Pediatric Case Report Advanced Childhood Testicular Yolk Sac Tumor With Bone Metastasis: A Case Report Masayuki Nagasawa, Kazuyoshi Johnin, Eiki Hanada, Tetsuya Yoshida, Keisei Okamoto, Yusaku Okada, Tomoko Ueba, Takashi Taga, Shigeru Ohta, and Akihiro Kawauchi We report a case of advanced childhood testicular yolk sac tumor with bone metastasis, which was successfully treated by multimodal treatment. Optimal management of bone metastases from testicular yolk sac tumor in childhood is discussed. UROLOGY 85: 671e673, 2015. 2015 Elsevier Inc.
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esticular tumor in childhood is rare and accounts for 1%-2% of childhood solid tumors with an incidence of 0.5-2.0 per 100,000 children.1 Yolk sac tumor (YST) is the most common testicular cancer in childhood.2 Bone metastasis from the childhood testicular YST is extremely rare, and management of such cases remains unknown.3-5 We report a case of advanced childhood testicular YST with bone metastasis, which has been successfully treated by multimodal treatment. This case highlights optimal management of bone metastasis from testicular YST in childhood.
CASE REPORT A 2-year-old boy presented with a 6-month history of growing scrotal mass. The patient had been diagnosed as having hydrocele testis by a local primary physician. On physical examination, a firm, goose eggesized mass was palpable in the left scrotum. Magnetic resonance imaging (MRI) demonstrated a heterogeneous testicular tumor, 8 cm in diameter, in the left scrotum and presence of ascites in the abdominal cavity (Fig. 1A). The serum level of a-fetoprotein was elevated (1225.4 ng/mL). Serum levels of total human chorionic gonadotropin (hCG) and hCG-b were within normal range. Based on the diagnosis of testicular germ cell tumor, the patient underwent left radical orchiectomy (Fig. 1B). The histologic diagnosis was YST (Fig. 1C). Simultaneous sampling of ascites showed hemorrhagic fluid. Cytologic diagnosis of the fluid was class II. Computed tomography (CT) revealed a bulky retroperitoneal lymphadenopathy and spinal and epidural Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Shiga University of Medical Science; and the Department of Pediatrics, Shiga University of Medical Science, Otsu City, Shiga-ken, Japan Address correspondence to: Kazuyoshi Johnin, M.D., Department of Urology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu City, Shiga-ken 520-2192, Japan. E-mail: [email protected] Submitted: August 12, 2014, accepted (with revisions): November 20, 2014
ª 2015 Elsevier Inc. All Rights Reserved
metastasis (Fig. 2A,B). Metastatic tumors were also identified in the pouch of Douglas and sciatic foramen. Poor prognosis was assigned to the patient using the International Germ Cell Consensus Classification. The stage of the Children’s Oncology Group classification was assigned as IV. Four cycles of cisplatin and etoposide (PE) therapy consisting of cisplatin (20 mg/m2 for 4 days) and etoposide (100 mg/m2 for 3 days) were performed. Bleomycin was not used because of its late pulmonary toxicity. After 4 cycles of PE, the level of serum a-fetoprotein was normalized. Furthermore, the size of both retroperitoneal tumor and lumbar metastasis was reduced (Fig. 3A). The tumors in the pouch of Douglas and sciatic foramen were diminished. The patient underwent retroperitoneal lymphadenectomy (RPLND). Histologic examination of the RPLND specimen showed necrotic tissue with hemorrhage and no sign of viable cancer cells. After performing the CT scans and/or MRIs every 3 or 4 weeks, just before the next chemotherapy, we found the residual spinal and/or epidural mass. We did not biopsy the mass because of the possible biopsy-related complications and false-negative results. We discussed whether active surveillance or additional chemotherapy was better. If the relapse occurred afterward, it would be difficult to treat this patient and would be possibly lethal. Additional high-dose chemotherapy consisting of carboplatin (240 mg/m2 for 4 days), etoposide (160 mg/m2 for 4 days), and melphalan (90 mg/m2 for 2 days) combined with peripheral stem cell transplantation was conducted for the residual lumbar metastasis. After chemotherapy, complete remission of the spinal and epidural metastasis was observed by MRI (Fig. 3B). The patient has been free from disease recurrence for 4 years after completion of the final chemotherapy. Also, the patient has no sign of developmental or gait disorder.
COMMENT In view of histology, YST among childhood shows predominantly pure histologic pattern and is not a mixed-type http://dx.doi.org/10.1016/j.urology.2014.11.019 0090-4295/15
671
Figure 1. Image and histology of primary testicular tumor. (A) Magnetic resonance imaging demonstrates a heterogeneous testicular tumor, 8 cm in diameter, in the left scrotum and presence of ascites in the abdominal cavity. (B) Gross section of the testicular tumor shows solid gray white with a gelatinous, myxoid, or mucoid appearance. (C) Pathologic findings show microcystic pattern and endodermal sinus structure consistent with yolk sac tumor of the testis. (Color version available online.)
Figure 2. Prechemotherapy computed tomography (CT). (A) Abdominal CT scan shows a bulky retroperitoneal lymphadenopathy, 8.5 cm in diameter (asterisk). (B) Lumbar spine CT scan shows spinal and epidural metastasis, 3.6 cm in diameter, at L3-L5 vertebra. Note that spinal compression fracture is seen at L4 (white arrow).
Figure 3. Postchemotherapy computed tomography and magnetic resonance imaging. (A) Abdominal computed tomography scan shows the decreased retroperitoneal lymphadenopathy, 3.6 cm in diameter (asterisk). (B) Lumbar spine magnetic resonance imaging scan shows complete remission of spinal and epidural metastasis at L3-L5 (white arrow).
testicular germ cell tumor with other histologic patterns as is the case in testicular germ cell tumor among adults.2 Therefore, YST in childhood and adults constitutes distinct pathologic entities.2 Hematologic spread is
672
common in childhood YST, and the most common visceral metastatic site is the lung.2 A recent surveillance, epidemiology, and end results data in the United States demonstrated that the 5-year
UROLOGY 85 (3), 2015
relative survival of prepubertal testicular cancer with distant metastasis is 72.6%.6 The data indicate that complete remission in childhood YST with distant metastasis remains challenging although YST in childhood is regarded as chemotherapy-sensitive disease.2,3 In the present case, we needed to conduct RPLND because of residual tumor after 4 cycles of PE therapy although there is a concern for the risk of RPLND complications in childhood testicular cancer.2 So far, there has been no reports on bone metastasis from childhood YST.3-5 Optimal management of bone metastases from testicular YST in childhood remains unknown. After completion of 4 cycles of PE therapy combined with RPLND, we conducted further chemotherapy rather than radiotherapy on the residual bone metastasis because spinal radiotherapy in childhood is significantly associated with neurogenic and developmental disorder such as short stature.7 As far as we know, this is the first report of complete remission in a bone metastatic case of childhood YST. A typical cause of painless scrotal swelling is a benign condition, such as hydrocele testis. A hydrocele is associated with a testicular tumor in 15%-50% of cases, and a thorough examination is needed to determine the presence of other serious pathology.2 We must throw away our assumptions and prejudices to be benign with a history of growing scrotal mass.
UROLOGY 85 (3), 2015
As conclusion, this case has highlighted that bone metastasis from childhood YST potentially can be cured by chemotherapy only although additional cases should be accumulated. References 1. Coppes MJ, Rackley R, Kay R. Primary testicular and paratesticular tumors of childhood. Med Pediatr Oncol. 1994;22:329-340. 2. Ahmed HU, Arya M, Muneer A, et al. Testicular and paratesticular tumours in the prepubertal population. Lancet Oncol. 2010;11:476-483. 3. Mann JR, Raafat F, Robinson K, et al. The United Kingdom Children’s Cancer Study Group’s second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol. 2000;18:3809-3818. 4. Rogers PC, Olson TA, Cullen JW, et al. Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup StudyePediatric Oncology Group 9048 and Children’s Cancer Group 8891. J Clin Oncol. 2004;22:3563-3569. 5. Schlatter M, Rescorla F, Giller R, et al. Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children’s Cancer Group/Pediatric Oncology Group. J Pediatr Surg. 2003;38:319-324; discussion 319-324. 6. Alanee S, Shukla A. Paediatric testicular cancer: an updated review of incidence and conditional survival from the Surveillance, Epidemiology and End Results database. BJU Int. 2009;104:1280-1283. 7. Ishida Y, Sakamoto N, Kamibeppu K, et al. Late effects and quality of life of childhood cancer survivors: part 2. Impact of radiotherapy. Int J Hematol. 2010;92:95-104.
673
T
esticular tumor in childhood is rare and accounts for 1%-2% of childhood solid tumors with an incidence of 0.5-2.0 per 100,000 children.1 Yolk sac tumor (YST) is the most common testicular cancer in childhood.2 Bone metastasis from the childhood testicular YST is extremely rare, and management of such cases remains unknown.3-5 We report a case of advanced childhood testicular YST with bone metastasis, which has been successfully treated by multimodal treatment. This case highlights optimal management of bone metastasis from testicular YST in childhood.
CASE REPORT A 2-year-old boy presented with a 6-month history of growing scrotal mass. The patient had been diagnosed as having hydrocele testis by a local primary physician. On physical examination, a firm, goose eggesized mass was palpable in the left scrotum. Magnetic resonance imaging (MRI) demonstrated a heterogeneous testicular tumor, 8 cm in diameter, in the left scrotum and presence of ascites in the abdominal cavity (Fig. 1A). The serum level of a-fetoprotein was elevated (1225.4 ng/mL). Serum levels of total human chorionic gonadotropin (hCG) and hCG-b were within normal range. Based on the diagnosis of testicular germ cell tumor, the patient underwent left radical orchiectomy (Fig. 1B). The histologic diagnosis was YST (Fig. 1C). Simultaneous sampling of ascites showed hemorrhagic fluid. Cytologic diagnosis of the fluid was class II. Computed tomography (CT) revealed a bulky retroperitoneal lymphadenopathy and spinal and epidural Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Shiga University of Medical Science; and the Department of Pediatrics, Shiga University of Medical Science, Otsu City, Shiga-ken, Japan Address correspondence to: Kazuyoshi Johnin, M.D., Department of Urology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu City, Shiga-ken 520-2192, Japan. E-mail: [email protected] Submitted: August 12, 2014, accepted (with revisions): November 20, 2014
ª 2015 Elsevier Inc. All Rights Reserved
metastasis (Fig. 2A,B). Metastatic tumors were also identified in the pouch of Douglas and sciatic foramen. Poor prognosis was assigned to the patient using the International Germ Cell Consensus Classification. The stage of the Children’s Oncology Group classification was assigned as IV. Four cycles of cisplatin and etoposide (PE) therapy consisting of cisplatin (20 mg/m2 for 4 days) and etoposide (100 mg/m2 for 3 days) were performed. Bleomycin was not used because of its late pulmonary toxicity. After 4 cycles of PE, the level of serum a-fetoprotein was normalized. Furthermore, the size of both retroperitoneal tumor and lumbar metastasis was reduced (Fig. 3A). The tumors in the pouch of Douglas and sciatic foramen were diminished. The patient underwent retroperitoneal lymphadenectomy (RPLND). Histologic examination of the RPLND specimen showed necrotic tissue with hemorrhage and no sign of viable cancer cells. After performing the CT scans and/or MRIs every 3 or 4 weeks, just before the next chemotherapy, we found the residual spinal and/or epidural mass. We did not biopsy the mass because of the possible biopsy-related complications and false-negative results. We discussed whether active surveillance or additional chemotherapy was better. If the relapse occurred afterward, it would be difficult to treat this patient and would be possibly lethal. Additional high-dose chemotherapy consisting of carboplatin (240 mg/m2 for 4 days), etoposide (160 mg/m2 for 4 days), and melphalan (90 mg/m2 for 2 days) combined with peripheral stem cell transplantation was conducted for the residual lumbar metastasis. After chemotherapy, complete remission of the spinal and epidural metastasis was observed by MRI (Fig. 3B). The patient has been free from disease recurrence for 4 years after completion of the final chemotherapy. Also, the patient has no sign of developmental or gait disorder.
COMMENT In view of histology, YST among childhood shows predominantly pure histologic pattern and is not a mixed-type http://dx.doi.org/10.1016/j.urology.2014.11.019 0090-4295/15
671
Figure 1. Image and histology of primary testicular tumor. (A) Magnetic resonance imaging demonstrates a heterogeneous testicular tumor, 8 cm in diameter, in the left scrotum and presence of ascites in the abdominal cavity. (B) Gross section of the testicular tumor shows solid gray white with a gelatinous, myxoid, or mucoid appearance. (C) Pathologic findings show microcystic pattern and endodermal sinus structure consistent with yolk sac tumor of the testis. (Color version available online.)
Figure 2. Prechemotherapy computed tomography (CT). (A) Abdominal CT scan shows a bulky retroperitoneal lymphadenopathy, 8.5 cm in diameter (asterisk). (B) Lumbar spine CT scan shows spinal and epidural metastasis, 3.6 cm in diameter, at L3-L5 vertebra. Note that spinal compression fracture is seen at L4 (white arrow).
Figure 3. Postchemotherapy computed tomography and magnetic resonance imaging. (A) Abdominal computed tomography scan shows the decreased retroperitoneal lymphadenopathy, 3.6 cm in diameter (asterisk). (B) Lumbar spine magnetic resonance imaging scan shows complete remission of spinal and epidural metastasis at L3-L5 (white arrow).
testicular germ cell tumor with other histologic patterns as is the case in testicular germ cell tumor among adults.2 Therefore, YST in childhood and adults constitutes distinct pathologic entities.2 Hematologic spread is
672
common in childhood YST, and the most common visceral metastatic site is the lung.2 A recent surveillance, epidemiology, and end results data in the United States demonstrated that the 5-year
UROLOGY 85 (3), 2015
relative survival of prepubertal testicular cancer with distant metastasis is 72.6%.6 The data indicate that complete remission in childhood YST with distant metastasis remains challenging although YST in childhood is regarded as chemotherapy-sensitive disease.2,3 In the present case, we needed to conduct RPLND because of residual tumor after 4 cycles of PE therapy although there is a concern for the risk of RPLND complications in childhood testicular cancer.2 So far, there has been no reports on bone metastasis from childhood YST.3-5 Optimal management of bone metastases from testicular YST in childhood remains unknown. After completion of 4 cycles of PE therapy combined with RPLND, we conducted further chemotherapy rather than radiotherapy on the residual bone metastasis because spinal radiotherapy in childhood is significantly associated with neurogenic and developmental disorder such as short stature.7 As far as we know, this is the first report of complete remission in a bone metastatic case of childhood YST. A typical cause of painless scrotal swelling is a benign condition, such as hydrocele testis. A hydrocele is associated with a testicular tumor in 15%-50% of cases, and a thorough examination is needed to determine the presence of other serious pathology.2 We must throw away our assumptions and prejudices to be benign with a history of growing scrotal mass.
UROLOGY 85 (3), 2015
As conclusion, this case has highlighted that bone metastasis from childhood YST potentially can be cured by chemotherapy only although additional cases should be accumulated. References 1. Coppes MJ, Rackley R, Kay R. Primary testicular and paratesticular tumors of childhood. Med Pediatr Oncol. 1994;22:329-340. 2. Ahmed HU, Arya M, Muneer A, et al. Testicular and paratesticular tumours in the prepubertal population. Lancet Oncol. 2010;11:476-483. 3. Mann JR, Raafat F, Robinson K, et al. The United Kingdom Children’s Cancer Study Group’s second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol. 2000;18:3809-3818. 4. Rogers PC, Olson TA, Cullen JW, et al. Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup StudyePediatric Oncology Group 9048 and Children’s Cancer Group 8891. J Clin Oncol. 2004;22:3563-3569. 5. Schlatter M, Rescorla F, Giller R, et al. Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children’s Cancer Group/Pediatric Oncology Group. J Pediatr Surg. 2003;38:319-324; discussion 319-324. 6. Alanee S, Shukla A. Paediatric testicular cancer: an updated review of incidence and conditional survival from the Surveillance, Epidemiology and End Results database. BJU Int. 2009;104:1280-1283. 7. Ishida Y, Sakamoto N, Kamibeppu K, et al. Late effects and quality of life of childhood cancer survivors: part 2. Impact of radiotherapy. Int J Hematol. 2010;92:95-104.
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