Age-incidence patterns of seminoma and nonseminoma among males and females in Germany and the United States, 2008–2016

Abstract

Background & Objectives:

The comparison of the incidence of gonadal germ cell tumors among males and females can provide insights that cannot be gained by separately studying these tumors.

Material and Methods:

Incidence data on male and female gonadal germ cell tumors (GCT) were drawn from the cancer registries of North Rhine-Westphalia (NRW), Germany and the U.S. SEER program, for non-Hispanic White persons only, for the years 2008–2016. We estimated age-standardized and age-, and histology-specific incidence rates.

Results:

We included 21,840 male and 716 female gonadal GCTs. Incidence rates among males were higher in Germany (95.8 per million, SE 1.1) than in the U.S. (68.0, SE 0.6), while incidence rates among females were lower in Germany (1.9, SE 0.2) than the U.S. (2.6, SE 0.1). The characteristic peak of infantile (ages 0–4 years) GCTs among males was missing among females. The age peak of ovarian GCTs occurred 15–20 years earlier (Germany: 10–14 years, US: 15–19 years) than the age peak of testicular GCTs (30–34 years). The three most common testicular GCT histologies were seminoma, mixed GCTs and embryonal carcinoma Among females, the three most common ovarian GCT histologies were teratoma, yolk sac tumor, and monodermal teratomas and somatic-type tumors arising from dermoid cysts in both countries.

Discussion:

The characteristic peak of infantile (ages 0–4 years) GCTs among males was missing among females. The shapes of the age-specific incidence curves are similar for males and females in Germany and the US, though with much lower incidence rates in females, suggesting a common pathogenesis.

Conclusion:

The lower rates among females may be due to the lower number of initiated tumors in the absence of the Y-chromosome, and the earlier peak among females may be due to a younger age at puberty.

Background

Approximately 98% of testicular cancers originate from germ cells. In the past, these testicular germ cell tumors (TGCT) were histologically classified as seminomas, nonseminomas (choriocarcinomas, teratomas, embryonal carcinomas, yolk sac tumors) and spermatocytic seminomas. The 4th edition of the WHO classification of testicular tumors, introduced some important changes to TGCT classification, including pathogenetic features (e.g. germ cell neoplasia in situ (GCNIS) associated germ cell tumors versus GCNIS-unrelated germ cell tumors), and some reclassifications of morphologies (expansion of the non-choriocarcinomatous trophoblastic tumor group, renaming of spermatocytic seminoma to spermatocytic tumor) among others.^1,2 The 5th edition of the WHO classification of testicular tumors introduces the term germinoma to replace seminoma and nongerminoma to replace nonseminoma for all anatomical localizations.³

In contrast to the changes in classification of TGCTs, the most recent classification of ovarian tumors in 2020 (5^th edition) did not include marked changes in classification, and was based only on morphological features.⁴ Ovarian cancers can arise from epithelial, germ cell, or stromal cells although approximately 90% originate from epithelium.⁵ Ovarian GCT (OGCT) thought to originate from germ cells, are subdivided into benign teratomas, immature teratomas, not otherwise specified (NOS), dysgerminomas (the female counterpart of seminomas), yolk sac tumors NOS, embryonal carcinomas NOS, and mixed germ cell tumors. In addition, ovarian monodermal teratomas and somatic type tumors arise from dermoid cysts (struma ovarii, NOS, struma ovarii malignant, strumal carcinoid, cystic teratoma NOS, and teratoma with malignant transformation). Gonadoblastoma is the counterpart of GCNIS in the ovary and dysgenetic gonad. Rarely yolk sac tumor and mixed GCT originate in epithelial cancers of the ovary, probably due to induction of pluripotency in somatic cells.^4,6,7

A diagnostic problem inherent with the morphologic classifications of TGCT and OGCT presented above, is that teratomas with similar histology can be benign or malignant. The WHO classification of TGCTs has partly addressed this problem by distinguishing between prepubertal-type (type I) teratomas, which are benign and postpubertal-type (type II) teratomas, which are malignant.^2,3 This is feasible for TGCTs, because all GCTs that arise in boys under the age of six years are type I. Among OGCTs, however the age range of type I teratomas overlaps with the age range of type II teratomas, and even with cystic teratoma (type IV). This difficulty may explain certain ICD-O coding errors, in particular relative to teratomas.

The TGCT types I (prepubertal GCTs) and II (postpubertal GCTs) as well as type III, the spermatocytic tumors, proposed in 2005,⁸ are terms used in the WHO classification of testicular GCT of 2016. More recently the classification in ‘GCT types’ has been expanded, resulting in a comprehensive classification in seven types⁷ encompassing all gonadal and extragonadal GCTs of males and females. The classification is based on the developmental potential of their cells of origin, upon reprogramming. Relevant for this study are the GCT types I, II, III and IV. Type I GCTs occur mainly under the age of 6. These tumors are derived from early, methylated primordial germ cells (PGCs), which have been reprogrammed to primed, pluripotent embryonic stem cells (ESCs), which are committed to somatic differentiation, accordingly type I GCTs are composed of teratoma. Teratoma may progress to YST when the tumor cells become aneuploid. Thus type I GCTs may consist of pure teratoma or pure YST, or the combination of the two. Type II GCTs are derived from late, demethylated PGCs, which have been reprogrammed to naïve, totipotent ESCs, which have high self-renewal capacity and germline competence. These naïve ESCs may differentiate towards extra-embryonic (yolk sac and trophoblast) and embryonic, i.e. somatic tissues. Hence type II-GCTs may consist of EC (result of self-renewal of the naïve stem cells), YST, trophoblastic elements, teratoma, and rarely early germ cells. Type III-GCTs (spermatocytic tumors) are derived from spermatogonial stem cells committed to spermatogenesis. Type IV-GCTs are derived from primary oocytes, which have escaped from meiotic arrest, and have been reprogrammed to very early embryonic cells with 2C, i.e. omnipotent, developmental potential. However, their bi-maternal imprinting characterizes them as gynogenotes, which give rise to somatic differentiation only, resulting in dermoid cysts of the ovary.

In contrast to male germ cell tumors, female germ cell tumors have been much less frequently studied epidemiologically. With rare exceptions, when examining the incidence of gonadal germ cell tumors, authors have previously limited their focus either to male or to female gonadal GCTs and correspondingly have published their results in urology or gynecology journals. This approach has prevented knowledge gains that can arise by directly comparing the incidence of male and female gonadal GCTs.

Therefore, the aim of this work was to compare the age-, sex-, and histology-specific incidence of male and female gonadal GCTs head-to-head, using the same source populations, cancer registry methodology, classifications, and statistical methods in two large samples of the general population in Germany and the U.S. In addition, we reviewed written pathology reports of female GCTs in the German cancer registry in order to quality-control the classification of female GCTs and their ICD-O coding.

Methods

North Rhine-Westphalia, Germany

Since 2007, the estimated completeness of the cancer registry of North Rhine-Westphalia (NRW), Germany has been 95% or greater. NRW is the most populous Federal State in Germany (18 million people) and includes about 22% of the total population of Germany. If several reports exist for the same primary malignant tumor, information on the date of diagnosis was taken from the report with the earliest date. Cancer reporting in NRW is mandatory and dominated by pathology reports. Cancer histologies are coded according to the International Classification of Diseases for Oncology, 3^rd edition (ICD-O).⁹ ICD-O coding takes place after synopsis of all available reports and is performed by trained medical tumor documentalists in a quality-controlled manner.

Because of the rarity of ovarian GCTs, a quality control was performed on all recorded cases of female GCTs of any anatomic subsite between 2008 and 2016, although ultimately only ovarian GCTs were of interest. Written reports of these tumors underwent a review by a pathologist (JWO). For males, the quality-controlled case file of malignant testicular germ cell tumors (by AS) diagnosed between 2008 through 2013 was used. Results of the quality control and histological distribution of TGCTs have been published previously¹⁰. This case file was supplemented by newly diagnosed TGCTs during the period 2014–2016.

United States

As a consequence of the U.S. Cancer Act of 1971, the Surveillance, Epidemiology and End Results (SEER) program began curating cancer data from nine U.S. state and metropolitan area cancer registries starting in 1973. The number of included registries has expanded over time to include an increasingly larger proportion of the U.S. population. Starting in 2000, eighteen registries were included (States: Connecticut, California, Hawaii, Iowa, Kentucky, Louisiana, New Mexico, New Jersey, Utah. Metropolitan areas: Detroit, Atlanta, Rural Georgia, Greater Georgia, San Francisco-Oakland, San Jose-Monterey, Los Angeles, Seattle-Puget Sound. Special Registry: Alaska Native Tumor Registry). The SEER-18 registries collect cancer data from 28% of the U.S. population, population i.e. approximately 55 million people. We extracted age-standardized incidence rates by sex of malignant gonadal germ cell tumors from the Surveillance, Epidemiology and End Results (SEER) 18 registries for the years 2008–2016¹¹. The cases were restricted to non-Hispanic White persons in order to have a population that was comparable in ancestral background to that of North Rhine-Westphalia.

Statistical methods

We used sex-specific population counts by calendar year (2008–2016) and 5-year age groups to estimate the sex-, age-specific and age-standardized incidence rates according to the US 2000 population standard. For the estimation of the incidence rate of male gonadal GCTs, spermatocytic tumors (ICD-O morphology code: 9063/3) were included. We stratified our analyses by histological group. Seminoma included ICD-O codes 9060/3* (dysgerminoma), 9061/3 (seminoma), 9062/3* (anaplastic seminoma), and 9064/3 (germinoma). Nonseminoma included the ICD-O codes 8240/3 (well-differentiated neuroendocrine tumor), 9065/3* (nonseminomatous germ cell tumor), 9070/3 (embryonal carcinoma), 9071/3 (yolk sac tumor, postpubertal type), 9080/3 (teratoma, postpubertal type in male GCTs and immature teratoma NOS in ovarian GCTs), 9084/3 (teratoma with somatic-type malignancy), 9085/3 (mixed germ cell tumor), 9090/3 (malignant struma ovarii), 9100/3 (choriocarcinoma), 9101/3* (choriocarcinoma combined with other germ cell elements), 9102/3* (malignant teratoma, trophoblastic), 9104/3 (placental site trophoblastic tumor), and 9105/3 (trophoblastic tumor, epithelioid). ICD-O codes marked with a star (*) do not exist in the updated WHO classification of testicular tumors.

For the head-to-head comparison of histology-specific incidence rates between males and females, we restricted our analyses to broad histology groups (seminoma versus all other types of GCTs including mixed GCT) and to specific histologies that included at least 10 female cases in the German data set. These histologies included yolk sac tumors of type I and type II (9071/3), teratomas of postpubertal-type (9080/3), and teratomas with somatic-type malignancy (9084/3) that includes dermoid cysts with somatic-type malignancy.

An ethical review for this project was neither required in the U.S. nor in North Rhine-Westphalia, Germany. Data are available on request.

Results

The review of the written pathology reports of 279 putative female GCTs (gonadal and extragonadal, any behavior) in North Rhine-Westphalia, Germany, resulted in the exclusion of 2 tumors. One exclusion was due to unclear histology of a neoplastic brain lesion and the other exclusion was due to a non-neoplastic process, most likely a duplication cyst (dermoid cyst) close to the cerebellum. The reviewing pathologist confirmed the distinction between ovarian and extra-ovarian tumors among the remaining 277 tumors in 99% of the cases. Among the remaining 176 ovarian tumors, three tumors were determined by the reviewing pathologist not to be GCTs. Among the remaining 173 GCTs of the ovary, the examining pathologist confirmed the division into dysgerminoma and non-dysgerminoma in 99%. The 14 ovarian GCTs that were benign (dermoid cysts) were excluded from the incidence estimates, so that 159 primary malignant ovarian germ cell tumors were included in the incidence analyses of Germany (Supplementary Figure 1).

Our analysis includes a total of 21,840 male and 716 female gonadal GCTs. With the exception of seven female GCTs, all tumors were morphologically verified. The proportion of mixed GCTs among all nonseminomas is markedly greater in men than in women. On the other hand, the proportion of pure forms of nonseminomas is larger in women (Supplementary Table 1). In North Rhine-Westphalia, Germany, the median age at diagnosis for mixed GCTs was intermediate between the median age at diagnosis of pure nonseminoma and pure seminoma. This was not the case for the U.S. (Supplementary Table 2). The age-standardized incidence rates for GCTs among males were higher in Germany than in the U.S. In contrast, the age-standardized incidence rates for GCTs among females were lower in Germany than in the U.S. The higher age-standardized incidence rate of GCTs among males in Germany was mainly due to the higher age-standardized incidence of seminomas (Germany 61.2 versus U.S. 41.0 per million person-years). In contrast, the lower age-standardized incidence of GCTs among females in Germany was due to the lower age-standardized incidence of non-dysgerminoma (Germany: 1.5 versus U.S. 2.1 per million person-years) (Table 1).

Table 1.

Characteristics of male and female gonadal germ cell tumors in North Rhine-Westphalia, Germany and in the United States, 2008–2016

	Germany (North Rhine-Westphalia)		United States (SEER-18)
Characteristic	Males	Females	Males	Females
Incidence period	2008–2016	2008–2016	2008–2016	2008–2016
Incident gonadal germ cell tumors (n)	7,499	159	14,341	557
Morphologically verified (n)	7,290	152	14,341	557
Death certificate only cases (n)	0	0	0	0
Histologies
Seminoma (dysgerminoma)	4,736	56	8,266	165
Nonseminoma (non-dysgerminoma)	2,725	103	5,958	392
Spermatocytic tumor	38	0	117	0
Incidence rates per million person-years (standard error)
All germ cell tumors
Crude rate	95.8 (1.1)	1.9 (0.2)	68.0 (0.6)	2.6 (0.1)
Age-standardized rate1)	99.1 (1.2)	2.4 (0.2)	71.5 (0.6)	3.0 (0.1)
Seminoma (dysgerminoma)
Crude rate	60.5 (0.9)	0.7 (0.1)	39.2 (0.4)	0.8 (0.1)
Age-standardized rate1)	61.2 (0.9)	0.9 (0.1)	41.0 (0.5)	0.9 (0.1)
Nonseminoma (non-dysgerminoma)
Crude rate	34.8 (0.7)	1.3 (0.1)	28.2 (0.4)	1.8 (0.1)
Age-standardized rate1)	37.5 (0.7)	1.5 (0.2)	30.1 (0.4)	2.1 (0.1)

¹⁾US 2000 population standard

The three most common testicular GCT histologies were seminoma, mixed GCTs and embryonal carcinoma in both countries. Among females, the three most common ovarian GCT histologies were teratoma, yolk sac tumor, and monodermal teratomas and somatic-type tumors arising from dermoid cysts in both countries. While the age-standardized incidence rates of yolk sac tumors among males were similar in Germany (0.89 per million person-years) and the U.S. (0.80 per million person-years), the age-standardized rates for teratoma of postpubertal type (males only) and teratoma with somatic-type malignancy (males & females) were markedly higher in Germany than in the U.S. (teratoma of postpubertal type: 2.59 versus 0.95; teratoma with somatic-type malignancy: 0.19 versus 0.02 per million person-years for Germany and the U.S. respectively) (Supplementary Table 3).

While the age-specific incidence rate among females rose in a strictly monotonic manner from 0–4 years until the age peak at ages 10–14 (Germany) and 15–19 years (U.S.), the incidence rate among males falls from the age group 0–4 years until it rises again in the age group 15–19 years in a strictly monotonic manner until the age peak at age 30–34 years in both countries. In males, the incidence of nonseminomatous GCT is higher than the incidence of seminomatous GCT up to the age of 25–29 years. From the age group 30–34 the incidence of seminomatous GCTs is higher. In females, incidence rates of nonseminomatous GCT is higher than the incidence of seminomatous GCT at all ages (Figure 1).

Figure 1. Age-specific incidence rates (cases per million person-years) of gonadal germ cell tumors among males and females in North Rhine-Westphalia, Germany and the United State, 2008–2016.

Legend: inset graph among males shows age-specific rates for ages 0-19 year

While the age peak of nonseminomatous GCTs among males occurs markedly earlier than for seminomatous GCTs, the age peaks of both dysgerminomas and non-dysgerminomas among females are earlier than the peaks among males, and appear to be closer together

In both countries, the age-specific incidence rate of non-dysgerminomas among females rose in a strictly monotonous manner until the age peak. For dysgerminomas among females, the age-specific incidence rate remains constant at the age of 0–4 and 5–9 years and then increases until 15–19 years in Germany, whereas in the U.S. the age-specific incidence rate increases strictly monotonically until 15–19 years (Figure 2).

Figure 2. Age-specific incidence rates (cases per million person-years) of gonadal seminoma (dysgerminoma) and nonseminoma (non-dysgerminoma) among males and females in North Rhine-Westphalia, Germany and the United State, 2008–2016.

Legend: red graphs indicate seminoma (dysgerminoma), blue graphs indicate nonseminoma (non-dysgerminoma); vertical reference lines indicate age-specific incidence peaks

Discussion

While there are many publications on the incidence of male GCTs, there are only a few publications on the incidence of female GCTs. Even rarer are publications that compare the incidence of male and female GCTs from the same cancer registries.^e.g.12,13 In our two-country cancer registry analysis, we found several differences in the incidence patterns by age between males and females. First, the characteristic peak of infantile (ages 0–4 years) GCTs among males was missing among females. Second, the incidence of male nonseminomatous GCT is higher than the incidence of male seminomatous GCT up to the age of 25–29 years. From the age group 30–34 the incidence of male seminomatous GCTs is higher. This is consistent with the well-established younger incidence peak of nonseminoma than seminoma in the testis. This is explained by the fact that seminoma, the default development of a type II GCT, is a rather indolent tumor.^2,7,14

A nonseminoma arises when a seminomatous tumor cell is reprogrammed to an embryonal carcinoma cell, the stem cell of nonseminoma.¹ As nonseminomas are more aggressive and more rapidly growing than seminomas, they manifest some ten years earlier than seminomas. In females, the incidence of non-dysgerminomas is higher than that of dysgerminomas in every age group. This discrepancy between ovarian and testicular GCTs is likely due to the fact that the non-dysgerminomas in the ovary consist not only of type II nonseminomas, but also of teratoma/YST of type I GCTs and teratomas of type IV, making the comparison with the testicular nonseminomas beyond the age of six years futile. Third, the age peak of OGCTs (Germany 10–14 years, U.S. 15–19 years) occurs about 10 years earlier than the age peak of TGCTs. The review of the written pathology and clinical reports of OGCTs in the German cancer registry data revealed excellent agreement between pathologists.

The missing peak of neonatal and infantile (ages 0–4 years) OGCT has been observed in several populations including Germany, England, Finland, U.S., and Denmark.^12,15–19 Moller & Evans speculated that the perinatal peak in testosterone that occurs in boys but is absent in girls may explain the infantile peak among males.¹⁶ This seems unlikely to be the entire explanation, however, as the infantile peak, which is comprised of type I GCTs (called prepubertal-type in the testis) occurs both in males and females in the mediastinum, the retroperitoneum, and the brain. The question is not why there is a neonatal peak in the testis, but rather why it is lacking in the ovary. Type I GCTs are, regardless of anatomical site, most likely derived from early primordial germ cells (PGCs) that have not yet completed epigenetic reprogramming. The normal fate of these cells is apoptosis, however some escape apoptosis by being reprogrammed to primed ESCs, which are the stem cells of type I GCTs with pluripotent developmental potential.^7,14,20 Early PGCs may persist in the periphery of the ovary through week 20 of gestation.^20,21 It is conceivable that the lower number of mitotic PGCs in the ovary compared to the testis explains the absence of the neonatal peak of type I GCTs in the ovary. However, type I GCTs do occur in the ovary, developing later than in the testis, but over a longer period, through childhood. In fact, they are more frequent in the ovary than the testis, comprising respectively 15–25% and 5–10% of all gonadal and extragonadal type I GCTs.¹⁴

The steep increase of the GCT incidence among boys and girls around the age of puberty and the decline with increasing age thereafter has been observed in other populations including Germany, England, Finland, U.S., and Denmark.^12,15–19 In males older than age 6 years, incident TGCTs represent only seminomas and nonseminomas (type II GCTs). However, in females, OGCTs include type I and type II GCTs and type IV GCTs over a broad age range. Spermatocytic tumors, which most commonly occur after the age of 40 years, have not been discussed in this manuscript because they are tumors derived from spermatogonial stem cells committed to spermatogenesis, and lack the pluri- and totipotency of type I and II GCTs.

For a meaningful comparison of incidence rates of GCTs in males and females, one should focus on the comparison of seminomas (males) with dysgerminomas (females), all of which are type II GCTs in both sexes. The shapes of the curves are similar for males and females in Germany and the US, though with much lower incidence rates in females, suggesting a common pathogenesis. Indeed, in both sexes type II GCTs are derived from PGCs, termed gonocytes once they have arrived in the gonads, which have completed epigenetic reprogramming to late PGCs/gonocytes in their niches in the testis and the ovary. These cells are the precursors of spermatogenesis in the testis, and oogenesis in the ovary. Few undergo neoplastic transformation to give rise to the precursor lesions GCNIS of the testis and gonodoblastoma in the dysgenetic gonad. By default, these lesions progress to seminoma/dysgerminoma unless a constituent cell which is a transformed primordial germ cell/gonocyte) is reprogrammed to an embryonal carcinoma cell which is the transformed counterpart of a naïve, totipotent ESC. This implies that a nonseminoma can arise directly from GCNIS. However, this does not imply that nonseminomas can only develop in a seminoma. For example, intratubular nonseminoma can develop from GCNIS or intratubular seminoma without the development of a seminoma.

The study of the earliest stage of neoplastic transformation of gonocytes both in the testis and the ovary/dysgenetic gonad has shown that disturbed maturation of gonocytes in a compromised niche during embryogenesis is the common pathogenesis of type II GCTs in the testis and ovary. The study of gonadal dysgenesis and extragonadal GCTs has shown that the presence of the Y chromosome, in particular the GBY locus with the multicopy TSPY gene, is the strongest risk factor for developing a type II GCT.^22,23 Co-expression of the pluripotency factor OCT4 and TSPY in gonocytes in a compromised niche puts them at risk for neoplastic transformation both in the testis and the ovary^24,25. Thus, the lower incidence of type II GCTs in the ovary than in the testis may be explained by women not having a Y chromosome.

Apparently, the initiated type II GCT cells stay dormant in the testis and the ovary, as well as in the mediastinum/thymus and midline brain. In both sexes, type II GCTs become clinically manifest at the start of puberty at all these sites, likely under the influence of the sex hormone concentrations increasing at puberty: androgens in males and estrogens in females. The lower peak in females is probably due to the lower number of initiated tumors in the absence of the Y-chromosome. The earlier peak may be explained by the earlier puberty in females. In addition, a large proportion of ovarian type II GCTs are associated with gonadal dysgenesis, in which they may appear from age four onwards. Finally, the inclusion of the type I GCTs in the nonseminomatous GCTs of the ovary contributes to the earlier peak in the ovary compared to the testis.

We can only speculate why the proportion of mixed GCT is lower in female nonseminoma compared with male nonseminoma. Among the ovarian non-dysgerminomas, there are type I tumors, which are most often pure teratomas or pure YSTs, and perhaps also some type IV GCTs (pure teratomas). Because of the broad, and overlapping age range of these ovarian GCT-types with the age range of ovarian type II GCTs, they can only be distinguished with certainty by molecular means.¹⁴

It is difficult to explain why the incidence rate of teratoma of postpubertal type (males) was higher in Germany than the US. Although only non-Hispanic white persons were included in this study, it cannot be ruled out that the ancestral mix in the US has a lower rate for type II GCTs than the German population, which shares the higher rates of Northern European countries.

The clearly higher rate of teratoma with somatic type malignancy (males & females) in Germany than the U.S. may be explained by different coding behaviors in these countries. According to ICD-O, 3^rd edition, teratoma can be coded as benign (9080/0), as neoplasms of uncertain or unknown behavior (9080/1), or as primary malignant (9080/3–9083/3). In contrast to the U.S. cancer registry data, the German cancer registry data for this project were quality controlled (male GCT by AS) or reviewed by a pathologist (female GCT by JWO) and the agreement as based on the pathology and clinical report review was excellent.

There are several factors that limit our results. First, although the underlying registry populations are very large, the absolute number of female OGCTs was still too small to evaluate histology-specific incidence rates more finely than differentiating dysgerminoma from non-dysgerminoma. Second, our study did not include a review of histological slides by a panel of reference pathologists and our review was only based on available pathology and clinical reports. Third, this study suffered from the lack of a comprehensive classification of benign and malignant GCTs of all anatomical sites including extragonadal GCTs that would allow a meaningful comparison of all GCTs, and not just of the seminomas/dysgerminomas.⁷

List of abbreviations

EC

embryonal carcinoma

ESC

embryonic stem cell

GCT

germ cell tumor

ICD-O

International Classification for Diseases in Oncology

NOS

not otherwise specified

NRW

North Rhine-Westphalia

OGCT

ovarian germ cell tumor

PGC

primordial germ cell

TGCT

testicular germ cell tumor

Data availability statement

The data underlying this article cannot be shared publicly due to the privacy of the patients. The data will be shared upon reasonable request to the corresponding author and ethical review of the study proposal.