NAD(P)H: Quinone oxidoreductase (NQO1) and catalase expression in nonseminomatous germ cell tumors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 413-413
Author(s):  
Neda Hashemi-Sadraei ◽  
Nabil Adra ◽  
Kenneth A. Kessler ◽  
Muhammad T. Idrees ◽  
Lawrence Einhorn ◽  
...  

413 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme which detoxifies quinones and reduces oxidative stress. NQO1 is expressed in multiple tumor types at levels up to 200-fold above normal tissue, including in breast, pancreatic, and non-small cell lung cancers. NQO1 bioactivatable drugs have the potential to deliver tumor-selective DNA damage and cell death by exploiting the elevation of NQO1. Alterations in catalase expression can cause marked cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no data available on NQO1 and catalase expression in germ cell tumors. Methods: Patients with germ cell tumor who underwent orchiectomy/tumor resection between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center database. Patients with non-seminomatous germ cell tumor of testis or primary mediastinal non-seminomatous germ cell tumor were selected. Immunohistochemistry staining for NQO1 and catalase was performed on tumor tissue. Results: NQO1 and catalase expression were assessed in 16 patients. Fifteen of 16 tumors stained positive for NQO1, 13 of which were moderately to strongly positive. Conversely, the majority of tumors were catalase deficient or only mildly positive for catalase. The details of the Immunostaining is summarized in the table below. Conclusions: Non-seminomatous germ cell tumors appear to have overexpression of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could be beneficial in treating patients with refractory non-seminomatous germ cell tumors.[Table: see text]

2021 ◽  
Vol 27 (1) ◽  
pp. 47-51
Author(s):  
Alexander G. Weil ◽  
Natalie Mathews ◽  
Jean-Pierre Farmer ◽  
Christine St. Martin ◽  
Steffen Albrecht ◽  
...  

Here, the authors present 2 cases of nongerminomatous germ cell tumor (NGGCT): a neonate with a mixed malignant germ cell tumor, 5% yolk sac tumor (YST) and 95% immature teratoma components, originating from the right mesial temporal lobe; and a 2-month-old infant with a pure YST originating from the left middle cranial fossa. These tumors with yolk sac components, which are thought to have a poor prognosis, were successfully treated with complete tumor resection alone and subtotal tumor resection with chemotherapy, respectively. Event-free survival exceeds 5 years for each patient even though neither received radiotherapy. The authors highlight the role of radical surgery and the successful treatment of neonatal YST with aggressive resection (and chemotherapy in 1 case) while avoiding radiation therapy. They also report the very rare non-midline location of these neonatal NGGCTs and emphasize the importance of considering YSTs and mixed NGGCTs with YST components in the differential diagnosis of non-midline hemispheric or skull base tumors in newborns.


2021 ◽  
pp. 1-10
Author(s):  
John K. Yue ◽  
Diana Chang ◽  
Taemin Oh ◽  
Ethan A. Winkler ◽  
Alex Y. Lu ◽  
...  

<b><i>Introduction:</i></b> Tumor-associated intracranial aneurysms are rare and not well understood. <b><i>Case Presentation:</i></b> We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. <b><i>Discussion:</i></b> We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii329-iii329
Author(s):  
Hiroki Yamada ◽  
Tomohiro Abiko ◽  
Hirokazu Fujiwara ◽  
Kazunari Yoshida ◽  
Hikaru Sasaki

Abstract INTRODUCTION Germ cell tumors in the central nervous system (CNS) typically arise either at suprasellar and/or pineal region, and occasionally at basal ganglia. We report a case of diagnostically challenging, recurrent germ cell tumor presented with diffuse intraaxial abnormality in and across the lower brainstem, which was diagnosed by the elevated placental alkaline phosphatase (PLAP) level in cerebrospinal fluid (CSF). CASE DESCRIPTION: A 28-year-old man had been treated by chemoradiotherapy at the previous hospital for bifocal suprasellar and pineal lesions with the provisional diagnosis of germinoma without histological confirmation. Three years later, he presented with progressive weakness of bilateral extremities for weeks. Magnetic resonance imaging showed a diffuse, bilaterally symmetric high intensity lesion on T2-weighted image with slight contrast enhancement across the ventral side of the medulla oblongata to the upper cervical spinal cord. Serum and CSF hCG, hCG-β, and AFP were all negative. Since the image findings were atypical for recurrent germ cell tumor, some kind of myelitis was initially suspected. Therefore, steroid pulse therapy was administered. However, the patient’s symptom was still gradually progressing. Then, the CSF PLAP turned out to be positive, indicating the recurrence of germinoma. Accordingly, platinum-based chemotherapy was administered, and the imaging findings, patient’s symptoms, and CSF PLAP began to improve. The patient is to be treated with radiotherapy following chemotherapy. CONCLUSION We report a rare case of CNS germ cell tumor that presented with diffuse intraaxial lesion in the lower brainstem in which examination of CSF PLAP was extremely useful.


Author(s):  
Faraz S. Vali ◽  
Amit Kyal ◽  
Parul I. Chaudhary ◽  
Sujatha Das ◽  
Aprateem Mukherjee ◽  
...  

Germ cell tumors represent only 20% to 25% of all benign and malignant ovarian neoplasms. Mixed germ cell tumors are a rare variety of non–dysgerminomatous germ cell tumors. They contain two or more elements; the most frequent combination being a dysgerminoma and an EST (Endodermal Sinus Tumor). We present a case of malignant mixed germ cell tumor comprising of yolk sac tumor, embryonal carcinoma and choriocarcinoma. A 13-year-old girl presented with a huge 25 x 18 cm mass in abdomen with raised values of CA-125, hCG, AFP (alpha-feto protein) and LDH (lactate dehydrogenase). She underwent laparotomy followed by unilateral salpingoopherectomy and infracolic omentectomy. Histopathology report revealed malignant mixed germ cell tumor comprising predominantly of EST with elements of embryonal carcinoma and non-gestational choriocarcinoma. Following surgery, she was started on adjuvant chemotherapy (Bleomycin, Etoposide and Cisplatin regimen). Mixed germ cell tumor (YST/EST, non-gestational choriocarcinoma and embryonal carcinoma) is a very rare tumor. Careful initial surgery with adequate staging biopsies followed by combination chemotherapy can greatly improve the prognosis of these patients


2020 ◽  
Vol 35 (2) ◽  
pp. 119-122
Author(s):  
SM Rashed Zahangir Kabir ◽  
Md Waheed Akhtar ◽  
Farida Yasmin

Introduction: Germ cell tumors are a group of tumors with different clinical presentation and histological and biological characteristics. Malignant germ cell tumors occur at all ages with a trend of bimodal distribution in infancy and adolescence. Objective: To evaluate the demographic characteristics, distribution of different types of germ cell tumor, treatment modalities and outcome of germ cell tumor in children in a tertiary care hospital of Bangladesh. Methods: In this retrospective study, data regarding age and sex distribution, location, types of tumors, management of germ cell tumor in children were retrieved from the medical records of pediatric oncology department in NICRH, Dhaka from 2008 to 2014. Results: Out of total 87 patients female were 50 and male 37. Most of the patients were up to 5 years of age. The gonadal germ cell tumors (80%) were more than extragonadal tumor (20%) in both male and female patients. The most common germ cell tumor was dysgerminoma (32%) followed by yolk sac tumor (29.8%) and teratoma (19.5%). Yolk Sac Tumor (51.4%) was the most common in male and dysgerminoma (56%) the commonest in female. Out of 87, seventy two (82.7%) received chemotherapy following surgery. Among those 72 patients who received chemotherapy 49 (68 %) patients completed their treatment. Until the last follow up 71.4% patients remained alive and tumor free. Conclusion: Germ cell tumors are the most variable tumor of all childhood malignancies that has difference in age, sex, location and histological subtypes. Gonadal tumors have better prognosis than extragonadal tumors in both the sex. DS (Child) H J 2019; 35(2) : 119-122


2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii23
Author(s):  
Kaishi Satomi ◽  
Hirokazu Takami ◽  
Shintaro Fukushima ◽  
Yoichi Nakazato ◽  
Shota Tanaka ◽  
...  

Abstract BACKGROUND Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs. MATERIALS AND METHODS We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH). RESULT 12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P&lt;0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). DISCUSSION 12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.


Author(s):  
Kimberley Bonouvrie ◽  
Jutte van der Werff ten Bosch ◽  
Machiel van den Akker

Abstract Objective The most common presentation of Klinefelter syndrome (KS) is infertility and features of hypogonadism. Currently no consensus exists on the risk of malignancy in this syndrome. Several case reports show an incidence of extragonadal germ cells tumors (eGCT) of 1.5 per 1000 KS patients (OR 50 against healthy population). Malignant germ cell tumors are rare in children. They account for 3% of all children cancers. Young patients with a germ cell tumor are not routinely tested for Klinefelter syndrome. This can therefore result in underdiagnosing. Literature data suggest a correlation between eGCT and KS. To the best of our knowledge there is no precise description of the primary locations of germ cell tumors in KS patients. The purpose of this study is to evaluate age groups and primary locations of extragonadal germ cell tumors in Klinefelter patients. With this data we investigate whether it is necessary to perform a cytogenetic analysis for KS in every eGCT patient. Study design This study is based on case report publications in PubMed/Medline published until march 2020 that described “Klinefelter Syndrome (MeSH) AND/OR extragonadal germ cell tumors”. Publications were included when patients age, location and histology of the germ cell tumor was known. Two double blinded reviewers selected the studies.Results: 141 KS patients with eGCTs were identified. Mean age at presentation was 17.3 years (StDev + − 10.2). In contrast to the extragonadal germ cell tumors in adults, most eGCT in children were mediastinal or in the central nervous system (respectively 90/141; 64% and 23/141; 16% of all tumors). Distribution of histologic subtypes showed that the largest fraction represented a teratoma, mixed-type-non-seminomateus GCT and germinoma, respectively 34/141; 24%, 26/141; 18% and 20/141; 14% of all tumors. Conclusion These data suggest a correlation between primary extragonadal germ cell tumors and Klinefelter syndrome. There appears to be an indication for screening on KS in young patients with an eGCT in the mediastinum. A low threshold for radiologic examinations should be considered to discover eGCT. We emphasize the need for genetic analysis in all cases of a male with a mediastinal germ cell tumor for the underdiagnosed Klinefelter syndrome.


2000 ◽  
Vol 86 (5) ◽  
pp. 431-433 ◽  
Author(s):  
María José Villanueva ◽  
Fátima Navarro ◽  
Antonio Sánchez ◽  
Mariano Provencio ◽  
Félix Bonilla ◽  
...  

The association between Down syndrome and testicular germ cell tumors may be more frequent than expected according to chance, but few reports have focused on this excess. We report two cases of this association and review the English medical literature.


1989 ◽  
Vol 75 (5) ◽  
pp. 505-509
Author(s):  
Sergio Crispino ◽  
Gabriele Tancini ◽  
Sandro Barni ◽  
Paolo Lissoni

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 μg as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, nonseminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the Physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.


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