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Objective: We presented a rare case of drug-induced thrombotic microangiopathy (DI-TMA) following chemotherapy with the regimen of bleomycin, etoposide, and cisplatin (BEP) in a patient with malignant ovarian germ cell tumor (MOGCT). The objective is to highlight the difficulty in diagnosing and treating DI-TMA associated with BEP chemotherapy., Case Report: A 21-year-old woman presented with a pelvic mass. Fertility-sparing staging surgery was performed, and a diagnosis of endodermal sinus tumor was confirmed. The patient received the first course of adjuvant chemotherapy with BEP regimen, but she developed symptoms of anemia, thrombocytopenia, and acute kidney injury. DI-TMA was diagnosed after thorough examinations, and she improved gradually by three courses of plasma exchange. Adjuvant chemotherapy was discontinued due to DI-TMA, and she kept disease-free for 17 months after the operation., Conclusion: DI-TMA, a rare lethal complication in MOGCT patients receiving the BEP regimen, requires prompt diagnosis and appropriate treatments., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST., Methods: Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay., Results: We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6 + GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance., Conclusions: In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST., (© 2023. The Author(s).)

Background: The objective of the study was to analyze the clinical features, treatment, and outcomes of primary vaginal endodermal sinus tumor (EST) in infants and children treated in a tertiary center., Methods: Clinical data of patients with pathologically confirmed primary vaginal EST in our hospital from January 1997 to December 2017 were retrospectively reviewed and analyzed., Results: A total of 21 patients were included in this study. The median age at diagnosis was 11 months (range, 4-44 months). The most common manifestations were abnormal vaginal bleeding, and a polypoid mass protruding from the vagina. Chemotherapy based on PEB (cisplatin, etoposide, bleomycin) regimen was given, and serum alpha-fetoprotein (AFP) levels dropped to normal levels after 2 to 4 cycles of chemotherapy (median, 2 cycles). After 3 to 13 cycles of chemotherapy, with a median of 5 cycles, 20 patients achieved complete remission (95.2%). The median follow-up time was 80 months (range, 4-281months). At the time of the last follow-up, 19 cases were alive without disease, and the survival rate was 90.5%., Conclusion: Vaginal EST is a very rare malignant germ cell tumor and is sensitive to chemotherapy. Conservative surgery combined with PEB chemotherapy is an effective way of treatment. Serum AFP and imaging examinations can monitor the treatment response and recurrence., (© 2022. The Author(s).)

Background and Purpose: Primary intracranial pure yolk sac tumor is very rare. Our aim was to summarize the characteristics of primary intracranial pure yolk sac tumors from the clinical and imaging aspects in a retrospective study., Materials and Methods: We studied 5 patients with primary intracranial pure yolk sac tumors in Guangzhou Women and Children's Medical Center from January 2015 to June 2021. A comprehensive literature search was performed on the electronic database of the China National Knowledge Infrastructure (1990 to June 2021). Clinical data based on age, sex, treatment, CT, and MR imaging findings were collected and analyzed., Results: A total of 25 patients were included in the study, 21 boys and 4 girls. Twenty-one patients underwent plain MR imaging and an enhanced examination, 9 patients underwent DWI, and 12 patients underwent plain CT and/or an enhanced examination. The tumors were posterior fossa in 9 cases and supratentorial in 16 cases. All tumors showed marked enhancement after enhanced scanning by MR imaging or CT. The signal on DWI was similar to that of the cerebral cortex, and the ADC map was similar to or slightly higher than that of the cerebral cortex. Among the cases, 13 were followed up from 2 months to 5 years. There was no recurrence or metastasis in 9 patients with postoperative chemotherapy or chemoradiotherapy followed up for 1.5-5 years. Four patients died 2 months to 1.5 years after only an operation, or chemoradiotherapy but no operation., Conclusions: There are some relatively specific imaging findings of primary intracranial yolk sac tumors that could assist in their diagnosis. Surgery combined with radiation therapy and/or chemotherapy can achieve a better prognosis., (© 2022 by American Journal of Neuroradiology.)

Background: Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm, and it is a kind of mediastinal non-seminomatous germ cell tumor. The current standard treatment in mediastinal non-seminomatous germ cell tumors is chemotherapy combined with postchemotherapy residual mass resection. We report on seven cases of primary mediastinal yolk sac tumor treated with platinum-based chemotherapy and extended resection., Methods: We experienced seven cases of primary mediastinal yolk sac tumor between August 2014 and August 2017. All cases had markedly raised α-fetoprotein and normal β-human chorion gonadotropin. Computed tomography scan revealed an anterior mediastinal tumor in all cases. Five patients underwent needle core biopsy, which showed a mediastinal yolk sac tumor. They received preoperative platinum-based chemotherapy and then underwent extended resection, and four of them received postoperative platinum-based chemotherapy. Two other patients did not receive preoperative biopsy, and they underwent surgical extended resection and then received postoperative platinum-based chemotherapy., Results: Two patients (29%) experienced a postoperative complication, including one pneumonia and one atelectasis. There were no operative deaths. R0 resection was achieved in six patients (86%), and R2 resection was achieved in the other patient. Three patients experienced pulmonary metastases within one year, and two of them soon died. Four other patients were alive without recurrence at the time of writing., Conclusion: Primary mediastinal yolk sac tumor is rare, and the prognosis is poor. A multimodality aggressive approach including adjuvant chemotherapy followed by surgical resection is the optimal treatment and may lead to long-term survival., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The safety and efficacy of chemotherapy for patients undergoing concomitant hemodialysis have not been fully established and optimal doses of anti-cancer drugs and best timing of hemodialysis remains unclear. Although chemosensitive cancers, such as germ cell tumors, treated with chemotherapy should have sufficient dose intensity maintained to achieve the desired effect, many patients with cancer undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remains unknown., Case Presentation: We describe a 31-year-old Japanese man with a mediastinal yolk sac tumor treated with surgery followed by five cycles of chemotherapy containing cisplatin and etoposide while concomitantly undergoing hemodialysis. The doses of these agents used in the first cycle were 50% of the standard dose of cisplatin (10 mg/m 2 ) and 60% of the standard dose of etoposide (60 mg/m 2 ) on days 1 through to 5; the doses were subsequently escalated to 75% with both agents. Hemodialysis was started 1 hour after infusions of these agents. Severe hematological toxicities were observed despite successful treatment. During treatment with concurrent hemodialysis, pharmacokinetic analysis of cisplatin was performed and its relationship with adverse effects was assessed. Compared with patients with normal renal function, the maximum drug concentration was higher, and concentration increased in the interval between hemodialysis and the subsequent cisplatin infusion, resulting in a higher area under the curve despite a reduction in the dose to 75% of the standard regimen., Conclusions: Because of the altered pharmacokinetics pharmacodynamics status of patients with renal dysfunction undergoing hemodialysis, pharmacokinetics pharmacodynamics analysis is deemed to be helpful for effective and safe management of chemotherapy in patients undergoing hemodialysis.

Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

Malignant germ-cell tumors (MGCT) are rare tumors of childhood accounting for less than 3% of pediatric malignancies. Yolk sac (endodermal sinus) tumor is one of the malignant germ cell tumor that usually involves the gonads (ovaries and testes). Its occurrence in the vagina is extremely rare. We report a 6-months old girl presented with a vaginal mass diagnosed as a yolk sac tumor. This diagnosis is confirmed by histopathologic examination, immunehistochemical studies as well as elevated serum alpha fetoprotein (AFP).

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.

Background: Malignant mediastinal germ cell tumors are a rare disease and represent only 1% to 4% of all mediastinal tumors. Gonadal germ cell tumors are generally the most common type and constitute 90% of germ cell tumors. The mediastinum is the second most frequently affected area ahead of other extragonadal areas, which include the retroperitoneum, the sacrococcygeal area, and the central nervous system. We report on the case of a mediastinal yolk sac tumor with a complete histological response to chemotherapy., Case Presentation: A 26-year-old Moroccan man, without a medical or surgical history, presented with a four-month history of chest distress, dyspnea, and a frequent dry cough for the previous month. A computed tomographic scan of the chest revealed a bulky mediastinal mass, which was biopsied. Histologically, the tumoral mass proved to be a yolk sac tumor. The serum level of alpha-fetoprotein of this patient was elevated to 19052 ng/ml.After 4 courses of preoperative chemotherapy, the patient underwent a surgical resection of the tumor, with a complete pathologic response.At the time of writing, the patient is alive with complete remission without any evidence of recurrence., Conclusion: Primary mediastinal Yolk sac neoplasm represent a unique entity, and as such require specialized management. The diagnosis should be made not only by morphological studies but the patient's age and the elevation of serum alpha-fetoprotein should also be considered. The utilization of cisplatin-based chemotherapy is associated with the best chance of a cure for this disease. This should be followed by surgical resection of the residual tumor in the nonseminomatous germ cell tumor.

Primary non-seminomatous germ cell tumours of anterior mediastinum are uncommon. Endodermal sinus tumour of the anterior mediastinum (yolk sac) is a rare but lethal neoplasm. We present a case of an 18-year-old man who presented with chest pain, cough and haemosputum with markedly raised serum α-fetoprotein (AFP) levels above 112,000 ng/mL. Chest roentgenogram and CT showed a giant anterior mediastinal mass. CT guided biopsy revealed a diagnosis of endodermal sinus tumour. After the completion of chemotherapy, extensive surgical resection was carried out along with the right lung metastastectomy. Five years postresection follow-up the patient is disease free with normal serum tumour markers. This is the longest survival ever reported of such tumours with highest AFP level (>112,000 ng/mL) and lung metastasis., (2014 BMJ Publishing Group Ltd.)

Purpose: Little data exist on characteristics, treatment, and outcome of patients with bone metastases from germ cell cancer., Methods: A total of 434 patients with poor prognosis germ cell cancer, who underwent primary high-dose chemotherapy (HD-CTX) within two phase II trials, were retrospectively analyzed., Results: 40 patients (9%) presented with primary bone metastases. Bone metastases were significantly more frequently observed in patients with primary mediastinal tumors, yolk sac tumor histology, and synchronous liver metastases. Overall response rate to HD-CTX was 85%. 20% of patients underwent consolidating radiotherapy, and 10% had resection of bone metastases revealing necrosis in all cases. Progression-free survival rate after primary treatment was 63% and, including salvage treatment after first relapse, overall long-term survival rate was 75%. Four patients (0.9%) relapsed with isolated bone metastases, all with bone metastases at primary diagnosis. None had previously received surgery or radiotherapy and all died within 1 year. 10 patients with primary bone metastases showed recurrences at other localizations. No patient relapsed with bone plus other metastases or with de novo bone metastases., Conclusions: Bone metastases were associated with a primary mediastinal nonseminoma, yolk sac histology, and liver metastases at first diagnosis. In this cohort of patients receiving HD-CTX as first-line treatment, 63% achieved long-term progression-free survival. Skeletal relapses were rare, but showed dismal outcome.

We report a case of a vaginal yolk sac tumor in a 5-month-old female infant who presented with short history of bleeding per vagina. Magnetic resonance imaging showed a mass occupying most of the vagina that had lobulated outlines and heterogeneous echo texture. The serum alpha-fetoprotein was elevated, and a biopsy revealed a vaginal yolk sac tumor. The patient was given six cycles of chemotherapy and continues to be disease-free on follow up. To preserve sexual and reproductive function, we encourage consideration of chemotherapy as a sole modality to treat this rare tumor.

The testicular yolk sac tumor (TYST) is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST., (© 2012 Zhao et al; licensee BioMed Central Ltd.)

Background: MDR1 gene encoding P-glycoprotein is an ATP-dependent drug efflux transporter and related to drug resistance of yolk sac carcinoma. Ultrasound microbubble-mediated delivery has been used as a novel and effective gene delivery method. We hypothesize that small interfering RNA (siRNA) targeting MDR1 gene (siMDR1) delivery with microbubble and ultrasound can down-regulate MDR1 expression and improve responsiveness to chemotherapeutic drugs for yolk sac carcinoma in vitro., Methods: Retroviral knockdown vector pSEB-siMDR1s containing specific siRNA sites targeting rat MDR1 coding region were constructed and sequence verified. The resultant pSEB-siMDR1 plasmids DNA were encapsulated with lipid microbubble and the DNA release were triggered by ultrasound when added to culture cells. GFP positive cells were counted by flow cytometry to determine transfection efficiency. Quantitative real-time PCR and western blot were performed to determine the mRNA and protein expression of MDR1. P-glycoprotein function and drug sensitivity were analyzed by Daunorubicin accumulation and MTT assays., Results: Transfection efficiency of pSEB-siMDR1 DNA was significantly increased by ultrasound microbubble-mediated delivery in rat yolk sac carcinoma L2 (L2-RYC) cells. Ultrasound microbubble-mediated siMDR1s delivery effectively inhibited MDR1 expression at both mRNA and protein levels and decreased P-glycoprotein function. Silencing MDR1 led to decreased cell viability and IC50 of Vincristine and Dactinomycin., Conclusions: Our results demonstrated that ultrasound microbubble-mediated delivery of MDR1 siRNA was safe and effective in L2-RYC cells. MDR1 silencing led to decreased P-glycoprotein activity and drug resistance of L2-RYC cells, which may be explored as a novel approach of combined gene and chemotherapy for yolk sac carcinoma.

Background: Malignant ovarian germ cell tumors are rare, and knowledge of their prognostic factors is limited, with little available randomized data. This study was conducted to evaluate the clinicopathologic characteristics of malignant ovarian germ cell tumors and to determine the association of their prognostic factors to primary treatment failure., Methods: The medical records of 57 patients with stages I to IV malignant ovarian germ cell tumor were retrospectively reviewed, and their clinicopathologic and treatment-related data were collected and analyzed., Results: The median age at the diagnosis was 23.3 years (range: 8-65 years), and the median follow-up period was 108 months (range: 48-205 months). The histological types of the tumors were immature teratoma (n = 24), dysgerminoma (n = 20), endodermal sinus tumor (n = 8), mixed germ cell tumor (n = 4), and choriocarcinoma (n = 1). 66.7% of the patients had stage I disease; 5.2%, stage II; 26.3%, stage III; and 1.8%, stage IV. After the initial surgery, 49 patients (86%) received cisplatin-based chemotherapy. The five-year survival rate was 96.5%. There were six primary treatment failures, with two of the patients dying of the disease, and the median time to the recurrence was 8 months. The histological diagnosis (P < 0.0001), tumor stage (P = 0.0052), elevation of beta-hCG (P = 0.0134), operation methods (P = 0.0006), and residual tumor after the salvage surgery (P < 0.0001) were significantly associated with the risk of primary treatment failure in the univariate analysis. In the multivariate analysis, the residual tumor after the salvage surgery was the only significant variable associated with primary treatment failure (P = 0.0011, Hazard ratio = 29.046, 95% Confidence interval 3.832-220.181)., Conclusion: Most malignant ovarian germ cell tumors have excellent prognoses with primary treatment, and good reproductive outcomes can be expected. Because primary treatment failure is associated with the residual disease after the salvage surgery, knowledge of the presence or absence of this risk factor may be helpful in risk stratification and individualization of adjuvant therapy in malignant ovarian germ cell tumors. Further large-scale prospective studies to confirm these results should be performed.

Background: Yolk sac tumours (YSTs) and germinomas are the two major pure histological subtypes of germ cell tumours. To date, the role of DNA methylation in the aetiology of this class of tumour has only been analysed in adult testicular forms and with respect to only a few genes., Methods: A bank of paediatric tumours was analysed for global methylation of LINE-1 repeat elements and global methylation of regulatory elements using GoldenGate methylation arrays., Results: Both germinomas and YSTs exhibited significant global hypomethylation of LINE-1 elements. However, in germinomas, methylation of gene regulatory regions differed little from control samples, whereas YSTs exhibited increased methylation at a large proportion of the loci tested, showing a 'methylator' phenotype, including silencing of genes associated with Caspase-8-dependent apoptosis. Furthermore, we found that the methylator phenotype of YSTs was coincident with higher levels of expression of the DNA methyltransferase, DNA (cytosine-5)-methyltransferase 3B, suggesting a mechanism underlying the phenotype., Conclusion: Epigenetic silencing of a large number of potential tumour suppressor genes in YSTs might explain why they exhibit a more aggressive natural history than germinomas and silencing of genes associated with Caspase-8-dependent cell death might explain the relative resistance of YSTs to conventional therapy.

Objective: We report an extremely rare case of germ-cell tumor localized at the level of the anterior mediastinum., Clinical Presentation: A 36-year-old man who presented with left subclavial vein thrombosis was admitted to our hospital for specific cure. Computed tomographic scan of the chest showed a large anterior mediastinal mass. Surgical intervention revealed an infiltrative mediastinal tumor involving the left subclavial vein, which was biopsied for morphological examination. Histologically, the tumoral mass proved to be a carcinoma, with papillary and tubular growth patterns. Immunohistochemical stains for alpha-fetoprotein were positive in the tumor cells while stains for carcinoembryonic antigen and placental like alkaline phosphatase were negative. The serum level of alpha-fetoprotein of this patient was elevated, as well. This supported the diagnosis of Yolk sac tumor, a rare primary tumor within the mediastinum. Postsurgery, the patient received a combination chemotherapy consisting of cisplatin, vepesid and bleomycin every 3 weeks for a total of 4 cycles. During the treatment, the alpha-fetoprotein level, was decreasing., Conclusion: Primary mediastinal Yolk sac neoplasm is a rare tumor. The diagnosis should be made not only by morphological studies but also the patient's age and the elevation of serum alpha-fetoprotein. In spite of modern chemotherapy, the prognosis of mediastinal yolk sac tumor remains poor. The single most important prognostic indicator is whether the tumor mass can be completely excised before or after chemotherapy.

Background: The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach., Case: A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle., Conclusion: In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Malignant tumors of the vagina in infants and children are rare, with primary germ cell tumor (endodermal sinus tumor [EST]) being rarer, which carries a dismal prognosis. This tumor is often clinically mistaken as botryoid rhabdomyosarcoma and, on histopathological examination, is often misdiagnosed as clear cell adenocarcinoma. Two cases of EST of the vagina in infants aged 9 and 17 months are reported. Both the patients presented with bleeding per vagina and clinically and by ultrasonography were diagnosed as sarcoma botryoides. Both were diagnosed as primary yolk sac tumors. The serum alfa fetoprotein (AFP) level was 4325 and 9328 ng/ml, respectively. One patient aged 9 months expired 2 months after receiving chemotherapy. The other, aged 17 months, was given chemotherapy followed by surgery with reduction of the AFP levels.

Objectives: Our objective was to explore the pathologic components of residual masses after primary chemotherapy in patients with metastatic nonseminomatous germ cell tumors., Methods: A multicenter retrospective study was conducted of 71 patients with thoracic residual masses (39 patients had bilateral lung metastasis) after first-line cisplatin-based chemotherapy for disseminated nonseminomatous germ cell tumors. Among the 71 patients, 52 also had a retroperitoneal lymph node dissection., Results: Pathologic findings in postchemotherapy residual masses included complete necrosis, teratoma, and viable cancer in 31%, 55%, and 14% of patients, respectively. Discordant pathologic findings were evidenced between retroperitoneal lymph node and thoracic (lung or mediastinal lymph nodes) residual masses in 27% of patients. When a bilateral pulmonary resection was performed, only 2 (5%) of 39 patients had discordant histologic findings between the two lungs. Among patients who had necrosis only in residual masses from their first lung (n = 20), 19 (95%) also had necrosis only in contralateral lesions. A single patient had necrosis only in the first lung and some teratoma in the contralateral lung., Conclusions: This report shows a high rate (95%) of pathologic concordance between the two lungs. Avoiding contralateral lung surgery could therefore be considered when complete necrosis is found in the first lung after induction chemotherapy for nonseminomatous germ cell tumor.

Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain types of squamous-cell carcinoma. The common adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up to 46% of patients treated with BLM-containing chemotherapy and lung toxicity usually appears during treatment. Here we describe a patient with lung fibrosis, who presented with slow progressive breathlessness and pneumothorax more than 10 years after cessation of BLM therapy. A 15 year-old girl presented with abnormal shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region at 1 year of age and obtained complete remission after being treated with tumor resection, radiation, and several anti-cancer drugs including BLM. There were no abnormal findings in chest X-ray until she reached 3 years of age, when she had developed respiratory distress that worsened with age. The patient had experienced an episode of pneumothorax at 13 years of age. Chest CT at the time revealed interstitial reticular opacities. Radiological findings and pathological examination of the lung tissue obtained during bullectomy with video-assisted thoracic surgery were compatible with BLM-induced pneumonitis. The present study suggests that lung fibrosis may surface more than 10 years after cessation of BLM therapy at the age of 1 year, with no chest radiographic findings 1 year after completion of chemotherapy. The use of BLM in infants requires strict supervision and observation and careful long-term follow up.

Background: Ovarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy. However, given the rarity of this tumor, ovarian YST-specific survival and outcome after such treatment are not precisely known., Patients and Methods: This report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission., Results: Thirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded., Conclusions: BEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.

Yolk sac tumors of the ovary (YST) are rare and highly malignant tumors occurring in children and young adults. Because of its rarity, YST prognostic factors remain unclear. Our purpose was to evaluate the prognostic factors in YST. We performed a retrospective review of 36 patients with pure YST from 1986 to 2006. The 5-year overall survival and progression-free survival were 66.6% and 68.8%, respectively. Patients with stage I-II disease had a more favorable prognosis than those with stage III-IV (p < 0.05). Those with an ascites volume of less than 100 ml or a residual tumor measuring less than 1 cm had improved to a relatively good prognosis. Neither serum AFP level nor age had any significant correlation with the prognosis in this study. In conclusion, the FIGO (International Federation of Gynecology and Obstetrics) stage, ascites volume and residual tumor size tended to affect the prognosis of YST.

Extragonadal germ cell tumors are relatively rare, particularly malignant yolk sac tumors arising in the lung parenchyma. We report a case of a huge malignant yolk sac tumor in the right middle lobe. The patient was successfully treated with neoadjuvant chemotherapy followed by complete resection of the tumor.

Hyperpigmentation is one of the cutaneous side effects of chemotherapautic agents, but it is usually accepted as a cosmetic problem. We report a child with yolk sac tumor who developed localized pigmentation after the first course of chemotherapy regimen that included cisplatin, etoposide and bleomycin. The hyperpigmentation was diffuse scattered, flagellate like and linear streaking which was thought to be mainly related to the skin toxicity of bleomycin.

Yolk sac tumors are common in children. By virtue of being chemosensitive, they are amenable to cure by chemotherapy alone and radical surgery is often not required. Yolk sac tumors occurring in the vagina are rare and thus may not be recognized early or may be inadvertently subjected to radical surgery. The authors report a case that presented to them after radical surgery with elevated Alpha-fetoprotein level is reported. The management of this case and review of the relevant literature are discussed here.

Background: Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31-42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor., Case Presentation: A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma., Conclusions: We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis.

The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.

The primary location of non-metastatic germ cell tumours of the chest is the anterior mediastinal compartment. Germ cell tumour arising from lung parenchyma is one of the rarest conditions in human and only a few cases of choriocarcinomas and yolk sac tumour have been reported to date. Here we report a case of intrapulmonary mixed type germ cell tumour, containing embryonal carcinoma, choriocarcinoma and yolk sac tumour elements. Diagnosis of the lesion was achieved by open thoracotomy and bulk of the tumour was resected by right upper lobectomy.

We report a 2 1/2 years old female child who presented with Malignant Sacrococcygeal Yolk sac (Endodermal Sinus) tumor as presacral mass with ulceration of overlying skin. Her ultrasonography (USG)abdomen revealed a huge presecral mass with irregular margins extending in to the pelvis, pushing the rectum antero-laterally. CT scanning of abdomen confirmed USG finding with out enlargement of retroperitoneal lymph nodes and no involvement of the liver. Serum AFP was abnormally elevated. The tumor was excised along with Coccyx in-toto through posterior approach dividing the sacrum and 3-Drugs (VAC) Chemotherapy started postoperatively i.e. 2-weeks after surgery. Here we discuss our experience with this extremely rare malignant extra-gonadal germ-cell tumor and review of literature.

Yolk sac tumours are rare conditions among the germ cell tumours. Intracerebral germ cell tumours are exceedingly rare. A 15 year old girl presenting with a one week history of raised intracranial pressure is described. She had bilateral papilloedema and a right 6th nerve palsy. CT scan showed an intra-parenchymatous right frontal ring enhancing lesion of 2 cms diameter. The patient underwent microsurgical total excision of the tumour, followed by chemotherapy. She was asymptomatic at three years following surgery.

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.

We report the establishment of a leukemia cell line (UoC-B10) from a patient who developed leukemia several months after the diagnosis of a mediastinal yolk sac tumor. The patient's yolk sac tumor responded to combination chemotherapy, and a mature teratoma with focal areas of hematopoiesis was subsequently resected. However, 5 months after the initial diagnosis, the patient developed an acute lymphoblastic leukemia with a precursor B-cell phenotype. Cytogenetic analysis showed an i(12p) abnormality in the patient's leukemia cells and in the UoC-B10 cell line. The i(12p) was also identified retrospectively in the mediastinal tumor cells by fluorescent in situ hybridization analysis. The UoC-B10 cell line, which has been growing continuously for > 24 months in culture, was Epstein-Barr virus negative and was generally concordant with the patient's leukemia cells by analysis of immunophenotype, karyotype, and genotype. The UoC-B10 cell line possesses receptors for granulocyte-colony-stimulating factor, a cytokine which the patient received as part of his treatment protocol. This cell line may be useful in studying the relationship between i(12p) and hematological differentiation of human mediastinal germ cell tumors.

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.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.