cytoplasm of clear cells that consist of AFP and Schiller-Duval bodies.

•Nearly all are managed with surveillance or platinum-based chemotherapy.

•Current chemotherapeutic regimens for yolksac tumors are platinum-based protocols. Common agents include etoposide, bleomycin, and cisplatin.

•Follow-up should include monthly tests of serum AFP levels, chest radiography every 2 months for 2 years, and CT scanning or MRI of the retroperitoneum every 3 months for the first year and then biannually.

•Because spread to the retroperitoneal lymph nodes is uncommon, routine prophylactic dissection of the nodes is not performed.

•Chemotherapy is administered in patients with radiographic evidence of metastatic disease or persistently elevated serum AFP levels. The use of combination chemotherapy with cisplatin, etoposide, and bleomycin has been an effective treatment for metastatic disease, with a survival rate approaching 90 %.

•More than 99 % of all patients with yolk-sac tumors are expected to survive.

•Retroperitoneal lymph node dissection, which plays a central role in the staging and therapy of adults with mixed germ cell tumors, is rarely employed in children.

•This is in part because prepubertal patients are less likely than adults to have metastases limited to the retroperitoneum.

•Furthermore 80% of prepubertal patients have clinical stage 1 disease and fewer than 20% will recur with no therapy beyond orchiectomy.

•Finally, the morbidity of retroperitoneal lymph node dissection is likely to be greater in children than in adolescents and adult.

•In children, retroperitoneal surgery is reserved for biopsy of radiographically equivocal nodes or for resection of a persistent retroperitoneal mass following chemotherapy.

•The specific management for patients with yolk sac tumor has been defined by several multicenter clinical trials.

•Stage 1 tumors are managed with orchiectomy followed by surveillance. Surveillance includes frequent physical examinations,

radiographic evaluation of the chest and retroperitoneum, and serum tumor marker measurement.

•Patients who developed metastatic disease are treated with two to four courses of multiagent platinum-based chemotherapy.

•Patients who present with locally advanced disease, metastases, or persistently elevated serum tumor markers are similarly treated with multiagent platinum-based chemotherapy.

•The survival for all patients with this approach was nearly 100 %.

27.10 Teratoma

•While metastatic disease occurs in up to 60 % of adults with teratoma, these tumors are universally benign in pre-pubertal patients.

•Adolescents with teratoma should undergo orchiectomy and a metastatic evaluation followed by surveillance for stage 1 disease.

•Because of its benign nature, prepubertal teratoma can be managed with testis-sparing surgery.

•Teratomas and teratocarcinomas contain elements derived from more than one of the three germ tissues: endoderm, mesoderm, and ectoderm. These tumors are often cystic, and tissues such as skin, hair, bone, and even teeth may be present. Although they contain areas of poorly differentiated cells with a malignant appearance, teratomas are consistently benign in children younger than 2 years.

•The vast majority of prepubertal teratomas are “mature” teratomas, and for these tumors, no further treatment or follow-up is necessary.

•Immature teratomas are characterized by the presence of embryonal or incompletely differentiated tissue components, most commonly primitive neuroectodermal structures.

•There is some uncertainty regarding the behavior of immature teratomas.

•Pediatric immature teratomas (regardless of site) generally behave in a benign fashion if completely resected.

•Somatic malignancies may also arise in immature teratomas leading to metastatic spread. This is exceedingly rare in children.

•Furthermore, if foci of yolk sac tumor are found in an immature teratoma, then it should be treated as a yolk sac tumor.

•While immature teratomas of the testis can be managed with complete tumor resection alone, these patients should be followed-up.

•Epidermoid cysts are composed entirely of keratin-producing squamous epithelium and are universally benign in children and adults.

•They can be treated by tumor enucleation with no chemotherapy or follow-up.

27.11 Mixed Germ Cell Tumor

•Mixed germ cell tumors are rare in prepubertal patients, but account for a significant proportion of testis tumors in adolescents.

•These tumors are managed as adults with observation, retroperitoneal lymph node dissection and/or chemotherapy depending on the specific histology and stage of the disease.

•Patients with stage 1 mixed germ cell tumors may be managed with surveillance.

• The recurrence rate on surveillance is 25–30 %.

•Recurrence may be prevented with a modified nerve-sparing retroperitoneal lymph node dissection or two cycles of platinum-based chemotherapy, but this “over-treats” the 70–75 % of patients who do not have occult metastatic disease.

•On the other hand, when recurrence occurs on surveillance, more intense therapy is required.

•Patients with low risk disease are usually followed with frequent chest x-rays, tumor marker measurements and abdominal CT scans.

•Nearly all recurrences occur within 2 years of orchiectomy and are treated with chemotherapy.

•Patients at higher risk for recurrence generally undergo a modified nerve-sparing retroperitoneal lymph node dissection:

–Those with vascular invasion

–Largely embryonal cell histology

–Those who are poorly compliant with therapy

•If microscopically positive nodes are found at the time of retroperitoneal lymph node dissection, these patients are treated with a course of chemotherapy.

•Patients with radiographic evidence of metastatic disease at presentation or persistently elevated tumor markers following orchiectomy are treated with three to four cycles of chemotherapy.

•The relapse rate following primary chemotherapy for metastatic disease is approximately 15 %, though it may be as high as 30 % for poor-risk patients.

•Retroperitoneal lymph node dissection may be considered for patients with very limited retroperitoneal lymph node disease at presentation and normalization of tumor markers after orchiectomy.

•Some patients with mixed germ cell tumors treated with chemotherapy for metastatic disease will have a residual retroperitoneal mass following therapy.

•If tumor markers have normalized, these residual masses should generally be resected.

–40–50 % of residual masses will contain only necrotic tissue and fibrosis.

–10–20 % will have persistent malignancy.

–40–45 % will contain mature teratoma.

27.12 Stromal Tumors

•Stromal tumors of the testis are rare in children and adolescents.

•Leydig cell tumors and juvenile granulosa cell tumors are universally benign in children.

•Leydig cell tumors:

–These are the second most common gonadal stromal tumors in children and are also benign.

–Leydig cell tumors usually present between 5 and 10 years of age with precocious puberty.

–The synthesis of testosterone may produce precocious puberty, gynecomastia, and elevated levels of 17-ketosteroids.

–Leydig-cell tumors must be differentiated from hyperplastic nodules that develop in

boys with poorly controlled congenital adrenal hyperplasia (CAH).

–They may be treated with orchiectomy or tumor enucleation.

–Contralateral tumors may also occur, though they are rare in children.

•Adrenal rests:

–Adrenal rests along the spermatic cord and in the testicular hilum may hypertrophy in patients with precocious puberty due to congenital adrenal hyperplasia mimicking a Leydig cell tumor.

–In patients with congenital adrenal hyperplasia the nodules are often multifocal and bilateral.

–The diagnosis of congenital adrenal hyperplasia can generally be made by demonstrating an elevated serum 17-hydroxyprogesterone level.

–The nodules will usually resolve or significantly reduce in size with steroid replacement therapy for congenital adrenal hyperplasia. If this occurs, the patient may be followed with serial examinations.

–Large nodules that fail to regress may be safely enucleated.

•Juvenile granulosa tumors:

–These account for approximately 3 % of all neonatal testicular tumors and commonly appear as cystic, painless testicular masses.

–Juvenile granulosa cell tumors occur almost exclusively in the first year of life, most commonly in the first 6 months.

–Chromosomal mosaicism, structural abnormalities of the Y chromosome, and ambiguous genitalia are common in boys with juvenile granulosa cell tumor.

–These tumors are hormonally inactive and benign.

–Although these children should undergo a chromosomal analysis, the tumor itself may be treated by orchiectomy or tumor enucleation with no metastatic evaluation or adjuvant therapy.

•Sertoli cell tumors:

–These are the most common gonadal stromal tumors in prepubertal children.

–These tumors tend to appear as painless masses in boys younger than 6 months and

produce no endocrinologic effects; however, 14 % of patients present with gynecomastia.

–Approximately 10 % of adult Sertoli cell tumors are malignant, malignancy however is very rare in children.

–All reported cases of Sertoli cell tumors in children under 5 years of age are benign but there have been a few cases of malignant Sertoli cell tumors in older children.

–Therefore, children younger than 5 years are adequately treated with orchiectomy and do not require metastatic evaluation.

–Older children should undergo chest radiography and abdominal CT scanning to rule out metastases.

–Tumor excision is usually adequate treatment for infants, but a metastatic evaluation should be considered such as:

•Large tumor size

•Areas of necrosis

•Vascular invasion

•Cellular atypia

•Increased mitotic activity.

–Older children with Sertoli cell tumors should undergo a full metastatic evaluation.

–Metastases are treated with a combination of radiotherapy, chemotherapy, and retroperitoneal lymph node dissection.

–Large-cell calcifying Sertoli cell tumors:

•These are clinically and histologically distinct tumors which occur predominantly in children and adolescents.

•These tumors are composed of large cells with abundant cytoplasm and varying degrees of calcification.

•Approximately one third of patients have an associated genetic syndrome and/or endocrine abnormality, the most common being Peutz-Jeghers syndrome and Carney’s syndrome.

•Peutz-Jeghers syndrome is an autosomal dominant disorder consisting of mucocutaneous pigmentation and hamartomatous intestinal polyposis.

•Features of Carney syndrome include myxomas of the skin, soft tissue, and heart; myxoid lesions of the breast; lentigines of the face and lips; cutaneous

blue nevi; Cushing syndrome; pituitary adenoma; and schwannoma.

•Patients and first-degree relatives of patients with large-cell calcifying Sertoli cell tumor should be screened for these potentially serious syndromes.

•Whereas these tumors are occasionally malignant in adults, they have been uni-

versally benign in patients under 25 years of age.

•Orchiectomy is sufficient treatment in children, but approximately one fourth of patients will have bilateral and/or multifocal disease.

•A testis-sparing approach has been described for this rare tumor.

•A mixed or poorly differentiated stromal tumor:

–Rarely a prepubertal patient may have a mixed or poorly differentiated stromal tumor.

–Most of these tumors are benign.

–Malignancy should be considered in those with:

•A large number of mitotic figures

•A tumor that is poorly differentiated

•Local invasion.

–Orchiectomy is the treatment of choice.

–Retroperitoneal lymph node dissection and adjuvant therapy are indicated in those with metastatic disease.

–These patients should be followed-up closely for the development of metastatic disease.

27.13 Simple Testicular Cyst

•Simple testicular cysts may be observed but if large in size, they should be excised.

•Cystic dysplasia of the rete testis is a benign tumor found primarily in children.

•Ultrasound typically reveals multiple small cysts arising from the testicular hilum, sometimes compressing the normal testicular parenchyma.

•These tumors are universally benign and may be managed by observation, tumor excision, or orchiectomy if extensive.

•Associated genitourinary anomalies, particularly renal agenesis, are common. Therefore, patients with cystic dysplasia of the rete testis should undergo upper tract imaging.

27.14 Epidermoid Cysts

•These are benign tumors of epithelial origin and account for 10–15 % of cases.

•These probably represent a monodermal variant of teratoma.

•Epidermoid cysts are composed entirely of keratin-producing squamous epithelium and are universally benign in children and adults.

•They can often be suspected by their typical appearance on ultrasound of a cyst filled with echogenic layered debris (corresponding to the desquamated keratin) giving an “onionskin” appearance.

•They may be treated by tumor enucleation with no oncological evaluation or follow-up.

•They are often firm and well-defined, with a central hypoechoic region or mixed internal echogenicity surrounded by an echogenic rim on ultrasonography.

•Following tumor enucleation, these tumors do not require follow-up.

27.15 Testicular Microlithiasis (TM)

•This has been identified as a possible risk factor for the development of testicular cancer.

•TM refers to the presence of microcalcifications, usually diffuse, within the parenchyma of the testis on ultrasound.

•The association with testicular malignancies was suggested by the finding that approximately 25 % of adult testes harboring cancer are found to have TM.

•But the causal relationship behind this finding is unclear.

•TM is found incidentally in approximately 2 % of boys and men undergoing ultrasound either for testicular symptoms or as part of a screening study of asymptomatic males.