Unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection in Stage II non-seminomatous germ cell tumor:A tertiary care experience

Objective Post-chemotherapy retroperitoneal lymph node dissection(PC-RPLND)represents an integral component of the management of patients with non-seminomatous germ cell tumor(NSGCT).Modified templates have been proposed to minimize the surgical morbidity of the procedure.Moreover,the implementation of robotic surgery in this setting has been explored.We report our experience with unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection(PC-rRPLND)for clinical Stages IIA and IIB NSGCTs.Methods A retrospective single institution review was performed including 33 patients undergoing PC-rRPLND for Stages IIA and IIB NSGCTs between January 2015 and February 2019.Following orchiectomy,patients were scheduled for chemotherapy with three cycles of bleomycin-etoposide-cisplatin.Patients with a residual tumor of<5 cm and an ipsilateral metastatic disease on pre-and post-chemotherapy CT scans were eligible for a unilateral template in absence of rising tumor markers.Descriptive statistics were provided for demographics,clinical characteristics,intraoperative and postoperative parameters.Perioperative,oncological,and functional outcomes were recorded.Results Overall,7(21.2%)patients exhibited necrosis or fibrosis;14(42.4%)had mature teratoma;and 12(36.4%)had viable tumor at final histology.The median lymph node size at surgery was 25(interquartile range[IQR]21-36)mm.Median operative time was 180(IQR 165-215)min and no major postoperative complications were observed.Anterograde ejaculation was preserved in 75.8%of patients.Median follow-up was 26(IQR 19-30)months and a total of three recurrences were recorded.Conclusion PC-rRPLND is a reliable and technically reproducible procedure with safe oncological outcomes and acceptable postoperative ejaculatory function in well selected patients with NSGCTs.

Testicular mixed germ cell tumor:A case report

BACKGROUND Testicular mixed germ cell tumors(TMGCTs)are rare malignant tumors that are more common in men aged 20–40 years.TMGCTs comprise two or more types of germ cell tumors that primarily affect the testis.Their onset is undetectable;thus,early diagnosis is challenging.However,early recognition and diagnosis substantially improve patient prognosis.CASE SUMMARY We evaluated a rare case of TMGCT in a male patient presenting with recurrent fever and left supraclavicular lymphadenectasis instead of testicular enlargement and pain,which may easily lead to misdiagnosis.We report the clinical signs and symptoms,histopathological characteristics,and immunohistochemical results of this case of malignant TMGCT.CONCLUSION Our case,which was typical with multiple components,along with a literature review,may serve as a basis for early diagnosis.

Laparoscopic uncontained power morcellation-induced dissemination of ovarian endodermal sinus tumors:A case report

BACKGROUND Endodermal sinus tumors(ESTs),which arise primarily in children and adolescents,account for 20%of malignant ovarian germ cell tumors,but constitute only 1%of all ovarian malignancies.Treatment of ESTs consists of surgical staging with fertility-sparing surgery and chemotherapy.CASE SUMMARY A 15-year-old nulliparous patient was diagnosed with disseminated ovarian ESTs after laparoscopic unilateral salpingo-oophorectomy using uncontained power morcellation for treatment of a ruptured solid adnexal mass in another hospital.Exploratory laparotomy;total abdominal hysterectomy,right salpingooophorectomy,and lymphadenectomy were performed with optimal debulking,and surgical stage 3C was assigned to the patient.CONCLUSION In 2014,the Food and Drug Administration noted that power morcellation was probably associated with a risk of disseminating suspected cancerous tissue.Furthermore,the use of power morcellation to remove solid adnexal mass is considered a contraindication because of the potential for a malignant tumor.This case report aims to warn of the dangers of using uncontained power morcellation to treat solid adnexal masses.

Gastric adenocarcinoma with features of endodermal sinus tumor

Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here a case where a middle aged man presented with typical symptoms of gastric cancer. After extensive workup, which included blood work, CT abdomen scan, upper endoscopy, and endoscopic ultrasound, the patient was diagnosed with gastric cancer. However, due to very high blood levels of alpha-fetoprotein, the specimen was sent for special histochemical staining, which demonstrated that the tumor had features of both adenocarcinoma and endodermal sinus tumor. This is a very aggressive tumor with a very poor prognosis.

Low hypoxia inducible factor-1α(HIF-1α)expression in testicular germ cell tumors--a major reason for enhanced chemosensitivity?

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors （GCT） has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of C＆T has been variously attributed to multiple factors -- an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-la （HIF-la） expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

Primary mixed germ cell tumor of the liver with sarcomatous components

Germ cell tumor(GCT)of the liver is extremely rare. Here,we describe a case of hepatic mixed GCT with significant sarcomatous components and elevated serum α-fetoprotein(AFP)in a 34-year-old man.Histopathologically,the tumor was composed of two GCTs components:yolk sac tumor and immature teratoma.The predominant components of immature teratoma consisted of several types of tissue that represented different germinal layers(endoderm,mesoderm and ectoderm) and showed varying degrees of differentiation with significant sarcomatous components.The yolk sac component showed positivity for AFP and cytokeratin(AE1/ AE3).The immature teratoma components showed positivity for varying differentiation markers.Interphase cytogenetic analysis revealed that the yolk sac tumor and immature teratoma were positive for i(12p)and 12p over-representation.In particular,the rhabdomyoblastic components also showed typical i(12p)and 12p overrepresentation.This suggested that sarcomatous components may be associated with dedifferentiation or malignant transformation of certain mesenchymal components within teratoma.

Prediction of radiosensitivity in primary central nervous system germ cell tumors using dynamic contrast-enhanced magnetic resonance imaging

Objective： To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging（DCEMRI） for predicting tumor response to radiotherapy in patients with suspected primary central nervous system（CNS） germ cell tumors（GCTs）.Methods： DCE-MRI parameters of 35 patients with suspected primary CNS GCTs were obtained prior to diagnostic radiation, using the Tofts and Kermode model. Radiosensitivity was determined in tumors diagnosed 2 weeks after radiation by observing changes in tumor size and markers as a response to MRI. Taking radiosensitivity as the gold standard, the cut-off value of DCE-MRI parameters was measured by receiver operating characteristic（ROC） curve. Diagnostic accuracy of DCE-MRI parameters for predicting radiosensitivity was evaluated by ROC curve.Results： A significant elevation in transfer constant（K^trans） and extravascular extracellular space（Ve）（P=0.000）, as well as a significant reduction in rate constant（Kep）（P=0.000） was observed in tumors. K^trans, relative K^trans, and relative Kep of the responsive group were significantly higher than non-responsive groups. No significant difference was found in Kep, Ve, and relative Ve between the two groups. Relative K^trans showed the best diagnostic value in predicting radiosensitivity with a sensitivity of 100%, specificity of 91.7%, positive predictive value（PPV） of 95.8%, and negative predictive value（NPV） of 100%.Conclusions： Relative K^trans appeared promising in predicting tumor response to radiation therapy（RT）. It is implied that DCE-MRI pre-treatment is a requisite step in diagnostic procedures and a novel and reliable approach to guide clinical choice of RT.

Primary Endodermal Sinus Tumor in the Posterior Cranial Fossa:Clinical Analysis of 7 Cases

Objective To clarify the clinical features,therapeutic method and outcomes of the primary endodermal sinus tumors(ESTs)in the posterior cranial fossa.Methods The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed.And a 4-year-old boy diagnosed with EST in our hospital was reported.The clinical manifestations,therapy,pathologic features,and prognosis of these cases were analyzed.Results Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review,including six cases searched from the PubMed and one case from our hospital.Six patients were boy and one patient’s gender was not available from the report.Ages ranged from 1 to 5 years(mean 3.14 years).The mean tumor size in our cohort was 4.4 cm.Six cases came from East Asia.Schiller-Duval bodies were found in all seven neoplasms.All tumors were positive for alpha-fetoprotein.The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy.The mean follow-up time was 24.4 months(range 5-52 months).Six tumors were totally removed,and four of them recurred.Three cases died including one whose tumor was partially removed.Conclusions The serum alpha-fetoprotein level is well correlated with the severity of the tumor.A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa.The prognosis of extragonadal intracranial EST is poor.

The clinical characteristics and treatment outcomeof 57 children and adolescents with primary central nervoussystem germ cell tumors

Primary central nervous system germ cell tumors(CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years(range, 2.7 to 18.0 years) at diagnosis; 43(75.4%) had non-germinomatous germ cell tumors(NGGCTs) and 14(24.6%) had germinomas; 44(77.2%) had localized disease and 13(22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB(cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months(range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival(EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs(P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively(P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Treatment results of childhood extracranial malignant germ cell tumors and the salvage approach for recurrent and refractory cases: a single-center report

Objective The aim of this study is to report the treatment result of childhood excranial malignant germ cell tumors and discuss the experience for recurrent and refractory cases treatment from our center.Methods We have retrospectively analyzed 58 extracranial malignant germ cell tumor patients treated with surgery and chemotherapy from our center over a 9-year period.Another 14 recurrent and refractory cases referred from other centers were added to the study for salvage approach.We evaluated the treatment results for primary cases and relapsed cases with a median follow-up of 61.5 months.Several factors were analysed to evaluate their power to the outcome of these cases.Results The 5-year event-free and overall survival for primary cases were 74.1±5.7%and 86.2±4.5%,respectively.25 recurrent or refractory cases entered the salvage approach study,and 17 patients were alive till the end of follow-up.We demonstrated superior survival outcome for those with successful local control through pre-operative and post-operative radiotherapy,second-look surgery and multi-drug secondline chemotherapies.Conclusion The outcome for childhood extracranial malignant germ cell tumors is generally favorable.For recurrent and refractory cases,multi-modality treatment approaches including radiotherapy,salvage chemotherapy and secondlook surgery are important for better local control.

Malignant histiocytosis associated with mediastinal germ cell tumor:A case report

BACKGROUND Germ cell tumors(GCTs)account for 2%of human malignancies but are the most common malignant tumors among males aged 15-35.Since 1983,an association between mediastinal GCT(MGCT)and hematologic malignancies has been recognized.CASE SUMMARY We report a case in which malignant histiocytosis was associated with mediastinal GCTs.The clinical data of a male patient with MGCT admitted to Beijing Children's Hospital were collected retrospectively.The patient was first diagnosed according to imaging and pathological features as having MGCT,and was treated with surgery and chemotherapy.One year after stopping chemotherapy,imaging showed metastases in the right supraclavicular,mediastinum,hilar region and retroperitoneal lymph node,right pleura,right lung,and right para-cardiac margin.Pathological diagnosis of the liver nodular and hilar lymph nodes included systemic juvenile xanthogranuloma and Rosai-Dorfman lesions with malignant transformation(i.e.,morphological characteristics and immunophenotype of histiocytic sarcoma).Following diagnosis,the patient accepted chemotherapy with vindesine,cytarabine and dexamethasone.Positron emission tomography–computed tomography showed partial remission.The patient was followed-up for 10 mo after the diagnosis of malignant histiocytosis,and no sign of progression or relapse was observed.CONCLUSION Physicians should recognize the possibility of hematologic malignancies being associated with MGCT.Suitable sites should be selected for pathological examination.

Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery

BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.

Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration

Isolated extragonadal germ cell tumors can be primary in nature or metastatic from a burned out testicular cancer.Accurate diagnosis is critical as appropriate therapy can be highly curative.We present the case of an isolated extragonadal germ cell tumor in the retroperitoneum diagnosed by endoscopic ultrasound-guided fi ne needle aspiration.This case underscores the importance of considering germ cell tumors in the differential diagnosis of an unexplained retroperitoneal mass,particularly since immunophenotypic staining may be necessary to establish the diagnosis.2010 Baishideng.All rights reserved.

Association between KITLG Gene Polymorphisms and Testicular Germ Cell Tumors:A Systematic Review and Meta-analysis

It has been reported that c-KIT ligand(KITLG)gene polymorphisms may be associated with testicular germ cell tumors(TGCT).Owing to mixed and inconclusive results,we con ducted a systematic review and meta-analysis to summarize and clarify this association.A systematic search of studies on the association between KITLG gene polymorphisms and TGCT susceptibility was conducted in databases.Odds ratios and 95%confidence intervals were used to pool the effect size.Six articles were included in our systematic review and meta-analysis.Compared with adenine(A),KITLG rs995030 guanine(G)might be associated with increased risk of TGCT.There are insufficient data to fully confirm the association between KITLG rs4474514 and TGCT susceptibility.Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.

Molecular and epigenetic pathogenesis of germ cell tumors

The development of germ cell tumors(GCTs)is a unique pathogenesis occurring at an early developmental stage during specification,migration or colonization of primordial germ cells(PGCs)in the genital ridge.Since driver mutations could not be identified so far,the involvement of the epigenetic machinery during the pathogenesis seems to play a crucial role.Currently,it is investigated whether epigenetic modifications occurring between the omnipotent two-cell stage and the pluripotent implanting PGCs might result in disturbances eventually leading to GCTs.Although progress in understanding epigenetic mechanisms during PGC development is ongoing,little is known about the complete picture of its involvement during GCT development and eventual classification into clinical subtypes.This review will shed light into the current knowledge of the complex epigenetic and molecular contribution during pathogenesis of GCTs by emphasizing on early developmental stages until arrival of late PGCs in the gonads.We questioned how misguided migrating and/or colonizing PGCs develop to either type Ⅰ or type Ⅱ GCTs.Additionally,we asked how pluripotency can be regulated during PGC development and which epigenetic changes contribute to GCT pathogenesis.We propose that SOX2 and SOX17 determine either embryonic stem cell-like(embryonal carcinoma)or PGC-like cell fate(seminoma).Finally,we suggest that factors secreted by the microenvironment,i.e.BMPs and BMP inhibiting molecules,dictate the fate decision of germ cell neoplasia in situ(into seminoma and embryonal carcinoma)and seminomas(into embryonal carcinoma or extraembryonic lineage),indicating an important role of the microenvironment on GCT plasticity.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States(1992–2015)

Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

Complete Remission by Primary Chemotherapy of Advanced Non-Seminomatous Germ Cell Tumor in an Intra-Abdominal Testis

Ectopic testis predisposes to a high risk of germ cell tumor development. Treatment of advanced testicular germ cell tumor developing in an uncorrected abdominal testis is based on primary chemotherapy followed by removal of the testis along with residual masses. However, persistence of viable tumor particularly in the testis is always noted since testis penetration of chemotherapeutic agents is reduced. We report a case of complete pathological remission of a patient with advanced non-seminomatous germ cell tumor in intra-abdominal testis by primary chemotherapy alone, with a review of the literature.

Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy:A focus on relapsed/refractory germ cell tumors

High-dose chemotherapy(HDCT)with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors(GCTs)who failed to be cured by conventional chemotherapy.Hematopoietic stem cells(HSCs)collected from the peripheral blood,after appropriate pharmacologic mobilization,have largely replaced bone marrow as the principal source of HSCs in transplants.As it is currently common practice to perform tandem or multiple sequential cycles of HDCT,it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure.Moreover,the CD34+cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment,with patients who receive>2×106 CD34+cells/kg having consistent,rapid,and sustained hematopoietic recovery.However,many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy,which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy.Therefore,alternative strategies that use novel agents in combination with traditional mobilizing regimens are required.Herein,after an overview of the mechanisms of HSCs mobilization,we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs,and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.

A Case of a Primary Endodermal Sinus Tumor of the Cerebellar Vermis

A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he had a ＂common cold＂, but treatment for 3 days produced no result. He was diagnosed as having viral encephalitis after an examination including an electroencephalogram （EEG）, blood biochemistry and lumbar puncture, etc. in a local hospital on November 15. After further treatment for 3 days his symptoms became aggravated showing instability of gait and involuntary movement of his head and extremities. Cranial CT showed： a 4.0 cm×4.0 cm×5.0 cm lump in the cerebellar vermis which intruded into the fourth ventricle inducing evident distention of the third and lateral ventricle. He was diagnosed with blastoma of the cerebellum.

Case Report of an Endodermal Sinus Vaginal Tumor in an Infant Girl

Case Report An female infant patient, aged 8 months old, suffered from irregular colporrhagia for a period of 1 month after which she was taken to our hospital on 30th April, 2003. A pelvic CT examination displayed a 6.5 cm×3.0 cm shadow of a soft-tissue tumor growing longitudinally in her supravaginal uterine area （Fig. 1）. The density of the shadow was uneven, in which there were irregular low-density loci, an indication of a compression of the colon and bladder and a diffuse boundary between the posterior wall of the urinary bladder and tumor. No abnormalities were found in either kidney or ovary, the liver or gall bladder. Also no obvious lesions were seen on the chest X-ray film, and routine blood and urine laboratory examinations were normal.