The clinical features and prognostic outcomes of primary mediastinal yolk sac tumors: A retrospective analysis of 15 rare cases from multiple centers.

ABSTRACT: Primary mediastinal yolk sac tumors (PMYSTs) are a rare occurrence. As such, the clinicopathological features, treatment, and prognosis, of this disease still remain unclear. In this study, we aimed to provide further information relating to this rare malignancy in order to facilitate the creation of more specific clinical guidelines for the diagnosis and treatment of patients with PMYSTs.In this retrospective study, we recruited 15 patients who had been diagnosed with PMYST from four medical institutions to create a population-based cohort. We then used Kaplan-Meier analysis and the log-rank test to investigate and compare overall survival (OS) and progression-free survival (PFS).A total of 15 cases were identified. The mean age was 27.3 years (range: 19-34 years). The estimated 1- and 2-year PFS rates were 66.7% and 60.0%, respectively. The 1- and 2-year OS rates were both 73.3%. Computer tomography scans revealed tumors were located in the anterior middle mediastinum (5 cases), the anterior superior mediastinum (1 case), the left anterior mediastinum (3 cases), and the right anterior mediastinum (6 cases). Of the 15 patients receiving extended resections, the majority (40.0%) underwent tumor resection, partial pericardiotomy, pulmonary wedge resection, and mediastinal lymphadenectomy. R0 resections were achieved in eleven patients. Four patients underwent R2 resection and experienced postoperative complications, including pneumonia (2 cases), atelectasis (1 case), and bronchopleural fistula (1 case). Four patients developed postoperative lung metastasis. Three patients died due to progressive diseases. Disease recurred in all patients at a median of 8.0 months (range: 6.0-11.0 months).PMYST is a rare but highly malignant tumor with a poor prognosis. Tumor resection, with optimal extended surgical management, may provide patients with the best chance of a cure although postoperative complications relating to the pulmonary systems should be treated with caution.

Clinical characteristics and prognostic factors of male yolk sac tumor: a Surveillance, Epidemiology, and End Results program study.

INTRODUCTION: Yolk sac tumor (YST) is a rare malignant germ cell tumor, which usually affects young males. Because of the low incidence, few studies on YST have been published. In our study, we aim to investigate the clinical characteristics, survival and risk factors of male YST patients based on the Surveillance, Epidemiology, and End Results (SEER) program. METHODS: We identified 569 male YST patients from the SEER-18 database with additional treatment fields. Clinical characteristics, survival and prognostic factors were described in the study. Chi-square tests were applied to analyze categorical and continuous variables between different groups. Univariate and multivariate Cox proportional hazard model were performed to assess the relative impacts of risk factors on cancer-specific survival (CSS) in YST patients. Kaplan-Meier method and the log-rank test were used to analyze differences in survival that were significant. RESULTS: The major primary sites of YST were testis (74.69%), mediastinum (15.47%), retroperitoneum (2.64%) and central nervous system (1.24%). The 3-year and 5-year CSS was 70.0%, 56.5% vs. 97.2%, 96.0% for the mediastinal and testicular YST patients, respectively (p < 0.001). Primary site of mediastinum, distant SEER Summary stage were independent factors of poor prognosis (hazard ratio (HR) = 2.010 (1.094-3.695), p = 0.025; HR = 6.501 (2.294-18.424), p < 0.001, respectively). Receiving surgery was a good prognosis factor for all patients (HR = 0.495 (0.260-0.940), p = 0.032) and for the mediastinal group (p = 0.0019). Being treated with chemotherapy indicated poor outcome in all patients (HR = 3.624 (1.050-12.507), p = 0.042) and in the localized testicular YST patients (p = 0.0077). CONCLUSION: For the first time, our study revealed the primary site distribution of male YST, and summarized the clinical characteristics, survival and prognostic factors based on the SEER database, which provided important epidemiological evidence for clinical practice.

Fluorescent In Situ Hybridization Analysis for 12p Alterations in Sarcomatoid Yolk Sac Tumors.

"Sarcomas" in patients with testicular germ cell tumors (GCTs) are a common form of "somatic-type malignancy." There is support, based on morphology and immunohistochemistry, that many such sarcomatous tumors represent an unusual form of yolk sac tumor (YST). A virtually universal chromosomal anomaly in GCTs is increase in 12p copy number, often in the form of isochromosome 12p [i(12p)], but this aspect of sarcomatoid YSTs has not hitherto been studied. We performed interphase fluorescent in situ hybridization assay for detection of increased 12p copy number in sarcomatoid YSTs using a bacterial artificial chromosome-derived probe localized to 12p12.1 and a commercially available centromeric probe. Sixteen formalin-fixed, paraffin-embedded specimens from 11 patients, along with normal controls, were studied. Overrepresentation of 12p was expressed as a ratio between the number of signals for 12p and the number of signals for centromere 12. A ratio ≥1.3 was considered overrepresentation. All cases were postchemotherapy recurrences or metastases. Ages ranged 22 to 38 years (mean: 36). Most tumors (12/16) showed myxoid or fibromyxoid stroma and 15 of 16 were high grade. Thirteen of 16 specimens (81%) showed overrepresentation of 12p by the above criteria. Two cases exhibited loss of 12p and 1 case had gain of a whole chromosome 12 (trisomy 12). We conclude that, as in other GCTs, sarcomatous differentiation of YST demonstrates 12p alterations that can be identified by interphase fluorescent in situ hybridization. Apart from 12p overrepresentation, these tumors may exhibit loss of 12p or even gain of an entire chromosome 12 (trisomy 12). Increase in 12p copy number of a sarcomatous neoplasm provides support for sarcomatoid YST in clinically ambiguous settings.

Management and prognosis of ovarian yolk sac tumors; an analysis of the National Cancer Data Base.

OBJECTIVE: To evaluate the clinico-pathological characteristics, management and prognosis of women diagnosed with ovarian yolk sac tumors (OYSTs). METHODS: The U.S National Cancer Data Base was queried for women diagnosed with OYST between 2004 and 2014. Overall survival (OS) was calculated following generation of Kaplan-Meir curves. Univariate analysis was performed with the log-rank test. A Cox model was constructed to determine independent predictors of mortality. RESULTS: A total of 561 women were identified with a median age of 23years. The majority (58.5%) had early stage (I-II), while 29.6% and 11.9% had stage III and IV disease respectively. Five-year OS for women with stage I, II, III and IV disease were 94.8%, 97.1%, 70.9% and 51.6% respectively, p<0.001. Better 5-yr OS was observed for adolescents (94.4%) and young adults (89.3%) compared to older premenopausal (67.6%) and postmenopausal women (30.6%), p<0.001. Omentectomy, hysterectomy and lymph node sampling/dissection (LND) were not associated with better OS. Women who received adjuvant chemotherapy had superior OS compared to those who did not, p=0.016. Early disease stage, younger age and receipt of adjuvant chemotherapy, but not LND were independently associated with better mortality. CONCLUSIONS: Women with OYST commonly present with early stage disease. Administration of adjuvant chemotherapy, early stage and younger age are associated with superior outcomes.

Ovarian yolk sac tumor in postmenopausal females: a report of five cases and a literature review.

PURPOSE OF INVESTIGATION: Little is known regarding ovarian yolk sac tumor (YST) in postmenopausal females. The authors aimed to investigate the clinical features and prognosis of postmenopausal patients with ovarian YST. MATERIALS AND METHODS: Five cases of ovarian YST in postmenopausal females were retrospectively reviewed. A MEDLINE search was performed to identify postmenopausal patients with ovarian YST. RESULTS: Four patients had Stage I or II disease (Stage IC, IIC, and IIB in one, two, and one patient, respectively), and one patient demonstrated an unclear stage. All five patients received surgery and postoperative chemotherapy. Four of the patients received chemotherapy with a regimen of bleomycin, etoposide, and cisplatin, and one patient received cisplatin as first-line chemotherapy. Of the four patients who had no residual tumors at the initial surgery, three patients recurred at 3.0, 8.5, and 9.0 months after diagnosis, respectively. The three patients who had recurrence lived for an additional time of 21.8, 10.0, and 11.5 months after relapse. Four patients died of the disease at 30.8, 18.5, 14.5, and 8.5 months after diagnosis; one patient survived without tumor at 40.0 months. The three-year survival was 20.0%. Of the 12 cases identified from the literature, the three-year survival was 34.0%. CONCLUSION: The clinical features of ovarian YST in postmenopausal females, such as stage distribution, were similar compared to young patients. Postmenopausal patients with ovarian YST may have a worse prognosis compared to young patients.

Yolk Sac Tumor of the Testis in Infants and Children: A Clinicopathologic Analysis of 33 Cases.

We report 33 pure yolk sac tumors of the testis from boys 5 to 71 months of age (mean 20.7 mo) diagnosed from 1918 to 2014. All except 1 underwent orchiectomy, with lymph node dissections (all negative) performed in 18; 21 also received chemotherapy and 12 radiotherapy. The tumors were 1.6 to 7.0 cm (mean 3.7 cm) and were nonencapsulated, with a gray to yellow, often mucoid, cut surface. The commonest pattern was reticular-microcystic, but macrocystic, papillary, endodermal sinus (Schiller-Duval bodies), labyrinthine, myxomatous, glandular, and solid patterns were also observed. Follow-up was available for 32 patients (mean 100.5 mo; range, 3 to 456 mo). Twenty-four patients (including 4 who did not receive adjuvant therapy) were without evidence of disease, 8 had metastatic disease; 5 of the latter died of tumor and 1 of treatment complications. Two patients with metastasis were cured with radiation with or without chemotherapy. Two or more of the following were associated with a poor outcome in patients presenting with stage I cases: tumor size >4.5 cm (4/6 tumors [67%]), invasion of rete testis and/or epididymis (3/7 tumors [43%]), and necrosis (6/17 tumors [35%]). In the nonmetastasizing group, 2 or more unfavorable features occurred in only 3/24 tumors (13%) (P=0.0001). It is crucial that this tumor be distinguished from the juvenile granulosa cell tumor, which occurs at a slightly younger age and has distinctive features, although there may be some morphologic overlap. The survival of young boys with testicular yolk sac tumor is very good because of both effective chemotherapy and likely, the inherent characteristics of the tumor in this age group.

Administration of standard-dose BEP regimen (bleomycin+etoposide+cisplatin) is essential for treatment of ovarian yolk sac tumour.

AIM: The aim of this study was to investigate prognostic factors, including postoperative chemotherapy regimen, for the treatment of ovarian yolk sac tumour (YST), and resulting fertility outcome. METHODS: A multi-institutional retrospective investigation was undertaken to identify patients with ovarian pure or mixed YST who were treated between 1980 and 2007. Postoperative chemotherapy regimen and other variables were assessed in univariate and multivariate analyses. Additionally, the reproductive safety of the BEP (bleomycin, etoposide and cisplatin) regimen was evaluated. RESULTS: There were 211 patients enrolled from 43 institutions. The BEP regimen and a non-BEP regimen were administered to 112 and 99 patients as postoperative chemotherapy, respectively. In univariate and multivariate analyses, age⩾22, alpha-fetoprotein⩾33,000 ng/ml, residual tumours after surgery and non-BEP regimen were independently and significantly associated with poor overall survival (OS). BEP was significantly superior to non-BEP in 5-year OS (93.6% versus 74.6%, P=0.0004). Reduced-dose BEP (<75% standard-dose bleomycin and<50% etoposide dose) was significantly associated with poorer 5-year OS compared with standard-dose BEP (89.4% versus 100%, P=0.02 and 62.5% versus 96.9%, P=0.0002). All patients who underwent fertility-sparing surgery recovered their menstrual cycles. Sixteen of 23 patients receiving BEP (70.0%) and 13 of 17 patients receiving non-BEP (76.5%) who were nulliparous at fertility-sparing surgery and married at the time of investigation gave birth to 21 and 19 healthy children, respectively. CONCLUSIONS: The results of the present study suggest that standard-dose BEP should be administered for ovarian YST. BEP is as safe as non-BEP for preserving reproductive function.

Prognosis of eight Chinese cases of primary vaginal yolk sac tumor with a review of the literature.

BACKGROUND: Primary vaginal yolk sac tumor is a rare malignancy in the pediatric population, and a diagnostic challenge and appropriate initial treatment remains unsolved. The aim of this study was to investigate the clinicopathologic features, treatment and prognosis of this tumor. MATERIALS AND METHODS: Eight cases of primary vaginal yolk sac tumor were reported with a literature review. RESULTS: There were 4 pure yolk sac tumor cases and four mixed germ cell tumors containing yolk sac tumor element, including two cases with embryonal carcinoma and two cases with embryonal carcinoma and dysgerminoma. Partial vaginectomy was performed in four cases and all patients received chemotherapy. 85 cases in literatures were reviewed and 9 cases were misdiagnosed. Follow-up data was available in 77 cases and 5-year overall survival rate was 87.6%. 5-year survival rate of biopsy with chemotherapy, conservative surgery with chemotherapy and radical surgery with chemotherapy was 91.1%, 100% and 28.6%, respectively (p<0.001). Compared to cases without relapse or metastasis after initial treatment, patients with relapse or metastasis had a shorter overall survival (35.6% vs 96.6%, p<0.001). CONCLUSIONS: Mixed germ cell tumor containing yolk sac tumor element was not uncommon and partial vaginectomy may be a good choice for primary vaginal mixed yolk sac tumor type to eradicate local tumor cells and provide complete information for pathological diagnosis and postoperative adjuvant therapy.

"Somatic-type" malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin.

Somatic-type malignancies (SMs) in patients with testicular germ cell tumors (GCT) are rare and mostly attributed to "transformation" of teratoma, although yolk sac tumor (YST) origin has also been proposed. We studied 124 cases of "SM" of testicular GCT origin from 106 patients to evaluate their morphology, immunohistochemical features (especially the utility of SALL4), and relationship to YST. Primitive neuroectodermal and nephroblastomatous tumors were excluded because of prior studies. Patients ranged in age from 15 to 68 years (mean, 33 y). The tumors ranged from 0.7 to 30 cm (mean, 7.6 cm) and involved the retroperitoneum (64%), abdomen/pelvis (10%), lung (10%), mediastinum (6%), supraclavicular region/neck (4%), testis (4%), and thigh (1%). Most initial diagnoses were sarcomas (n=68) or carcinomas (n=51). On review and immunohistochemical analysis, 7 of 45 adenocarcinomas were reclassified as glandular YSTs (GYST) on the basis of glypican-3 (GPC3) and/or α-fetoprotein positivity and scant/absent reactivity for EMA and CK7. These occasionally (29%) had subnuclear and sometimes supranuclear vacuoles (endometrioid-like), whereas adenocarcinomas were more frequently mucinous (17%) or enteric-type (11%) than endometrioid-like (9%). Both expressed CDX2 frequently (83% and 63%, respectively). MUC protein 2, 4, 5, and 6 expression was more common in adenocarcinomas (7% to 36%) than in GYSTs (0% to 20%) but was infrequent. Both were often positive for SALL4, BerEP4, and MOC31; all were negative for TTF-1. On follow-up (GYST: range, 23 to 169 mo; mean, 81mo; adenocarcinoma: range, 1 to 170 mo; mean, 55 mo), 50% and 33% of patients with GYST and adenocarcinoma, respectively, died of disease. We reclassified 26 of 76 sarcomatoid tumors as sarcomatoid YSTs (SYST) on the basis of positive reactivity for both AE1/3 and GPC3. These tumors often had spindled and epithelioid cells in a fibromyxoid stroma. SYSTs were often (60%) SALL4 positive, whereas sarcomas were all negative. On follow-up (SYST: range, 1 to 259 mo; mean, 62 mo; sarcoma: range, 1 to 327 mo; mean, 70 mo), 50% and 29% of patients with SYST and sarcoma, respectively, died of disease, with most mortality occurring in those with high-grade tumors. We conclude that, on the basis of a panel of immunoreactivities, a significant number of "SMs" in testicular GCT patients are more accurately classified as either GYSTs or SYSTs. Ambiguous glandular tumors should be evaluated for GPC3, α-fetoprotein, CK7, and EMA reactivity and sarcomatoid ones for GPC3, AE1/3, and SALL4 reactivity.

[Treatment of endodermal sinus tumor in children].

OBJECTIVE: To study the treatment and outcome of childhood endodermal sinus tumor. METHODS: The clinical data of twelve children with endodermal sinus tumor between April 2000 and July 2013 were reviewed. The basic demographics, stages of the lesion and the treatment outcome were analyzed. Of the twelve patients, seven were boys and five were girls. The age of the disease onset was between 1 and 3.3 years, except one in 11 years. Two patients were in Brodeur Stage I, four in Stage II, two in Stage III, and four in Stage IV. One patient underwent surgery alone, one underwent surgery plus a combination therapy with vincristine, actinomycin and cyclophosphamide (VAC), and the other ten were treated by surgery with the use of cisplatin, etoposide and bleomycin (PEB) before or after the operation. RESULTS: Eleven patients were successfully followed up and ten were alive. The length of survival was 4.5 to 66 months in the 10 patients. In the 10 patients treated with PEB before or after surgery, 8 achieved complete remission, one achieved partial remission and one was not followed up. The major complications associated with the PEB regimen included myelosuppression and gastrointestinal upset symptoms and no late toxicity was observed. CONCLUSIONS: Preoperative or postoperative administration of PEB may be an effective and safe management modality for childhood endodermal sinus tumor. Nevertheless, further validation is warranted in prospective studies involving a larger sample size.

Relationship between primary and metastatic testicular germ cell tumors: a clinicopathologic analysis of 100 cases.

Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with viable GCTs after chemotherapy and compared them with their corresponding orchiectomy specimens. The mean age of patients was 28 years (range, 15-58 years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18), seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no viable tumor (n = 2). Somatic malignant components were found in 5 cases. The metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non-teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but not in the testis, and 10 patients had metastatic non-teratomatous GCT components that were not observed in the testis. Six patients had somatic malignant components in the RPLNs, but only one of them had such a component in the testis. Overall, 13 patients died of disease in a mean of 42 months, and the patients with only teratoma in the RPLNs had a lower mortality rate (9%) than those with non-teratomatous components (26%) (P = .044). One patient with somatic components in the primary GCT and 3 patients with somatic components in the metastases died of disease. Our study demonstrates that there is frequent discordance of histologic composition between primary and metastatic testicular GCTs. Teratoma is the most common component in treated GCTs and is usually associated with a more favorable clinical outcome than non-teratomatous GCTs. The presence of somatic components in the RPLNs metastasis indicates a poor prognosis.

PARP expression in germ cell tumours.

BACKGROUND: Poly(ADP-ribose)polymerase (PARP) inhibitors represent a new class of promising drugs in anticancer therapy. AIMS: To evaluate PARP expression in testicular germ cell tumours (GCTs) and to correlate expression patterns with clinicopathological variables. METHODS: In this translational study, tumour specimens from 124 patients with GCTs (114 patients with testicular primary tumours and 10 with extragonadal GCTs) were identified. PARP expression was detected by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method and compared to PARP expression in normal testicular tissue. RESULTS: We observed higher expression of PARP in testicular tumours compared to normal testicular tissue (mean QS=10.04 vs 3.31, p<0.0000001). Mean QS±SD for each histological subtype was as follows: intratubular germ cell neoplasia unclassified (IGCNU)=18.00±0.00, embryonal carcinoma=9.62±5.64, seminoma=9.74±6.51, yolk sac tumour=7.8±7.20, teratoma=5.87±5.34, and choriocarcinoma=4.50±8.33. The PARP overexpression (QS>9) was most often detected in IGCNU (100% of specimen with PARP overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolk sac tumour (33.3%), teratoma (26.7%) and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimens. There was no association between PARP expression and clinical variables. CONCLUSIONS: In this pilot study, we showed for the first time, that PARP is overexpressed in testicular germ cell tumours compared to normal testis.

A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors.

PURPOSE: To evaluate whether a multimodal approach including craniospinal irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor (NGGCT) patients. METHODS AND MATERIALS: We reviewed the records of 32 patients with NGGCTs. Fourteen patients belonged to the intermediate prognosis group (immature teratoma, teratoma with malignant transformation, and mixed tumors mainly composed of germinoma or teratoma), and 18 patients belonged to the poor prognosis group (other highly malignant tumors). Patients with pure germinoma or mature teratoma were excluded from this study. Nineteen patients were treated with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient received RT alone. Twenty-seven patients received CSI with a median of 36 Gy (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole-brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and subtotal resection was 71.9%. The median follow-up for surviving patients was 121 months. RESULTS: Treatment failed in 7 patients. Three of the 5 patients who received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF) failures occurred after CSI. No failure occurred in the intermediate prognosis group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology and CSI were significant prognostic factors for RFS, and CSI was significantly associated with OS. CONCLUSIONS: A multimodal approach was effective for treating NGGCTs. CSI should be considered for patients with poor prognostic histology.

[Ovarian yolk sac tumour: general review]. / Tumeurs du sac vitellin de l'ovaire : revue de la littérature.

Ovarian yolk sac tumour (OYST) is a very rare malignancy arising most often in young women. Preoperative clinical, biological (alpha-foetoprotein) and radiological findings should help to establish the diagnosis of OYST, in order to propose adequate surgical treatment. The aim of surgery is to remove the primary tumour, to obtain an accurate histological diagnosis and to assess the disease extent. In young women, fertility-sparing surgery should be performed, in order to preserve the possibility of pregnancy later on. Chemotherapy has substantially modified the prognosis of these tumours, and practically all patients will be cured. The overall 5-year survival rate is 94% when patients are treated with BEP chemotherapy. Depending on the clinical situation, two to four cycles of the BEP regimen should be administered after surgery. Identification of prognostic factors may help to propose risk-adapted treatment in order to increase the cure rate in patients with a poor prognosis and to decrease toxicity in patients with a low risk of relapse. Fertility preservation represents a major objective in women treated for OYSTs.

Prognostic factors in women treated for ovarian yolk sac tumour: a retrospective analysis of 84 cases.

BACKGROUND: Ovarian yolk sac tumour (OYST) is a very rare malignancy arising in young women. Our study aimed to evaluate long-term outcomes and to identify prognostic parameters likely to help make appropriate risk-based decisions about therapy in this disease. METHODS: This retrospective study is based on prospectively recorded OYST cases at the Institut Gustave-Roussy. A univariate analysis using the logrank test evaluated possible associations between survival and patient or disease covariates. The multivariate analysis was performed using the Cox proportional hazard regression method. RESULTS: Between 1976 and 2006, 84 patients were registered. Since 1991, most of the patients have undergone fertility-sparing surgery. With a median follow-up of 71 months, the overall 5-year and event-free survival rates are 84% and 79%, respectively. In the multivariate model only the absence of ascites and a favourable serum AFP decline rate were significantly associated with better overall survival. CONCLUSIONS: Patients with a poor prognosis factor such as an unfavourable serum AFP decline may be considered for aggressive treatment whereas those with good prognostic factors could be given less courses of chemotherapy.

Survival after an antiangiogenetic therapy and surgery in a wide spread growing teratoma originating from a testicular mixed malignant germ cell tumor.

Growing teratoma is still an often unsolved problem especially in male with mixed malignant GCTs of the testis or the mediastinum. This specific situation with progressive tumor growth and simultaneous normalization of tumor markers during or after treatment of malignant GCTs with teratomatous elements is judged as a fatal situation if this situation can not be controlled by extensive surgery, as teratoma are not sensible to chemotherapy or irradiation. Here, we report the case history of a 17-year old male patient with a testicular malignant GCT and wide spread lymph node metastases, who developed a rapidly progressive growing teratoma within the lymph node metastases. Within the molecular profile of the tumor we could find a cytogenetic picture typically found in malignant adult GCTs. In view of the bulky abdominal, thoracic and cervical metastases and the uncontrolled tumor progression, the situation was considered incurable. However, following an individual treatment attempt, this patient was treated with a four-agent combination of drugs with antiangiogenetic potential as well as low-dose cyclic chemotherapy. This approach resulted in a sustained disease stabilization followed by extensive surgical resection of the metastases. We therefore would like to highlight this treatment approach in unresectable growing teratoma and would like to stimulate further research and collaboration to come to an optimized treatment suggestion for this group of poor prognostic patients.

Prognostic factors of patients with ovarian yolk sac tumors: a study in Chinese patients.

BACKGROUND: The aim of this study was to investigate the prognostic factors of ovarian yolk sac tumors (YST) and the survival rates in Chinese patients. PATIENTS AND METHODS: We retrospectively reviewed 76 patients with ovarian YST from the Department of Obstetrics and Gynecology, Liaoning Cancer Hospital & Institute, China, between 1984 and 2007. RESULTS: Five-year overall survival rates in stages I, II, III, and IV were 91.8, 88.9, 39.5, and 25.0%, respectively. Age, histologic type, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, tumor size and lymphadenectomy did not affect the prognosis of YST in our study. Multivariate analysis confirmed cisplatin-based chemotherapy (hazard ratio (HR) = 4.945), chemotherapy courses > 3 (HR = 2.954), residual tumor < or = 2 cm (HR = 0.224) and ascites volume < or = 100 ml (HR = 0.389) as independent predictors for overall survival. CONCLUSIONS: Our study demonstrated that the 5-year overall survival rate of YST was 53.9% for the Liaoning Cancer Hospital & Institute, China. Cisplatin-based chemotherapy, chemotherapy courses, residual tumor size and ascites volume were independent prognosis factors.

Endodermal sinus tumor of the ovary: the Hacettepe University experience.

OBJECTIVE: The purpose of this study was to evaluate the treatment regimens used for patients with endodermal sinus tumors (EST), and also to examine the prognostic value of surgicopathological variables. STUDY DESIGN: Twenty-two patients treated for pure EST, and seven patients who had mixed germ cell tumors with EST components were included. Initial surgery consisting of surgical staging to achieve optimal debulking was the principal mode of therapy. Data were obtained from patients' files, a special gynecologic oncology database, and pathology records. RESULTS: The median age at the time of diagnosis was 18 (range 8-45). Sixteen patients had stage I (55%), and 13 (45%) had stage II-IV disease. As an adjuvant therapy 18 patients (62%) received platin-based chemotherapy, three patients (10%) had non-platin-based chemotherapy, four patients (14%) had radiotherapy, and four patients (14%) had combined radiotherapy plus non-platin-based chemotherapy. The 5-year disease-free and overall survival rates were 47 and 48%, respectively. Survival rates were dismal in patients with stage II-IV disease (P < 0.001). Platin-based chemotherapy achieved significant survival benefit (P = 0.03 and P < 0.001, respectively). Fertility-saving surgery had an overall survival no worse than those who underwent more extensive surgery. There was no significant survival difference with respect to age, histology, and tumor size. CONCLUSION: Fertility-sparing surgery with a postoperative platin-based combination chemotherapy should be the selected mode of treatment.

Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and adolescence: an analysis of 31 cases.

A 20-year single-institution experience of clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in relation to clinical characteristics, treatment modalities, and survival. Thirty-one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14 children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the children, whereas mixed histologies, including embryonal carcinoma, were predominant in the adolescents. After orchiectomy, the children were assigned to surveillance and the adolescents to active treatment: 16 underwent retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based chemotherapy because of a high-risk histology. Three of the 14 children (21.4%) relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and presented with increased alpha-fetoprotein levels. No patients had retroperitoneal relapse; two recurred locally and one in the lung. All three children were treated with cisplatin-based chemotherapy with or without surgery. Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7, and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with or without surgery. Five-year relapse-free and overall survival rates for the whole series were 80.6% and 100%, respectively. This series enabled the authors to pinpoint several important aspects of stage I NSGCTT in children and adolescents. In particular, almost all the childhood cases had the same yolk sac tumor histology, the children tended to have localized disease, and an increased alpha-fetoprotein level had a very high predictive value, suggesting that follow-up should include AFP measurements. A conservative approach is the best option in children, while adolescent NSGCTT behaves like the adult disease and management must include similar treatment strategies.