Germ Cell Tumors of the Ovary: An Update

2014 ◽  
Vol 138 (3) ◽  
pp. 351-362 ◽  
Author(s):  
Francisco F. Nogales ◽  
Isabel Dulcey ◽  
Ovidiu Preda
Keyword(s):  
Germ Cell ◽  
Correct Diagnosis ◽  
Relevant Literature ◽  
Germ Cell Tumors ◽  
Autoimmune Encephalitis ◽  
University Hospital ◽  
Ovarian Teratoma ◽  
Tumor Type ◽  
Pluripotency Markers ◽  
The Impact

Context.—The field of ovarian germ cell tumors (OGCTs) has remained relatively unchanged in the last 2 decades. However, the introduction of new stem cell pluripotency markers has provided a new understanding into the identification and taxonomy of OGCT types. New data have provided new insights into unusual teratoma-associated autoimmune disorders and the origin of gliomatosis peritonei. Objective.—To review the impact of new pluripotency markers in the diagnosis of malignant OGCT (MOGCT) and analyze new nomenclature proposals and clinicopathologic entities. Data Sources.—Ovarian germ cell tumors from routine material and expert consultation files at San Cecilio University Hospital, Granada, Spain, and the relevant literature were reviewed. Conclusions.—Although a correct diagnosis of MOGCT can often be made with histologic and classic immunohistochemical studies, the new immunohistochemical pluripotency markers give higher diagnostic accuracy. Germ cell tumors represent a caricature of the phases of normal embryonic differentiation from primordial germ and stem cells to extraembryonal and somatic tissue differentiation. Since every stage of differentiation and its related tumor type exhibit characteristic markers, the analysis of their expression facilitates tumor typing, thus complementing the use of classic antibodies. They also allow a more precise evaluation of the degree of immaturity in teratoma. The new term, primitive endodermal tumors, simplifies the understanding of the complex histology of the yolk sac tumor group, as this terminology encompasses its multiple endodermal differentiations. Recently described autoimmune encephalitis due to antibodies against the N-methyl-d-aspartate receptor has become the most frequent autoimmune disorder associated with ovarian teratoma.

scholarly journals Assessment of Preoperative Endometrial Histopathological Sampling as a Predictor of Final Surgical Pathology in Endometrial Cancer

2020 ◽  
Vol 42 (10) ◽  
pp. 642-648
Author(s):  
Mario Augusto Silveira Bueno Piotto ◽  
Gustavo Rubino de Azevedo Focchi ◽  
Renato Moretti Marques ◽  
Andressa Melina Severino Teixeira ◽  
Wagner José Gonçalves ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Surgical Management ◽  
Correct Diagnosis ◽  
University Hospital ◽  
Lower Grade ◽  
Tumor Type ◽  
The Impact

Abstract Objective To evaluate the agreement between the histopathological diagnoses of preoperative endometrial samples and surgical specimens and correlate the agreement between the diagnoses with the impact on surgical management and the survival of patients with endometrial adenocarcinomas. Methods Sixty-two patients treated for endometrial cancer at a university hospital from 2002 to 2011 were retrospectively evaluated. The histopathological findings of preoperative endometrial samples and of surgical specimens were analyzed. The patients were subjected to hysterectomy as well as adjuvant treatment, if necessary, and clinical follow-up, according to the institutional protocol. Lesions were classified as endometrioid tumor (type 1) grades 1, 2, or 3 or non-endometrioid carcinoma (type 2). Results The agreement between the histopathological diagnoses based on preoperative endometrial samples and surgical specimens was fair (Kappa: 0.40; p < 0.001). However, the agreement was very significant for tumor type and grade, in which a higher concordance occurred at a higher grade. The percentage of patients with lymph nodes affected was 19.2%. Although most patients presenting with disease remission or cure were in the early stages (90.5%), there were no significant differences between those patients who had a misdiagnosis (11/16; 68.8%) and those who had a correct diagnosis (25/33; 75.8%) based on preoperative endometrial sampling (p = 0.605). Conclusion Our findings corroborate the literature and confirm the under staging of preoperative endometrial samples based on histopathological assessment, especially for lower grade endometrial tumors. We suggest that the preoperative diagnosis should be complemented with other methods to better plan the surgical management strategy.

scholarly journals OTHR-16. CONCURRENT USE OF APREPITANT AND IFOSFAMIDE IN PEDIATRIC CANCER PATIENTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii424-iii424
Author(s):  
Shelby Winzent ◽  
Nathan Dahl ◽  
Molly Hemenway ◽  
Rachel Lovria ◽  
Kathleen Dorris
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Hepatic Metabolism ◽  
High Dose ◽  
Tumor Type ◽  
Age Related ◽  
Concurrent Use ◽  
Pediatric Cancer Patients ◽  
Nongerminomatous Germ Cell Tumor ◽  
Neurokinin 1

Abstract BACKGROUND Aprepitant, a selective neurokinin-1 receptor antagonist, is commonly used for prevention of chemotherapy-induced nausea and vomiting. Its use with ifosfamide is controversial due to the putative risk of potentiating neurotoxicity via inhibition of cytochrome P450 3A4 (CYP3A4). The current literature examining this interaction is inconclusive, and little data exists in pediatrics. We seek to describe a single-institution experience with concurrent aprepitant and ifosfamide administration. METHODS A retrospective review of patients treated with ifosfamide and aprepitant from 2009–2018 was conducted. Data collected included demographics, tumor type, number of days of concurrent therapy, dosing, and documented of neurotoxicity. RESULTS Twenty patients aged 7–21 years (median 17 years) were identified. Diagnoses included thirteen sarcomas and seven CNS tumors (6 germ cell tumors; 1 intracranial sarcoma). Five patients received high dose ifosfamide (&gt;2,000mg/m2/day). The number of concurrent ifosfamide and aprepitant doses ranged from 2–18 (median, 8.5). Only one patient (5%) developed ifosfamide-induced neurotoxicity: a 7-year-old female with a nongerminomatous germ cell tumor who presented with seizures and somnolence. She received methylene blue and returned to her neurologic baseline. She completed her ifosfamide course without incident. She was the only patient to require weight-based aprepitant dosing and to receive the liquid formulation. CONCLUSIONS Aprepitant should be used with caution when administered concurrently with ifosfamide due to the risk of neurotoxicity. However, the incidence of neurotoxicity in this retrospective pediatric cohort was low. This interaction may be more significant in younger patients due to age-related differences in hepatic metabolism, but further study is required.

scholarly journals Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

2021 ◽  
pp. 1-7
Author(s):  
Pia Paffenholz ◽  
Tim Nestler ◽  
Yasmine Maatoug ◽  
Melanie von Brandenstein ◽  
Barbara Köditz ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Advanced Tumor Stage ◽  
Testicular Germ Cell Tumors ◽  
Relapse Free Survival ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
Advanced Tumor ◽  
The Impact

<b><i>Introduction:</i></b> The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. <b><i>Methods:</i></b> We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. <b><i>Results:</i></b> Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, <i>p</i> = 0.031), visceral metastases (58 vs. 32%, <i>p</i> = 0.015), and poor prognosis (<i>p</i> = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, <i>p</i> = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, <i>p</i> = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (<i>p</i> = 0.049) during a median follow-up of 36 months (10–115.5). <b><i>Conclusions:</i></b> The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

scholarly journals Late and Rapid Relapse in Mediastinum from Testicular Germ Cell Tumor Stage I Over 13 Years after Surgery

2019 ◽  
Vol 12 (2) ◽  
pp. 500-505
Author(s):  
Toshirou Fukushima ◽  
Takuro Noguchi ◽  
Takashi Kobayashi ◽  
Nodoka Sekiguchi ◽  
Takesumi Ozawa ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mediastinal Lymph Node ◽  
Relevant Literature ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Careful Examination ◽  
Late Relapse ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Testicular Seminoma

Patients with stage I testicular germ cell tumors have a long life expectancy, but the tumors have a potential to relapse after treatment. Although relapse is observed within a few years in most cases, late relapse over 10 years after initial treatment has also been reported in patients with stage I testicular germ cell tumors. We encountered a case of testicular seminoma that developed mediastinal lymph node metastasis 13 years after radical surgery for the primary tumor. The relapsed disease progressed rapidly and the patient died within 1 month due to respiratory failure without any chance for therapy. On postmortem examination, the thoracic lesions were pathologically confirmed to be metastases from the testicular seminoma with yolk sac tumor. Here, we report the clinical course and a review of the relevant literature. Based on our experience, we emphasize long-term follow-up and/or careful examination in patients with stage I testicular germ cell tumors.

scholarly journals Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up―A Copenhagen Experience

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 759
Author(s):  
Nina Mørup ◽  
Ewa Rajpert-De Meyts ◽  
Anders Juul ◽  
Gedske Daugaard ◽  
Kristian Almstrup
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Primary Diagnosis ◽  
University Hospital ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Circulating Mirna ◽  
Serum Tumor Markers

New microRNA-based serum biomarkers (miRNA-367-3p, -371a-3p, -372-3p, and -373-3p) have shown great potential for the detection of testicular germ cell tumors (TGCTs), but few studies have investigated the clinical utility and performance of these tests in treatment monitoring. In this study, circulating miRNA levels were measured, together with serum tumor markers alpha-fetoprotein (AFP), β-subunit of human chorionic gonadotropin (β-HCG) and lactate dehydrogenase (LDH) in 406 consecutive blood samples obtained during the treatment and follow-up of 52 TGCT patients at the Copenhagen University Hospital. After testing three different methods of RNA isolation from peripheral blood and PCR quantification in a subset of samples (n = 15), the best performing setup of targeted isolation of miRNAs inside and outside exosomes was selected to analyze all samples. At primary diagnosis, the miRNAs significantly outperformed the serum tumor markers, with a sensitivity and specificity of 78% and 100% (based on 40 patients), respectively. The picture was not as clear when patient trajectories were investigated, with both positive and negative signals for miRNAs and serum tumor markers. To establish whether measuring miRNAs adds value beyond the primary diagnosis, large prospective clinical trials comparing miRNAs and classical tumor markers during the treatment and follow-up of TGCT patients are needed.

scholarly journals Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study

2019 ◽  
Vol 37 (34) ◽  
pp. 3283-3290 ◽  
Author(s):  
Jason Fangusaro ◽  
Shengjie Wu ◽  
Shannon MacDonald ◽  
Erin Murphy ◽  
Dennis Shaw ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Germ Cell Tumors ◽  
Primary Objective ◽  
Craniospinal Irradiation ◽  
Oncology Group ◽  
Tumor Bed ◽  
Tumor Bed Boost ◽  
The Impact

PURPOSE Stratum 1 of ACNS1123 (ClinicalTrials.gov identifier: NCT01602666 ), a Children’s Oncology Group phase II trial, evaluated efficacy of reduced-dose and volume of radiotherapy (RT) in children and adolescents with localized nongerminomatous germ cell tumors (NGGCTs). The primary objective was to evaluate the impact of reduced RT on progression-free survival (PFS) with a goal of preserving neurocognitive function. PATIENTS AND METHODS Patients received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide, as used in the Children’s Oncology Group predecessor study (ACNS0122; ClinicalTrials.gov identifier: NCT00047320 ). Patients who achieved a complete response (CR) or partial response (PR) with or without second-look surgery were eligible for reduced RT, defined as 30.6 Gy whole ventricular field and 54 Gy tumor-bed boost, compared with 36 Gy craniospinal irradiation plus 54 Gy tumor-bed boost used in ACNS0122. RESULTS A total of 107 eligible patients were enrolled. Median age was 10.98 years (range, 3.68 to 21.63) and 75% were male. Sixty-six of 107 (61.7%) achieved a CR or PR and proceeded to reduced RT. The 3-year PFS and overall survival and standard error values were 87.8% ± 4.04% and 92.4% ± 3.3% compared with 92% and 94.1%, respectively, in ACNS0122. There were 10 recurrences, prompting early study closure; however, after a retrospective central review, only disease in eight of 66 (12.1%) patients eligible for reduced RT subsequently progressed; six patients had distant spinal relapse alone and two had disease with combined local plus distant relapse. Serum and CSF α-fetoprotein and β-human chorionic gonadotropin levels were not associated with PFS. CONCLUSION Patients with localized NGGCT who achieved a CR or PR to chemotherapy and received reduced RT had encouraging PFS similar to patients in ACNS0122 who received full-dose craniospinal irradiation. However, the patterns of failure were distinct, with all patients having treatment failure in the spine.

A single center experience of the impact of treatment-related toxicity in the clinical outcomes of elderly patients with metastatic germ cell tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16048-e16048
Author(s):  
Anand Sharma ◽  
David Palmer ◽  
Hannah Brown ◽  
Sophie Merrick ◽  
Andrew Gogbashian ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Germ Cell ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Mount Vernon ◽  
Single Center Experience ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting ◽  
The Impact

e16048 Background: Germ cell tumours (GCT) are predominantly a disease of the young, with < 10% of cases being diagnosed at ≥45 years. Platinum based chemotherapy is the gold standard in treating these patients. Data regarding outcomes and treatment toxicities in elderly patients is lacking. We studied the efficacy, toxicities and survival rates in a cohort of men diagnosed with GCT aged ≥45 years receiving chemotherapy in a metastatic setting. Methods: Data was collected retrospectively from 48 patient’s ≥45 years with GCT’s identified at Mount Vernon Cancer Centre, London. The histology, stage and international germ cell consensus (IGCC) risk classification was identified in all patients. Data was collected regarding chemotherapy regimens, number of cycles completed, toxicities and complications that led to treatment modifications or early cessation. Treatment toxicities were evaluated using the common terminology criteria for adverse events (ctCAE) grading. We then assessed progression free survival, relapse rates and overall survival (OS). Results: We identified 48 patients diagnosed with GCTs aged ≥45 years. The median age at diagnosis was 52 (range 45-70) and 75% of patients were aged ≥50. Classic seminoma and nonseminomatous GCTs were seen in 65% and 35% of patients, respectively. 75% of patients were ≥stage II at diagnosis. In total 29 patients received BEP, 4 EP, 7 Carboplatin AUC10, 2 Carboplatin AUC7 and 5 received POMBACE. 73 % (35/48) of patients experienced one or more complication/s from chemotherapy (15/48 ctCAE grade ≥3), of which the most common were neuropathies (27%), thromboembolism (10%) and tinnitus (10%). In 8 cases omissions or dose reductions had to be made and treatment delays occurred in 3 cases. Only 2 patients did not complete all intended cycles. Over 70% (35/48) of patients had an OS of > 5 years. One patient died during chemotherapy due to gastro-intestinal bleed. Conclusions: Survival rates in patients with GCTs aged ≥45 treated with chemotherapy are good with the majority achieving a > 5 year OS. Although age is not a prognostic factor, these patients are more prone to toxicities and have underlying comorbidities. This data will be of value to oncologists weighing up the risks versus benefits of treatment in this older cohort of patients in combination with similar studies.

scholarly journals Anti-N-Methyl-D-Aspartate Encephalitis as Paraneoplastic Manifestation of Germ-Cells Tumours: A Cases Report and Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Claudia Geraldine Rita ◽  
Israel Nieto Gañan ◽  
Adriano Jimenez Escrig ◽  
Ángela Carrasco Sayalero
Keyword(s):  
Nmda Receptor ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Cell Tumour ◽  
Clinical Manifestations ◽  
Autoimmune Encephalitis ◽  
Cell Tumour ◽  
Ovarian Teratoma ◽  
Surgical Removal ◽  
Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by the interaction between an antibody and its target, located on glutamate receptor type N-methyl-D-aspartate (NMDA) of neuronal surface. There is a wide spectrum of clinical features starting by a viral-like prodrome, followed by symptoms such as psychosis, aggressive behaviour, memory loss, seizures, movement disorders, and autonomic instability. Up to 50% of the affected young female patients have germ-cells tumours as ovarian teratoma, making it essential to establish an early diagnosis through detection of specific antibodies in serum and cerebrospinal fluid (CSF). This retrospective observational study was performed in patients whom positive anti-NMDA receptor antibodies have been tested, associated with clinical manifestations that suggest autoimmune encephalitis and a germ-cell tumour confirmed by pathology. Six patients have tested positive for anti-NMDA receptor antibodies associated with a germ-cell tumour and clinical manifestations of autoimmune encephalitis. Management includes aggressive immunosuppression and surgical removal.

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