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Journal of Cancer Research and Therapeutics, Vol. 5, No. 3, July-September, 2009, pp. 206-207 Case Report Metachronous bilateral testicular germ cell tumors: Report of two cases James FrancisV, Kumar Aswin, Jayaprakash PG, Mathews Anitha Section of Genitourinary Oncology, Regional Cancer Centre, Trivandrum, Kerala Code Number: cr09050 PMID: 19841564 DOI: 10.4103/0973-1482.57128 Abstract Metachronous bilateral testicular germ cell tumors is a rare known problem. However, no report of metachronus bilateralism was identified in the PubMed database published from India so far, where testicular cancer is relatively rare. We report the cases of two gentlemen. One had stage 1 nonseminomatous germ cell tumor (NSGCT) at the age of 32 in 1990 and developed marker relapse on surveillance and had chemotherapy using cisplatin and etoposide for four cycles. He developed contralateral seminoma in the testis 13 years later. Another patient had left orchidectomy in 2003 for NSGCT, had adjuvant BEP for two cycles, and developed a contralateral testicular tumor 5 years later, which was also seminoma. As more patients with germ cell tumors are cured with chemotherapy, long-term problems become important. Contralateral testicular tumor is one of them. As it can be very late, many years of continued follow-up examination and patients' awareness are necessary.Keywords: Bilateral testicular germ cell tumor, incidence, seminoma Background Testicular germ cell tumor is curable, and long-term survivors present with many rare problems like second cancers, cardiovascular problems, and contralateral tumors. [1] The incidence of contralateral testicular tumor varies from 1 to 5.2%. [2],[3],[4],[5] To our best knowledge, after reviewing the PubMed database, we found that there is no report of contralateral metachronous testicular tumors available from India. Hence, we are reporting these cases from Regional Cancer Centre, Trivandrum, India. Case Reports Case 1 A 32-year-old male patient presented with a history of right scrotal swelling in 1990. He was detected to have a right testicular tumor and underwent right orchidectomy on January 9, 1990. The histopathological examination revealed a mixed germ cell tumor consisting of seminoma 50%, embryonal carcinoma 30%, and teratoma 20%. No lymphovascular invasion was reported and therefore staged pT1 disease. A clinical examination at that time was unremarkable except for atrophic testis on contralateral side. He was found to have stage 1 disease after the staging work-up and was kept on a surveillance program. His disease relapsed in September 1990 which was evidenced by serum AFP of 900 units and serum Beta HCG of 168 units. There was no radiologically demonstrable disease. He was given four cycles of chemotherapy with cisplatin and etoposide (cisplatin 20 mg/square meter and etoposide 100 mg/square meter from day 1 to 5 repeated in three weekly cycles) with marker remission. He remained well until September 2003 when he presented with left testicular swelling of 5.7 x 4.9 cm. His tumor markers remained normal. Ultrasound revealed multiple calcifications in testicular parenchyma, and he underwent left orchidectomy on October 23, 2003. A histological examination revealed classical seminoma, stage pT1. His metastatic work-up, including a CT scan of the abdomen and pelvis, and chest X-rays were again negative. He was given prophylactic radiotherapy to para-aortic lymph nodes to a dose of 25 Gy in 15 fractions over 3 weeks. He has been started on testosterone supplement and is on follow-up with clinical examination, serum markers, and chest X-ray. Case 2 A 19-year-old young man with a history of bilateral orchiopexy at 9 years of age presented with stage 1 left testicular tumor and underwent high orchidectomy on September 3, 2003. Histology revealed immature teratoma and yolk sac tumor 60% and 40% each, respectively, with stage pT1 disease. Tumor markers, and a CT scan of the chest, abdomen, and pelvis were normal. He received adjuvant chemotherapy using two cycles of BEP and remained well until May 2008 when an ultrasound scan of the remaining testicle showed abnormal hypoechoic areas of size 17, 16, and 14 mm. He underwent right orchidectomy on June 9, 2008. The histopathology report confirmed stage pT1 seminoma at few foci of about 10 mm size. A postoperative CT scan of the abdomen and chest, and tumour markers were normal. He received prophylactic para-aortic radiotherapy (20 Gy in 10 fractions over 2 weeks), and is on follow-up three monthly with clinical examination, serum markers (serum beta HCG, AFP, and LDH), and chest X-ray. Discussion Testicular tumor is uncommon in Asia compared to Western countries. In Asia, the incidence of testicular tumors is as low as 0.4 per 100,000. [6] There were only two metachronous contralateral testicular tumors at the authors′ centre so far where 540 patients were treated from 1990 to 2008. This may be related to actual lower incidence or inadequate follow-up. It has not been our policy to perform biopsy of contralateral testis and hence, the incidence of intratubular germ cell neoplasia is not known. The incidence of bilateral testicular cancers has varied in different reports published so far. It was found to be as low as 1% in MD Anderson series and 1.2% at Memorial Sloan Kettering Cancer Centre, 1.9% in Institute Gustave Roussy, and 2.7% in Denmark. [2],[3],[4],[7] There are questions, which remain unanswered. Has the use of platinum decreased the contralateral tumors? According to Bokemeyer et al., the use of chemotherapy has abolished contralateral testicular tumours. In their report, none of 157 patients receiving chemotherapy for metastatic disease of the first tumor developed a metachronus contralateral tumor. [10] Bilateralism was reduced to 1% at MD Anderson Cancer Center in the chemotherapy era. [1] In the Netherlands, a difference of 1.8% versus 5% was seen for patients who received chemotherapy or did not. The use of chemotherapy did not appear to eliminate contralateral tumors in Glasgow, where the incidence was 3.3% in the platinum era. [8] The patients reported here had chemotherapy in the past and this did not prevent the second cancer. There is again controversy whether first histology of seminoma or nonseminoma leads to higher contralateral testicular tumors. According to the MD Anderson group, if the first tumor was seminoma, it had an incidence of 1.6% and if it was nonseminoma, its incidence was 0.6%. At Institute Gustave Roussy, the overall incidence of contra lateral testicular tumors in patients with a previous testicular germ cell tumor was 1.9%. Bilateralism was 3.2% in patients presenting with a seminoma and 1.4% in patients presenting with a nonseminomatous germ cell tumor. [6] But in Denmark, the risk of bilateral tumors was 8.4% for nonseminomas compared to 3.6% for seminomas. The gentlemen reported here had histology of NSGCT of the testis initially, and the contralateral testicular tumors were seminoma, which developed 13 and 5 years later. From the reports cited, the prognosis of the patients is very good and needs modified treatment in a small percentage due to earlier treatment. [2] From the available data, the incidence of testicular tumors as well as contralateral testicular tumors varies in different parts of the world. More studies are needed to elucidate the cause. Meanwhile, we have to educate the patients who had treatment for testicular tumors to examine their contralateral testis themselves and discuss biopsy of atrophic testis with low sperm counts or history of cryptorchidism. As the second patient′s tumor was picked up earlier by ultrasound, it may be worth exploring the use of annual ultrasound examination of the testis. Once detected to have a contralateral tumor, conservative surgical treatment may be an option as reported [9] or classical orchidectomy can be used, which warrants continued hormone supplement. [10] Conclusions There is a small but definite risk of contralateral testicular cancer in survivors of germ cell tumors of the testis. This may be late and hence awareness of the patient and physicians is necessary. References
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