Extragonadal Germ Cell Tumors Research Articles

Case Report: Germ cell tumor presenting as cecal mass

Extra gonadal germ cell tumors most frequently occur in the anterior mediastinum, retro-peritoneum, and pineal and suprasellar regions. The infrequency of its occurrence inside gastrointestinal tract makes it an arduous diagnostic challenge. A 23 year old male with no significant past medical history presented to the emergency department with increasing abdominal pain, diarrhea, episodic vomiting for 3 weeks. Review of systems was positive for melena and shortness of breath on exertion. Fullness and irregularity along with tenderness was noted around the right iliac region. CT scan (computed tomography) of the abdomen revealed a cecal mass with multiple metastases to liver, lungs and abdominal lymph nodes. Colonic endoscope was performed but it could not be advanced beyond the cecal mass. Biopsies from the mass were reported as poorly differentiated metastatic carcinoma. During the course of hospitalization, he developed symptomatic small bowel obstruction with perforation. Colonic resection was performed and histology showed Germ-Cell Tumor. Beta HCG level was 118789 IU/L suggestive of a non-seminomatous germ cell tumor. Ultrasound of the scrotum, MRI brain (magnetic resonance imaging) and CT scan of the chest did not reveal a primary tumor. Chemotherapy was started with Bleomycin, Etoposide and Cisplatin after which beta human chorionic gonadotropin (HCG) levels dropped dramatically. His hospital course got complicated with neutropenic sepsis with shock which progressed to multi-organ dysfunction and unfortunately, he succumbed to the disease burden. This case demonstrates one of the rare presentations of extragonadal germ cell tumors and the diagnostic challenges associated with it. Very few cases have been reported in the literature, and none of them presented as a cecal mass. Early recognition of this presentation will help in reducing the tumor burden and the mortality associated with it, as germ cell tumors are highly susceptible to chemotherapy.

913PD - APACHE: An open label, randomized, phase II study of durvalumab (Durva), alone or in combination with tremelimumab (Treme), in patients (pts) with refractory germ cell tumours (GCT): Results from the expanded combination therapy cohort

BackgroundInterim results from APACHE (NCT03081923) have been presented, with the monotherapy arm stopped for futility (Necchi, Eur Urol 2018). Updated results with the expanded combination therapy cohort are presented. MethodsApache is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens received Durva, 1.5gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). The primary endpoint is the modified objective response-rate (mORR=RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction >10%). H0: mORR rate ≤10%, H1: mORR ≥25% (α and β=10%). The total sample size of 120 pts is split into 3 stages: in stage 1, each arm is terminated whenever no response is observed in 11 pts/arm. In stage 2, 29 additional pts/arm are enrolled. Biomarker analyses include: PD-L1 expression on immune cells (Ventana SP142) and comprehensive genomic profiling (CGP) with FoundationOne assay. ResultsFrom 02/17-11/18, 29 pts were enrolled (11 arm A and 18 arm B). 22 had gonadal and 7 extragonadal GCT, 19 had received >/=3 prior CT regimens. Median tumour mutational burden (TMB) was 4 mutations (mut)/mb, 1pt showed microsatellite instability in arm A. 10 pts (34.5%) experienced any-Grade AEs, without differences between arms. In the expanded arm B, 2 responses (11.1%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) and 2 SD were observed. PD occurred regardless of PD-L1 expression and TMB. After median follow-up of 16.3 months, 12-month OS in arm A was 30% (95%CI: 7.2-57.7) and in arm B was 29.6% (95%CI: 10.2-52.2). Further CT post-PD was administered in 8 pts (27.6%), but was mostly ineffective (7/8 SD/PD). ConclusionsDespite objective responses were rare with IO, long-term OS results are encouraging in very highly pre-treated GCT pts, suggesting a role for maintenance approach in earlier setting (2nd-line CT), and privileging Durva+Treme due to more responses. Conventional IO biomarkers did not allow for patient selection, and further research is warranted. Clinical trial identificationNCT03081923. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureS.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. J.S. Ross: Full / Part-time employment: Foundation Medicine. A. Necchi: Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Spouse / Financial dependant: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

2523 A Rare Location for a Rare Gastrointestinal Tumor With a Classical Presentation of Abdominal Pain, and Gastrointestinal Bleeding

INTRODUCTION: Yolk sac tumors belong to the class of nonseminomatous germ cell tumor (NSGCT), which rarely present as extragonadal germ cell tumors (GCT) of the retroperitoneum. Patients present with small bowel obstruction or gastrointestinal bleeding. Most commonly, these retroperitoneal tumors affect the ileum or jejunum, but here we present a case of a 31-year-old man who presented with a retroperitoneal yolk sac tumor with associated fistulization to the duodenum, jejunum, and ileum. CASE DESCRIPTION/METHODS: A 31 year-old man with no medical or surgical history was admitted with abdominal pain and melena. He underwent contrast-enhanced abdominal computed tomography (CT) showing an enlarging mass with central necrosis, and small bowel fistulization. Gastroenterology was consulted and upper endoscopy was performed, showing evidence of a duodenal mass and fistula, which was biopsied. Initial biopsies were inconclusive. Surgical oncology was consulted, and the patient underwent attempted surgical resection but the majority of the small intestine, colon, and associated mesentery were tethered and resection was not possible. A repeat EGD-guided biopsy was performed and pathology had the histological and immunohistochemical features of a yolk sac tumor. Laboratory studies revealed elevated serum alpha-fetoprotein (AFP) of 992 ng/mL [<6.0 ng/mL], normal serum beta-human chorionic gonadotropin (beta-hCG), and elevated serum lactic acid dehydrogenase (LDH) of 421 U/L [122-222 U/L]. Testicular ultrasound was negative for any abnormalities. Oncology initiated the patient on neoadjuvant cisplatin, etoposide, and bleomycin (BEP) every three weeks for three cycles. Two weeks after starting first cycle, AFP had dropped to 65 ng/mL, and thereafter to 11 ng/mL. Repeat imaging showed that the tumor had decreased in size. Approximately three months after completion of the last cycle of chemotherapy the patient underwent retroperitoneal tumor resection, along with partial small bowel resection. There was no evidence of malignancy in the final surgical pathology. One year later he is cancer free. DISCUSSION: This case highlights a successful collaboration between gastroenterology, radiology, surgery and oncology. There are no randomized trials in the treatment of retroperitoneal GCTs, thus case reports such as this provide much needed guidance in the treatment of this rare condition. It also illustrates the importance of tissue diagnosis via EGD in order to provide prompt diagnosis without invasive surgical biopsy.

Primary Mediastinal Malignant Mixed (Non-seminomatous) Germ Cell Tumor Presenting as Superior Vena Cava Syndrome

Abstract Introduction Mediastinal germ cell tumors are commonly seen in children and young adults with male preponderance. They are clinically classified as teratomas, seminomas and nonseminomatous germ cell tumors. Primary mediastinal mixed germ cell tumor falls under the nonseminomatous classification and are very rare. These patients have poor prognoses despite multidimensional strategic approach (chemotherapy, radiotherapy, surgical intervention). Case Discussion A previously well 27-year old male initially presenting with non-productive cough and a right anterior neck mass unresponsive to antibiotic therapy is subsequently diagnosed to be an extra-gonadal germ cell tumor of the anterior mediastinum. Two months through the course of disease, patient’s symptoms have progressed presenting with facial edema, engorged neck veins and cardio-respiratory distress. He is later found to be admitted in the intensive care unit where further work-ups led to the diagnosis of primary mediastinal mixed (non-seminomatous) germ cell tumor. Chemotherapy (cisplatin, bleomycin, etoposide - 1 cycle) and chest radiotherapy (4 sessions) were initiated causing resolution of symptoms. One week after discharge, patient presented with seizures and sudden onset of dyspnea. Patient was brought to the emergency room where he subsequently expired. Discussion This case report presents an account of this rare disease entity from its initial presentation to post-mortem analysis. Primary mediastinal germ cell tumors are rare with a poor prognosis and should be strongly considered in the diagnosis of young men with a mediastinal mass and superior vena cava syndrome.

Extragonadal germ cell tumors: Not just a matter of location. A review about clinical, molecular and pathological features.

Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms, which arise in anatomical locations other than gonads. The pathogenesis of these neoplasms is still poorly understood and it is a matter of debate if they really represent extragondal primary neoplasms or rather extragondal metastasis from occult gonadal neoplasms. The actual observations suggest that EGGCTs represent a unique entity, so their biology and behavior are substantially different from gonadal counterparts. The diagnosis of EGGCTs is often challenging, and differential diagnosis is particularly wide. Nevertheless, a correct diagnosis is essential for the correct management of the patient. We summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.

Spontaneous Complete Regression of Testicular Germ Cell Tumor: A Case Report

Abstract Testicular germ cell tumors (TGCTs) may spontaneously regress, making it a diagnostic challenge. We present here a case of 39-year-old African American male with constant abdominal pain radiating into the back. Computed tomography identified bulky retroperitoneal lymphadenopathy. There was no history of testicular trauma. Ultrasonography of right testicle revealed multiple microcalcifications, and a laboratory test indicated elevated beta-hCG and LDH. Patient underwent right orchiectomy, which revealed a grossly well-demarcated white oval lesion (3.1 cm). Histologic examination identified a fibrotic lesion in a background of atrophic parenchyma consistent with scar tissue. The specimen was completely submitted for microscopic evaluation, but neoplasia was not identified. A placental alkaline phosphatase (PLAP) immunohistochemical stain failed to reveal residual germ cell neoplasm in situ. Biopsy of retroperitoneal lymph node identified malignant neoplastic cells expressing PLAP, CD117, CD30, and cytokeratin AE1/AE3. The morphology and immunophenotype were consistent with metastatic germ cell tumor. Spontaneous regression of TGCT is defined as partial or complete tumor disappearance without any treatment. The clinical presentation could be nonspecific. Histologically, tumor regression is indicated by formation of fibrous scar, testicular atrophy, microcalcification, lymphoplasmacytic infiltration, and hemosiderin-phagocytosed macrophages, all of which were present in the current case. However, similar histological features could be identified in testicular ischemia or infraction. Therefore, the diagnosis of complete regression of TGCT is challenging and frequently relies on the present of extragonadal germ cell tumor. In the current case, we reported a spontaneous complete regression of TGCT, supported by a spectrum of histological features and metastasis to retroperitoneal lymph node. Spontaneous regression of TGCT is rare, with less than 150 cases reported in the literature. Since there is a lack of definitive histologic criteria to diagnose complete spontaneous regression of TGCT, when scarring is seen in the testis, additional clinical and imaging evaluation should be followed.

DIAGNOSIS OF GERM CELL TUMORS OF EXTRAGONADAL LOCALIZATION IN TERMS OF ALGORITHMS FOR DETECTING METASTASIS OF CARCINOMAS OF UNKNOWN PRIMARY LOCALIZATION

The analysis of cases of extragonadal teratomas makes it clear that tumours derived from germ cells and mainly characteristic of adult gonads can also occur in other areas, such as the anterior mediastinum (thymus) and midline brain (germinomas of the epiphysis and the area above the Turkish saddle), that requires differential diagnosis with metastases of carcinomas of other origin. Accurate diagnosis of estrogenic germ-cell tumours by only routine staining with haematoxylin-eosin requires high expertise and experience due to their non-specific clinical symptoms and variability of morphological characteristics. Tumour morphologists consider that immunohistochemical investigation plays an important role in accurate histological diagnosis of these tumours. The goal of this study is to explore the expression features of immunohistochemical markers and morphometric parameters of the area, perimeter and "roundness" of the nuclei in various types of extragonadal germ-cell tumours compared to similar primary ovarian / testicular tumours in order to improve diagnostic algorithms. A study was conducted on biopsy or postoperative samples taken from 8 patients (group 1) with extragonadal germ-cell tumours and from 16 patients with primary germ cell tumours of testicles / ovaries (group 2). The diagnoses were confirmed by immunohistochemical investigation on the basis of the pathologic department of the “Pharmacy of Medical Academy” Diagnostic Centre for 2015 to 2018. PLAP and CD117 had the highest percentage of expression in seminomas and gerninomas of both studied groups; morphological parameters were 3-fold higher in area and ̴2-fold higher around the perimeter then the values of normal lymphocytes (p<0.05). Expression of markers CD30, EMA and CK AE1/3 was diagnostically significant in samples of embryonic carcinoma, and morphological parameters ̴were ̴ 2.1 times higher in area and ̴ 1.7 along the perimeter that exceeded the values of normal lymphocytes (p<0.05). αFP-positive staining was indicative of yolk sac tumours, which morphological parameters were more than ̴ 1.7 times higher in the area and ̴ 1.5 times higher along the perimeter compared with the normal lymphocytes (p<0.05). Taking into account the variability of morphological characteristics and the possibility of extragonadal location of tumours derived from germ cells, immunohistochemical research supported by morphometry is an important tool in the differential diagnosis of carcinomas of unknown primary localization.

Pediatric mediastinal germ cell tumors.

Mediastinal germ cell tumors (GCTs) are a rare and heterogeneous group of neoplasms. Although histologically resembling their gonadal counterparts, they differ considerably in their clinical characteristics, biological behavior and prognostic outcome. The rarity of mediastinal GCTs has hindered their meaningful analysis, with most studies and clinical trials including them along with other extragonadal GCTs, which has led to a lack of consensus on optimal treatment strategies, and a lull in improvement in patient outcomes. Diagnosis of mediastinal GCT requires a multipronged approach, and encompasses multidisciplinary treatment including chemotherapy followed by surgery, with or without radiotherapy. In view of sustained response rates to current management protocols, the focus needs to be shifted to identifying patients in whom treatment regimens can be downscaled with the aim of decreasing long term morbidity and improving quality of life in low risk patient groups, while improving survival rates in poor risk patient subsets. In this scenario, better understanding of the molecular pathogenesis of these tumors may lead to identification of novel biomarkers and therapeutic targets, as well as improved disease segmentation and risk stratification, thus helping to avoid the toxicity and morbidity associated with current one-fits-all treatment strategies. Multi-institutional collaborations across continents are necessary to generate meaningful data, and are the face of future developments in this arena.

Japanese clinical practice guidelines for sacrococcygeal teratoma, 2017.

Sacrococcygeal teratoma (SCT) is the most common extragonadal germ cell tumor in neonates and infants. Although most cases of infantile SCT are benign tumors by nature, some develop into extremely large lesions, leading to massive bleeding, high-output heart failure, disseminated intravascular coagulation, and even fatal outcomes during the neonatal period. In addition, some patients may present with tumor recurrence, malignant transformation, long-term sequelae (including bladder and bowel dysfunction) and lower leg palsy during the long-term follow up. SCT, however, is very rare, and there are few opportunities to encounter this disease, therefore general physicians without expert credentials currently lack information relevant to clinical practice. For this reason, the research project committee has compiled guidelines concerning SCT. The purpose of these guidelines was to share information concerning the treatment and follow up of infantile SCT. The guidelines were developed using the methodologies in the Medical Information Network Distribution System. A comprehensive search of the English- and Japanese-language articles in PubMed and Ichu-Shi Web identified only case reports or case series, and the recommendations were developed through a process of informal consensus. The clinical questions addressed the risk factors, the efficacy of cesarean section, the initial devascularization of tumor feeding vessels, interventional radiology, recommended clinical studies for follow up and possible long-term complications. These are the first guidelines for SCT to be established in Japan, and they may have huge clinical value and significance in terms of developing therapeutic strategies and follow up, potentially contributing to the improvement of the prognosis and quality of life of SCT patients.

Pure Primary Extragonadal Yolk Sac Tumor involving stomach in a Young Child: A Case Report

Germ Cell Tumors (GCTs) constitute approximately only 3% of all malignancies in children younger than 15 years of age. Primary extragonadal GCTs constitute only 1-5% of all GCTs and a retroperitoneal site is seen only in 4% of all extragonadal GCTs. Yolk sac tumor is the predominant variant in newborns and younger children. GCTs of stomach are very very rare.We report for the first time, the presentation of a primary yolk sac tumor arising from the stomach of a small child.

Site, age, and gender distribution of extra-gonadal germ cell tumors in the US from 1973 to 2015.

e16051 Background: Germ cell tumors (GCT) commonly arise in post pubertal gonads where they are influenced by sexually dimorphic hormone signaling. More rarely, extra-gonadal GCTs (EGGCTs) arise in midline sites, coinciding with the route of primordial germ cell migration. EGGCTs are proposed to arise from cells not completing this migration. We characterized the incidence of EGGCTs according to patient and tumor features in an attempt to elucidate tumor origins. Methods: In Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database SEER 9 Regs Research Data, 1973-2015, primary EGGCT cases were identified by ICD-O-3 histologic types (seminoma: 9060-9062, 9064; non-seminoma 9065-9101) grouped into central nervous system (CNS), mediastinum, and other EGGCT sites. Age-specific incidences for males and females were divided into adolescents and young adults (AYA) defined by the National Cancer Institute as 15-39 years of age, and younger childhood and older adult groups. Results: In AYAs and older adults, age-adjusted incidence of males exceeded that of females at all sites (p≤0.006, all comparisons) (Table). Male incidence was highest in AYAs (all EGGCT, 4.35/1,000,000 person-years (Mpy); mediastinum, 2.17/Mpy; other 0.68/Mpy). Female incidence was highest in childhood (CNS, 0.86/Mpy; mediastinum, 0.14/Mpy; other 0.64/Mp-y). Conclusions: Patterns of EGGCT incidence differ substantially between sexes. Permissive extra-gonadal sites of males or male-predominant exposures may explain higher incidence in males. Alternatively, EGGCT precursor cells may have sex-specific features affecting malignant potential. [Table: see text]

The clinical features of extragonadal germ cell tumors: A SEER analysis.

e16064 Background: Extragonadal germ cell tumor is an uncommon type of malignancy. We aim to identify the clinical features and the prognosis in various histological subtypes in these patients using the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: We used the (SEER) database to identify the patients with non-gonadal germ cell tumors between 1998-2015. 1299 patients were identified and included in our analysis. Results: 1299 patients had non-gonadal germ cell tumors between 1998-2015. The mean age was 26 years-old. 568 patients (44%) were females and 731 patients (56%) were males. 276 patients (21%) died after a mean follow up time of 41.16 months (1-60 months). The mean overall survival (OS) was 49.4 months (95%CI 48.21-50.52) with the median being unreached. The Females had better OS compared to the males with a Hazard ratio (HR) = 0.50 (95%CI 0.40-0.63). Age more than 60 years-old at the time of diagnosis was associated with a substantially significant increase in mortality with an HR = 43 (95% CI 19.17-94.41). The mediastinal germ cell tumors were associated with worse OS compared to other sites with a HR = 4.69 (95%CI 3.37-6.52). The median OS for Embryonal cell carcinoma was 22 months, and it was associated with worse OS compared to seminoma and other histological subtypes with a HR = 4.10 (95% CI 1.69-9.72) and 2.77 (95% 1.16-6.58) respectively. On the other hand, Seminoma was associated with better OS compared to other histological subtypes with an HR = 0.66 (95%CI 0.52-0.84). Moreover, tumor size less than 80 mm was associated with better OS with a HR = 0.42 (95%CI 0.30-0.64). In multivariate analysis, patients above the age of 60 had worse OS with an HR = 4.04 (95%CI 1.71-9.58), patients with mediastinal germ cell tumors had poorer OS compared to other sites with an HR = 2.38 (95%CI 1.51-3.79). Furthermore, embryonal carcinoma, mixed germ cell tumors and choriocarcinoma were associated with worse OS compared to seminoma and immature teratoma with an HR = 10.39 (95% CI 4.36-24.72), HR = 2.07 (95% CI 1.23-3.46) and HR = 6.16 (95%CI 2.98-12.74) respectively. Conclusions: Non-gonadal seminoma and immature teratoma carry better prognosis compared to other histological subtypes. Also, among non-gonadal germ cell tumors, non-mediastinal seminoma has the best survival outcome.

Mediastinal Germ Cell Tumors – A Clinicopathologic Study

Background: Primary mediastinal extragonadal germ cell tumors (GCT) are relatively rare lesions and account for only 1 to 2 percent of all germ cell tumors. They are clinically distinct from testicular germ cell tumors despite their similar histologic features. Objective of this study is to classify and evaluate the histomorphology of mediastinal germ cell tumors and correlate the clinical findings with radiological and other serologic parameters. Method: A 5 year study was done in Dept. of Pathology, of a private Medical College on mediastinal lesions. Total number of cases studied was 66, with GCTs making up 7 cases. Histopathology sections taken were stained with routine Hematoxylin and Eosin stains. Results: The age range of patients with mediastinal GCTs were 6 months to 43 years with a mean of 23 years. Only one case was seen above 40 years. Both malignant GCTs were below 20 years. There was a male predominance with male:female ratio of 2.5:1. Conclusion: Mediastinal GCTs are rare & interesting neoplasms, usually located in anterior compartment of mediastinum. A histomorphological analysis aided by radiology and serology permits an exact diagnosis in many cases.

Poor prognosis of retroperitoneal mixed extragonadal germ cell tumors in an HIV-infected man with severe immunosuppression and bilateral cryptorchidism: a case report

BackgroundNonseminomatous germ cell tumors (NSGCTs) represent one of the main groups of germ cell tumors (GCTs), and they have a more invasive course than seminomatous GCTs. Human immunodeficiency virus (HIV) positivity is considered to be a risk factor for testicular seminoma patients, but reports about HIV-infected individuals with NSGCTs are rare.Case presentationWe report a case of a retroperitoneal mixed extragonadal germ cell tumor in an HIV-infected man who has been diagnosed with bilateral cryptorchidism since birth. A 30-year-old man presented with a large heterogeneously mixed echo mass located in the right lower abdomen according to an abdominal ultrasound; he was HIV-positive and had a low CD4 count of 70 cells/ml in the followed test, which suggested severe immunosuppression, and ultrasound-guided biopsy histology revealed a malignant yolk sac tumor of the testis. First, the patient received combination antiretroviral therapy; then, to relieve his symptoms, an exploratory laparotomy and retroperitoneal neoplasm resection under general anesthesia were performed for subsequent treatment. The postoperative histopathological examination indicated that the patient exhibited malignant mixed GCTs of the undescended testis that were composed predominantly of yolk sac tumors with foci of embryonal cell carcinoma and seminoma; It is a rare type in various GCTs, especially in HIV-infected patients. After the operation, the patient underwent computed tomography follow-up scans at 1 week and 2 weeks, and the results showed that the size of the right inguinal mass gradually increased, which suggested a poor outcome. To limit the growth of the tumors, right inguinal mass resection under local anesthesia was performed 17 days after the initial operation, and pathological examination revealed mixed GCT metastasis. Subsequently, the patient received salvage chemotherapy with a regimen of cisplatin, etoposide, and ifosfamide. Unfortunately, the patient died 1 week after the first cycle of chemotherapy because of severe immunosuppression, a low platelet count and cancer cachexia.ConclusionsBecause of severe immunosuppression, the treatment of advanced extragonadal NSGCTs in an HIV-infected patient resulted in a poor prognosis. This outcome should be considered in further research, and appropriate management for achieving long-term survival needs to be established.

Autologous Hematopoietic Stem Cell Transplantation for Male Germ Cell Tumors: Improved Outcomes Over 3 Decades.

The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCTs) is well established. The optimal timing and number (single transplant [ST] versus tandem transplants [TT] versus triple transplants) of autoHCT are controversial, with wide practice variations. We examined survival trends among 2395 recipients of autoHCT for male GCTs between 1990 and 2015 reported to the Center for International Blood and Marrow Transplant Research. Trends and outcomes were analyzed by year of transplantation for intervals 1990 to 1994 (N = 288), 1995 to 1999 (N = 351), 2000 to 2004 (N = 376), 2005 to 2009 (N = 509), and 2010 to 2015 (N = 871). Multivariate analysis was restricted to the subset from 2000 to 2015 with research-level data (n = 267). The median duration of follow-up was 51 months. The median age at autoHCT was 31 years; 633 patients (26%) had primary extragonadal GCT, and 1167 (49%) underwent TT. The 3-year progression-free (PFS) and overall survival (OS) improved from 24% (95% confidence interval [CI], 18% to 31%) and 35% (95% CI, 29% to 40%), respectively, in 1990 to 1994 to 47% (95% CI, 43% to 50%) and 54% (95% CI, 50% to 57%), respectively, in 2010 to 2015 (P <.0001). TT recipients were more likely than ST recipients to undergo autoHCT as first salvage treatment. The proportion of TTs increased from 38% of all autoHCTs in 2000 to 2004 to 77% in 2010 to 2015. Nonseminoma histology, residual disease at autoHCT, >1 line of pretransplantation chemotherapy, and ST versus TT were associated with inferior PFS and OS. Post-transplantation survival has improved significantly over time for relapsed/refractory male GCT and is associated with the increased use of TTs (compared with STs) and performance of autoHCT earlier in the disease course.

Extragonadal germ cell tumor with testicular "burned-out" phenomenon

Extragonadal germ cell tumor with testicular "burned-out" phenomenon

A 54-year-old man with primary mediastinum choriocarcinoma

Primary mediastinum choriocarcinoma, an extragonadal germ cell tumor, is a rare malignant tumor that is more common in men. We present a case of primary mediastinum choriocarcinoma in a male patient who initially presented with gynecomastia and progressed to superior vena cava syndrome. Both surgical biopsy and pathologic diagnosis were challenging. After standard induction chemotherapy, the resected tumor underwent squamous cell transformation, which has rarely been reported in cases of choriocarcinoma. His critical condition was resolved using induction chemotherapy with a combination of bleomycin, etoposide, and cisplatin, followed by resection of the residual tumor. However, tumor recurrence occurred 9 months later, and he was treated with salvage radiotherapy and chemotherapy. This was a rare and challenging case from the aspects of initial approaches, pathologic differential diagnosis, and different treatment modalities.

A synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome

Özyörük D, Kocayozgat A, Yaman-Bajin İ, Çetindağ F, Oğuz- Erdoğan AS, Güneş A. A synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome. Turk J Pediatr 2019; 61: 456-459. Klinefelter syndrome (KS) is characterized by an additional X chromosome in males leading to a karyotype of 47,XXY. It is associated with an increased risk of certain malignancies, including leukemia, breast cancer and extragonadal germ cell tumor such as mediastinal germ cell tumors and rarely intracranial germ cell tumors. It is possible that the increased risk of developing certain cancers can be attributed to a direct effect of the chromosomal abnormality or the combined action of the abnormal chromosomes and hormonal imbalances. Here we describe a synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome. The synchronous occurrence of the dual tumors in this patient with Klinefelter`s syndrome might be resulted from the migration defect during embriyogenesis due to underlying genetic disease or it is a coincidental condition, yet there has been no case reported in the literature, so far.

Sperm cryopreservation for fertility preservation in male patients with cancer at a single-center in Japan

Advanced treatment modalities for cancer have led to improved prognosis in patients with cancer. However, these treatments may adversely affect the fertility of these patients. Therefore, peritreatment preservation of fertility in adolescent and young adult populations is very important. For male patients, sperm cryopreservation before the initiation of treatment for cancer is currently the most effective method for the preservation of fertility. We performed a retrospective cohort analysis of a sperm cryopreservation protocol at the Yokohama City University Medical Center between 2012 and 2017. A total of 235 men were referred and attempted sperm cryopreservation during this period. The most prevalent diseases were hematological malignancies (38.7%; leukemia, malignant lymphoma, and multiple myeloma), testicular cancer (32.3%, including extragonadal germ cell tumor), bone and soft tissue sarcoma (8.5%), lung cancer (4.7%), prostate cancer (4.3%), and brain tumor (2.6%) in descending order. The median age of patients was 31 (range: 13–65) years, mean sperm density and motility were 28.54±30.25 106/mL, and 20.38±20.62%, respectively. Sperm cryopreservation was successfully performed in 195 patients (83.0%). In those with cryopreservation failure (36 patients; 15.3%), the primary causes were azoospermia or poor semen quality. In the remaining 4 patients (1.7%), testicular spermatozoa were successfully cryopreserved through surgical extraction. In the cryopreservation failure group (n=36), 23 patients (63.9%) were referred after initiation of treatment. Of those, 17 patients were referred from the departments of hematology and oncology. Moreover, sperm density was significantly lower in patients who under gone treatment than in those of the pretreatment group (P=0.003). Cryopreserved sperm from 18 patients was used in 23 in vitro fertilization cycles, resulting in a clinical pregnancy rate of 56.5% per cycle. It is important to inform other departments regarding the option for sperm cryopreservation before initiating treatment in patients with cancer.

Renal Protective Effect of Quercetin on Cisplatin-Induced on Some Blood Parameters and Nephrotoxicity in Male Rats

This work was carried out to investigate the possible protective effect of quercetin some blood parameters and nephrotoxicity in male rats treated with cisplatin. Cisplatin is an important chemotherapeutic agent useful in the treatment of several cancers such as tumors of the testis (including extragonadal germ cell tumors), ovarian cancer, small cell and non-small cell lung cancer, squamous cell carcinomas of the head and neck, and despite the availability of some newer and less toxic quercetin drugs. Eighteen blood samples were obtained from male rats which divided into three groups for each group (n = 6), the first group (control), the second group (Cisplatin) and third group (Cisplatin + Quercetin). There is a significant decrease (P <0.05) in Creatinine, urea and TNF-ά concentrations in second group compared with the control and third groups. Also, the result showed a significant increase Creatinine, urea and TNF-ά concentrations in second group compared with the control group. The results showed a significant increase (P≤0.05) in red blood cell count(RBC), packed cell volume (HCT), hemoglobin (Hb) and Platelet in second groups compared with the control and third groups, also it showed a significant decreasein third group compared with control group. Therefore, the present study is undertaken to investigate the possible some blood parameter and renal protective effect of quercetin in rats treated with cisplatin