CEN Case Rep (2012) 1:90–95 DOI 10.1007/s13730-012-0020-7
CASE REPORT
A case report of mediastinal seminoma arising after renal transplantation Michiko Anzai • Takashi Kenmochi • Hiroshi Kitamura • Hideaki Kurayama • Yuichi Takiguchi • Chieko Matsumura Katsuyoshi Kanemoto
•
Received: 20 December 2011 / Accepted: 10 May 2012 / Published online: 6 June 2012 Ó Japanese Society of Nephrology 2012
Abstract Recipients of organ transplantation on immunosuppressive medications are at increased risk for developing de novo malignancies, including skin cancer, Kaposi’s sarcoma, in situ carcinomas of the uterine cervix, anogenital cancers, renal cell carcinoma, and post-transplant lymphoproliferative disorders (PTLD). However, there are few case reports of germ cell tumors after organ transplantation. There are some case reports of testicular seminoma, but not mediastinal seminoma. This case report is the first description of a mediastinal seminoma that developed de novo 28 months after renal transplantation and that was initially diagnosed as PTLD. To improve outcomes of organ transplant recipients, it is important to report rare cases of malignancies arising while on immunosuppressive medications. When we detect mediastinal tumor arising after organ transplantation while on immunosuppressive therapy, diseases other than PTLD should be considered in the differential diagnosis.
M. Anzai (&) H. Kurayama C. Matsumura K. Kanemoto Department of Pediatrics, Chiba-East National Hospital, National Hospital Organization, 673 Nitona-cho, Chuo, Chiba, Chiba 260-8712, Japan e-mail: [email protected] T. Kenmochi Department of Surgery, Chiba-East National Hospital, National Hospital Organization, Chiba, Japan H. Kitamura Department of Pathology, Chiba-East National Hospital, National Hospital Organization, Chiba, Japan Y. Takiguchi Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Keywords Mediastinal seminoma Post renal transplantation
Introduction Outcomes for organ transplant recipients depend on a number of factors, including the function of the organ transplanted, initial recrudescence of the original disease, the possibility of rejection, infection, and the development of de novo malignancies while on immunosuppressive medications. Some of these complications are unavoidable. After organ transplantation on immunosuppressive medications, the incidence of malignancy is about four times that of the general population [1]. It is important to detect and treat malignancies early. This case report is the first description of a mediastinal seminoma developing de novo after renal transplantation. Though 12 months elapsed between detection of the tumor and the final diagnosis of mediastinal seminoma in this case, the outcome was relatively favorable.
Case report The patient was born in 1988, the second infant in a set of fraternal twins. Due to hypoxic ischemic encephalopathy at birth, he sustained brain damage characterized by mental retardation, epilepsy and quadriplegia. His renal function slowly deteriorated. Renal biopsy was performed in 2003, when his serum creatinine level reached 1.7 mg/dl. Pathological diagnosis confirmed the cause of chronic renal failure to be juvenile nephronophthisis. In 2004, he was referred to our hospital with a serum creatinine level of 4.7 mg/dl. His family and health care
CEN Case Rep (2012) 1:90–95
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Fig. 1 a Plane chest CT before renal transplantation in November 2004. b Plane chest CT at the time of detect mediastinal tumor in April 2007
Fig. 2 Ga-67 citrate scintigraphy showing accumulation of Ga-67 in the upper anterior mediastinum
providers, including the surgeon, pediatrician, and transplant coordinator, worked together to devise a treatment plan. His family considered both peritoneal dialysis and hemodialysis to be impossible considering his intellectual limitations. After due consideration, living donor kidney transplantation was performed in December 2004, with his mother serving as the donor. After transplantation, his renal function improved with serum creatinine levels reaching approximately 1.0 mg/dl. Immunosuppressive medications,
including cyclosporine A, mycophenolate mofetil, prednisolone (PSL), and basiliximab, were started. After 3 months, PSL was withdrawn with no signs of rejection. In April 2007, he was brought to our hospital with a chief complaint of fever. Chest computed tomography (CT) was performed to identify the focus of the fever, and revealed pneumonia in the left lung and a mediastinal tumor in the supra-anterior region, which had not been observed before transplantation (Fig. 1a, b). Use of Ga-67 citrate showed significant accumulation of Ga-67 in the upper anterior mediastinum (Fig. 2). We initially thought the tumor could be PTLD, which is the most common malignancy in transplant patients after nonmelanoma skin cancer and in situ cervical cancer [1]. Epstein-Barr virus DNA (EBVDNA) measurement yielded a value of 4.0 9 10* copies. Thus, needle biopsy of the mediastinal tumor was carried out under CT guidance. The cytology result suggested a PTLD. As the tumor was becoming smaller without intervention, we monitored its diameter on an outpatient basis (Fig. 3a, b). In January 2008, the tumor showed enlargement (Fig. 4a, b). A fluorodeoxyglucose positron emission tomography (FDG-PET) scan was obtained. High accumulation was detected in the upper anterior mediastinum in an area 60 mm in diameter (Fig. 5a–c). A tissue biopsy was performed. On light microscopic examination, there was a diffuse proliferation of tumor cells on the desmoplastic tissue. The tumor cells were large with round nuclei, small distinct nucleoli, forming lobular structures, and accompanied by some small lymphocytes. Mitotic figures were occasionally seen, but not cytotrophoblasts or syncytiotrophoblasts (Fig. 6a, b). Immunostainings for leukocyte common antigen (Fig. 7a), CD3 (Fig. 7b), CD79a (Fig. 7c), latent membrane protein 1 (EBV-LMP), and EBV encoding small RNAs (EBER) were all negative, ruling out PTLD. Alpha-fetoprotein (Fig. 8b) was also negative, whereas human chorionic gonadotropin (Fig. 8a),
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CEN Case Rep (2012) 1:90–95
Fig. 3 a Enhanced chest CT in April 2007. b Enhanced chest CT in May 2007. Mediastinal tumor is smaller in natural course
Fig. 4 a Plane chest CT in January 2008. b Enhanced chest CT in February 2008. Mediastinal tumor shows enlargement
CAM5.2 (Fig. 8c), and placental alkaline phosphatase (Fig. 8d) were positive. Serum b-hCG was weakly positive (0.6 ng/ml). Pregnancy-t reaction was also negative. Observation of the testes showed only contraction, indicating a final diagnosis of mediastinal seminoma. Chemotherapy with three courses of BEP (bleomycin, etoposide, cisplatin) was administered. After chemotherapy the tumor shrank from 60 to 36 mm in maximum diameter (Fig. 9). However, the diameter of remnant tumor was adaptive for surgery ([30 mm).Given the risk of malignant invasion associated with surgery, we decided to follow tumor progression in this case on an outpatient basis. The seminoma continued to shrink on chest CT without rescue agent. In November 2010, the patient was hospitalized for pneumonia with pleural effusion in the right lung and hypereosinophilic syndrome. We performed thoracentesis. Pleural effusion was serous, and there was no culture growth or presence of tumor cells. In December 2010, we
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performed FDG-PET to further investigate the hypereosinophilic syndrome, which we were unable to account for. Significant accumulation of FDG was not detected, so we did not believe active seminoma tumor cells were present. Gradually, the hypereosinophilic syndrome went into remission without treatment. Pleural effusion in the right lung decreased slightly, followed later by a change in organization. No other examinations, including bone marrow and anti-parasitic antibody, showed significant clinical effects. The cause of both episodes was not clear, but no recurrence was observed. The patient underwent a recent chest CT in February 2012, and the shadow of the mass had disappeared. There was only residual connective tissue of approximately 2 mm width, indicating that the seminoma may be in complete remission. The patient is now 23 years old. His mental age is approximately 5–6 years old, the same level as during the first inspection in 2004. He is able to move with a
CEN Case Rep (2012) 1:90–95
wheelchair and eat regular food on his own. He works in a small-scale workplace for mentally handicapped people when his physical condition is good. However, his daily recovery from a respiratory infection has been long and is sometimes accompanied by acute gastritis. He was subsequently hospitalized 12 times for bronchitis or pneumonia due to viral infections. His physical status, which includes narrow lung volume with organized
93
pleural effusion, has deteriorated, which could be lifethreatening if an infection is contracted. His renal function will also be getting worse; thus, the limitation of his therapy needs to be determined. This will depend not on medical limitations, but his physical condition. The health care providers are working together with his family to devise a treatment plan considering his ongoing condition.
Discussion
Fig. 5 Fluorodeoxyglucose (FDG) positron emission tomography scan shows high accumulation of FDG in the upper anterior mediastinum (a transverse, b coronal, c sagittal)
In this case of mediastinal tumor, making the differential diagnosis between PTLD and some other malignancy was difficult. Suspecting various possible underlying diseases, we initially conducted precise examinations of the tumor, using simple and minimally invasive tests. The time elapsed from initial detection of the mediastinal tumor until confirmation of the seminoma diagnosis was nearly 12 months. Considering the regression that occurred as part of the natural course of this tumor, one hypothesis is that the supra-anterior mass was PTLD, while the posterior malignancy was a mediastinal seminoma. Though mediastinal seminomas constitute approximately one-third of malignant mediastinal germ cell tumors, they only account for 2–4 % of mediastinal masses [2]. Two such events in a single patient would be extremely rare, so we think that mediastinal seminoma in this case was the malignancy following organ transplantation while on immunosuppressive therapy. There have been very few case reports of germ cell tumor after organ transplantation and administration of immunosuppressive medications. For example, after renal transplantation, there was a case of mixed germcell ovarian tumor with a choriocarcinoma component [3], a germ-cell tumor, more likely to be seminoma, in the pelvic region [4], and some cases of testicular seminoma
Fig. 6 Light microscopic photographs of tumor cells, from tissue biopsy of mediastinal tumor (H&E staining a 940, b 9400)
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Fig. 7 Result of immune staining. Leukocyte common antigen (a 940), CD3 (b 940), and CD79a (c 940) are negative, so PTLD is denied
Fig. 8 Result of immune staining. Alpha-fetoprotein is negative (b 9100); human chorionic gonadotropin (a 9100), CAM5.2 (c 9100), and placental alkaline phosphatase (d 9100) are positive
[5–11]. After cardiac transplantation, there was a seminoma in the retroperitoneum [12] and another case of a seminoma of multiple bony metastases [13]. This is the first case report of mediastinal seminoma, a malignancy arising in patients after organ transplantation while on immunosuppressive therapy. This case underscores the importance of considering mediastinal seminoma in differential diagnoses of malignancies arising after
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organ transplantation. Though the clinical course of this mediastinal seminoma case was relatively favorable, to further improve outcomes of transplant recipients, it will be increasingly important to detect and treat tumors early. We have reported this unique case, with a mediastinal seminoma arising in a patient after renal transplantation while on immunosuppressive medication, as a contribution to the international literature.
CEN Case Rep (2012) 1:90–95
95
Fig. 9 Clinical course of mediastinal seminoma after three course of BEP therapy
When a suppressed other than differential
mediastinal tumor is detected in an immunopatient after organ transplantation, diseases PTLD should be considered in an unbiased diagnosis.
References 1. Penn I. Cancers complicating organ transplantation. N Engl J Med. 1990;323(25):1767–9. 2. Moran CA, Suster S, Przygodzki RM, Koss MN. Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas—a clinicopathologic and immunohistochemical study of 120 cases. Cancer. 1997;80(4):691. 3. Ketata H, Bouacida M, Bouhlel A, Sahnoun A, Bahloul A, Yaich S, et al. A transplant recipient with a mixed germ-cell ovarian tumor. Saudi J Kidney Dis Transpl. 2008;19(6):973–5. 4. Kosmas C, Tsavaris NB, Vadiaka M, Chiras T, Boletis J, Kostakis A. Extragonadal seminoma after renal transplantation and immunosuppression; treatment in the presence of renal dysfunction: a case report and literature review. Med Oncol. 2001;18(3): 221–5. 5. Nellans RE, Ravera J. Seminoma in a renal transplant recipient. J Urol. 1975;113(6):871–3.
6. Dieckmann KP, Du¨e W, Offermann G. Testicular seminoma in an immunosuppressed renal transplant recipient. Br J Urol. 1989; 63(5):549–50. 7. Fisher KS, Birtch AG. Seminoma in renal transplant patient: a patient report and review of the literature. Curr Surg. 1990; 47(3):181–5. 8. Villalona-Calero MA, Ducker T, Holasek M, Najarian J, Kennedy BJ. Management of testicular seminoma following organ transplantation. Med Pediatr Oncol. 1992;20(4):338–40. 9. Viddeleer AC, Lycklama a` Nijeholt GA, Beekhuis-Brussee JA. A late manifestation of testicular seminoma in the bladder in a renal transplant recipient: a case report. J Urol. 148(2 Pt 1):401–2 (1992). 10. Modlin CS, Flechner SM, Penn I. Testicular seminoma originating in an undescended testis in a renal allograft recipient. Urology. 1996;48(1):145–8. 11. Popov Z, Ivanovski O, Kolevski P, Stankov O, Petrovski D, Cakalaroski K, et al. De novo malignancies after renal transplantation—a single-center experience in the Balkans. Transpl Proc. 2007;39(8):2589–91. 12. Hollingsworth JM, Shuster TG, Wolf JS Jr. Seminoma nine years after cardiac transplantation. Transplantation. 2004;77(9):1472. 13. de Bono JS, Fraser JA, Lee F, Simpson A, Lim C, Naik S, et al. Metastatic extragonadal seminoma associated with cardiac transplantation. Ann Oncol. 2000;11(6):749–52.
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CASE REPORT
A case report of mediastinal seminoma arising after renal transplantation Michiko Anzai • Takashi Kenmochi • Hiroshi Kitamura • Hideaki Kurayama • Yuichi Takiguchi • Chieko Matsumura Katsuyoshi Kanemoto
•
Received: 20 December 2011 / Accepted: 10 May 2012 / Published online: 6 June 2012 Ó Japanese Society of Nephrology 2012
Abstract Recipients of organ transplantation on immunosuppressive medications are at increased risk for developing de novo malignancies, including skin cancer, Kaposi’s sarcoma, in situ carcinomas of the uterine cervix, anogenital cancers, renal cell carcinoma, and post-transplant lymphoproliferative disorders (PTLD). However, there are few case reports of germ cell tumors after organ transplantation. There are some case reports of testicular seminoma, but not mediastinal seminoma. This case report is the first description of a mediastinal seminoma that developed de novo 28 months after renal transplantation and that was initially diagnosed as PTLD. To improve outcomes of organ transplant recipients, it is important to report rare cases of malignancies arising while on immunosuppressive medications. When we detect mediastinal tumor arising after organ transplantation while on immunosuppressive therapy, diseases other than PTLD should be considered in the differential diagnosis.
M. Anzai (&) H. Kurayama C. Matsumura K. Kanemoto Department of Pediatrics, Chiba-East National Hospital, National Hospital Organization, 673 Nitona-cho, Chuo, Chiba, Chiba 260-8712, Japan e-mail: [email protected] T. Kenmochi Department of Surgery, Chiba-East National Hospital, National Hospital Organization, Chiba, Japan H. Kitamura Department of Pathology, Chiba-East National Hospital, National Hospital Organization, Chiba, Japan Y. Takiguchi Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Keywords Mediastinal seminoma Post renal transplantation
Introduction Outcomes for organ transplant recipients depend on a number of factors, including the function of the organ transplanted, initial recrudescence of the original disease, the possibility of rejection, infection, and the development of de novo malignancies while on immunosuppressive medications. Some of these complications are unavoidable. After organ transplantation on immunosuppressive medications, the incidence of malignancy is about four times that of the general population [1]. It is important to detect and treat malignancies early. This case report is the first description of a mediastinal seminoma developing de novo after renal transplantation. Though 12 months elapsed between detection of the tumor and the final diagnosis of mediastinal seminoma in this case, the outcome was relatively favorable.
Case report The patient was born in 1988, the second infant in a set of fraternal twins. Due to hypoxic ischemic encephalopathy at birth, he sustained brain damage characterized by mental retardation, epilepsy and quadriplegia. His renal function slowly deteriorated. Renal biopsy was performed in 2003, when his serum creatinine level reached 1.7 mg/dl. Pathological diagnosis confirmed the cause of chronic renal failure to be juvenile nephronophthisis. In 2004, he was referred to our hospital with a serum creatinine level of 4.7 mg/dl. His family and health care
CEN Case Rep (2012) 1:90–95
91
Fig. 1 a Plane chest CT before renal transplantation in November 2004. b Plane chest CT at the time of detect mediastinal tumor in April 2007
Fig. 2 Ga-67 citrate scintigraphy showing accumulation of Ga-67 in the upper anterior mediastinum
providers, including the surgeon, pediatrician, and transplant coordinator, worked together to devise a treatment plan. His family considered both peritoneal dialysis and hemodialysis to be impossible considering his intellectual limitations. After due consideration, living donor kidney transplantation was performed in December 2004, with his mother serving as the donor. After transplantation, his renal function improved with serum creatinine levels reaching approximately 1.0 mg/dl. Immunosuppressive medications,
including cyclosporine A, mycophenolate mofetil, prednisolone (PSL), and basiliximab, were started. After 3 months, PSL was withdrawn with no signs of rejection. In April 2007, he was brought to our hospital with a chief complaint of fever. Chest computed tomography (CT) was performed to identify the focus of the fever, and revealed pneumonia in the left lung and a mediastinal tumor in the supra-anterior region, which had not been observed before transplantation (Fig. 1a, b). Use of Ga-67 citrate showed significant accumulation of Ga-67 in the upper anterior mediastinum (Fig. 2). We initially thought the tumor could be PTLD, which is the most common malignancy in transplant patients after nonmelanoma skin cancer and in situ cervical cancer [1]. Epstein-Barr virus DNA (EBVDNA) measurement yielded a value of 4.0 9 10* copies. Thus, needle biopsy of the mediastinal tumor was carried out under CT guidance. The cytology result suggested a PTLD. As the tumor was becoming smaller without intervention, we monitored its diameter on an outpatient basis (Fig. 3a, b). In January 2008, the tumor showed enlargement (Fig. 4a, b). A fluorodeoxyglucose positron emission tomography (FDG-PET) scan was obtained. High accumulation was detected in the upper anterior mediastinum in an area 60 mm in diameter (Fig. 5a–c). A tissue biopsy was performed. On light microscopic examination, there was a diffuse proliferation of tumor cells on the desmoplastic tissue. The tumor cells were large with round nuclei, small distinct nucleoli, forming lobular structures, and accompanied by some small lymphocytes. Mitotic figures were occasionally seen, but not cytotrophoblasts or syncytiotrophoblasts (Fig. 6a, b). Immunostainings for leukocyte common antigen (Fig. 7a), CD3 (Fig. 7b), CD79a (Fig. 7c), latent membrane protein 1 (EBV-LMP), and EBV encoding small RNAs (EBER) were all negative, ruling out PTLD. Alpha-fetoprotein (Fig. 8b) was also negative, whereas human chorionic gonadotropin (Fig. 8a),
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Fig. 3 a Enhanced chest CT in April 2007. b Enhanced chest CT in May 2007. Mediastinal tumor is smaller in natural course
Fig. 4 a Plane chest CT in January 2008. b Enhanced chest CT in February 2008. Mediastinal tumor shows enlargement
CAM5.2 (Fig. 8c), and placental alkaline phosphatase (Fig. 8d) were positive. Serum b-hCG was weakly positive (0.6 ng/ml). Pregnancy-t reaction was also negative. Observation of the testes showed only contraction, indicating a final diagnosis of mediastinal seminoma. Chemotherapy with three courses of BEP (bleomycin, etoposide, cisplatin) was administered. After chemotherapy the tumor shrank from 60 to 36 mm in maximum diameter (Fig. 9). However, the diameter of remnant tumor was adaptive for surgery ([30 mm).Given the risk of malignant invasion associated with surgery, we decided to follow tumor progression in this case on an outpatient basis. The seminoma continued to shrink on chest CT without rescue agent. In November 2010, the patient was hospitalized for pneumonia with pleural effusion in the right lung and hypereosinophilic syndrome. We performed thoracentesis. Pleural effusion was serous, and there was no culture growth or presence of tumor cells. In December 2010, we
123
performed FDG-PET to further investigate the hypereosinophilic syndrome, which we were unable to account for. Significant accumulation of FDG was not detected, so we did not believe active seminoma tumor cells were present. Gradually, the hypereosinophilic syndrome went into remission without treatment. Pleural effusion in the right lung decreased slightly, followed later by a change in organization. No other examinations, including bone marrow and anti-parasitic antibody, showed significant clinical effects. The cause of both episodes was not clear, but no recurrence was observed. The patient underwent a recent chest CT in February 2012, and the shadow of the mass had disappeared. There was only residual connective tissue of approximately 2 mm width, indicating that the seminoma may be in complete remission. The patient is now 23 years old. His mental age is approximately 5–6 years old, the same level as during the first inspection in 2004. He is able to move with a
CEN Case Rep (2012) 1:90–95
wheelchair and eat regular food on his own. He works in a small-scale workplace for mentally handicapped people when his physical condition is good. However, his daily recovery from a respiratory infection has been long and is sometimes accompanied by acute gastritis. He was subsequently hospitalized 12 times for bronchitis or pneumonia due to viral infections. His physical status, which includes narrow lung volume with organized
93
pleural effusion, has deteriorated, which could be lifethreatening if an infection is contracted. His renal function will also be getting worse; thus, the limitation of his therapy needs to be determined. This will depend not on medical limitations, but his physical condition. The health care providers are working together with his family to devise a treatment plan considering his ongoing condition.
Discussion
Fig. 5 Fluorodeoxyglucose (FDG) positron emission tomography scan shows high accumulation of FDG in the upper anterior mediastinum (a transverse, b coronal, c sagittal)
In this case of mediastinal tumor, making the differential diagnosis between PTLD and some other malignancy was difficult. Suspecting various possible underlying diseases, we initially conducted precise examinations of the tumor, using simple and minimally invasive tests. The time elapsed from initial detection of the mediastinal tumor until confirmation of the seminoma diagnosis was nearly 12 months. Considering the regression that occurred as part of the natural course of this tumor, one hypothesis is that the supra-anterior mass was PTLD, while the posterior malignancy was a mediastinal seminoma. Though mediastinal seminomas constitute approximately one-third of malignant mediastinal germ cell tumors, they only account for 2–4 % of mediastinal masses [2]. Two such events in a single patient would be extremely rare, so we think that mediastinal seminoma in this case was the malignancy following organ transplantation while on immunosuppressive therapy. There have been very few case reports of germ cell tumor after organ transplantation and administration of immunosuppressive medications. For example, after renal transplantation, there was a case of mixed germcell ovarian tumor with a choriocarcinoma component [3], a germ-cell tumor, more likely to be seminoma, in the pelvic region [4], and some cases of testicular seminoma
Fig. 6 Light microscopic photographs of tumor cells, from tissue biopsy of mediastinal tumor (H&E staining a 940, b 9400)
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CEN Case Rep (2012) 1:90–95
Fig. 7 Result of immune staining. Leukocyte common antigen (a 940), CD3 (b 940), and CD79a (c 940) are negative, so PTLD is denied
Fig. 8 Result of immune staining. Alpha-fetoprotein is negative (b 9100); human chorionic gonadotropin (a 9100), CAM5.2 (c 9100), and placental alkaline phosphatase (d 9100) are positive
[5–11]. After cardiac transplantation, there was a seminoma in the retroperitoneum [12] and another case of a seminoma of multiple bony metastases [13]. This is the first case report of mediastinal seminoma, a malignancy arising in patients after organ transplantation while on immunosuppressive therapy. This case underscores the importance of considering mediastinal seminoma in differential diagnoses of malignancies arising after
123
organ transplantation. Though the clinical course of this mediastinal seminoma case was relatively favorable, to further improve outcomes of transplant recipients, it will be increasingly important to detect and treat tumors early. We have reported this unique case, with a mediastinal seminoma arising in a patient after renal transplantation while on immunosuppressive medication, as a contribution to the international literature.
CEN Case Rep (2012) 1:90–95
95
Fig. 9 Clinical course of mediastinal seminoma after three course of BEP therapy
When a suppressed other than differential
mediastinal tumor is detected in an immunopatient after organ transplantation, diseases PTLD should be considered in an unbiased diagnosis.
References 1. Penn I. Cancers complicating organ transplantation. N Engl J Med. 1990;323(25):1767–9. 2. Moran CA, Suster S, Przygodzki RM, Koss MN. Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas—a clinicopathologic and immunohistochemical study of 120 cases. Cancer. 1997;80(4):691. 3. Ketata H, Bouacida M, Bouhlel A, Sahnoun A, Bahloul A, Yaich S, et al. A transplant recipient with a mixed germ-cell ovarian tumor. Saudi J Kidney Dis Transpl. 2008;19(6):973–5. 4. Kosmas C, Tsavaris NB, Vadiaka M, Chiras T, Boletis J, Kostakis A. Extragonadal seminoma after renal transplantation and immunosuppression; treatment in the presence of renal dysfunction: a case report and literature review. Med Oncol. 2001;18(3): 221–5. 5. Nellans RE, Ravera J. Seminoma in a renal transplant recipient. J Urol. 1975;113(6):871–3.
6. Dieckmann KP, Du¨e W, Offermann G. Testicular seminoma in an immunosuppressed renal transplant recipient. Br J Urol. 1989; 63(5):549–50. 7. Fisher KS, Birtch AG. Seminoma in renal transplant patient: a patient report and review of the literature. Curr Surg. 1990; 47(3):181–5. 8. Villalona-Calero MA, Ducker T, Holasek M, Najarian J, Kennedy BJ. Management of testicular seminoma following organ transplantation. Med Pediatr Oncol. 1992;20(4):338–40. 9. Viddeleer AC, Lycklama a` Nijeholt GA, Beekhuis-Brussee JA. A late manifestation of testicular seminoma in the bladder in a renal transplant recipient: a case report. J Urol. 148(2 Pt 1):401–2 (1992). 10. Modlin CS, Flechner SM, Penn I. Testicular seminoma originating in an undescended testis in a renal allograft recipient. Urology. 1996;48(1):145–8. 11. Popov Z, Ivanovski O, Kolevski P, Stankov O, Petrovski D, Cakalaroski K, et al. De novo malignancies after renal transplantation—a single-center experience in the Balkans. Transpl Proc. 2007;39(8):2589–91. 12. Hollingsworth JM, Shuster TG, Wolf JS Jr. Seminoma nine years after cardiac transplantation. Transplantation. 2004;77(9):1472. 13. de Bono JS, Fraser JA, Lee F, Simpson A, Lim C, Naik S, et al. Metastatic extragonadal seminoma associated with cardiac transplantation. Ann Oncol. 2000;11(6):749–52.
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