Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

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.

Clinical and Radiologic Features of Pediatric Basal Ganglia Germ Cell Tumors.

BACKGROUND AND OBJECTIVE: Pediatric basal ganglia germ cell tumors (GCTs) represent a rare subset of tumors about which little is known. We aimed to summarize the clinical features and radiological findings of this special subgroup of GCTs. METHODS: From January 2010 to January 2015, 12 pediatric patients with basal ganglia GCTs were treated in our hospital. The clinical features, radiologic findings, diagnosis, treatment, and outcome of these patients were analyzed retrospectively. Our institutional diagnostic principle and treatment strategy of this disease were discussed. RESULTS: GCTs accounted for 25.5% of all the pediatric basal ganglia tumors treated in our hospital. There were 9 male and 3 female patients with a mean age of 11.5 ± 2.1 years. The most common symptom was progressive hemiparesis (n = 9, 75%). The radiologic findings showed that the lesions predominately located in caput of caudate nucleus (n = 9, 75.0%), followed by lenticular nucleus (n = 3, 25.0%). Hemiatrophy was commonly observed (n = 8, 66.7%). Eight patients were diagnosed as having germinomas, and 4 patients as having nongerminomatous germ cell tumors. During the follow-up period, preoperative neurologic dysfunctions improved in 7 patients and remained stable in 3. Two patients developed new onset of neurologic dysfunction after the treatment. Two patients suffered from tumor recurrence. CONCLUSIONS: GCTs are not as rare as considered in pediatric basal ganglia tumors. They bear some distinctive clinical and radiologic features, which can help with the accurate diagnosis and successful management of such tumors.

A rare case of bilateral massive hemothorax from spontaneous rupture of a primary mediastinal mixed germ cell tumor.

Spontaneous rupture of a mediastinal germ cell tumor, while rare, is always accompanied by bleeding. In this report, we describe a case of a primary mediastinal mixed germ cell tumor that presented with bilateral massive hemothorax and hemorrhagic shock. An urgent thoracotomy, which was performed to control bleeding, confirmed bilateral hemothorax secondary to a ruptured mediastinal tumor. Pathologic diagnosis revealed the mediastinal tumor to be mixed choriocarcinoma and immature teratoma, with lung metastatic choriocarcinoma. The patient recovered well from the operation and received salvage chemotherapy. Two years after diagnosis, the patient remains in remission with no evidence of disease.

Primary sinonasal choriocarcinoma.

Primary choriocarcinoma of sinonasal tract has not been previously documented. The aim of the study was to report, for the first time, 2 cases of primary sinonasal choriocarcinoma. The differential diagnosis is discussed and also the theories concerning the histogenesis of this neoplasm are briefly reviewed. Two male patients of 44 and 49 years of age complained of epistaxis and nasal obstruction of 2-week duration. Computerized axial tomographic scan of the head revealed an opacity of the left nasal cavity in one patient and a destructive lesion of the maxillary sinus in the other. Histopathologically, the lesions disclosed a dual cell population composed of cytotrophoblastic cells with uniform, round nuclei, clear cytoplasm, admixed with large multinucleated syncytiotrophoblastic cells, with bizarre nuclei, and abundant eosinophilic cytoplasm. Immunohistochemically, the tumors were notable for strong keratin and beta-chorionic gonadotrophin (HCG) positivity. The serum levels of HCG were 13 000 and 779 mIU/mL, respectively. One patient treated with maxillectomy, postoperative radiotherapy, and 5 courses of VIP chemotherapy (cisplatinum, etoposide, ifosfomide) died with brain metastases 10 months after diagnosis. The other patient received 4 courses of etoposide, and he is alive without tumor, 10 months after diagnosis. The serum levels of HCG are still negative. The present cases demonstrated the widespread distribution of germ cell tumors in the human body and lead to further support of the existence of primary choriocarcinomas in the sinonasal tract. Correct identification of this neoplasm is therefore important for institution of specific therapy.

Primary ovarian choriocarcinoma mimicking ectopic pregnancy managed with laparoscopy -- case report.

Nongestational ovarian choriocarcinomas are extremely rare and pose diagnostic challenges in reproductive-aged patients because of elevated human chorionic gonadotrophin (hCG). A 23-year-old nulliparous Chinese woman with nongestational ovarian choriocarcinoma escaped diagnostic testing and was initially treated for an ectopic pregnancy. Three months after her first visit, a diagnostic laparoscopy demonstrated a nongestational ovarian choriocarcinoma. Comprehensive surgical staging was performed by laparoscopy. The tumor was confined to the left ovary. The patient was categorized as FIGO Stage IA. She was given four courses of combined chemotherapy after laparoscopic surgery and has been disease-free for 36 months.

The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies.

OBJECTIVES: The diagnosis of a gestational trophoblastic tumour (GTT) should be considered in all women presenting with a malignancy and an elevated human chorionic gonadotrophin (hCG) level. Whilst some non-gestational malignancies can also produce hCG, most non-gestational tumours can be distinguished from GTT on the basis of histopathological examination. However, some non-gestational tumours can exhibit trophoblastic differentiation and so make establishing the definitive diagnosis difficult. In these cases, molecular genetic investigation can establish the differential diagnosis between gestational and non-gestational tumours and facilitate optimal management. The objective of this study is to demonstrate the clinical value of distinguishing these two diagnoses by genetic analysis in patient care at a major GTT treatment centre. METHODS: Between 1994 and 2005, fluorescent microsatellite genotyping was used to examine the genetic origin of 35 cases of metastatic hCG-producing tumours with trophoblastic differentiation, three cases of atypical uterine tumours, three cases of uterine choriocarcinoma with a very long interval and one atypical ovarian tumour. RESULTS: Of the 42 cases examined, 24 were proved to be of gestational origin, 14 were non-gestational and in 4 cases genetic analysis was inconclusive. We illustrate the clinical value of this diagnostic technique by presenting five individual cases in which molecular genetic results helped determine the appropriate clinical management. CONCLUSION: Analysis of the genetic origin of atypical hCG-producing tumours in women allows the optimisation of individual patient care and should be considered in the management of these unusual cases.

Immature teratoma with choriocarcinoma-like lesion of testis: case report of an unusual presentation.

An eighteen year old male presented with hemoptysis and superior vena caval syndrome. History and clinical examination revealed a testicular mass which was previously diagnosed as hematocele. Chest x-ray showed a four cm diameter shadow and several smaller shadows. Histological examination of the testicular mass established it as immature teratoma with choriocarcinoma-like lesion (CCLL)--a rare association in testicular tumours. Focal positivity for betaHCG was noted in the testicular tumour. Guided aspiration of the lung showed features of a metastatic non seminomatous germ cell tumour.

Regulatory role of hepatocyte nuclear factor-4alpha on gastric choriocarcinoma function.

Gastric choriocarcinoma is a highly aggressive carcinoma, most probably originating from somatic cells in the gastric mucosal layer. We herein investigated the regulatory role of hepatocyte nuclear factor (HNF)-4alpha, a transcriptional regulator expressed in non-neoplastic and neoplastic gastric tissues, on functions of gastric choriocarcinoma cells. HNF-4alpha cDNA was stably transfected to a gastric choriocarcinoma cell line, SCH. Alterations in SCH cell functions such as histology, ultrastructure, proliferation, production of trophoblast-specific proteins, and chemosensitivity to methotrexate (MTX) were examined. Neither in vitro and in vivo proliferations nor HLA-G expression differed significantly between the mock-transfected and HNF-4alpha-transfected SCH cells, while suppressed human chorionic gonadotropin (hCG) secretions, increased human placental lactogen (hPL) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) immunoreactivity, and decreased chemosensitivity to MTX were seen in HNF-4alpha-transfected SCH cells. General histologic features in xenograft nodules were unaltered, but, ultrastructurally, fascicles of paranuclear filaments were significantly more numerous in HNF-4alpha-transfected SCH cells. These results indicated an HNF-4alpha-rendered functional regulation in SCH cells, suggesting a role of transcriptional factors abundant in gastric but not in trophoblastic tissues/cells on the functional modulation of gastric choriocarcinoma cells.

Primary pulmonary choriocarcinoma--a series of 7 cases.

Primary pulmonary choriocarcinoma is a rare manifestation of extra-genital malignant germ cell tumour. This is a report of seven such cases, seen in autopsy and surgical materials in a span of 20 years. The age range was from 25 to 60 years, affecting six women and one male. These are aggressive tumours requiring prompt therapy. Only one among the seven survived.