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.

Primary yolk sac tumour of the prostate mimicking small round blue cell tumour.

Prostatic yolk sac tumour is a germ cell tumour with a wide range of age of occurrence, unusual anatomic locations, diverse morphologic patterns, and aggressive biologic behavior, posing challenges both to diagnosis and clinical management. We report a rare case of primary yolk sac tumour of the prostate with extensive local and liver metastasis, the latter of which exhibited sheets of small blue cells expressing CD99 and focal sall4 on biopsy. Positivity for CD99 and gata3 in the initial biopsy raised the differential diagnosis of Ewing sarcoma and poorly differentiated carcinoma. The primary tumour demonstrated an admixture of solid and glandular growth patterns and occasional Schiller-Duval bodies. A panel of immunohistochemical stains showing positivity for AE1/3, sall4, cdx2, and focal alpha-fetoprotein, and negativity for oct-4, facilitated the diagnosis. A thorough review of the literature and our current report indicate that a large tumour load, incomplete tumour resection, limited response to preoperative neoadjuvant chemotherapy, and late stage of the disease are predictive factors for a poor clinical outcome.

Cushing syndrome in a child due to pro-opiomelanocortin (POMC) secretion from a yolk sac tumor.

CONTEXT: Pituitary microadenomas and adrenal tumours are the most common causes for endogenous Cushing syndrome (CS) in children. CASE DESCRIPTION: We describe a two-year old girl with Cushing syndrome due to ectopic pro-opiomelanocortin (POMC) production from an abdominal yolk sac tumor. Cortisol concentrations were elevated but adrenocorticotropic hormone (ACTH) concentrations were equivocal. The use of antibodies specifically detecting ACTH precursors revealed that plasma ACTH precursors were elevated. Additionally, an ACTH assay with a low cross-reactivity for precursors showed low concentrations of ACTH. Immunohistochemistry suggested POMC but not ACTH production by the tumour. CONCLUSION: We describe a yolk sac tumour as a novel source of ectopic POMC production leading to CS in a young girl.

Atypical presentation of sacrococcygeal yolk sac tumor in infant: beware of the injuries of the gluteal region.

Malignant sacrococcygeal yolk sac tumor is a rare extra-gonadal germ cell tumor of infancy and childhood. We report the case of a 14-month-old white female infant with a rapidly growing supra-gluteal mass at first misdiagnosed as hemangioma after a clinical assessment. The lesion was then classified as extra-gonadal yolk sac tumor due to alarming ultrasound features, later confirmed at MRI and pathology. This report remarks the need of a rigorous methodology in the ultrasound exploration of the gluteal region.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

BACKGROUND: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. METHODS: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. RESULTS: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. CONCLUSIONS: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. CONFLICT OF INTEREST STATEMENT: No conflict of interest.

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours.

BACKGROUND: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups. METHODS: We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients. RESULTS: The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples. CONCLUSIONS: The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs.

Primary yolk sac tumor of endometrium: report of two cases and review of literature.

Primary YST of the endometrium is very rare, therefore there is no guideline for treatment. We report two cases of endometrial YSTs presenting different symptoms and showing different prognoses and discuss the clinical management of these tumors. The present report shows first time that bone and lung metastasis in primary YSTs of endometrium. As the number of reported cases with endometrial YSTs, more information about the prognosis of the disease may be obtained.

Testicular yolk sac tumor and impaired spermatogenesis in a Holstein Friesian calf.

Yolk sac tumors are testicular germ-cell tumors of the non-seminoma type. In cattle, this neoplasm is very rare and to date has only been described three times. In human males, it usually occurs in infants and children. Immunohistochemistry provides solid criteria for diagnostics. Especially present pathognomonic Schiller-Duval bodies are helpful for identification. In this report, a 32-day-old Holstein Friesian calf presented with a highly enlarged right testis. Sonographic examination was performed and blood samples were taken to measure testosterone and estrogen levels. Furthermore, the testis was surgically removed and macroscopically, histologically, and immunohistochemically examined which lead to the diagnosis of testicular yolk sac tumor. The second testis was descended until the age of nine months and histology revealed impaired spermatogenesis. This report provides the first sonographic images of bovine testicular yolk sac tumor as well as the first information about hormone levels in calves with this neoplasm. It also shows the importance to combine anamnesis, histomorphological, and immunohistochemical findings in order to diagnose yolk sac tumors when pathognomonic structures are not present.

Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors.

Role of neoadjuvant chemotherapy in the management of advanced ovarian yolk sac tumor.

OBJECTIVE: The aim of the study was to identify the role of neoadjuvant chemotherapy (NACT) in the treatment of the patients with advanced stage ovarian yolk sac tumor (OYST). METHODS: The comparative study was based on 53 cases with advanced stage OYST registered at Peking Union Medical College Hospital from 1995 to 2010. Twenty one cases were treated with NACT followed by interval debulking surgery (IDS). Thirty two cases were treated with primary debulking surgery (PDS). Data on patient characteristics, treatment and survival were analyzed and compared between two groups to assess the outcome of NACT. RESULTS: After NACT, the overall status of the patients was improved significantly. Patients in NACT had better optimal cytoreduction rate and less peri-operative morbidities. Seven patients (13.2%) suffered from relapse. There was a significantly better PFS for patients with ovarian tumor size >20cm in the NACT than those underwent PDS. Residual disease >2cm was the independent risk factor of relapse. CONCLUSIONS: NACT is the better treatment option for some patients with advanced stage OYST, especially for those with unresectable tumors and poor general condition.

Yolk sac tumour: a rare cause of raised serum alpha-foetoprotein in a young child with a large liver mass.

BACKGROUND: Primary yolk sac tumour of the liver is extremely rare, and when it occurs in a young child it can be confused with hepatoblastoma. OBJECTIVE: To present a retrospective case series of primary hepatic yolk sac tumour from two institutions to highlight the imaging features. MATERIALS AND METHODS: We conducted a retrospective review of pathological and imaging findings in biopsy-proven pure primary yolk sac tumour of the liver. RESULTS: A total of three children (15 months to 6 years) presented between 2006 and 2012 with primary hepatic yolk sac tumour. Two children presented with acute abdomen after minor trauma caused by tumour rupture and haemoperitoneum. We identified five additional paediatric cases of pure hepatic yolk sac tumour with descriptions of imaging findings in the literature. In seven of these eight children, central necrosis was seen on cross-sectional imaging. CONCLUSION: Primary yolk sac tumour should be considered as an alternative diagnosis to hepatoblastoma in a young child with a large liver mass and significantly raised serum alpha-foetoprotein, but in view of the nonspecific imaging features histological examination is essential for diagnosis. Although there are no specific imaging findings of primary yolk sac tumour, presence of cystic or necrotic areas and a tendency for tumour rupture are suggestive features.

Germ cell tumors in atypical locations: experience of the TGM 95 SFCE trial.

The yolk sac tumor is one of the most common malignant germ cell tumors in young children and typically occurs in the gonads. We report 6 cases of children less than 30 months old with extragonadal atypical locations of yolk sac tumor. These rare diagnoses were established by raised serum α-fetoprotein levels and biopsies. These patients were treated according to the French TGM 95 trial. All the patients are alive disease-free after ≥2.5 years of follow-up. We want to highlight the importance of measuring the α-fetoprotein levels in very young children presenting with any midline tumor, even if the tumor is not located in the typical extragonadal sites such as the sacrococcyx, mediastinum, retroperitoneum, or vagina.

Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.

Prepubertal testicular and paratesticular tumors in China: a single-center experience over a 10-year period.

OBJECTIVE: Prepubertal testicular tumors are rare and fundamentally distinct from adult testicular tumors. We reviewed our 11-year experience in a single medical center of China. MATERIAL AND METHODS: This study reports the clinical characteristics, histopathologic diagnosis, treatment methods, and outcome in a series of 63 prepubertal boys who were treated between 1997 and 2008. RESULTS: A total of 63 primary prepubertal testicular and paratesticular tumors were identified. The median age at presentation was 11 months. Of these tumors, 27 (42.9%) were mature teratomas, 5 (7.9%) were immature teratomas, 21 (33.3%) were yolk sac tumors, 4 (6.3%) were epidermoid cyst, 2 (3.2%) were Leydig cell tumors, 1 (1.6%) was a mixed malignant germ cell tumor, and 3 (4.8%) were paratesticular tumors. The most common clinical presentation (95.2%) was a painless scrotal mass or swelling. Forty-eight tumors were treated with radical inguinal orchiectomy, and 15, with a testis-sparing procedure. Follow-up was available in 59 cases, range from 4 to 128 months (median, 50 months). One patient with yolk sac tumor had recurrence and progression to metastasis at the end of 4 months after surgery. Other patients were disease free at last follow-up. CONCLUSIONS: Most of the prepubertal testicular lesions were benign, and the most common histologic subtype was teratoma. Our experience with testis-sparing procedures supports the current trends that less invasive treatment should be performed for benign lesions. This study confirms the excellent cure rates obtained in children with prepubertal testicular tumors.

Advanced extragonadal yolk sac tumor serially followed up with (18)F-fluorodexyglucose-positoron emission tomography and computerized tomography and serum alpha-fetoprotein.

Although yolk sac tumors (YSTs) are the second most common malignant germ cell tumor of the ovary, those arising from the omentum or pelvic peritoneum are extremely rare and have no established treatment guidelines. We report a case of a primary YST disseminated throughout the abdomen and associated with a high serum alpha-fetoprotein (AFP) elevation (441 611 ng/ml). Optimal cytoreduction was not achieved in order to preserve the patient's fertility and avoid adjacent organ injury. Residual tumor responded to adjuvant chemotherapy with a sharp decline in AFP levels, and confirmed remission was documented by serial (18)F-fluorodexyglucose-positoron emission tomography and computerized tomography (FDG-PET/CT). In cases of advanced YST with unresectable residual disease, AFP levels combined with FDG-PET/CT scans may be a helpful way to monitor treatment response and assist in treatment planning for a disease that primarily affects young women who may desire to preserve fertility.

Conservative treatment and long-term follow up of endodermal sinus tumor of the vagina.

OBJECTIVE: Six cases of endodermal sinus tumor (EST) of the vagina were reported focusing on the results of conservative treatment and outcome of long-term follow up. METHODS: We reviewed a cohort of six cases with EST of the vagina diagnosed and treated in our hospital. CT scan, detection of serum AFP level, examination under anesthesia and biopsy were performed before and after treatment to evaluate the tumor status. The diagnoses were confirmed by pathological and imaging findings. All patients were treated with bleomycin, etoposide and cisplatin (BEP) combination chemotherapy alone. Complete remission (CR) includes the normal level of serum AFP, no tumor detected by CT scan and the negative result of pathology. Long-term follow up was carried out according to our regulation. RESULTS: The mean onset age was 18.2 months. The average tumor size was 4.5 cm. Serum AFP level was markedly elevated before treatment and decreased dramatically after chemotherapy and drop to the normal level after two to three courses of chemotherapy (average 2.5 courses). The patients received averagely six courses of chemotherapy and all the six patients obtained CR. The mean follow-up time is 75.5 months and there was no evidence of recurrent disease. CONCLUSION: The result of this conservative treatment for EST of the vagina is excellent. BEP chemotherapy without surgery should be considered as a good choice of treatment. Close follow up with serial determinations of serum AFP level together with imaging tests and physical examination in the first two years of follow-up are recommended.

Yolk sac tumor of the thyroid gland: a case report.

Extragonadal yolk sac tumors are uncommon and usually seen in sacrococcygeal, mediastinal, intracranial, and retroperitoneal sites. Yolk sac tumors of the head and neck region are rare, and the few reported cases have arisen in neonates or infants in conjunction with a teratoma or other germ cell tumor subtypes. We report a unique case of a pure yolk sac tumor presenting as a primary lesion in the right thyroid lobe of a 10-year-old girl. The diagnosis was suspected after fine-needle aspiration, and extensive sampling of the thyroidectomy specimen revealed no teratoma or other germ cell tumor. Serum α-fetoprotein levels were markedly elevated 6 days after excision, and imaging disclosed numerous bilateral pulmonary nodules suggestive of metastatic disease but did not reveal a mediastinal mass. The tumor has shown a favorable response to bleomycin, etoposide, and cisplatin chemotherapy. To the best of our knowledge, this is the 1st description of a primary pure yolk sac tumor of the thyroid.

Intracranial yolk sac tumor in a patient with Down syndrome.

The authors report a rare case of intracranial yolk sac tumor in a 13-year-old boy with Down syndrome who presented with left hemiparesis. Admission MR imaging revealed a tumor in the right basal ganglia. Serum α-fetoprotein was markedly elevated. Yolk sac tumor was diagnosed radiologically and serologically. The standard therapy for intracranial yolk sac tumor is platinum-based chemotherapy with concomitant radiotherapy. However, the authors used reduced-dose chemotherapy and asynchronized radiotherapy because of the well-known low tolerance of patients with Down syndrome to chemotherapy. This treatment was successful with no complications. Blood cancers are frequently associated with Down syndrome, whereas solid tumors occur less frequently in these patients, and the risk of chemoradiotherapy is unclear. The results indicate that dose-reduction therapy can be effective for treatment of a brain tumor in a patient with Down syndrome.