Carcinoma of the Bladder
Testicular Cancer (Non–Germ Cell)
Ovarian Cancer (Non–Germ Cell)
Carcinoma of the Cervix and Vagina

Genital/urinary tumors include carcinoma of the bladder, non–germ cell testicular cancer, non–germ cell ovarian cancer, and carcinoma of the cervix and vagina. The prognosis, diagnosis, classification, and treatment of these genital/urinary tumors are discussed below. It must be emphasized that these tumors are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Carcinoma of the bladder is extremely rare in children. The most common carcinoma to involve the bladder is transitional cell carcinoma, which generally presents with hematuria.[1] In contrast to adults, most pediatric bladder carcinomas are low grade, superficial, and have a good prognosis following transurethral resection.[1-3] Squamous cell and more aggressive carcinomas, however, have been reported.[4,5] Bladder cancer in adolescents may develop as a consequence of alkylating-agent chemotherapy given for other childhood tumors or leukemia.[6,7] The association between cyclophosphamide and bladder cancer is the only established relationship between a specific anticancer drug and a solid tumor.[6] One of the most important risk factors for bladder cancer in adults is cigarette smoking, which may be associated with as many as 50% of these cancers in men and 33% in women.[7] (Refer to the PDQ summary on adult Bladder Cancer Treatment ¹ for more information.)

Testicular tumors are very rare in young boys and account for an incidence of 1% to 2% of all childhood tumors.[8][Level of evidence: 3iii] The most common testicular tumors are benign teratomas followed by malignant non-seminomatous germ cell tumors. (Refer to the PDQ summary on Childhood Extracranial Germ Cell Tumors ² for more information.) Non–germ cell tumors such as stromal tumors are exceedingly rare in prepubertal boys. In a small series, gonadal stromal tumors accounted for 8% to 13% of pediatric testicular tumors.[9,10][Level of evidence: 3iiiA] In newborns and infants, juvenile granulosa cell tumors (JGCT) are the most common stromal cell tumor.[11] In older males, Leydig cell tumors are more common. Stromal cell tumors have been described as benign in young boys.[12][Level of evidence: 3iii][13][Level of evidence: 3iiiA] There are conflicting data about malignant potential in older males. Most case reports suggest that in the pediatric patient, these tumors can be treated with surgery alone. However, given the rarity of this tumor, the surgical approach in pediatrics has not been well studied.[12][Level of evidence: 3iii][14][Level of evidence: 3iiiA]

The majority of ovarian masses in children are not malignant. The most common neoplasms are germ cell tumors, followed by epithelial tumors, stromal tumors, and then miscellaneous tumors such as Burkitt lymphoma.[15,16] Ovarian tumors derived from malignant epithelial elements include: adenocarcinomas,[17] cystadenocarcinomas, endometrioid tumors, clear cell tumors, and undifferentiated carcinomas. Treatment is stage-related and may include surgery, radiation, and chemotherapy with cisplatin, carboplatin, etoposide, topotecan, paclitaxel, and other agents. In one series of 19 patients younger than 21 years with epithelial ovarian neoplasms, the average age at diagnosis was 19.7 years. Dysmenorrhea and abdominal pain were the most common presenting symptoms; 79% of the patients had stage I disease with a 100% survival rate, and only those who had small cell anaplastic carcinoma died. Girls with ovarian carcinoma (epithelial ovarian neoplasia) fare better than adults with similar histology, probably because girls usually present with low-stage disease.[18] (Refer to the PDQ summaries on Childhood Extracranial Germ Cell Tumors ², adult Ovarian Epithelial Cancer Treatment ³, and adult Ovarian Low Malignant Potential Tumor Cancer Treatment ⁴ for more information.)

Ovarian sex cord-stromal tumors are a heterogeneous group of rare tumors that derive from the gonadal nongerm cell component.[19] Histologic subtypes display some areas of gonadal differentiation and include JGCT, Sertoli-Leydig cell tumors, and sclerosing stromal tumors. The most common type in girls younger than 18 years is JGCT (median age, 7.6 years; range, 6 months to 17.5 years in one study).[20] JGCT represent about 5% of ovarian tumors in children and adolescents and are distinct from the granulosa cell tumors seen in adults.[19,21-23] Most patients with JGCT present with precocious puberty.[24] Other presenting symptoms include abdominal pain, abdominal mass, and ascites. JGCT has been reported in children with Ollier disease and Maffucci syndrome.[25] As many as 90% of children will have low-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I) and are usually curable with unilateral salpingo-oophorectomy alone. Patients with advanced disease (FIGO stage II–IV) and those with high mitotic activity tumors have a poorer prognosis. Use of a cisplatin-based chemotherapy regimen has been reported in both the adjuvant and recurrent disease settings with some success.[20,23,26-28] Sertoli-Leydig cell tumors are rare in young girls but may present with virilization [29] or precocious puberty.[30][Level of evidence: 3iiB] These tumors may also be associated with Peutz-Jegher syndrome.[31][Level of evidence: 3iii] Small cell carcinomas of the ovary are exceedingly rare and aggressive tumors and may be associated with hypercalcemia.[32][Level of evidence: 3iiB] Successful treatment with aggressive therapy has been reported in a few cases.[32][Level of evidence: 3iiB][33][Level of evidence: 3iiiA][34][Level of evidence: 3iiiA]

Adenocarcinoma of the cervix and vagina is rare in childhood and adolescence with fewer than 50 reported cases.[35] Two-thirds of the cases are related to the exposure of diethylstilbestrol in utero. The median age at presentation is 15 years, with a range of 7 months to 18 years, and with most patients presenting with vaginal bleeding. Adults with adenocarcinoma of the cervix or vagina will present with stage I or stage II disease 90% of the time. In children and adolescents, there is a high incidence of stage III and stage IV disease (24%). This difference may be explained by the practice of routine pelvic examinations in adults and the hesitancy to perform pelvic exams in children. The treatment of choice is surgical resection [36] followed by radiation therapy for residual microscopic disease or lymphatic metastases. The role of chemotherapy in management is unknown, though drugs commonly used in the treatment of gynecologic malignancy, carboplatin and paclitaxel, have been used. The 3-year event-free survival (EFS) for all stages is 71% ± 11%; for stage I and stage II EFS is 82% ± 11%, and for stage III and stage IV EFS is 57% ± 22%.[35]

References

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2. Serrano-Durbá A, Domínguez-Hinarejos C, Reig-Ruiz C, et al.: Transitional cell carcinoma of the bladder in children. Scand J Urol Nephrol 33 (1): 73-6, 1999.  [PUBMED Abstract]
   
   
3. Fine SW, Humphrey PA, Dehner LP, et al.: Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification. J Urol 174 (5): 1976-80, 2005.  [PUBMED Abstract]
   
   
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5. Lezama-del Valle P, Jerkins GR, Rao BN, et al.: Aggressive bladder carcinoma in a child. Pediatr Blood Cancer 43 (3): 285-8, 2004.  [PUBMED Abstract]
   
   
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9. Pohl HG, Shukla AR, Metcalf PD, et al.: Prepubertal testis tumors: actual prevalence rate of histological types. J Urol 172 (6 Pt 1): 2370-2, 2004.  [PUBMED Abstract]
   
   
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19. Schneider DT, Jänig U, Calaminus G, et al.: Ovarian sex cord-stromal tumors--a clinicopathological study of 72 cases from the Kiel Pediatric Tumor Registry. Virchows Arch 443 (4): 549-60, 2003.  [PUBMED Abstract]
    
    
20. Calaminus G, Wessalowski R, Harms D, et al.: Juvenile granulosa cell tumors of the ovary in children and adolescents: results from 33 patients registered in a prospective cooperative study. Gynecol Oncol 65 (3): 447-52, 1997.  [PUBMED Abstract]
    
    
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24. Kalfa N, Patte C, Orbach D, et al.: A nationwide study of granulosa cell tumors in pre- and postpubertal girls: missed diagnosis of endocrine manifestations worsens prognosis. J Pediatr Endocrinol Metab 18 (1): 25-31, 2005.  [PUBMED Abstract]
    
    
25. Gell JS, Stannard MW, Ramnani DM, et al.: Juvenile granulosa cell tumor in a 13-year-old girl with enchondromatosis (Ollier's disease): a case report. J Pediatr Adolesc Gynecol 11 (3): 147-50, 1998.  [PUBMED Abstract]
    
    
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27. Schneider DT, Calaminus G, Wessalowski R, et al.: Therapy of advanced ovarian juvenile granulosa cell tumors. Klin Padiatr 214 (4): 173-8, 2002 Jul-Aug.  [PUBMED Abstract]
    
    
28. Schneider DT, Calaminus G, Harms D, et al.: Ovarian sex cord-stromal tumors in children and adolescents. J Reprod Med 50 (6): 439-46, 2005.  [PUBMED Abstract]
    
    
29. Arhan E, Cetinkaya E, Aycan Z, et al.: A very rare cause of virilization in childhood: ovarian Leydig cell tumor. J Pediatr Endocrinol Metab 21 (2): 181-3, 2008.  [PUBMED Abstract]
    
    
30. Choong CS, Fuller PJ, Chu S, et al.: Sertoli-Leydig cell tumor of the ovary, a rare cause of precocious puberty in a 12-month-old infant. J Clin Endocrinol Metab 87 (1): 49-56, 2002.  [PUBMED Abstract]
    
    
31. Zung A, Shoham Z, Open M, et al.: Sertoli cell tumor causing precocious puberty in a girl with Peutz-Jeghers syndrome. Gynecol Oncol 70 (3): 421-4, 1998.  [PUBMED Abstract]
    
    
32. Distelmaier F, Calaminus G, Harms D, et al.: Ovarian small cell carcinoma of the hypercalcemic type in children and adolescents: a prognostically unfavorable but curable disease. Cancer 107 (9): 2298-306, 2006.  [PUBMED Abstract]
    
    
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36. Abu-Rustum NR, Su W, Levine DA, et al.: Pediatric radical abdominal trachelectomy for cervical clear cell carcinoma: a novel surgical approach. Gynecol Oncol 97 (1): 296-300, 2005.  [PUBMED Abstract]
    
    

Glossary Terms

Consecutive case series (not population-based) with cause-specific mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.

Nonconsecutive case series. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.

Nonconsecutive case series with total mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.