Questions About Cancer? 1-800-4-CANCER

Unusual Cancers of Childhood Treatment (PDQ®)

Health Professional Version
Last Modified: 04/03/2014

Genital/Urinary Tumors

Carcinoma of the Bladder
        Incidence, risk factors, and clinical presentation
        Prognosis and treatment
Testicular Cancer (Non-Germ Cell)
        Incidence
        Treatment
Ovarian Cancer (Non–Germ Cell)
        Epithelial ovarian neoplasia
        Sex cord–stromal tumors
        Small cell carcinoma of the ovary
Carcinoma of the Cervix and Vagina
        Incidence, risk factors, and clinical presentation
        Treatment

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

Incidence, risk factors, and clinical presentation

Carcinoma of the bladder is extremely rare in children. The most common childhood carcinoma to involve the bladder is papillary urothelial neoplasm of low malignant potential, which generally presents with hematuria.[1-3] High-grade, invasive, urothelial carcinomas are extremely rare in young patients.[3]

Bladder cancer in adolescents may develop as a consequence of alkylating-agent chemotherapy given for other childhood tumors or leukemia.[4,5] The association between cyclophosphamide and bladder cancer is the only established relationship between a specific anticancer drug and a solid tumor.[4]

Prognosis and treatment

In contrast to adults, most pediatric bladder carcinomas are low grade, superficial, and have a good prognosis following transurethral resection.[2,3,6-9] Squamous cell carcinoma and more aggressive carcinomas, however, have been reported and may require a more aggressive surgical approach.[3,10-12]

(Refer to the PDQ summary on adult Bladder Cancer Treatment for more information.)

Testicular Cancer (Non-Germ Cell)

Incidence

Testicular tumors are very rare in young boys and account for an incidence of 1% to 2% of all childhood tumors.[13,14] The most common testicular tumors are benign teratomas followed by malignant nonseminomatous germ cell tumors. (Refer to the PDQ summary on Childhood Extracranial Germ Cell Tumors for more information.) Non–germ cell tumors such as sex cord–stromal tumors are exceedingly rare in prepubertal boys. In a small series, gonadal stromal tumors accounted for 8% to 13% of pediatric testicular tumors.[15,16] In newborns and infants, juvenile granulosa cell and Sertoli cell tumors are the most common stromal cell tumor.[17] Juvenile granulosa cell tumors usually present in infancy (median age, 6 days) and Sertoli cell tumors present later in infancy (median age, 7 months). The prognosis is usually excellent after orchiectomy.[18] In older males, Leydig cell tumors are more common. Stromal cell tumors have been described as benign in young boys.[19-21]

Treatment

There are conflicting data about malignant potential in older males. Most case reports suggest that in the pediatric patients, these tumors can be treated with surgery alone.[19][Level of evidence: 3iii]; [22][Level of evidence: 3iiiA]; [21][Level of evidence: 3iiiDii] In a retrospective study, 42 patients with sex cord–stromal tumors were identified. All tumors were confined to the testes. They were treated with surgery alone, according to specific germ cell tumor guidelines. There were no recurrences.[18][Level of evidence: 3iiiA] However, given the rarity of this tumor, the surgical approach in pediatrics has not been well defined.

Ovarian Cancer (Non–Germ Cell)

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.[23-26] The majority of malignant ovarian tumors occur in girls aged 15 to 19 years.[27]

Epithelial ovarian neoplasia

Ovarian tumors derived from malignant epithelial elements include: adenocarcinomas, cystadenocarcinomas, endometrioid tumors, clear cell tumors, and undifferentiated carcinomas.[28] 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.[29]

Treatment is stage-related and may include surgery, radiation, and chemotherapy with cisplatin, carboplatin, etoposide, topotecan, paclitaxel, and other agents.

Ovarian surface epithelial neoplasms comprise a small subset of ovarian epithelial neoplasms; in children, most of the cases are of serous or mucinous histology and have a low malignant potential. Surgery and chemotherapy have been used to treat ovarian surface epithelial neoplasms.[30]

Sex cord–stromal tumors

Ovarian sex cord–stromal tumors are a heterogeneous group of rare tumors that derive from the gonadal non-germ cell component.[31] Histologic subtypes display some areas of gonadal differentiation and include juvenile granulosa cell tumors, Sertoli-Leydig cell tumors, and sclerosing stromal tumors. Ovarian sex-cord stromal tumors in children and adolescents are commonly associated with the presence of germline DICER1 mutations and may be a manifestation of the familial pleuropulmonary blastoma syndrome.[32]

Juvenile granulosa cell tumors

The most common histologic subtype in girls younger than 18 years is juvenile granulosa cell tumors (median age, 7.6 years; range, birth to 17.5 years).[33,34] Juvenile granulosa cell tumors represent about 5% of ovarian tumors in children and adolescents and are distinct from the granulosa cell tumors seen in adults.[31,35-37]

Most patients with juvenile granulosa cell tumors present with precocious puberty.[38] Other presenting symptoms include abdominal pain, abdominal mass, and ascites. Juvenile granulosa cell tumors has been reported in children with Ollier disease and Maffucci syndrome.[39]

As many as 90% of children with juvenile granulosa cell tumors 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.[33,37,40-42]

Sertoli-Leydig cell tumors

Sertoli-Leydig cell tumors are rare in young girls but may present with virilization [43] or precocious puberty.[44,45] These tumors may also be associated with Peutz-Jeghers syndrome.[46] A Chinese group reported on 40 women with FIGO stage I or IC Sertoli-Leydig cell tumors of the ovary, with an average age of 28 years.[47][Level of evidence: 3iiA] Of 34 patients with intermediate or poor differentiation, 23 received postoperative chemotherapy (most regimens included cisplatin); none recurred. Of the 11 patients who did not receive postoperative chemotherapy, two recurred; both were salvaged with chemotherapy. In contrast to juvenile granulosa cell tumors, a recent study suggested that Sertoli-Leydig tumors with abdominal spillage (FIGO stage IC) should be treated with cisplatin-based chemotherapy.[42]

Small cell carcinoma of the ovary

Small cell carcinomas of the ovary are exceedingly rare and aggressive tumors and may be associated with hypercalcemia.[48] Successful treatment with aggressive therapy has been reported in a few cases.[48,49][Level of evidence: 3iiB]; [50,51][Level of evidence: 3iiiA]

Carcinoma of the Cervix and Vagina

Incidence, risk factors, and clinical presentation

Adenocarcinoma of the cervix and vagina is rare in childhood and adolescence, with fewer than 50 reported cases.[26,52] Two-thirds of the cases are related to in utero exposure to diethylstilbestrol.

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.

Treatment

The treatment of choice is surgical resection,[53] followed by radiation therapy for residual microscopic disease or lymphatic metastases. The role of chemotherapy in management is unknown, although drugs commonly used in the treatment of gynecologic malignancies, 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, the EFS is 82% ± 11%, and for stage III and stage IV, the EFS is 57% ± 22%.[52]

References
  1. Alanee S, Shukla AR: Bladder malignancies in children aged <18 years: results from the Surveillance, Epidemiology and End Results database. BJU Int 106 (4): 557-60, 2010.  [PUBMED Abstract]

  2. Paner GP, Zehnder P, Amin AM, et al.: Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol 18 (1): 79-89, 2011.  [PUBMED Abstract]

  3. Stanton ML, Xiao L, Czerniak BA, et al.: Urothelial tumors of the urinary bladder in young patients: a clinicopathologic study of 59 cases. Arch Pathol Lab Med 137 (10): 1337-41, 2013.  [PUBMED Abstract]

  4. Johansson SL, Cohen SM: Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13 (5): 291-8, 1997 Sep-Oct.  [PUBMED Abstract]

  5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. International Agency for Research on Cancer.: Overall evaluations of carcinogenicity: an updating of IARC monographs, volumes 1 to 42. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Supplement 7. Lyon, France: International Agency for Research on Cancer, 1987. 

  6. Hoenig DM, McRae S, Chen SC, et al.: Transitional cell carcinoma of the bladder in the pediatric patient. J Urol 156 (1): 203-5, 1996.  [PUBMED Abstract]

  7. 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]

  8. 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]

  9. Lerena J, Krauel L, García-Aparicio L, et al.: Transitional cell carcinoma of the bladder in children and adolescents: six-case series and review of the literature. J Pediatr Urol 6 (5): 481-5, 2010.  [PUBMED Abstract]

  10. Sung JD, Koyle MA: Squamous cell carcinoma of the bladder in a pediatric patient. J Pediatr Surg 35 (12): 1838-9, 2000.  [PUBMED Abstract]

  11. 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]

  12. Korrect GS, Minevich EA, Sivan B: High-grade transitional cell carcinoma of the pediatric bladder. J Pediatr Urol 8 (3): e36-8, 2012.  [PUBMED Abstract]

  13. Hartke DM, Agarwal PK, Palmer JS: Testicular neoplasms in the prepubertal male. J Mens Health Gend 3 (2): 131-8, 2006. 

  14. Ahmed HU, Arya M, Muneer A, et al.: Testicular and paratesticular tumours in the prepubertal population. Lancet Oncol 11 (5): 476-83, 2010.  [PUBMED Abstract]

  15. 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]

  16. Schwentner C, Oswald J, Rogatsch H, et al.: Stromal testis tumors in infants. a report of two cases. Urology 62 (6): 1121, 2003.  [PUBMED Abstract]

  17. Carmignani L, Colombo R, Gadda F, et al.: Conservative surgical therapy for leydig cell tumor. J Urol 178 (2): 507-11; discussion 511, 2007.  [PUBMED Abstract]

  18. Hofmann M, Schlegel PG, Hippert F, et al.: Testicular sex cord stromal tumors: analysis of patients from the MAKEI study. Pediatr Blood Cancer 60 (10): 1651-5, 2013.  [PUBMED Abstract]

  19. Agarwal PK, Palmer JS: Testicular and paratesticular neoplasms in prepubertal males. J Urol 176 (3): 875-81, 2006.  [PUBMED Abstract]

  20. Dudani R, Giordano L, Sultania P, et al.: Juvenile granulosa cell tumor of testis: case report and review of literature. Am J Perinatol 25 (4): 229-31, 2008.  [PUBMED Abstract]

  21. Cecchetto G, Alaggio R, Bisogno G, et al.: Sex cord-stromal tumors of the testis in children. A clinicopathologic report from the Italian TREP project. J Pediatr Surg 45 (9): 1868-73, 2010.  [PUBMED Abstract]

  22. Thomas JC, Ross JH, Kay R: Stromal testis tumors in children: a report from the prepubertal testis tumor registry. J Urol 166 (6): 2338-40, 2001.  [PUBMED Abstract]

  23. Morowitz M, Huff D, von Allmen D: Epithelial ovarian tumors in children: a retrospective analysis. J Pediatr Surg 38 (3): 331-5; discussion 331-5, 2003.  [PUBMED Abstract]

  24. Schultz KA, Sencer SF, Messinger Y, et al.: Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer 44 (2): 167-73, 2005.  [PUBMED Abstract]

  25. Aggarwal A, Lucco KL, Lacy J, et al.: Ovarian epithelial tumors of low malignant potential: a case series of 5 adolescent patients. J Pediatr Surg 44 (10): 2023-7, 2009.  [PUBMED Abstract]

  26. You W, Dainty LA, Rose GS, et al.: Gynecologic malignancies in women aged less than 25 years. Obstet Gynecol 105 (6): 1405-9, 2005.  [PUBMED Abstract]

  27. Brookfield KF, Cheung MC, Koniaris LG, et al.: A population-based analysis of 1037 malignant ovarian tumors in the pediatric population. J Surg Res 156 (1): 45-9, 2009.  [PUBMED Abstract]

  28. Lovvorn HN 3rd, Tucci LA, Stafford PW: Ovarian masses in the pediatric patient. AORN J 67 (3): 568-76; quiz 577, 580-84, 1998.  [PUBMED Abstract]

  29. Tsai JY, Saigo PE, Brown C, et al.: Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years. Cancer 91 (11): 2065-70, 2001.  [PUBMED Abstract]

  30. Hazard FK, Longacre TA: Ovarian surface epithelial neoplasms in the pediatric population: incidence, histologic subtype, and natural history. Am J Surg Pathol 37 (4): 548-53, 2013.  [PUBMED Abstract]

  31. 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]

  32. Schultz KA, Pacheco MC, Yang J, et al.: Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol 122 (2): 246-50, 2011.  [PUBMED Abstract]

  33. 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]

  34. Capito C, Flechtner I, Thibaud E, et al.: Neonatal bilateral ovarian sex cord stromal tumors. Pediatr Blood Cancer 52 (3): 401-3, 2009.  [PUBMED Abstract]

  35. Bouffet E, Basset T, Chetail N, et al.: Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study of three cases and review of the literature. J Pediatr Surg 32 (5): 762-5, 1997.  [PUBMED Abstract]

  36. Zaloudek C, Norris HJ: Granulosa tumors of the ovary in children: a clinical and pathologic study of 32 cases. Am J Surg Pathol 6 (6): 503-12, 1982.  [PUBMED Abstract]

  37. Vassal G, Flamant F, Caillaud JM, et al.: Juvenile granulosa cell tumor of the ovary in children: a clinical study of 15 cases. J Clin Oncol 6 (6): 990-5, 1988.  [PUBMED Abstract]

  38. 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]

  39. 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]

  40. Powell JL, Connor GP, Henderson GS: Management of recurrent juvenile granulosa cell tumor of the ovary. Gynecol Oncol 81 (1): 113-6, 2001.  [PUBMED Abstract]

  41. 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]

  42. 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]

  43. 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]

  44. Baeyens L, Amat S, Vanden Houte K, et al.: Small cell carcinoma of the ovary successfully treated with radiotherapy only after surgery: case report. Eur J Gynaecol Oncol 29 (5): 535-7, 2008.  [PUBMED Abstract]

  45. 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]

  46. 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]

  47. Gui T, Cao D, Shen K, et al.: A clinicopathological analysis of 40 cases of ovarian Sertoli-Leydig cell tumors. Gynecol Oncol 127 (2): 384-9, 2012.  [PUBMED Abstract]

  48. 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]

  49. Pressey JG, Kelly DR, Hawthorne HT: Successful treatment of preadolescents with small cell carcinoma of the ovary hypercalcemic type. J Pediatr Hematol Oncol 35 (7): 566-9, 2013.  [PUBMED Abstract]

  50. Christin A, Lhomme C, Valteau-Couanet D, et al.: Successful treatment for advanced small cell carcinoma of the ovary. Pediatr Blood Cancer 50 (6): 1276-7, 2008.  [PUBMED Abstract]

  51. Kanwar VS, Heath J, Krasner CN, et al.: Advanced small cell carcinoma of the ovary in a seventeen-year-old female, successfully treated with surgery and multi-agent chemotherapy. Pediatr Blood Cancer 50 (5): 1060-2, 2008.  [PUBMED Abstract]

  52. McNall RY, Nowicki PD, Miller B, et al.: Adenocarcinoma of the cervix and vagina in pediatric patients. Pediatr Blood Cancer 43 (3): 289-94, 2004.  [PUBMED Abstract]

  53. 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]