gonads.19Other potential explanations for the higher sur-
vival rate noted in patients with gonadal GCTs include
differences in sensitivity to chemotherapy and induction
The SEER dataset has many strengths, including a
high rate of case ascertainment and high quality data.
However,severallimitations must also be considered. The
of cancer cases for approximately 9% of the US popula-
tion. Differences in demographic characteristics78and
cancerincidencerates79mayexistin the91%of thepopu-
lation not covered by the SEER 9 registries. Teratomas in
children are frequently considered benign, and misreport-
ing of these tumors is a possibility. Clinical and diagnostic
practiceshave changedduring the longtimeperiod ofcase
ascertainment for this analysis (1975-2006), which may
have influenced our results. Improved imaging and diag-
nosis 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 analy-
ses, particularly for analyses of tumor histology, is also a
limitation of this analysis, because unstable estimates
causedbysmallcells couldleadto 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-docu-
mented 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
theetiologyof thispoorlyunderstoodgroup oftumors.
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