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.[1-4] High-grade, invasive, urothelial carcinomas are extremely rare in young patients.
Bladder cancer in adolescents may develop as a consequence of alkylating-agent chemotherapy given for other childhood tumors or leukemia.[4-6] The association between cyclophosphamide and bladder cancer is the only established relationship between a specific anticancer drug and a solid tumor.
Prognosis and treatment
In contrast to adults, most pediatric bladder carcinomas are low grade, superficial, and have a good prognosis following transurethral resection.[2,3,7-10] Squamous cell carcinoma and more aggressive carcinomas, however, have been reported and may require a more aggressive surgical approach.[3,11-13]
(Refer to the PDQ summary on adult Bladder Cancer Treatment for more information.)
Testicular Cancer (Non-Germ Cell)
Testicular tumors are very rare in young boys and account for an incidence of 1% to 2% of all childhood tumors.[14,15] 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.[16,17] In newborns and infants, juvenile granulosa cell and Sertoli cell tumors are the most common stromal cell tumor. 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. In older males, Leydig cell tumors are more common. Stromal cell tumors have been described as benign in young boys.[20-22]
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.[Level of evidence: 3iii]; [Level of evidence: 3iiiA]; [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.[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.[24-27] The majority of malignant ovarian tumors occur in girls aged 15 to 19 years.
Epithelial ovarian neoplasia
Ovarian tumors derived from malignant epithelial elements include: adenocarcinomas, cystadenocarcinomas, endometrioid tumors, clear cell tumors, and undifferentiated carcinomas. 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.
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.
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. 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.
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).[34,35] 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.[32,36-38]
Most patients with juvenile granulosa cell tumors present with precocious puberty. 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.
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.
Sertoli-Leydig cell tumors
Sertoli-Leydig cell tumors are rare in young girls but may present with virilization  or precocious puberty.[45,46] These tumors may also be associated with Peutz-Jeghers syndrome. 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.[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.
Small cell carcinoma of the ovary
Small cell carcinomas of the ovary are exceedingly rare and aggressive tumors and may be associated with hypercalcemia. Successful treatment with aggressive therapy has been reported in a few cases.[49,50][Level of evidence: 3iiB]; [51,52][Level of evidence: 3iiiA]
Carcinoma of the Cervix and Vagina
Incidence, risk factors, and clinical presentation
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, 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%.
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