Maternal exposure to environmental endocrine disruptors during pregnancy is associated with pediatric germ cell tumors.

Environmental endocrine disruptors (EEDs) are natural or synthetic chemical compounds that interfere with normal endocrine function in both wildlife and humans. Previous studies have indicated that EEDs may contribute to oncogenesis. This study explores the relationship between EEDs and pediatric germ cell tumors (GCTs). A case-control study was conducted in 84 pediatric patients from 2014 to 2017, including 42 subjects with immature teratoma, yolk sac tumor, or germinoma, and 42 controls who experienced pneumonia or trauma. Serum PFASs, including PFBS, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUA, PFOSA, and PFDoA, were measured in each subject, and their history of possible EED exposure was reviewed. Six of the 10 measured PFASs were significantly increased in the GCT group relative to the control group. With respect to lifestyle history, only PFHxS levels were statistically significantly associated with GCTs as determined by logistic regression analysis. The odds ratio for a 1 ng/L increase in PFHxS was 19.47 (95% CI: 4.20-90.26). Furthermore, in the GCT and control groups, both parental consumption of barbecued foods and hair dye use among parents were significantly correlated with elevated serum PFHxS levels (ρ = 0.383, 0.325 in the patient group and ρ = 0.370, 0.339 in the control group; p < 0.05). Our study confirmed that children with GCTs from our institute had relatively high serum levels of PFASs relative to those of tumor-free pediatric patients. Serum PFHxS levels were independently associated with germ cell tumor occurrence.

Pituitary germinomas: a multi-institutional study analyzing patient demographics and management patterns.

PURPOSE: Intracranial germinomas are exceedingly rare tumors found in the pineal and suprasellar regions. The extremely low incidence of pituitary germinoma has resulted in a significant gap in knowledge regarding its demographics, management, and treatment outcomes. We present the largest multicenter analysis of pituitary germinomas to date, focused on analyzing demographic and management patterns. METHODS: This study utilizes the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (2004-2016) to study patients with a primary intracranial germinoma of the pituitary gland. We analyzed demographic information and management strategies among adult and pediatric populations and conducted a 20-year overall survival analysis using Kaplan-Meier curve for a descriptive evaluation of survival outcomes between age groups and treatment groups. RESULTS: 92 patients were included in the study, consisting of 58% pediatric patients and 42% adults, with overall 60% males. 82% patients received radiation as part of the treatment, with no significant difference between pediatric and adult groups. Chemotherapy was used significantly more in pediatrics (p = 0.0002) while surgery was significantly more common in adults (p = 0.0117). The most common treatment in pediatrics was radiation + chemotherapy (47%), while the most common treatment in adults was radiation + gross total resection + chemotherapy (23%) followed by radiation + gross total resection (19%). Younger age, radiotherapy, and chemotherapy were associated with increased 20-year survival on Kaplan-Meier curves. CONCLUSIONS: There exist significant differences in the management of pediatric and adult populations with pituitary germinomas. The low incidence of these tumors makes them challenging to study, but also highlights the importance of national cancer registries in amassing sufficient patient data from which to draw evidence-based conclusions.

Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Engrosamiento del tallo hipofisario en niños y adolescentes con diabetes insípida central: causas y consecuencias / Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences

Introducción: La diabetes insípida central (DIC) es una entidad poco frecuente en la edad pediátrica, siendo su etiología heterogénea. El objetivo de nuestro trabajo es demostrar que el seguimiento clínico y neurorradiológico de la región hipotálamo-hipofisaria, puede ayudar a establecer el diagnóstico etiológico de DIC y la presencia de otros déficits hormonales. Métodos: Se revisaron de forma retrospectiva 15 pacientes diagnosticados de DIC en un hospital pediátrico. Se analizaron las características clínicas y auxológicas; así como la valoración de la función adenohipofisaria junto con RM craneal de manera periódica. Resultados: La mediana de edad al diagnóstico fue de 9,6 años (rango: 1,3-15,9). El diagnóstico etiológico pudo establecerse en 9 de los 15 pacientes (germinomas: 7 e histiocitosis: 2). Tras una mediana de seguimiento de 5,5 años (rango: 1,6-11,8), los casos idiopáticos se redujeron a la mitad. Finalmente, los diagnósticos etiológicos fueron: germinoma 9 (60%), histiocitosis 3 (20%) y DIC idiopática 3 (20%). Existe una asociación estadísticamente significativa entre el engrosamiento del tallo y la etiología tumoral. El 67% desarrolló, al menos, una deficiencia hormonal adenohipofisaria, la mayoría en los dos primeros años de seguimiento. El déficit más prevalente fue el de hormona de crecimiento (60%). Conclusiones: En todos los pacientes con DIC se deberá realizar un control auxológico y hormonal, con especial atención, por su frecuencia, a la deficiencia de GH, y en aquellos con DIC idiopática se debería incluir una RM semestral, al menos durante los 2-3 primeros años después del diagnóstico, pues en nuestro estudio el 50% fueron diagnosticados de germinomas o histiocitosis en este periodo

Background: Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. Methods: Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. Results: The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. Conclusion: The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period

[Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences]. / Engrosamiento del tallo hipofisario en niños y adolescentes con diabetes insípida central: causas y consecuencias.

BACKGROUND: Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. METHODS: Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. RESULTS: The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. CONCLUSION: The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period.

Visual complaints in intracranial germinomas.

OBJECTIVE: Patients with brain tumors often report having visual complaints. This may be due to increased intracranial pressure, compression/invasion of the optic pathway or diplopia. We assessed the incidence and the etiology of visual symptoms in patients with intracranial germinoma tumors (ICGTs). METHODS AND MATERIALS: We performed a blinded retrospective review of the clinical charts and the initial magnetic resonance imaging (MRI) of 28 patients with ICGT. Thirteen tumors were pineal, five suprasellar, seven bifocal, and further three involved either the optic nerve, the corpus callosum, or the brainstem. RESULTS: Twelve patients reported visual disturbances, seven of whom mainly experienced a decrease in vision. Two of those were initially managed as "retrobulbar neuritis" when endocrinologic symptoms prompted assessment by MRI. Involvement of the optic pathway was underestimated, and both relapsed. Field deficits were definitive sequelae, whereas visual acuity was sometimes regressive in the absence of optic atrophy. CONCLUSIONS: Compression or invasion of the optic pathway by germinomas is not a rare occurrence, and this possibility should not be overlooked when thickening or contrast enhancement is detected. Radiotherapy fields should be extended accordingly.

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

BACKGROUND: Pediatric and young adult central nervous system (CNS) germinomas have favorable cure rates. However, long-term follow-up data are limited because of the rarity of this tumor. We report the long-term overall survival (OS) and causes of late mortality for these patients. METHODS: Data between 1973 and 2005 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Kaplan Meier survival analysis was performed on 5-year survivors of childhood CNS germinomatous germ cell tumors (GGCTs) and nongerminomatous germ cell tumors (NGGCTs). Standardized mortality ratios (SMRs) were calculated using US population data to compare observed versus expected all-cause death and death from stroke. Cumulative incidence was calculated using a competing risk model. RESULTS: Four hundred five GGCTs and 94 NGGCTs cases were eligible. OS at 20 and 30 years for GGCTs was 84.1% and 61.9%, respectively, and was 86.7% for NGGCTs at both time points. Five-year survivors of GGCTs and NGGCTs experienced a 10-fold increase in mortality risk compared with their peers (SMR, 10.41; 95% confidence interval [CI], 7.71-13.76 vs SMR, 10.39;95% CI, 4.83-19.73, respectively). Five-year survivors GGCTs also experienced a nearly 59-fold increase in risk of death from stroke (SMR, 58.93; 95% CI, 18.72-142.10). At 25 years, the cumulative incidence of death due to cancer and subsequent malignancy was 16% and 6.0%, respectively. CONCLUSION: Although CNS germinomas have favorable cure rates, late recurrences, subsequent malignancies, and stroke significantly affect long-term survival. Close attention to long-term follow-up with assessment of stroke risk factors is recommended.

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

PURPOSE: Malignant germ cell tumors (GCTs) are a heterogeneous group of neoplasms putatively originating from the primordial germ cell. In adults, an increasing incidence of GCTs, particularly testicular tumors, has been reported in recent decades. However, population-based evidence in children and adolescents remains limited. We investigated the incidence of malignant GCTs diagnosed in childhood or adolescence, using population-based nationwide data from Finland. METHODS: We obtained information from the Finnish Cancer Registry on all malignant GCTs registered in 1969-2008 in children or adolescents aged 0-19 years. Data on tumor location, histology, stage, and survival were collected. Age-standardized incidence and survival rates were calculated. RESULTS: A total of 334 cases of malignant GCT were identified. Their proportion among all malignant tumors among 0- to 19-year-olds increased from 3 to 9.7% in boys with time, but remained stable in girls (3%). The overall incidence rate was 0.6 per 100,000 (0.8 in boys and 0.4 in girls), and differed significantly between the age groups. A significant increase in the incidence of testicular GCTs was seen in boys in the age group of 15-19 years. CONCLUSIONS: Although malignant GCTs are rare, their relative frequency in children and adolescents has increased during recent decades, the change being mainly due to an increasing frequency of the testicular tumors among teenagers. The causes of the increase remain unknown, but environmental exposures are likely to be involved.

[Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010].

OBJECTIVE: To examine the recent incidences and trends of childhood malignant solid tumors in Shanghai. METHOD: Data from the population-based Shanghai Cancer Registry and related retrospective survey were used to analyze the patterns of incidence and trends of malignant solid tumors diagnosed between 2002 and 2010 in children aged 0-14 years. The distributions of incidences were described according to gender, age and cancer types which were classified according to International Classification of Childhood Cancer (ICCC). Annual age-standardized rates (ASRs) were adjusted by the world standard population. Approximate confidence intervals for standardized rate ratios (SRR) based Poisson distribution test-based methods were used to assess changes in incidence over the period 2002 - 2006 and 2007 - 2010. RESULT: (1)A total of 868 cases of childhood malignant solid tumors were diagnosed in Shanghai during 2002 - 2010, accounting for 65.8% of all childhood cancers. The ASR of 2002 - 2010 was 80.2 per million for all solid tumors. (2) The ASR was higher in boys (86.3 per million) than in girls (73.8 per million) with SRR 1.2 (95%CI 1.0 - 1.3). Incidence rate was the highest in the first five years of life with 93.4 per million. The age-specific incidence rates in 5 - 9 and 10 - 14 age groups were 65.2 and 79.3 per million, respectively. (3) CNS tumors, lymphomas, germ cell tumors, neuroblastoma, and soft tissue sarcomas were the top 5 most common solid tumors in children, with the incidence rate of 23.8, 11.0, 7.8, 7.7 and 6.8 per million, respectively. The patterns of subgroups varied in different age groups. Blastomas, such as neuroblastoma, retinoblastoma, were more common in the children aged 0 - 4 years, whereas epithelial carcinomas and bone tumors developed more frequently in elder children aged 10 - 14 years. (4) Compared with the ASR in 2002 - 2006, the ASR for both genders in 2007 - 2010 had no substantial changes (78.7 per million in 2002 - 2006 and 82.9 per million in 2007 - 2010). However, among boys, the incidence rate in 2007 - 2010 was significantly higher than that in 2002 - 2006 with SRR 1.2 (95%CI: 1.0 - 1.4). For specific subgroups of cancer, there were no substantial changes. Some cautions should be taken when interpreting results involving a small number of cases per year and those with wide 95% confidence intervals. CONCLUSION: The incidence rate of pediatric malignant solid tumors among males was higher than females during 2002 - 2010, and it differed among different age groups with the highest in the first five years of life. CNS tumor was the most common type of solid tumors in children. This was a unique characteristics comparing with adult reflected in disease spectrum and age of onset. The patterns of incidence and its trends for childhood malignant solid tumors in Shanghai could provide a basis for etiologic research and preventive interventions. The findings also suggest an urgent need for longer population-based surveillance to verify the pattern and changing trends.

The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis?

OBJECT: Intracranial germ cell tumors (GCTs) frequently present with bifocal lesions in both the suprasellar and pineal areas. The pathogenesis of these bifocal GCTs has been the subject of controversy. Bifocal GCTs may be caused by synchronous tumors or by metastatic spread of tumor cells from one site to the other. The prognosis associated with bifocal GCTs has also been a cause of concern. METHODS: The authors constructed a single-institution patient cohort comprising 181 patients with intracranial GCTs. The clinical characteristics of bifocal GCTs were compared with those of suprasellar and pineal GCTs. RESULTS: Bifocal GCTs were observed in 23 patients (12.8%). Eighteen patients presented with bifocal GCTs that were diagnosed as germinomas, but 5 patients exhibited mixed GCTs. Analyses of age distributions and comparisons of tumor sizes were compatible with a model of a metastatic origin of bifocal GCTs. Eleven patients (47.8%) presenting with bifocal GCTs exhibited tumor seeding at presentation. Tumor seeding was significantly associated with bifocal lesions (p < 0.001). Patients with bifocal germinomas showed significantly shorter event-free survival and overall survival than did those presenting with germinomas from a single site of origin. CONCLUSIONS: Bifocal GCTs are not restricted to germinomas, as had been previously reported, but do include mixed GCTs. The authors hypothesize that bifocal GCTs may result from the metastatic spread of suprasellar or pineal GCTs. The bifocal presentation of germinomas may be a poor prognostic sign and should alert clinicians to the possibility of a disseminated disease.

Shedding light on testicular cancer.

Testicular cancer, though generally uncommon, is the most common cancer NPs will see in young men. Advances in surgery, radiation, and cisplatin-based chemotherapy, have made testicular cancer a "model" for a curable cancer. Survivors will likely live many years, but will require lifelong follow-up for possible recurrence and long-term treatment sequelae.

[Primary central nervous system tumours reported in Cartagena, 2001-2006]. / Tumores primarios del sistema nervioso central en Cartagena, 2001- 2006.

OBJECTIVES: Determining the frequency of primary central nervous system tumours diagnosed in Cartagena; Colombia, from 2001-2006 and determining the demographic, epidemiological and clinical characteristics of patients having central nervous system tumours reported by a single institution in Cartagena between 2001 and 2006. METHODS: A passive epidemiological surveillance descriptive study was carried out. The pathology reports of new diagnosed central nervous system primary tumours from all laboratories in Cartagena were taken and the available clinical records regarding these cases were analysed. The overall incidence rate and incidence rates by year, gender, age and histological type were estimated, with 95 % confidence intervals. Standardised morbidity rates were also calculated. RESULTS: There were 390 such cases during 2001-2006. The overall incidence rate was 6.91/100,000 people-year. Meningiomas were the most frequently occurring histological types (3.46/100,000 people-year). The provenance could only be determined in 43.1 % of cases. Standardised morbidity rates were higher in Cartagena regarding those reported in the United States and by the Colombian National Cancer Institute and the Population-based Cali Cancer Registry. CONCLUSIONS: There was a higher incidence of primary central nervous system tumours in Cartagena than in the rest of the country. Registry and surveillance systems should be improved and research into risk factors encouraged.

Tumores primarios del sistema nervioso central en Cartagena, 2001- 2006 / Primary central nervous system tumours reported in Cartagena, 2001-2006

Objetivos Determinar la frecuencia de los tumores primarios del sistema nervioso central, diagnosticados en Cartagena de Indias durante el periodo de 2001-2006 y, determinar las características demográficas, epidemiológicas y clínicas de los pacientes con tumores del sistema nervioso central de una institución de la ciudad, en el mismo periodo. Métodos Se realizó un estudio descriptivo de vigilancia epidemiológica pasiva. Se tomaron los reportes de patología con diagnóstico nuevo de tumor primario del sistema nervioso central de todos laboratorios de Cartagena y se analizaron las historias clínicas disponibles de estos casos. Se estimaron las tasas de incidencia general, por año, género, grupos de edad y tipo histológico con intervalos de confianza al 95 por ciento. Además se calcularon razones estandarizadas de morbilidad. Resultados Durante los años 2001 y 2006 se encontraron 390 casos. La tasa incidencia general fue de 6,91/100 000 personas-año. El tipo histológico más frecuente fue meningioma (3,46/100 000 personas-año). Sólo se determinó la procedencia en el 43,1 por ciento de los casos. Las razones estandarizadas de morbilidad fueron más altas en Cartagena con respecto a las de los Estados Unidos, el Instituto Nacional de Cancerología de Colombia y el Registro Poblacional de Cáncer de Cali. Conclusiones Hubo una frecuencia de tumores primarios del sistema nervioso central más elevada en Cartagena que en el resto del país. Se recomienda mejorar los sistemas de registro y vigilancia para determinar la magnitud real del problema y fomentar investigaciones en busca de factores de riesgo.

Objectives Determining the frequency of primary central nervous system tumours diagnosed in Cartagena; Colombia, from 2001-2006 and determining the demographic, epidemiological and clinical characteristics of patients having central nervous system tumours reported by a single institution in Cartagena between 2001 and 2006. Methods A passive epidemiological surveillance descriptive study was carried out. The pathology reports of new diagnosed central nervous system primary tumours from all laboratories in Cartagena were taken and the available clinical records regarding these cases were analysed. The overall incidence rate and incidence rates by year, gender, age and histological type were estimated, with 95 percent confidence intervals. Standardised morbidity rates were also calculated. Results There were 390 such cases during 2001-2006. The overall incidence rate was 6.91/100,000 people-year. Meningiomas were the most frequently occurring histological types (3.46/100,000 people-year). The provenance could only be determined in 43.1 percent of cases. Standardised morbidity rates were higher in Cartagena regarding those reported in the United States and by the Colombian National Cancer Institute and the Population-based Cali Cancer Registry. Conclusions There was a higher incidence of primary central nervous system tumours in Cartagena than in the rest of the country. Registry and surveillance systems should be improved and research into risk factors encouraged.

Familial coaggregation of cryptorchidism, hypospadias, and testicular germ cell cancer: a nationwide cohort study.

BACKGROUND: Cryptorchidism, hypospadias, and testicular germ cell cancer (TGCC) may be symptoms of a testicular dysgenesis syndrome that manifests during fetal life. To address the inheritability of this syndrome, we examined whether family history of cryptorchidism or hypospadias is associated with an increased risk of TGCC. METHODS: A total of 2,159,883 men born since 1953, identified through Danish health registers, were followed from April 2, 1968, through May 31, 2008. First-, second-, and third-degree relatives were identified in the Danish Family Relations Database; cryptorchidism and hypospadias patients were identified in the Danish Hospital Discharge Register; and TGCC patients were identified in the Danish Cancer Register. Poisson regression was used to calculate the risk ratio for TGCC by family history of cryptorchidism or hypospadias. RESULTS: A total of 5441 patients developed TGCC. A personal history of cryptorchidism or hypospadias was associated with an increased relative risk (RR) of developing TGCC (RR = 3.71, 95% confidence interval [CI] = 3.29 to 4.19; and RR = 2.13, 95% CI = 1.26 to 3.61, respectively). For example, in men in their thirties, the overall rate per 100 000 is 25.1 in the cohort, but 88.6 and 55.4 in men born with cryptorchidism or hypospadias, respectively. In contrast, relatives of a hypospadias patient did not have a statistically significantly increased risk of TGCC nor did the first- and second-degree relatives of cryptorchidism patients. However, we found a small increased risk of TGCC for third-degree relatives of patients with cryptorchidism. CONCLUSIONS: Having hypospadias or cryptorchidism was associated with an increased risk of developing TGCC. However, our finding that family history of hypospadias or cryptorchidism generally was not associated with increased risk of developing TGCC does not support the hypothesis of shared inheritability of cryptorchidism, hypospadias, and TGCC.

Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview.

Central nervous system germ cell tumors are neoplasms that affect children and young adults. They are subclassified into germinoma and nongerminomatous germ cell tumors. The latter include teratoma (mature teratoma, immature teratoma, teratoma with malignant transformation), choriocarcinoma, embryonal carcinoma, yolk sac tumors, and mixtures of these entities. Germinoma with syncytiotrophoblastic giant cells is a variant of germinoma. Germinomas respond well to radiation therapy, but late sequelae due to irradiation have been reported. The results of radiation treatment alone for nongerminomatous germ cell tumor are not satisfactory. Combination radiochemotherapy has been applied, and this yields a good outcome with less toxicity for germinomas and better survival of nongerminomatous germ cell tumors. This article also discusses other issues, including the controversy regarding spinal irradiation and the treatment of recurrent disease.

Statistical analysis of pineal tumors based on the data of Brain Tumor Registry of Japan.

In this study, we present statistical analyses of pineal tumors based on the data from Brain Tumor Registry of Japan. The most frequent tumor in the pineal region was germinoma, and it accounted for 49.2% of all pineal tumors; it was followed by pineocytoma (8.5%), glioma (6.5%), pineoblastoma (5.1%), malignant teratoma (5.2%) and teratoma (5.1%). Germinoma is most frequent among patients between 10 and 19 years of age, and there are some patients aged >30 years; however, there are few patients with choriocarcinoma, embryonal carcinoma, and yolk sac tumor who are aged >30 years. Pineoblastoma is most frequent among patients under 5 years of age, while pineocytoma is evenly distributed in patients between 10 and 60 years of age. The 5-year survival rate of germinoma was 89.4%, while those of embryonal carcinoma, yolk sac tumor and choriocarcinoma were 35.3, 37.3 and 58.1%, respectively.

Increased risk of testicular germ cell cancer among infertile men.

BACKGROUND: The risk of testicular cancer is thought to be higher among men seeking infertility treatment compared with the general population. Confirmation of this risk in a large US cohort of at-risk patients is lacking. This study explored the association between male infertility and subsequent development of testicular cancer in a US-based cohort. METHODS: A total of 51 461 couples evaluated for infertility from 1967 to 1998 were recruited from 15 California infertility centers. We linked data on 22 562 identified male partners to the California Cancer Registry. The incidence of testicular cancer in this cohort was compared with the incidence in an age-matched sample of men from the general population using the Surveillance Epidemiology and End Results program. We analyzed the risk for testicular cancer in men with and without male factor infertility using a Cox proportional hazards regression model. RESULTS: Thirty-four post-infertility-diagnosis cases of histologically confirmed testicular cancer were identified. Men seeking infertility treatment had an increased risk of subsequently developing testicular cancer (standardized incidence ratio, 1.3; 95% confidence interval, 0.9-1.9), with a markedly higher risk among those with known male factor infertility (2.8; 1.5-4.8). In multivariable analysis, men with male factor infertility were nearly 3 times more likely to develop testicular cancer compared with those without (hazard ratio, 2.8; 95% confidence interval, 1.3-6.0). CONCLUSION: Men with male factor infertility have an increased risk of subsequently developing testicular cancer, suggesting the existence of common etiologic factors for infertility and testicular cancer.

Reducing treatment toxicities in the management of good prognosis testicular germ cell tumors.

Testicular germ cell tumors are the most frequent solid tumor to affect young adult males and are increasing in incidence for reasons that are poorly understood. Increasingly, patients present with localized disease where disease-specific survival approaches 100%. Even in the presence of metastatic disease, the majority of patients with good prognostic features should expect to be cured. However, toxicities from treatment are increasingly recognized, with patients experiencing increased rates of second malignancies, cardiovascular disease and a range of circulatory, neurological and endocrine sequelae. High cure rates in a young population make reducing this long-term treatment-related morbidity and mortality imperative. In stage I disease, options following orchidectomy range from surveillance to adjuvant therapy, in the form of carboplatin or para-aortic radiotherapy for seminoma, and combination chemotherapy for nonseminoma. Metastatic disease requires combination chemotherapy with the exception of low-volume para-aortic nodal disease in seminoma, where radiotherapy with or without carboplatin may be curative. These various treatment options are discussed with a focus on reducing long-term treatment-related toxicities while preserving the high rates of long-term disease control.

Testis cancer: a 20-year epidemiological review of the experience at a regional military medical facility.

PURPOSE: Testis cancer is the most common solid malignancy in the young adult population and the incidence in this population is increasing. We present a 20-year epidemiological review of testis cancers treated at our institution. MATERIALS AND METHODS: The records of testis cancer cases diagnosed between January 1988 and June 2007 were reviewed. Patient demographics, cancer histology and stage, adjuvant therapy, temporal trends and survival data are presented. Our experience was compared to trends published in the SEER (Surveillance, Epidemiology and End Results) database and the National Cancer Database. RESULTS: A total of 338 testis cancers (330 germ cell tumors) were diagnosed during the study period. Median patient age at diagnosis was 26.6 years vs 34 in the SEER database. We observed a temporal increase in stage I tumors (57% to 75%) and a decrease in the proportion of seminomas (52% to 43%) during the study period. In terms of adjuvant therapy for stage I seminoma the use of radiotherapy decreased (91% to 75%), while the use of chemotherapy increased (1.5% to 7.5%). For stage I nonseminomatous germ cell tumors the use of adjuvant chemotherapy increased (12% to 20%), while the use of staging retroperitoneal lymph node dissection decreased (88% to 63%). Five-year cancer specific survival was 97.7%. CONCLUSIONS: We are seeing an increase in localized disease at diagnosis, an increase in surveillance for stage I disease and 5-year survival in excess of 95%, similar to data in SEER and the National Cancer Database. However, unlike in SEER and the National Cancer Database, our patients are younger, we are seeing less seminoma and we are performing significantly more staging retroperitoneal lymph node dissection.

Tumores germinales mediastínicos / Mediastinal germ-cell tumours

Los tumores de células germinales del varón habitualmente se originan en los testículos. Sin embargo, en el 2-5% de los casos pueden aparecer de forma primaria en localizaciones extragonadales, sin evidencia de un tumor testicular. Esta infrecuente entidad suele aparecer en la línea media corporal, predominántemente en el mediastino y en el retroperitoneo. Los tumores germinales extragonadales mediastínicos (TGEM) deben incluirse en el diagnóstico diferencial de cualquier tumor mediastínico de origen desconocido. Un diagnóstico exacto es fundamental, debido a que son tumores potencialmente curables con quimioterapia. En este artículo se revisan las características histopatológicas y clínicas de losTGEM, y sus diferencias los tumores germinales de origen testicular

Germ-cell tumours of male ussually arise from the testis. However, in 2-5% of the cases, they also occur outside of the testis as a primary site without evidence of testicular primary tumour. This infrequent entity often appears in the body midline, predominantly in mediastinum and retroperitoneum. Mediastinal germ-cell tumours (MGCT) shall be included in the differential diagnosis of any mediastinic tumour of unknown origin. An accurate diagnosis is essential, due to the fact that these tumours are curable with chemotherapy. The histopathologic and clinical features, and its differences with germ-cell tumours from testicular origin are revised in this article