Multimodal Treatment of Children With Sacrococcygeal Yolk Sac Tumor: Retrospective Analysis of Clinicopathology Characteristics and Relapse-free Survival.

The aim of the study was to explore the clinicopathologic characteristics of sacrococcygeal yolk sac tumor (SYST) associated with relapse and the role of sensitivity to neoadjuvant chemotherapy in predicting outcome. The authors investigated prognostic factors of age, stage, initial tumor size, pathologic response to neoadjuvant chemotherapy, and alfa fetoprotein. A total of 26 patients with SYST were enrolled. Neoadjuvant chemotherapy was administered to 20 cases. Six patients underwent resection as initial therapy. Recurrence occurred in 12 patients. Nine patients with specimens exhibiting no malignant component after chemotherapy did not experience recurrence. By contrast, relapses occurred in 7 of 11 patients with viable residual tumor after neoadjuvant chemotherapy. All relapsed patients still achieved partial remission or complete remission after salvage therapy. Five-year relapse-free survival and overall survival rates were 55.2% and 100%, respectively (median follow-up, 59.5 mo; range, 16 to 155). Patients with complete necrosis after neoadjuvant chemotherapy had a better outcome compared with children with viable residual tumor. Relapse-free survival of pediatric SYSTs in this cohort were still low and warrants the multidisciplinary effort.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

[A case report for primary yolk sac tumor of endometrium].

A case of primary yolk sac tumor of endometrium was retrospectively analyzed and relevant literature was systematically reviewed. We found that the primary yolk sac tumor of endometrium showed low incidence rate and was clinically characterized by abnormal vaginal bleeding, intrauterine lesions and significantly elevated alpha-fetoprotein (AFP) level. The final diagnosis should be confirmed by pathological examination. There is no guideline for the treatment of primary yolk sac tumor of endometrium due to its rareness. For now, surgery and chemotherapy are the major therapies and the curative effect is satisfactory in some cases.

Yolk sac tumor of the ovary: a retrospective multicenter study of 33 Japanese women by Tohoku Gynecologic Cancer Unit (TGCU).

Yolk sac tumor (YST) of the ovary is a rare germ cell tumor comprising about 1% of all ovarian malignancies. YST usually occurs as a rapidly growing unilateral tumor in young women. With the introduction of cisplatin, YST has been changed from a fatal tumor to a curable tumor. The standard treatment of YST consists of fertility-preserving surgery and 3 or 4 courses of adjuvant combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP). However, the long-term prognosis of BEP-treated YST patients has not been well studied. We therefore conducted a retrospective multicenter study to investigate the prognostic factors of 33 YST patients, including 25 patients treated with BEP. The median age at initial treatment was 20 years (range 10-53). There were 15 patients (at stage I), one (stage II), 16 (stage III), and one (stage IV). Nominal and grouped numerical values were analyzed by the Kaplan-Meier method. All patients had unilateral tumor, with right-side predominance (23 patients; P = 0.02). Eighteen patients had pure YST, 13 had mixed germ cell tumor with YST component, and other 2 patients were not specified. Twenty-eight patients received fertility-preserving surgery. Twenty-seven patients had optimal surgery with less than 1 cm residual tumor diameter. Median number of chemotherapy courses was 5. Median follow-up period was 49 months. The cumulative 5-year survival rate was 87%. Univariate analysis revealed the following significant prognostic factors (P < 0.05): stage, tumor diameter, and residual tumor. Extensive debulking surgery to minimize residual tumor would improve the prognosis.

Malignant testicular tumors in children: overview on 10 years of Saudi Cancer Registry.

BACKGROUND/OBJECTIVE: The aim of this study was to identify epidemiological and histopathological patterns of pediatric testicular tumor (TT) in Saudi population over 10 years. METHODS: Retrospective data extracted from the Saudi Cancer Registry for Saudi children diagnosed with TT from 2008 to 2017. The data collected included patient's factors as age, year of diagnosis, survival status, and tumor factors as basis of diagnosis, origin of the tumor, histopathological group and subtype, and tumor behavior, stage, and laterality. RESULTS: A total of 115 patients with a median age of 14 (IQR 1.5-17) were included. The primary tumor site was a normal descended testis in 98.3% (115). Yolk sac tumor was the most common 28.2% (33), followed by embryonal carcinoma in 27.4% (32) and mixed germ-cell tumors in 23.1% (27). Kaplan-Meier analysis revealed significant association between survival and the stage of the tumor (p = 0.002). However, there was a lack of significant association between survival and age groups, histopathological groups, and histopathological subtypes (p = 0.541, p = 0.609, and p = 0.733, respectively). The overall mortality rate of TT 5.2% with all deaths caused by non-seminomatous germ-cell tumor diagnosed with stage 3. CONCLUSIONS: The median age of the patients was 14 years. Yolk sac tumors were the most common while testicular choriocarcinomas were the least in incidence. No increase in the incidence of TT was seen and the mortality rate over the 10-year period was 5.2%. Shorter survival was associated with higher tumor stage.

Clinicopathologic Characteristics and Survival of Patients with Rare Malignant Ovarian Yolk Sac Tumors: A Population-based Analysis.

Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect young females. To date, there have been few studies on YSTs. We evaluated the relationship between clinicopathologic characteristics of patients with ovarian YSTs and disease outcome based on Surveillance, Epidemiology, and End Results data. The Kaplan-Meier method and log-rank test were used to evaluate differences in survival rates. Data for 269 patients were analyzed. The incidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%; median patient age was 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%), localized disease (49.1%), and regional spread (8.9%). American Joint Committee on Cancer stage was available for 13 patients (stage IA, n=2; stage IC, n=1; stage IIIA, n=1; stage IIIB, n=3; stage IIIC, n=2; and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%, respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and 92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarian spread (P<.001 for both OS and DSS). Age >50 years was associated with shorter OS and DSS (both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49 for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localized to the ovary; extra-ovarian spread has a poor outcome, and postmenopausal women have worse prognosis than premenopausal women.

Prepubertal testicular tumors: a 20-year experience with 40 cases.

Testicular tumors are rare in children. In addition, prepubertal testicular tumors (PTT) are fundamentally different from their postpubertal counterparts.We reviewed our 20-year experience with 40 cases to suggest an algorithm for the appropriate surgical approach for patients with PTT. All tumors ultrasonographically suspected of being benign were confirmed to be benign postoperatively. There was a significant difference between median preoperative a-fetoprotein (AFP) levels of infants with yolk sac tumor and teratoma. The majority of our cases were benign, with the most common histopathological subtype being teratoma, as recently reported. Testis-sparing surgery was carried out in five patients with teratoma and three patients with epidermoid cyst. Other than one patient with teratoma, none of the patients developed recurrence or testicular atrophy after testis-sparing surgery. When testis-sparing surgery is considered, our algorithm based on ultrasonographic findings and preoperative AFP levels might be helpful.

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.

Prenatal Exposure to Air Toxics and Malignant Germ Cell Tumors in Young Children.

OBJECTIVE: To assess prenatal air toxics exposure and risk for childhood germ cell tumors (GCTs) by histological subtype (yolk sac tumor and teratoma). METHODS: In this case-control study, GCT cases less than 6 years (n = 243) identified from California Cancer Registry records were matched by birth year to cancer-free population controls (n = 147,100), 1984 to 2013. Routinely monitored air toxic exposures were linked to subjects' birth address. Logistic regression estimated GCT risks per interquartile range increase in exposure. RESULTS: Prenatal exposure to various highly-correlated, traffic-related air toxics during the second trimester increased GCT risk, particularly 1,3-butadiene (odds ratio [OR] = 1.51; 95% confidence interval [CI] = 1.01, 2.26) and meta/para-xylene (OR = 1.56; 95% CI = 1.10, 2.21). Analyses by subtype indicated elevated ORs for yolk sac tumors but not teratomas. CONCLUSION: Our estimated ORs are consistent with positive associations between some prenatal traffic-related air toxics and GCT risk, notably yolk sac tumors.

A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females.

Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. The objective of this study is to compare the patient characteristics and survival of YST in males and females. Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program from 1973 to 2003. Statistical analysis was performed using Independent-sample t-test, chi(2) test, Kaplan-Meier methods and Cox proportional hazards regression. Seven hundred eighty-eight patients were identified, 451 (57%) were males and 337 (43%) were females. The mean age at diagnosis was similar in males and females. The age at diagnosis showed a bimodal distribution with an increased incidence in the first 4 years of life and during the 2nd to 4th decade of life. The most common site of the primary tumor was gonadal, namely testis 336 (42.6%) and ovary 257 (32.6%). Among the extragonadal sites, tumor site of origin differed in males and females. The 5-year survival of extragonadal YST (66%) was worse than gonadal YST (86%) (p < 0.05). The overall median survival for the cohort was 87 months. This was similar in males (81 months) and females (91 months) (p > 0.05). As the year of diagnosis progressed from 1973 to 2003, survival of both males and females with YST consistently improved. The bimodal age distribution of YST generates the hypothesis that sex steroids may play a role in selected YST. Although the overall survival in all YST patients has improved over the past few decades, the primary sites of origin differ in males and females and impact prognosis.

Survival of metastatic germ cell cancer patients assessed by international germ cell consensus classification in Japan.

BACKGROUND: As a risk classification system of metastatic germ cell tumors, the International Germ Cell Consensus (IGCC) classification was proposed in 1997 and has received broad approval. Since the IGCC classification was based on patients treated between 1975 and 1990, we aimed to investigate whether survival has improved for more recently treated Japanese patients. METHODS: We analyzed 296 patients with metastatic germ cell tumors treated at seven hospitals in Japan between 1990 and 2001. These cases are classified as good, intermediate or poor prognosis groups by the IGCC classification. The 5-year progression-free and the 5-year overall survivals were calculated for each prognosis group. RESULTS: The median follow-up period of all patients was 53 months. In 227 non-seminomatous germ cell tumor cases, the 5-year progression-free survival (95% confidence interval) for good (n = 55), intermediate (n = 106) and poor (n = 66) prognosis was 96% (91-100), 71% (62-80) and 52% (39-65) (P < 0.001), respectively. The 5-year overall survival was 94% (88-100), 81% (73-89) and 61% (49-73) (P < 0.001), respectively. In 69 seminoma cases, the 5-year progression-free survival for good (n = 64) and intermediate (n = 5) prognosis was 78% (67-89) and 80% (45-100) (P = 0.98), respectively. The 5-year overall survival was 90% (82-99) and 80% (45-100) (P = 0.49), respectively. CONCLUSIONS: There was a trend of increase in survival for any risk groups and, in particular, large increase in survival for patients with a poor prognosis. This increase is most likely attributed to more effective chemotherapy regimens and more extensive care in the experienced institutes.

Prepubertal testicular tumors: a single-center experience of 44years.

PURPOSE: To present the clinical and histological features of prepubertal testicular tumors (PTTs), the long-term experience of a single institution was reviewed. MATERIALS AND METHODS: A total of 62 prepubertal children who were treated for testicular tumors at Kanagawa Children's Medical Center from 1971 to 2014 were retrospectively reviewed. Histopathological findings, age at operation, clinical stage, and outcomes were analyzed. Clinical findings between the two eras, 1971-1990 and 1991-2014, were also compared. RESULT: The median age at operation was 17months. Pathology revealed 29 teratomas (47%), 26 yolk sac tumors (42%), 5 epidermoid cysts (8%), 1 Sertoli cell tumor (1.5%), and 1 benign cyst (1.5%). Teratoma was the most common tumor in this series, and children with immature teratomas were operated at a significantly younger age than those with mature teratomas. Yolk sac tumor was the second most common. The clinical stages of yolk sac tumors were stage I in 23 (89%) and stage II in 3 (11%). Clinical findings were not significantly different between the early and late eras. CONCLUSIONS: To the best of our knowledge, this is the largest single-center study of PTTs in Japan. The most common PTT in this study was teratoma, followed by yolk sac tumor. There was no significant difference in the histological distribution of PTTs between the two eras. Compared with the current data of single-center series in North America, the incidence of yolk sac tumor was markedly higher in the present study. This discrepancy is possibly explained by racial differences.

Distribution of testicular tumors in Lebanon: a single institution overview.

BACKGROUND: Testicular tumors constitute a rare type of cancer affecting adolescents and young adults with recent reports confirming an increase in incidence worldwide. The purpose of this study was to estimate the epidemiological characteristics and histological subtypes of testicular tumors in the Lebanese population according to the WHO classification of testicular and paratesticular tumors. MATERIALS AND METHODS: In this single institutional retrospective study, all patients diagnosed with a testicular tumor in Hotel-Dieu de France Hospital University in Beirut between 1992 and 2014 were enrolled. The age, subtype based on the 2004 WHO classification and body side of tumor were analyzed. RESULTS: A total of two hundred and forty-four (244) patients diagnosed with a testicular tumor in our institution were included in the study. Two hundred and one patients (82.4% of all testicular tumors) had germ cell tumors (TGCT). Among TGCT, 50% were seminomatous tumors, 48% non-seminomatous tumors (NST) and 2% were spermatocytic seminomas. The NST were further divided into mixed germ cell tumors (63.9%), embryonic carcinomas (18.6%), teratomas (15.4%) and yolk sac tumors (2.1%). The mean age for testicular tumors was 32 years. The mean age for germ cell tumors was 31 years and further subtypes such as seminomatous tumors had a mean age of 34 years, 28 years in non-seminomatous tumors and 56 years in spermatocytic seminoma. Patients with right testicular tumor were the predominant group with 55% of patients. Three patients (1.2%) presented with bilateral tumors. CONCLUSIONS: The distribution of different subgroups and the mean age for testicular tumors proved comparable to most countries of the world except for some Asian countries. Germ cell tumors are the most common subtype of testicular tumors with seminomatous tumors being slightly more prevalent than non-seminomatous tumors in Lebanese patients.

Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States.

PURPOSE: To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). PATIENTS AND METHODS: Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. RESULTS: In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications. CONCLUSION: Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.

Posterior mediastinal endodermal sinus (yolk sac) tumor in a female patient.

Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon. Most patients are young and male, and the great majority of tumors are found in the anterior mediastinum. We report a case of primary posterior mediastinal endodermal sinus tumor occurring in a female patient. Surgical excision was performed and three courses of combination chemotherapy were subsequently given. The serum alpha-fetoprotein level returned to normal.

Long-term outcome for infants and children with sacrococcygeal teratoma: a report from the Childrens Cancer Group.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) are a relatively uncommon tumor affecting neonates, infants, and children. This study was designed to determine the effect of therapy on the long-term outcome of neonates and children with sacrococcygeal teratomas (SCT). METHODS: The authors conducted a retrospective review of children with SCT treated at 15 Childrens Cancer Group institutions from 1972 to 1994. RESULTS: One hundred twenty-six children presented with SCT diagnosed prenatally (n = 32), at birth (n = 79), or later in infancy (n = 15). For neonates, complete resection was performed except in two babies with lethal associated defects. All others (n = 15) underwent resection at the age of diagnosis. Six had a sacral mass identified at birth but had delayed surgery (1.5 to 11 months) and of these, two were malignant. Resection was via sacral (n = 96) or abdominosacral (n = 28) approach. Histology showed mature teratoma (MT, 69%), immature teratoma (IT, 20%), or endodermal sinus tumor (EST, 11%) at presentation. Seven neonates (5.6%) died of perioperative complications, whereas the remaining 117 were available for long-term follow-up. Between 6 and 34 months postresection, recurrent disease developed in 9 of 80 MT patients (11%) followed-up for a mean of 5 years. Recurrent disease was MT (n = 2) and EST (n = 7). The recurrent EST patients were treated with adjuvant chemotherapy. Six are alive with mean follow-up of 114 months, whereas one with metastatic disease was lost to follow-up. Recurrence (MT) developed in only 1 of 24 IT patients, and all are alive and well at mean follow-up of 39 months. Patients presenting with EST (n = 13) underwent excision, with two dying from non-EST causes. Six EST patients received no chemotherapy, with two of the six (33%) experiencing recurrence within 11 months and both disease free after salvage chemotherapy. The remaining five EST patients received adjuvant chemotherapy; four are alive and one died of metastatic disease. Of the 18 EST patients followed-up after resection (presentation, 11, recurrent teratoma, 7), 16 (89%) are free of disease with a mean follow-up of 91 months. CONCLUSIONS: (1) Benign teratomas have a significant recurrence rate mandating close follow-up for more than 3 years. (2) Surgical resection alone is adequate therapy for nonmetastatic malignant tumors. (3) Survival for malignant lesions with metastases is excellent with modern chemotherapy.

Malignant ovarian germ cell tumors: analysis of 32 cases.

OBJECTIVE: In this study, some clinicopathologic characteristics and the outcome of patients with malignant ovarian germ cell tumors (MOGCT) were evaluated. MATERIALS AND METHODS: The clinical charts and pathologic reports of 32 patients with MOGCT treated at the Department of Obstetrics and Gynecology, and diagnosed at the Department of Pathology, Medical Faculty of Dicle University, Turkey from 1983 to 1999 were reviewed. RESULTS: Thirteen patients (40.6%) had dysgerminoma, nine (28.1%) had immature teratoma (four grade 1, three grade 2, and two grade 3), eight (25%) had endodermal sinus tumor, and two (6.3%) patients had mixed germ cell tumors. Site of involvement was unilateral in 30 (19 on the right and 11 on the left) and bilateral in two. All patients underwent primary surgery and 26 patients combination chemotherapy. There seemed to be a relationship between pathologic findings and clinical outcome, and MOGCT histologic types may affect the prognosis. CONCLUSION: Dysgerminoma had a better prognosis than the nondysgerminomatous group (p < 0.05). This study provides additional data in confirmation of previous reports that management of MOGCT with fertility preservation is safe.

Endodermal sinus (yolk sac) tumor of the urachus.

A rare case of endodermal sinus (yolk sac) tumor of urachal remnants in a two-year-old infant is described. The tumor was located in the upper part of the bladder and appeared to arise from urachal remnants. The tumor could be entirely removed. The patient is free of tumor after three years and eight months follow-up.

[Analysis of 110 cases of sacrococcygeal lesions in children].

110 cases of sacrococcygeal lesions seen in the Guangzhou Children's hospital were reviewed. 42 cases were anomalies, 66 cases were tumors and 2 were inflammatory granulomas. As compared to data in western literatures, the morbidity of anomalies in this series was lower than that of tumors, whereas in western reports the morbidity of anomalies was much higher than that of tumors. Another interesting point was that the morbidity of meningocele (MC) in this series was much higher than that of myelomeningocele (MMC) of spina bifida (7:1). According to a study in Australia, the MC:MMC was 1:5. We suggest that endodermal sinus tumor should be considered as an independent entity of there was no other tissue component (organlike component) found in tumor section. We also suggest that if neuroblastoma and/or other immature neuroectodermal component is observed in a teratoma, it should be classified as malignant rather than benign.