Campbell-Walsh Urology, 11th Edition

PART XV

Pediatric Urology

SECTION G

Oncology

156

Pediatric Urologic Oncology

Bladder and Testis

Fernando Ferrer

Questions

1. A 3-year-old girl has vaginal rhabdomyosarcoma. Her mother has a history of breast cancer. This patient most likely has:
2. Beckwith-Wiedemann syndrome (BWS).
3. Li-Fraumeni syndrome.
4. Perlman syndrome.
5. fragile X syndrome.
6. Sotos syndrome.
7. A 3-year-old boy has rhabdomyosarcoma of the prostate. An unfavorable prognostic feature of this tumor is:
8. alveolar histologic type.
9. embryonal histology.
10. loss of heterozygosity (LOH) for chromosome 11p15.
11. botryoid pattern.
12. spindle cell variant.
13. A 1-year-old girl previously had a partial cystectomy for rhabdomyosarcoma of the bladder. After completion of vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy, biopsy of the bladder reveals rhabdomyoblasts. Abdominal and chest computed tomography (CT) are negative. The next step is:
14. radiation therapy.
15. continue chemotherapy.
16. cystectomy with diversion.
17. observation.
18. a change in chemotherapy regimen.
19. A 4-year-old boy has paratesticular rhabdomyosarcoma noted on biopsy of the spermatic cord lesion. The next step is radical orchiectomy and:
20. vincristine, dactinomycin, and cyclophosphamide.
21. retroperitoneal lymph node dissection.
22. retroperitoneal lymph node sampling.
23. radiation therapy to the retroperitoneum.
24. cisplatin, etoposide, and vincristine.
25. A 2-year-old boy undergoes left orchiectomy. Pathology reveals a yolk sac tumor confined to the testis. CT findings of the chest and abdomen are negative. No preoperative tumor markers were obtained. At 4 weeks after surgery, tumor markers are negative. The next step is:
26. lymph node dissection.
27. observation.
28. chemotherapy.
29. staining of the tumor for α-fetoprotein.
30. retroperitoneal lymph node sampling.
31. A 6-year-old, phenotypic boy with hypospadias and bilateral cryptorchidism has a 3-cm lower abdominal mass. His karyotype is XO/XY. At abdominal exploration, a tumor is found in the right gonad. Right orchiectomy is performed. Frozen section reveals gonadoblastoma. The best next step is:
32. left orchiopexy.
33. retroperitoneal lymphadenectomy node sampling.
34. left orchiectomy.
35. chemotherapy.
36. observation.
37. A 2-year-old boy has a left upper pole testicular mass that is cystic on ultrasonography. Excision of the lesion is performed by an inguinal approach leaving the lower half of the testis. Frozen section demonstrates clear margins. Final pathology reveals teratoma, and the margins are negative for tumor. Serum α-fetoprotein and β-human chorionic gonadotropin (hCG) are negative. Chest and abdominal CT are negative. The next step is:
38. radical orchiectomy and modified retroperitoneal lymph node dissection.
39. observation.
40. radical orchiectomy and combination chemotherapy.
41. radical orchiectomy.
42. radical orchiectomy and abdominal irradiation.
43. A 3-month-old boy undergoes removal of a solid yolk sac tumor. The margins of resection are negative for tumor. Chest and abdominal CT results show no signs of metastatic disease. Two weeks postoperatively, the serum α-fetoprotein value is 35 ng/dL. The next step is:
44. chemotherapy.
45. retroperitoneal lymph node dissection.
46. observation.
47. retroperitoneal lymph node sampling.
48. abdominal irradiation.
49. A 10-year-old boy presents with one episode of gross hematuria. Ultrasound of the bladder demonstrates a small (less than 1-cm) lesion at the bladder base, and cystoscopy reveals a small papillary lesion that is completely resected. Pathology reveals superficial low grade transitional cell carcinoma (TCC). Appropriate next steps include:
50. a course of bacille Calmette-Guérin (BCG) therapy in an attempt to prevent recurrence.
51. routine cystoscopic surveillance for 5 years.
52. no further treatment and surveillance consisting of bladder sonography.
53. mitomycin C bladder instillations.
54. staging abdominal-pelvic CT scan and lung radiograph.
55. A 5-year-old male who presents with hematuria is discovered to have a 5-cm mass, which is biopsied and found to be consistent with embryonal rhabdomyosarcoma (RMS). The patient undergoes therapy according to Cooperative Oncology Group intermediate risk protocols (chemotherapy and radiation). At the completion of treatment, the child has a residual 0.5-cm mass, which is biopsied and confirmed to consist of mature rhabdomyoblasts. Future treatment should consist of:
56. cystoprostatectomy with assessment of margins to determine future treatment.
57. salvage chemotherapy.
58. observation only.
59. cystoprostatectomy followed by adjuvant chemotherapy.
60. implantation of radiotherapy beads.
61. An 11-year-old male presents with a right paratesticular mass. A inguinal orchiectomy is performed. The pathologic diagnosis is RMS completely excised (clinical group 1). A consulting physician orders a CT scan of the retroperitoneum, which is negative. The next step should be:
62. observation only.
63. right staging ipsilateral retroperitoneal lymph node dissection (RPLND).
64. right staging ipsilateral RPLND plus inguinal lymph node dissection.
65. right inguinal lymph node dissection.
66. chemotherapy.
67. A 4-month-old male is noted to have a right testicular mass. Ultrasound reveals a well-circumscribed, heterogenous, cystic mass with calcifications. Serum hCG is within normal limits. The serum α-fetoprotein is elevated at 90 ng/mL. The most likely appropriate treatment is:
68. radical inguinal orchiectomy.
69. transscrotal exploration and biopsy.
70. inguinal exploration, cord control, biopsy, and partial orchiectomy.
71. transscrotal partial orchiectomy.
72. staging CT scan.
73. A 5-year-old male presents with difficulty voiding and gross hematuria as well as right flank discomfort. Ultrasound demonstrates a 5-cm mass at the level of the trigone with moderate-to-severe right-sided hydronephrosis. A pelvic CT scan confirms these findings and does not suggest the presence of pelvic adenopathy. The next appropriate steps would be:
74. open resection and right ureteral reimplantation.
75. endoscopic biopsy followed by right internal stent placement if possible.
76. attempt a complete endoscopic resection.
77. percutaneous nephrostomy tube placement followed by open biopsy.
78. transrectal sonography-guided needle biopsy.

Pathology

1. A 4-year-old boy presents with urinary retention. He has had constipation and progressively increased stranguria of 2 months’ duration. Cystoscopy reveals a polypoid mass arising from the prostate extending into the bladder. The biopsy is depicted in Figure 156-1A,B, and C, which is reported as rhabdomyosarcoma. Note the intensely eosinophilic-stained cytoplasm of the rhabdomyoblasts (Fig. 156-1B). Before treatment is begun, the pathologist should be queried as to:

FIGURE 156-1 From Bostwick DG, Cheng L. Urologic surgical pathology. 3rd ed. Edinburgh: Mosby; 2014.

1. the depth of invasion.
2. the histologic type.
3. the degree of differentiation.
4. the dominant pattern.
5. the percent of rhabdomyoblasts in the tumor.

Answers

1. b. Li-Fraumeni syndrome.Subgroups of children with a genetic predisposition to the development of rhabdomyosarcoma have been identified. The Li-Fraumeni syndrome associates childhood sarcomas with mothers who have an excess of premenopausal breast cancer and with siblings who have an increased risk of cancer. A mutation of the TP53 tumor suppressor gene was found in the tumors in all patients with this syndrome.
2. a. Alveolar histologic type.The second most common form is alveolar, which occurs more commonly in the trunk and extremities than in genitourinary sites and has a worse prognosis. Alveolar rhabdomyosarcoma also has a higher rate of local recurrence and spread to regional lymph nodes, bone marrow, and distant sites.
3. d. Observation.If tumor is shrinking during chemotherapy, and another biopsy after completing radiotherapy shows maturing rhabdomyoblasts without frank tumor cells, total cystectomy can be postponed or avoided altogether.
4. a. Vincristine, dactinomycin, and cyclophosphamide.Before effective chemotherapy, surgery alone produced a 50% 2-year relapse-free survival rate. With current multimodal treatment, survival rates of 90% are expected. Currently, the Intergroup Rhabdomyosarcoma Study Group recommends that children 10 years and older undergo ipsilateral retroperitoneal lymph node dissection before chemotherapy.
5. b. Observation.It is important to note that an elevated α-fetoprotein level after orchiectomy for yolk sac tumor in an infant does not always represent persistent disease. Normal adult reference laboratory values for α-fetoprotein cannot be used in young children, because α-fetoprotein synthesis continues after birth. Normal adult levels (less than 10 mg/mL) are not reached until 8 months of age.
6. c. Left orchiectomy.Early gonadectomy is advocated, because tumors have been reported in children younger than 5 years. In patients with mixed gonadal dysgenesis who are reared as males, all streak gonads and undescended testes should be removed. Scrotal testes can be preserved, because they are less prone to tumor development.
7. b. Observation.Prepubertal mature teratomas have a benign clinical course, which contrasts with the clinical behavior of teratomas in adults, which have the propensity to metastasize. This benign behavior has led to the consideration of testicular-sparing procedures rather than radical orchiectomy.
8. c. Observation.The initial treatment for yolk sac tumor is radical inguinal orchiectomy. This treatment is curative in most children. Routine retroperitoneal lymph node dissection and adjuvant chemotherapy are not indicated.
9. c. No further treatment and surveillance consisting of bladder sonography. TCC in children is uncommon and the lesions are unifocal, typically low grade and not prone to recurrence; therefore treatment consisting of resection only is adequate. Ultrasound is remarkably accurate and is an adequate surveillance strategy.
10. c. Observation only. Mature rhabdomyoblasts found after treatment for RMS do not require further treatment if confirmed by an experienced pathologist. Furthermore, prior studies have demonstrated that some residual mass does not necessarily mean active residual disease exists. In the case presented, further aggressive therapy is not warranted, but serial radiographic evaluation is indicated
11. b. Right staging ipsilateral retroperitoneal lymph node dissection (RPLND).Prior studies have shown that children older than age 10 should always undergo siRPLND and not observation because of a high occurrence of retroperitoneal failure. Paratesticular RMS rarely involves the inguinal nodes
12. e. Inguinal exploration, cord control, biopsy, and partial orchiectomy.Teratomas are common benign prepubertal tumors that can be treated by partial orchiectomy. Although not always accurate, the ultrasound features of this tumor are suggestive of teratoma. α-Fetoprotein levels do not reach normal adult levels until close to 1 year of life; therefore this elevation is not necessarily reflective of a yolk sac tumor. In fact, yolk sac tumors typically have α-fetoprotein elevations higher than 100 ng/mL. The likelihood of a benign etiology warrants attempt at partial orchiectomy
13. b. Endoscopic biopsy followed by right internal stent placement if possible.This presentation is concerning for bladder RMS. In this case organ preservation strategies should be pursued, and endoscopic biopsy is the correct answer. Chemotherapy for RMS can be deleterious to renal function, so stenting to prevent any renal deterioration during treatment should be performed. Internal stent placement is typically more confortable than percutaneous nephrostomy.

Pathology

1. b. The histologic type.Rhabdomyosarcomas have three histologic types: embryonal, alveolar, and undifferentiated. The most common type in the genitourinary tract is embryonal and has a better prognosis than the other two. Therapy is determined by stratification as to risk, and histology is one of the parameters used to stratify patients.

Chapter review

1. Of rhabdomyosarcomas, 15% to 20% occur in the genitourinary system. RMS is the most common soft tissue sarcoma in children.
2. Rhabdomyosarcoma has three histologic types: embryonal, alveolar, and undifferentiated.
3. In the genitourinary tract, embryonal histology is by far the most common.
4. Alveolar rhabdomyosarcoma has a higher rate of local recurrence and spread to regional lymph nodes, bone marrow, and distant sites when compared to embryonal.
5. There are two variants of embryonal histology: botryoid (bunch of grapes), which occur in the bladder, and spindle cell, which are common in the paratesticular region.
6. For patients with rhabdomyosarcoma, generally, chemotherapy and radiation precede surgical resection unless the tumor is amenable to a partial cystectomy. Organ preservation is the goal of treatment.
7. Mature rhabdomyoblasts found after treatment do not require further treatment.
8. Radiation therapy for patients with bladder or prostate rhabdomyosarcoma results in a markedly reduced functional bladder capacity and abnormal voiding patterns. Only 40% of patients treated will have normal bladder function—usually these are patients who have not received radiation therapy.
9. Patients with rhabdomyosarcoma of the bladder or prostate typically present with symptoms of outlet obstruction and hematuria. A urethral catheter for the lower tract and an internal stent for the upper tracts are the preferred methods of decompression.
10. In paratesticular rhabdomyosarcoma, children who are 10 years and older should have an ipsilateral retroperitoneal lymph node dissection. Those less than 10 years of age do not require an RPLND.
11. Favorable sites of origin for rhabdomyosarcoma include paratesticular, vulvar-vaginal, and uterine. In the female, the vagina is the most common site. Bladder and prostate are unfavorable sites.
12. Only one third of patients are fertile following treatment for rhabdomyosarcoma.
13. Treated patients are at risk for secondary malignancies, which include osteosarcoma, Ewing sarcoma, lymphoma, cancer of the colon, and cervical cancer.
14. The Li-Fraumeni syndrome associates childhood sarcomas with mothers who have an excess of premenopausal breast cancer and with siblings who have an increased risk of cancer. A mutation of the TP53tumor suppressor gene is found in the tumors of these patients.
15. TCC of the bladder in children is uncommon and the lesions are unifocal, often located on the trigone, typically low grade, and not prone to recurrence; therefore, treatment consisting of resection only is adequate. Ultrasound is remarkably accurate and is an adequate surveillance strategy. Cyclophosphamide and dantrolene exposure in selected cases may be etiologic.
16. Patients with a history of smoking, those with end-stage renal disease, and those with transplants who are immunosuppressed and have bladder intestinal augments are at greatest risk for cancer in the augment.
17. Patients with bladder exstrophy are at increased risk for adenocarcinoma of the bladder. Squamous cell carcinoma has also been reported in these patients.
18. Nephrogenic adenoma is a benign lesion usually associated with bladder injury.
19. Ovarian germ cell tumors in children include teratoma, gonadoblastoma, and yolk sac tumor. Sex cord tumors include thecofibroma, Sertoli cell tumors, Leydig cell tumors, and granulosa cell tumors.
20. Teratoma and yolk sac tumors are the most common childhood testicular tumors.
21. Schiller-Duval bodies are a characteristic finding in yolk sac tumors of the testis.
22. Teratomas are classified as mature, immature, and malignant.
23. Mature teratomas have a benign course in childhood and are successfully treated with radical orchiectomy alone. This is not true in the adult.
24. Immature teratomas generally behave in a benign fashion in childhood unless they have foci of yolk sac tumor. If the latter is the case, they should be treated as one would treat a yolk sac tumor.
25. All streak gonads in patients with gonadal dysgenesis should be removed. In patients with mixed gonadal dysgenesis who are reared as males, all streak gonads and undescended testes should be removed. Scrotal testes can be preserved, because they are less prone to tumor development.
26. α-Fetoprotein is secreted by yolk sac tumors.
27. Normal adult reference laboratory values for α-fetoprotein cannot be used in young children, because α-fetoprotein synthesis continues after birth. Normal adult levels (less than 10 mg/mL) are not reached until 8 months.
28. Reinke crystals are diagnostic of Leydig cell tumors.
29. The most common metastatic tumors to the testis in children are leukemia and lymphoma.
30. Testicular microlithiasis in children does not require periodic imaging follow-up unless it is associated with a risk factor such as a previous testicular tumor.
31. Testis organ-sparing surgery is preferred for most testicular tumors in children as they are often benign. Yolk sac tumor is not benign, and testis-sparing surgery is not advised.