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Introduction: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity., Patients and Methods: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts., Results: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining., Interpretation: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.)

A 40-year-old man was referred to our hospital for treatment of metastatic testicular cancer. Computerized tomography revealed multiple lung, liver, and retroperitoneal lymph node metastases. In addition, magnetic resonance imaging revealed multiple brain metastases. Induction chemotherapy with bleomycin, etoposide, and cisplatin was started the day after a high orchiectomy. The pathological diagnosis of the surgical specimen was yolk sac carcinoma. The serum human chorionic gonadotropin (hCG) was markedly increased to 630,000 mIU/ml, which suggested the presence of a choriocarcinoma element at metastatic sites. The patient subsequently suffered respiratory failure due to pulmonary hemorrhage. Intensive supportive care prevented a fatal outcome. Physicians who treat advanced testicular tumors should be aware of the potential complication of acute pulmonary hemorrhage, called choriocarcinoma syndrome, in cases with a high hCG level, which indicates a rapidly progressive and high-volume choriocarcinoma.

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.

Primary germ cell tumors of the chest often localize in the anterior mediastinal compartment. Such tumors originating from lungs and pleura are rare. Chest tomography revealed a mass in the middle lobe of the right lung in a 25-year-old man. A middle lobe medial segmentectomy was performed, and chemotherapy was applied postoperatively.

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.

A 31-year-old female was clinically diagnosed as having a anterior mediastinal yolk sac tumor because of the elevation of the AFP (17,500 ng/ml), a large mass lesion (9 x 5 cm) in the anterior mediastinum and bilateral lung metastases. After 4 courses of chemotherapy with cisplatin (CDDP), etoposide (VP-16) and bleomycin hydrochloride (BLM), the mediastinal mass reduced in size significantly and the serum AFP level reached within normal range. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a weak uptake in the mediastinum, accordingly the operation was performed. The tumor was completely removed and there were no viable foci of the tumor in part of the tumor. After the operation, 4 courses of chemotherapy with carboplatin (CBDCA), VP-16 and ifosfamide (IFM) were performed. She is alive without evidence of recurrence in 5 months after operation. It was noticed that the serum AFP is a useful indicator for determing the chance of operation after chemotherapy.

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 case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage IIIB2). After three courses of chemotherapy with a PVB regimen (cisplatin, vinblastine and bleomycin), complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-fetoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide, etoposide, actinomycin D, bleomycin and cisplatin), followed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.