Paclitaxel in extensively pretreated nonseminomatous germ cell tumors

Paclitaxel was given as a single agent to previously treated, cisplatin-refractory, and relapsed patients with metastatic nonseminomatous germ cell tumors (GCT). Fifteen patients received paclitaxel at 250 mg/m² as a 24-hour continuous intravenous infusion, repeated every 21 days. The regimen was premedicated to prevent hypersensitivity reactions. Patients were supported with granulocyte-colony stimulating factor until resolution of the neutropenia. Of 15 patients, I I patients had received at least three previous chemotherapy regimens; 80% of the patients were cisplatin-refractory at study entry. A total of 34 courses of paclitaxel were delivered. A serologic partial response and a partial remission for an overall response rate of 13.3% (95% C.I. 2–39%), with a median duration of 9.5 weeks, were achieved. Thirteen (86.6%) patients developed progressive disease. The toxicity of the regimen consisted of grade 3/4 neutropenia, with only one infectious complication and no life-threatening events. Nonhematologic toxicity was significant for progressive peripheral neuropathy in 8 patients. No hypersensitivity reactions or symptomatic cardiac toxicity occurred. In conclusion, paclitaxel in the dose and schedule given has minimal activity in this extensively treated, cisplatin-refractory group of patients with nonseminomatous GCT. Further investigation is warranted to find the role of paclitaxel in GCT by either selecting a better patient population and/or combining it with cisplatin, which would use the synergistic cytotoxicity that has been reported.     

原发性睾丸非精原细胞性生殖细胞肿瘤26例分析

目的：总结原发性睾丸非精原细胞性生殖细胞肿瘤(NSGCT)的诊断与治疗体会。方法：回顾性分析收治的26例NSGCT的临床资料。26例中，胚胎癌7例(26．9％)，畸胎瘤5例(19．2％)，卵黄囊瘤4例(15．4％)，绒毛膜上皮癌1例(3．9％)，混合性生殖细胞瘤(MGCT)9例(34．6％)。睾丸无痛性肿大为其主要临床表现。Ⅰ期16例，Ⅱ期8例，Ⅲ期2例。在根治性睾丸切除基础上采用腹膜后淋巴结清扫术及化疗等综合治疗措施。结果：22例获随访，随访时间6个月～6．5年，术后复发2例，2例死于全身广泛转移，其余患者均健康生存。结论：NSGCT中以MGCT及胚胎癌最为常见，B超、CT或MRI为其诊断和临床分期的主要手段。肿瘤标记物对肿瘤的治疗与及预后判断有一定参考价值。     

Clinical epidemiology of testicular germ cell tumors

Clinical epidemiology is sometimes called the basic science of clinical medicine. In terms of the pathogenesis of testicular germ cell tumors (GCTs), clinical epidemiology analyzes suspected risk factors. The present review highlights the risk factors established so far and briefly summarizes those factors currently under investigation. In analogy to the methods of evidence based medicine, this review attributes levels of evidence to each of the putative risk factors. Level I represents highest quality of evidence while level V denotes the lowest level. So far, undescended testis (UDT), contralateral testicular GCT and familial testis cancer are established risk factors attaining high levels of evidence (levels I–III a). In a meta-analysis of 21 studies exploring the association of UDT with GCT risk, an over-all relative risk (RR) of 4.8 (95% confidence interval 4.0–5.7) was found. Contralateral testicular GCT involves a roughly 25-fold increased RR of GCT, while familial testis cancer constitutes a RR of 3–10. Infertility, testicular atrophy, and twin-ship represent risk factors with lesser levels of evidence (level III a). There is also some evidence for HIV infection being a predisposing factor for GCT (level IV a). Scrotal trauma is probably not associated with GCT risk. The estrogen excess theory implies high estrogen levels during the first trimester of pregnancy. As a consequence, primordial germ cells lose track of the normal developmental line and transform into premalignant cells that later become testicular intraepithelial neoplasia (TIN), the precursor of full-blown testicular GCT. Surrogate parameters for high gestational estrogen levels are investigated in case control studies. Such factors are maternal age >30 years, first-born, low birth weight, maternal breast cancer, high sex-ratio of siblings. So far, the sum of evidence is promising but still conflicting (especially for level III b). Another novel theory is the childhood nutrition hypothesis. This concept postulates a modulating or catalyzing effect by high dietary intake during childhood on the pathogenesis of testicular GCT. A surrogate parameter of early childhood nutrition is adult height. So far, 12 controlled studies have looked to the possible association of attained height and GCT risk of which six demonstrated a significant association. Thus, the sum of evidence corresponds to level III b. This concept is appealing because it would explain several hitherto unexplained epidemiological features of GCT.     

Bilateral methachronous testicular germ cell tumor and testicular microlithiasis in a child: Genetic analysis and insights. A case report

ObjectivesTo report our experience with a case of a child with bilateral testicular micro-lithiasis (TML) who developed bilateral metachronous testicular germ cell tumor (TGCT) and determine the most appropriate follow-up and care management in children with testicular micro calcifications in regards to the theoretical risk of testicular cancer.Case reportA 12 year-old boy was diagnosed with TGCT and TML. Ten years after complete remission, he presented with a recurrence on the contralateral testis. Genetic screening was performed on both resected and the patient’s karyotype was analyzed.ResultsBlood karyotype was normal. Aberrations were found in the tumor karyotype. CGH array showed alterations in chromosome arm 12p.DiscussionTML is frequently associated with testicular malignancy in adults: in 16.9% of cases the normal contralateral testicle develops TML in TGCT. Recent works of literature find no relationship between TML and cancer in general, but in patients with additional risks, the relationship becomes stronger. Some authors suggest that environmental components and genetics are determinant factors. This is highly suspected in our reported case. It would seem that TML is not a precancerous lesion per se, but rather a marker of an at-risk situation. Long term evolution is uncertain and regular self-palpation that starts before puberty is the only way to ensure proper screening and monitoring.ConclusionTML have been suspected to be a sign of testicular dysgenesis syndrome, which yields a risk of developing TGCT in case of noxious associations.In patients with a history of TGCT contralateral TML is alarming and aggressive surgical management should be discussed. Therapeutic education of these patients on self-palpation is the best way to ensure proper follow-up.     

Current and future biologic markers for disease progression and relapse in testicular germ cell tumors: A review

Testicular germ cell tumors represent a biologically unique disease process. These tumors are exquisitely sensitive to platinum-based chemotherapy, can be cured with surgical metastasectomy, and are known for the integration of biologic markers to stage and assign risk. Exploring further biologic markers that offer insight into the molecular mechanisms that contribute to disease biology is important. In this review, we attempt to summarize the utility of the current and some future biologic markers for disease monitoring and relapse.     

Intratubular germ cell neoplasia of the testis: testicular intraepithelial neoplasia

The observations of Skakkebaek and the evolution of the concept of intratubular germ cell neoplasia (or testicular intraepithelial neoplasia (TIN)) indicate that most, but not all, germ cell tumors of the testis evolve from a common neoplastic precursor lesion: intratubular germ cell neoplasia, unclassified type (IGCNU). It is defined as the presence of malignant germ cells within the seminiferous tubules. At 5 years about 50% of patients with a testicular biopsy positive for IGCNU have developed invasive germ cell tumors, and only a small fraction remain free of invasive tumors by 7 years. Orchiectomy is the treatment of choice in patients with unilateral IGCNU, and low-dose radiation is efficacious in patients with bilateral IGCNU (although sterility is certain). So far, there is only one published report of occurrence of two cases of germ cell cancer despite previous local radiotherapy to the testis. A recent study demonstrated an estimated risk of recurrent IGCNU following chemotherapy of 21% and 42% at 5 and 10 years, respectively.     

Expression of human chorionic gonadotropin in testicular germ cell tumors

BackgroundWe have shown that most patients with seminomas have elevated serum concentrations of the free β subunit of human chorionic gonadotropin (hCGβ) and that in nonseminomatous testicular cancer, most of the hCG in the serum is hyperglycosylated (hCG-h). However, the tissue expression of hCG-h or hCGβ in germ cell tumors (GCTs) has not been reported. Our objective was to study the expression and diagnostic value of hCG-h and hCGβ in testicular GCTs.MethodsWe studied the immunohistochemical expression of hCG, hCG-h, hCGβ, and the free α subunit of hCG (hCGα) in GCTs from 154 patients. We compared the tissue expression with serum concentrations and evaluated the correlation between staining intensity, established prognostic variables, and outcome.ResultsThe expression varied between tumor types. All forms of hCG, including hCG-h, were detected in embryonal carcinomas (22%) and mixed GCTs (48%). Polyclonal hCG and monoclonal hCGβ antibodies detected immunoreactivity in some seminomas (7%). No form of hCG was found in spermatocytic seminomas, pure teratomas, or a yolk sac tumor. The serum concentrations correlated with the corresponding tumor expression. The staining intensities of hCG, hCGβ, hCG-h, and hCGα correlated with disease stage but not significantly with relapse, disease-related mortality, or progression-free survival.ConclusionTrophoblastic tissue expresses hCG, hCG-h, and free subunits together whereas seminoma tissue occasionally expresses hCGβ. This difference might aid in differential diagnosis of some difficult-to-classify cases.     

Brain metastases from testicular germ cell tumors: A retrospective analysis

Objectives:   To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them.
Methods:   Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed.
Results:   Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis.
Conclusion:   Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy.     

Current knowledge of risk factors for testicular germ cell tumors

The development of the human gonads is tightly regulated by the correct sequential expression of many genes and hormonal activity. Disturbance of this regulation does not only prevent proper development of the gonads, but it also contributes to the development of testicular germ cell tumors. Recent genetic studies, especially genome‐wide association studies, have made great progress in understanding genetic susceptibility. Although there is strong evidence of inherited risks, many environmental factors also contribute to the development of testicular germ cell tumors. Histopathological studies have shown that most testicular germ cell tumors arise from germ cell neoplasia in situ, which is thought to be arrested and transformed primordial germ cells. Seminoma has features identical to germ cell neoplasia in situ or primordial germ cells, whereas non‐seminoma shows varied differentiation. Seminomas and embryonic cell carcinomas have the feature of pluripotency, which is thought to be the cause of histological heterogeneity and mixed pathology in testicular germ cell tumors. Testicular germ cell tumors show high sensitivity to chemotherapies, but 20–30% of patients show resistance to standard chemotherapy. In the present review, the current knowledge of the epidemiological and genomic factors for the development of testicular germ cell tumors is reviewed, and the mechanisms of resistance to chemotherapies are briefly mentioned.     

Quantitative DNA measurement by flow cytometry and image analysis of human nonseminomatous germ cell testicular tumors

Current clinical staging, which includes the use of serum tumor markers and imaging techniques, fails to identify the 30–40% of clinical stage I (CS I) nonseminomatous germ cell testicular tumor (NSGCT) patients who have occult metastatic disease. Therefore, there is a real clinical need to evaluate new biological parameters of the primary tumor that might be useful as predictors of occult metastatic disease. This study was undertaken to compare quantitative DNA measurements by flow cytometry and image analysis in CS I NSGCT, and to analyze the relevance of these parameters for predicting occult lymph node involvement. Different blocks of formalin-fixed, paraffin-embedded NSGCTs of 62 CS I patients who underwent retroperitoneal lymph node dissection between 1985 and 1989 were prepared according to the Hedley technique, and analyzed by quantitative cytometry. Thirty-six (58.1%) patients had histologically proven lymph node involvement (pathological stage II), whereas 26 (41.9%) patients (pathological stage I) had neither lymph node metastases according to retroperitoneal lymph node dissection (RPLND) specimens nor tumor recurrence during follow-up. Concordant results were found in 76.5% of the samples by both cytometric techniques. For flow cytometry, the percentages of aneuploid cells in the S- and the G2M+S-phase were the most robust predictive parameters for lymph node involvement, whereas for image analysis the 5c exceeding rate (5cER) had the most predictive significance. Based on the experience obtained in this study, both cytometric techniques provide additional information on tumor aggressiveness that might be useful in therapeutic selection of early stage NSGCT patients for either RPLND or surveillance only.     

Late relapse after treatment for nonseminomatous testicular germ cell tumors according to a single center-based experience

The introduction of cisplatin-based systemic chemotherapy into the clinical routine has resulted in a substantial improvement of the recurrence-free and long-term survival of patients with metastatic testicular germ cell tumors. Late relapses after the completion of first-line therapy, comprising systemic chemotherapeutic treatment in combination with a complete resection of residual tumor masses visible in about 25–50% of patients, have been reported to occur in 1–5% of patients later than 2 years following the initial treatment. It has been reported that the risk for the development of late recurrence is correlated to the tumor burden at first diagnosis and/or the presence of teratomatous components within the primary testicular cancer. Second-line chemotherapy in combination with surgery, although not very well standardized, has been recommended as the most effective therapeutic regimen during the treatment of patients suffering from late recurrent germ cell tumors. Herein, we report our single-center experience with 14 patients in different clinical stages who developed late relapse after successful first-line therapy. In the present series, the risk for late relapse was not correlated to the clinical stage at first diagnosis or the presence of teratomatous elements within the primary tumor. It became evident that in selected cases chemotherapy alone can be considered a curative treatment option.     

m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor

BackgroundN6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT.MethodsWe collected TGCT patients’ information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles ({"type":"entrez-geo","attrs":{"text":"GSE3218","term_id":"3218"}}GSE3218 and {"type":"entrez-geo","attrs":{"text":"GSE10783","term_id":"10783"}}GSE10783) as an independent external validation cohort.ResultsDistinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles ({"type":"entrez-geo","attrs":{"text":"GSE3218","term_id":"3218"}}GSE3218 and {"type":"entrez-geo","attrs":{"text":"GSE10783","term_id":"10783"}}GSE10783).ConclusionsBased on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.     

Retroperitoneal germ cell tumors: a clinical study of 12 patients

Purpose

The aim of the study was to examine the clinical presentation, method(s) of treatment, complications, and results in newborns and infants with retroperitoneal germ cell tumors (GCTs).

Methods

A retrospective chart review of all patients treated between 1974 and 2002 for GCT located in the retroperitoneum in 2 institutions identified 12 patients with histologically proven retroperitoneal GCT. Vital data concerning pregnancy and delivery were analyzed. Age at diagnosis and symptoms were recorded, as well as possibly associated anomalies. Data concerning surgical treatment, perioperative and postoperative complications, histological staging, and final outcome were all analyzed.

Results

In 3 patients, the diagnosis had been made antenatally between 31 and 35 weeks of gestation. In 1 patient, the diagnosis was made at birth, and in 8 later in life (ages 3, 5, 7, 8, 8, 11, 18, and 24 months). Symptoms in these 8 boys and 4 girls were abdominal distension and a palpable upper abdominal mass, right-sided in 5, left-sided in 5, and central in 2; the tumor was usually big. Associated anomalies were noted in 4 patients and were chromosomal in 3 (Down syndrome in 2 and Klinefelter syndrome in 1). One baby died of uncontrollable bleeding during an emergency operation immediately after traumatic birth. The other 11 infants survived. Four other patients showed serious perioperative complications (1 caval vein tear, 1 choledochal tear, 1 cyst rupture, and 1 esophagogastric tear) which were managed without further consequences. Histologically, 4 tumors were mature teratomas, 6 were immature teratomas (grade I in 4, grade II in 1, and grade II-III in 1), and 2 were malignant yolk sac tumors (YSTs). The patients with YSTs underwent surgical biopsy, followed by chemotherapy and excision of the remaining tumor and of the metastases. No adjuvant treatment was administered in the patients with benign disease. Nine survivors with benign tumor are disease-free between 1 and 30 years after surgery. Two patients with YST have now been in remission for 6 and 5 years, respectively.

Conclusions

Both this study and the literature review performed testify to the extreme rarity of GCTs in the retroperitoneum. Surgical removal of the tumors appeared to be hazardous because of the extent of the tumor, the displacement and elongation of adjacent structures and organs, and/or the adhesion of the tumor to surrounding tissues; this resulted in several perioperative complications. The long-term results are good, however, with 9 of 10 patients with benign tumors in good health after a mean follow-up of 12 years, and with the 2 patients with YST in remission for 6 and 5 years, respectively.     

High-risk clinical stage I nonseminomatous germ cell tumors: the case for chemotherapy

Testis cancer is the most frequent solid malignancy in young men. The majority of patients present with clinical stage I disease and about 50% of them are nonseminomatous germ cell tumors. In this initial stage of disease there is a subgroup of patients at high risk with a likelihood of more than 50% for relapse. Treatment options for these patients include: retroperitoneal lymph node dissection (RPLND), albeit 6–10% of patients will relapse outside the field of RPLND, active surveillance with even higher relapse rates and adjuvant chemotherapy. As most of these patients have the chance to become long-term survivors, avoidance of long-term side effects is of utmost importance. This review provides information on the potential of chemotherapy to achieve a higher chance of cure for patients with high-risk clinical stage I disease than its therapeutic alternatives and addresses toxicity and dose dependency.     

Late relapse of testicular germ cell tumors

The successful multidisciplinary approach for the management of germ cell tumors of the testis has resulted in survival rates of greater than 90% overall. While the majority of relapses in patients with germ cell tumors occur within the first 2 years of treatment, the incidence of late relapse beyond 2 years has been increasing over recent years. The pattern of late relapse suggests that an inadequately controlled retroperitoneum is a major predisposing factor, with up to 80% of late relapses occurring in the retroperitoneum. These tumors tend to be chemorefractory and overall prognosis for patients with late relapse of germ cell tumors is relatively poor, with survival rates of approximately 30% to 40%. In this review, we present the recent data regarding the clinical presentation, patterns of relapse, histologic findings, appropriate treatment options, and outcomes for men with late relapse of germ cell tumors.     

Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure

OBJECTIVE: To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. PATIENTS AND METHODS: Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. RESULTS: In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26-217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9-184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. CONCLUSION: Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.     

睾丸混合性生殖细胞肿瘤临床病理分析

目的:探讨原发性睾丸混合性生殖细胞肿瘤(MGCT)的临床病理特征。方法:对我院13例原发性睾丸MGCT患者的临床病理资料进行回顾性分析,并结合相关文献进行讨论。结果:睾丸MGCT占我院同期睾丸生殖细胞肿瘤的24.1%(13/54),患者年龄2~53岁,平均28.3岁。全部病例均发生于单侧睾丸,左侧6例,右侧7例,左右侧比为0.86∶1。睾丸MGCT病理形态多样,肿瘤成分包括胚胎性癌(11例,84.6%)、精原细胞瘤(8例,61.5%)、畸胎瘤(6例,46.2%)、绒毛膜癌及卵黄囊瘤(均为4例,23.1%)。其中9例(69.2%)包含2种不同的生殖细胞肿瘤成分,3例(30.8%)包含3种不同的肿瘤成分,1例(7.7%)包含5种不同的肿瘤成分。结论:睾丸MGCT非常少见,好发于青壮年男性,不同的肿瘤成分其生物学行为、临床治疗和预后不同,因此准确的病理诊断非常必要,免疫组化标记对病理诊断与鉴别诊断具有重要作用。     

Metachronous testicular tumor developing eight years after retroperitoneal extragonadal germ cell tumor

Abstract:   A 30 year-old man was admitted to our hospital with a chief complaint of left flank pain. Computed tomography revealed a retroperitoneal tumor. Levels of lactic dehydrogenase, human β-chorionic gonadotropin, α-fetoprotein, DUPAN-2 and carbohydrate antigen 19–9 were elevated. No abnormal findings were present according to palpation and ultrasonography of the testes. The patient was diagnosed as having a retroperitoneal extragonadal germ cell tumor (EGCT) considering the elevated markers. Resection of the tumor, two cycles of neoadjuvant and one cycle of adjuvant chemotherapy (cisplatin and etoposide) were performed. The surgical specimen showed total necrotic tissue. Eight years later, the patient noticed an enlargement of his left testicle. The tumor felt elastic and firm on his left testis. Neither distant metastasis nor lymph node metastasis was present according to computed tomography. Left high orchiectomy was performed and histology revealed seminoma. Twenty-three cases have been reported previously about metachronous testicular tumor developing after retroperitoneal EGCT. We report the 24th case.