Gonadal Germ Cell Tumors Research Articles

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

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. 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. 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). 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.

Quimioterapia de alta dose com suporte hematopoiético autólogo em tumores de células germinativas Experiência do Instituto Português de Oncologia de Lisboa Francisco Gentil.

High dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) has been administered to patients with high-risk germ cell tumours (GCT). The role of this treatment for GCT still remains unclear, including the identification of subgroups more likely to benefit from such strategy. A retrospective review was conducted of all male patients with gonadal and extra gonadal GCT treated with HDCT-ASCT between 1996 and 2008 at the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). Twenty patients were treated with HDCT-ASCT, 17 with primary testicular tumours, two mediastinal and one retroperitoneal GCT. According to the International Germ Cell Cancer Consensus Group (IGCCCG) classification, at diagnosis three patients had good risk, four intermediate, eight poor but for the patients left the risk group could not be ascertained. In eight patients HDCT-ASCT was used upfront, after induction with first-line conventional chemotherapy, and in the remaining 12 for relapsed GCT. One patient had platinum-resistant and another platinum-refractory disease. Only two patients had Beyer score > 2. All but one patient were treated with ICE (Ifosfamide, Carboplatin, Etoposide). Six patients underwent a second HDCT-ASCT course. The 5-year overall survival and progression free survival were respectively 53% and 44%; both patients with mediastinal GCT are long term survivors. Randomized studies to date have failed to indicate a survival advantage for HDCT-ASCT in GCT. This series is small and heterogeneous which prevents us from drawing conclusions regarding the benefit of this treatment for GCT. However, we could confirm the lack of benefit of HDCT-ASCT for platinum-resistant GCT and to question the absolute contraindication to this therapeutic modality in mediastinal GCT. HDCT-ASCT should therefore be performed exclusively in experienced centers and, preferably, in the setting of clinical trials.

Extragonadal Tumor and Testicular Microlithiasis: “Burned-out” Tumors Are Represented by Macrocalcification

To the Editor: The recent case report 1 and subsequent correspondence 2,3 raise some important issues surrounding the presence of testicular microlithiasis and nontesticular microlithiasis (macrocalcification) in both the pediatric and adult testis. We note the opinion of Harris 2 with regard to the occurrence of macrocalcification as more likely to represent the presence of a “burned-out” tumor rather than the presence of microlithiasis as advocated by Meyer and Gilbertson-Dahdal. 1,3 It seems to us unlikely that testicular microlithiasis is representative of a burned-out tumor as advocated by Meyer and Gilbertson-Dahdal. 1 Unfortunately the description and depiction of intratesticular calcification in many of the older articles they cite would not stand up to modern-day scrutiny; vague sonographic methods and assessment are only too evident (eg, Figure 4 in the article by Grantham et al 4 depicts areas of macrocalcification described as bright echogenic foci), likely a manifestation of the less sophisticated transducers of that period. The histologic characteristics of testicular microlithiasis are very different from those of the necrosis, macrocalcification, and possible tumor cell remnants associated with a burned-out tumor 5 ; testicular microlithiasis clearly shows calcified intratubular bodies on histologic specimens. 6 The sonographic features of testicular microlithiasis as classically described are unique to this entity and are not mimicked by other forms of intratesticular calcification. However, the underlying association of testicular microlithiasis as well as burned-out tumors (manifested by macrocalcification) with intratubular germ cell neoplasia, a precursor of a germ cell tumor, indicates an increased risk of tumor development in both testicular microlithiasis and macrocalcification groups. Hence, testicular microlithiasis is associated with intratubular germ cell neoplasia and with that association an increased risk of developing a tumor. Thus, an area of macrocalcification may represent a burned-out tumor, but the remainder of the testis remains at risk if intratubular germ cell neoplasia is present, and it usually is present. We believe that the finding of testicular microlithiasis in the case of Meyer and Gilbertson-Dahdal 1 is more likely to indicate the simultaneous presence of intratubular germ cell neoplasia and not areas of a burned-out tumor. The finding of testicular microlithiasis is incidental and is a marker of the risk associated with intratubular germ cell neoplasia, with no manifestation in the testis of a focal tumor or macrocalcification to indicate the origin in the testis of the retroperitoneal germ cell tumor: a truly “silent” testis for the presence of the source of the retroperitoneal germ cell tumor. Harris was unable to identify any studies that address the prevalence of macrocalcification. We have addressed the prevalence of all types of calcification on scrotal sonography and related it to the presence of primary testicular tumors in 3447 patients, 7 having earlier described in detail the types of scrotal calcification that may be encountered. 8 Any intratesticular calcification not typical of the description of microlithiasis was termed “nontesticular microlithiasis calcification (macrocalcification),” and this is the type of calcification that may be shown when a burnedout tumor is diagnosed in the presence of an extragonadal germ cell tumor, as indicated by the experience of Harris. 2 The prevalence of testicular microlithiasis in our study population was 2.0% (95% confidence interval [CI], 1.6%– 2.6%), and that of nontesticular microlithiasis calcification was 1.7% (95% CI, 1.3%–2.3%). The association with a metachronous primary germ cell tumor was significant in both types of intratesticular calcification. 7 A small subset of pediatric patients (n = 198) was also analyzed, with the prevalence of testicular microlithiasis recorded as 2.0% (95% CI, 0.6%–5.1%) and that of nontesticular microlithiasis recorded as 0.5% (95% CI, 0.0%–2.8%). Our figures, although not significant in the pediatric group with the small cohort analyzed, warrant further evaluation. A possible scenario would advocate that testicular microlithiasis is present in the pediatric population at the same level as that seen in the adult population, but nontesticular microlithiasis increases in the adult patient. This scenario would support the theory that nontesticular microlithiasis is a manifestation of a burned-out tumor that puts the patient at risk of developing a further germ cell tumor of the testis or is responsible for an existing extra gonadal germ cell tumor. There are scarce data to support this theory; it is time we looked more closely at the prevalence of testicular calcification in the pediatric population. We would agree with Harris 2 that a burned-out tumor is represented by nontesticular microlithiasis macrocalcification, and testicular microlithiasis has associations with germ cell tumors and extragonadal tumors. However, areas of testicular microlithiasis, as classically described on sonography, do not represent tumor involution.

Age-Specific Incidence Data Indicate Four Mutations Are Required for Human Testicular Cancers

Normal human cells require a series of genetic alterations to undergo malignant transformation. Direct sequencing of human tumors has identified hundreds of mutations in tumors, but many of these are thought to be unnecessary and a result of, rather than a cause of, the tumor. The exact number of mutations to transform a normal human cell into a tumor cell is unknown. Here I show that male gonadal germ cell tumors, the most common form of testicular cancers, occur after four mutations. I infer this by constructing a mathematical model based upon the multi-hit hypothesis and comparing it to the age-specific incidence data. This result is consistent with the multi-hit hypothesis, and implies that these cancers are genetically or epigenetically predetermined at birth or an early age.

Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—Shifting the paradigm

Recent morphologic, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. Type I tumors comprise low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas, and Brenner tumors. They are generally indolent, present in stage I (tumor confined to the ovary), and are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN, PIK3CA, ARID1A, and PPP2R1A, which target specific cell signaling pathways. Type I tumors rarely harbor TP53 mutations and are relatively stable genetically. Type II tumors comprise high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. They are aggressive, present in advanced stage, and have a very high frequency of TP53 mutations but rarely harbor the mutations detected in type I tumors. In addition, type II tumors have molecular alterations that perturb expression of BRCA either by mutation of the gene or by promoter methylation. A hallmark of these tumors is that they are genetically highly unstable. Recent studies strongly suggest that fallopian tube epithelium (benign or malignant) that implants on the ovary is the source of low-grade and high-grade serous carcinoma rather than the ovarian surface epithelium as previously believed. Similarly, it is widely accepted that endometriosis is the precursor of endometrioid and clear cell carcinomas and, as endometriosis, is thought to develop from retrograde menstruation; these tumors can also be regarded as involving the ovary secondarily. The origin of mucinous and transitional cell (Brenner) tumors is still not well established, although recent data suggest a possible origin from transitional epithelial nests located in paraovarian locations at the tuboperitoneal junction. Thus, it now appears that type I and type II ovarian tumors develop independently along different molecular pathways and that both types develop outside the ovary and involve it secondarily. If this concept is confirmed, it leads to the conclusion that the only true primary ovarian neoplasms are gonadal stromal and germ cell tumors analogous to testicular tumors. This new paradigm of ovarian carcinogenesis has important clinical implications. By shifting the early events of ovarian carcinogenesis to the fallopian tube and endometrium instead of the ovary, prevention approaches, for example, salpingectomy with ovarian conservation, may play an important role in reducing the burden of ovarian cancer while preserving hormonal function and fertility.

Protocol for the Examination of Specimens From Pediatric and Adult Patients With Extragonadal Germ Cell Tumors

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Pediatric germ cell tumors and parental infertility and infertility treatment: A Children's Oncology Group report

BackgroundFew risk factors have been established for childhood germ cell tumors (GCT). Parental infertility and infertility treatment may be associated with GCT development but these risk factors have not been fully investigated. MethodsA case–control study of childhood GCT was conducted through the Children's Oncology Group (COG). Cases, under the age of 15 years at diagnosis, were recruited through COG institutions from January 1993 to December 2002. Controls were obtained through random digit dialing. Information about infertility and infertility treatment along with demographic factors was collection through maternal interviews. Subgroups created by gender, age at diagnosis, and tumor location were examined separately. Statistical analysis was performed using multivariate logistic regression models. ResultsOverall, no association between GCT and infertility or its treatment was found. In subgroup analysis, females whose mothers had two or more fetal losses were found to be at increased risk for non-gonadal tumors (Odds ratio (OR)=3.32, 95% Confidence interval (CI)=1.12–9.88). Younger maternal age was associated with a lower risk of gonadal GCT in females (OR=0.52, 95% CI=0.28–0.96). There was an increased risk of all GCT and gonadal GCT in males born to older mothers (OR=2.88, 95% CI=1.13–7.37 and OR=3.70, 95% CI=1.12–12.24). ConclusionWhile no association between parental infertility or its treatment and childhood GCT was found overall, possible associations with maternal age and history of recurrent fetal loss were found in subgroups defined by gender.

Ovarian Choriocarcinoma as the First Manifestation of 46,XY Pure Gonadal Dysgenesis

We report a case of 46,XY pure gonadal dysgenesis (Swyer syndrome) in a phenotypically normal 12-year-old girl with a history of vaginal bleeding and early breast development, with ovarian choriocarcinoma as the first manifestation. The clues leading to the diagnosis included the failure to establish any relationship between normal menstrual cycles postoperatively and a small remaining contralateral ovary. The correct diagnosis is important for cancer prophylaxis and hormonal replacement therapy. Prepubertal and peripubertal girls presenting with gonadal germ cell tumors should be carefully evaluated for the possibility of underlying gonadal dysgenesis. A history of vaginal bleeding or early signs of puberty does not exclude the diagnosis.

Treatment and survival patterns for germ cell tumors among 13- to 24-year olds in Yorkshire, UK

Teenage and young adult (TYA) patient care can fall into gaps between adult and children's services. Increasingly UK TYA multi-disciplinary teams manage germ cell tumors (GCT) in locally agreed collaborations and age ranges. Patterns of care are changing rapidly. However, between disciplines protocols define different assessment and management in GCT. We aimed to document changes in incidence, treatment, and survival since 1990, to record the baseline to which future trends can be compared. Details were extracted from the UK population-based Yorkshire Specialist Cancer Register on 237 TYA aged 13-24 years diagnosed with a GCT between 1990 and 2004, followed-up until 2009. Incidence and survival patterns were assessed using Poisson and Cox regression. Testicular (n = 190; 80%) and ovarian (n = 22; 9%) GCT were the most common malignancies, and 90% of GCT occurred aged 17-24 years. The overall incidence rate was 26.9 per million person years. Rates increased significantly by 4.0% (95% CI: 1.0-7.1%) per year on average. The most common treatment modality was surgery combined with chemotherapy (49%). Initial treatment changed significantly over time (P = 0.003) and by age (P = 0.005). There were significant differences in the management of stage 1 testicular tumors by age. Among 13- to 16-year olds, 56% were treated exclusively in adult departments. Five-year survival rates were 93-95% for gonadal GCT, and 70-75% for other sites. Survival did not differ by age (P = 0.65) or period (P = 0.41). The age-related differences observed in the approach to GCT treatment suggest a collaborative approach to the models of care among TYA is required.

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

BackgroundSex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity.Case PresentationWe performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein.ConclusionOur results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors.

Pediatric cancer spectrum in Kenya: a histopathologic review

Pediatric malignancies constitute a unique health care burden especially in resource-poor settings such as Africa, and the use of external epidemiologic data in managing these children may lead to erroneous approaches. A retrospective histopathologic analysis of 6,771 pathology reports between March 1992 and August 2006 was undertaken in children under the age of 18. Data were derived from the Kijabe Hospital pathology database, which receives pathologic specimens from 70 different mission hospitals, clinics, and regional hospitals throughout Kenya. 1,217 of these specimens represented malignancies. The top ten pediatric malignancies were Burkitt's lymphoma (16.6%), non-Hodgkin's lymphoma (8.5%), Hodgkin's lymphoma (7.6%), Kaposi's sarcoma (7.6%), osteosarcoma (7.3%), gonadal germ-cell tumors (5.8%), rhabdomyosarcoma (3.5%), nephroblastoma (3.4%), epithelial carcinoma (2.8%), and chondrosarcoma (1.8%). Comparison with several previous African and western pediatric cancer databases is undertaken, revealing significant trends useful for the care of children with cancer in the region.

A case of intra cardiac yolk sac tumour

Germ cell tumours (GCTs) are benign or malignant neoplasms arising from primordial germ cells which can be gonadal or extragonadal in origin. In contrast to adult patients, the incidence of extragonadal tumours exceeds gonadal ones in patients younger than 15 years old. Heart is an extremely rare site for a GCT and the outcome is not as good as other extra gonadal GCTs due to its lethal cardiac complications. Index words: yolk sac tumour, malignant intracardiac tumour DOI: 10.4038/cmj.v55i2.2003 Ceylon Medical Journal Vol.55(2) 2010 pp.40-44

Primary Gonadal Germ Cell Tumor Associated With Acute Leukemia With Common Cytogenetics

Primary Gonadal Germ Cell Tumor Associated With Acute Leukemia With Common Cytogenetics

Diagnostic Utility of SALL4 in Extragonadal Yolk Sac Tumors

Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in 58) and 10 (17%) of them also showed focal epithelial membrane antigen staining (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the staining was often focal (in less than 30% tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%); however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and 60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.

Placental Site Trophoblastic Tumor in the Ovary of a Young Child with Isosexual Precocious Puberty

The authors report a unique case of a primary ovarian placental site trophoblastic tumor (PSTT) in a 30-month-old girl who presented with isosexual precocious puberty of 1 month duration. Laboratory studies revealed mildly elevated beta human chorionic gonadotropin (37.5 mIU/ml; reference range <3.0 mIU/ml) and estradiol (74 pg/ml; reference range 0 to 56 pg/ml) serum levels. A 3.5-cm right ovarian mass was detected radiographically. The tumor was confined to the ovary as proven by the preoperative staging workup and the exploratory laparotomy. Microscopically, it was composed of intermediate trophoblastic cells with angioinvasive growth and deposition of fibrinoid material. The tumor cells were diffusely positive for human leukocyte antigen G, melanoma cell adhesion molecule (CD146), and cytokeratins (AE1/AE3, CK18, and CAM 5.2). Stains for human chorionic gonadotropin, alpha-inhibin, and human placental lactogen showed focal immunoreactivity. Serum markers returned to normal postoperatively. The patient remains disease-free at 24-months follow-up. We propose that tumors morphologically identical to uterine PSTT may rarely occur as gonadal germ cell tumors in children.

Cytologic features of extragonadal germ cell tumors

The objective of the current study was to evaluate and describe the cytologic features of extragonadal germ cell tumors (GCTs), both primary and metastasis from gonadal sites, in fine-needle aspiration cytology. Aspirates from 88 extragonadal GCTs were retrieved with their clinical features and cytologic smears. The smears were assessed for cellularity, cell patterns, and cytologic features, which were summarized. Histopathology was available in 47 cases, and cytohistologic correlation was done in all such cases. Of 88 cases, 57 with adequate cytologic material were analyzed. Each type of GCT, except for embryonal carcinoma, had characteristic morphologic features. Seminomas had dyscohesive tumor cells with well defined, vacuolated cytoplasm; prominent nucleolus; and background lymphocytes. 'Tigroid' background was noted in only a minority of cases. Yolk sac tumors revealed papillary fragments of tumor cells with metachromatic basement membrane-like material in the fragments. Mixed germ cell tumors were difficult to diagnose except for cases in which more than 1 type of GCT was observed on cytologic smears. In 37% of cases with mixed GCT, only 1 component was observed on cytology. Fine-needle aspiration cytology can reliably offer a diagnosis of GCT at extragonadal sites, even in rare locations and in patients in whom metastatic tumor may be the first clinical presentation. Immature teratoma and mixed GCTs pose a significant problem in cytology because of sampling error on needle aspiration. At extragonadal sites, the list of differential diagnoses is wider than that for gonadal GCTs.

Sex-specific incidence and temporal trends in solid tumours in young people from Northern England, 1968-2005.

BackgroundThis study examined sex-specific patterns and temporal trends in the incidence of solid tumours in the Northern Region of England from 1968 to 2005. This updates earlier analyses from the region where sex was not considered in depth. Sex-specific analyses were carried out to determine whether sex differences might provide clues to aetiology.MethodsDetails of 3576 cases, aged 0–24 years, were obtained from a specialist population-based cancer registry. There were 1843 males (886 aged 0–14 years and 957 aged 15–24 years) and 1733 females (791 aged 0–14 years and 942 aged 15–24 years). Age-standardized incidence rates (per million population) were calculated. Linear regression was used to analyze temporal trends in incidence and annual percentage changes were estimated. Analyses were stratified by sex and by age-group.ResultsThere were marked differences in incidence patterns and trends between males and females and also between age-groups. For males central nervous system (CNS) tumours formed the largest proportion of under-15 cases and germ cell tumours was the largest group in the 15–24's, whilst for females CNS tumours dominated in the under-15's and carcinomas in the older group. For 0–14 year olds there were male-specific increases in the incidence of rhabdomyosarcoma (2.4% per annum; 95% CI: 0.2%–4.5%) and non-melanotic skin cancer (9.6%; 95% CI: 0.0%–19.2%) and female-specific increases for sympathetic nervous system tumours (2.2%; 95% CI: 0.4%–3.9%), gonadal germ cell tumours (8.6%; 95% CI: 4.3%–12.9%) and non-gonadal germ cell tumours (5.4%; 95% CI: 2.8%–7.9%). For 15–24 year olds, there were male-specific increases in gonadal germ cell tumours (1.9%; 95% CI: 0.3%–3.4%), non-gonadal germ cell tumours (4.4%; 95% CI: 1.1%–7.7%) and non-melanotic skin cancer (4.7%; 95% CI: 0.5%–8.9%) and female-specific increases for osteosarcoma (3.5%; 95% CI: 0.5%–6.5%), thyroid cancer (2.8%; 95% CI: 0.1%–5.6%) and melanoma (4.6%; 95% CI: 2.2%–7.1%).ConclusionThis study has highlighted notable differences between the sexes in incidence patterns and trends for solid tumours. Some of these sex-specific differences could have been obscured if males and females had been analysed together. Furthermore, they suggest aetiological differences or differential susceptibility to environmental factors between males and females.

Metastatic Malignant Teratoma Arising from Mediastinal Nonseminomatous Germ Cell Tumor: A Case Report

Primary mediastinal nonseminomatous germ cell tumors (NSGCT) have a worse prognosis than gonadal germ cell tumors (GCTs). Malignant transformation of teratomatous components of GCT to a somatic malignancy is rare. We present a case of primary mediastinal NSGCT with malignant transformation of a teratoma in an active duty airman who presented with a 12-cm anterior mediastinal mass and vertebral body lesion. Pathology confirmed NSGCT with yolk sac and teratomatous components. Chemotherapy for GCT normalized serum tumor markers with little effect on the mediastinal mass. Incomplete resection of the residual tumor revealed high-grade mixed sarcoma. Serum tumor markers rose 3 months following resection with metastatic disease to bone and liver. Chemotherapy targeting sarcoma induced a partial response, but the patient developed acute myeloid leukemia refractory to chemotherapy. We discuss our approach to management of this complicated patient.

Influence of Tumor Site and Histology on Long-Term Survival in 193 Children with Extracranial Germ Cell Tumors

Although germ cell tumors (GCT) supposedly share the same cell type of origin, their clinical course differs considerably depending on tumor site and histology. The aim of this work was to study long-term survival stratified for tumor site and tumor histology. The medical records of 193 consecutive infants and children with extracranial GCT were studied. The GCT arose in the following anatomical sites: sacrococcygeal (n = 70), ovary (n = 66), testis (n = 20), retroperitoneum (n = 12), neck (n = 8), mediastinum (n = 7), and miscellaneous (n = 10). Histological analysis revealed 152 teratomas (mature: 115, immature: 37), 27 yolk sac tumors, 8 mixed tumors, 2 dysgerminomas, 2 gonadoblastomas, 1 choriocarcinoma and 1 embryonal carcinoma. Overall survival (OS) for the whole patient group was 0.91 +/- 0.02, and event-free survival (EFS) was 0.88 +/- 0.02 at ten years. Patients with gonadal GCT had a higher probability of OS than those with extragonadal GCT (p = 0.029). Patients with cervical and mediastinal tumors had a lower probability of EFS than those with gonadal, retroperitoneal or sacrococcygeal GCT (p = 0.018). Patients with choriocarcinoma, embryonal carcinoma, immature teratoma, yolk sac tumor and mixed GCT had a lower probability of EFS than patients with mature teratoma or gonadoblastoma (p < 0.001). Mortality in children with extracranial germ cell tumors is not only dictated by malignant histology, but also, as in the case of mature teratomas, by occurrence at certain sites.

Pediatric germ cell tumors

Pediatric germ cell tumors are a diverse group of neoplasms with variable clinical behaviors, depending upon the age and site of presentation. Most result from sporadic mutations, although environmental exposures and other genetic aberrations may play a role. Platinum-based chemotherapy has dramatically improved the event-free and overall survival outcomes of pediatric patients with malignant germ cell tumors over the past two decades. Prognosis is dependent on tumor stage and location. Patients with gonadal germ cell tumors have at least a 95% 5-year survival for early stage disease and at least a 85% 5-year survival for advanced stages. In general, extragonadal germ cell tumors carry a poorer prognosis with mediastinal location having the worst outcomes (70% 4-year survival). Current trials are focused on maintaining similar excellent outcomes while reducing morbidity by reducing the dose and duration of chemotherapy. Cytogenetic research studies have found chromosomal aberrations specific to some of these tumors that may serve as prognosticators and even direct therapy.