Nicholas G. Cost, MD
Paul H. Noh, MD, FACS, FAAP
BASICS
DESCRIPTION
• Important to distinguish prepubertal “pediatric” testis tumors from the postpubertal “adolescent” testis tumors (1).
• Prepubertal testicular tumors in children are much more often benign than the postpubertal tumors which are more often malignant.
• Must differentiate a true testicular tumor or mass from paratesticular and scrotal masses
• The most common causes of painless scrotal swelling in a child include hernias, hydrocele, varicocele, and scrotal wall swelling
• Testis accounts for 2% of pediatric tumors
EPIDEMIOLOGY
Incidence
• 0.5–2 per 100,000 children/yr
• Peak age of 2 yr
• Lower incidence of germ cell tumors (GCTs) when compared to adults
• 25–30% of pediatric tumors are malignant (2).
• Rare in black and Asian children
• Testicular tumors in children (2):
– Teratoma: 40–50%
– Epidermoid cyst: 10–15%
– Yolk sac tumor (YST): 25–35%
– Gonadal stromal tumors: 10–15%
– Others: Gonadoblastoma: 1–2% (3), leukemia: 1–2%, cystic dysplasia: <1%
Prevalence
N/A
RISK FACTORS
• Risk factors for GCTs:
– Cryptorchidism (4)
– Family history
– Intratubular germ cell neoplasia
– Past personal history
• Congenital adrenal hyperplasia (CAH) increases risk for intratesticular adrenal rests
Genetics
• Gonadoblastoma is associated with gonadal dysgenesis and a 45XO/46XY karyotype.
• YST: Abnormalities in 1p, 6q, and 3p
• GCTs: Excess genetic material from the short arm of chr 12, including isochromosome 12p.
• Large-cell calcifying Leydig tumor is associated with Peutz–Jeghers syndrome and Carney complex.
PATHOPHYSIOLOGY
• GCTs typically develop from a precursor lesion, which, in turn, appears to develop from arrested primordial germ cells or gonocytes
• Teratoma: Monodermal (epidermoid cyst) or multiple histologic types present
– Not associated with an elevated AFP
– Metastasis not reported before puberty
– Testis-sparing enucleation via an inguinal incision is possible in prepubertal patients and normal serum tumor markers.
• YST (also called endodermal sinus tumor):
– AFP elevated in 80% of YST, and normally elevated in a neonate (physiologic).
AFP half-life is 5–7 days; elevation after orchiectomy implies metastatic disease.
– Yolk sac elements stain positive for AFP
– β-hCG produced by syncytiotrophoblast indicates a mixed GCT.
• Gonadoblastoma:
– Most common tumor in disorders of sexual development; germ cell component prone to malignant degeneration
• Seminomas and mixed GCT rare in prepubertal children.
• Gonadal stromal tumors (3):
– Leydig cell tumors:
Peak age of 4–5 yr; increased testosterone production with normal LH
Differential diagnosis includes pituitary lesions, Leydig cell hyperplasia, CAH based on hormonal production
Reinke crystals classically described in adults, rare in children on histology
Malignancy not reported in Leydig cell tumors in children
– Sertoli cell tumor:
Peak age <4; most not hormonally active
Gynecomastia when hormonally active
Retroperitoneal spread rarely reported
– Granulosa cell tumor:
Rarely metastasizes
• Testis tumor of adrenogenital syndrome:
– Benign, suppressible with glucocorticoids
• Lymphoma, leukemia
– May serve as a sanctuary site of these malignancies because of blood–testis barrier
• Cystic dysplasia of the testis:
– Irregular cysts in rete testis; associated with renal agenesis and multicystic dysplasia
• Children’s Oncology Group (COG) staging:
– Stage 1: Limited to testis, markers normalize according to half-life. No radiologic evidence of metastatic disease
– Stage 2: Transscrotal orchiectomy or tumor rupture during orchiectomy, persistent elevated markers, residual disease in scrotum or disease on pathology <5 cm from testicular cord margin
– Stage 3: Nodes >4 cm, no visceral or distant disease. Nodes 2–4 cm require biopsy.
– Stage 4: Distant metastases
• Postpubertal GCTs staged and managed according to adult testicular cancer guidelines
ASSOCIATED CONDITIONS
• Disorders of sexual development with a dysgenetic gonad and the presence of a Y chromosome
• Congenital adrenal hyperplasia (CAH)
• Cryptorchidism
• Precocious puberty
GENERAL PREVENTION
• Orchidopexy does not eliminate the risk of developing testicular cancer in cryptorchidism, but early intervention may reduce the risk (4).
• Early orchidopexy permits earlier detection of testicular masses. Other benefits include improved fertility and a reduced risk of torsion.
• Routine exam of the scrotal contents
DIAGNOSIS
HISTORY
• Asymptomatic scrotal mass or asymmetry
• Acute pain or fever with hemorrhage, trauma, rapid growth of the tumor, infection
• Precocious sexual development
• Breast tenderness with gynecomastia
• Undescended testicle or hernia repair
• Family history of testicular tumors
PHYSICAL EXAM
• Scrotal asymmetry
• Abnormality intratesticular vs. intrascrotal, testicular vs. paratesticular
• Diffusely enlarged testicle or palpable nodularity in the testicle
• Does not transilluminate (solid)
• Inguinal canal and cord structures are usually normal in a boy with a testicular tumor
• Signs of precocious puberty
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum markers AFP and β-hCG:
– Obtain prior to orchiectomy in all patients with a testicular mass
– Marked AFP elevations present in newborn; may be detectable up to 8 mo of age
• Serum testosterone, LH, and FSH levels if a gonadal stromal tumor is suspected.
Imaging
• Scrotal ultrasound (US):
– Differentiate intratesticular vs. extratesticular
– Does not differentiate benign from malignant
– Paratesticular rhabdomyosarcoma (PT-RMS):
Hypervascular, solid extratesticular mass
Often large; testicle not seen on US
– Indeterminate lesions on US that resemble testicular neoplasm include tubular ectasia of the rete testis, inflammation, and hematoma.
• Chest x-ray: Evaluate for metastatic YST
• Abdominal and pelvic CT or MRI:
– Obtained after histology confirms malignancy
– Evaluate retroperitoneum for lymph node metastases and liver for metastases
• MRI may have utility in the evaluation of indeterminate lesions seen on US.
Diagnostic Procedures/Surgery
• All suspicious testicular and paratesticular lesions should be approached inguinally.
• Prepubertal patients with a primary testicular lesion and normal tumor markers may be considered for testis-sparing surgery (TSS).
– Such approaches require intraoperative assessment including immediate frozen-section analysis to ensure complete resection
– If frozen section reveals GCT elements or concern for incomplete resection, radical orchiectomy should be performed
– Intraoperative US may be helpful
– Postpubertal patients with a normal contralateral testicle should undergo radical inguinal orchiectomy.
– Paratesticular lesions consistent with malignancy should be managed with radical inguinal orchiectomy
Pathologic Findings
• GCTs
– Teratoma: Contain elements of at least 2 of the 3 germ cell layers of endoderm, mesoderm, and ectoderm.
– YST: Epithelioid cells that form glandular and ductal structures arranged in columns, papillary projections, or solid islands within a primitive mesenchymal stroma. The cells have poorly defined cell borders and vacuolated cytoplasm with glycogen and fat.
– Seminoma: Islands or sheets of relatively large cells with clear cytoplasm and densely staining nuclei.
– Embryonal carcinoma: Malignant epithelioid cells arranged in glands or tubules. Cell borders indistinct, cytoplasm pale or vacuolated, and nuclei rounded with coarse chromatin.
– Choriocarcinoma: 2 distinct cell types must be demonstrated to satisfy the histologic diagnosis of choriocarcinoma: Syncytiotrophoblasts and cytotrophoblasts.
– Gonadoblastoma: Must have 3 elements: Sertoli cells, interstitial tissue, and germ cells
• Stromal tumors
– Leydig cell tumors: Uniform, closely packed cells with round, slightly eccentric nuclei and eosinophilic granular cytoplasm with lipoid vacuoles, brownish pigmentation, and inclusions known as Reinke crystals.
– Sertoli cell tumors: Epithelial elements resembling Sertoli cells and varying stroma.
– Granulosa cell tumors: Characteristic Call–Exner bodies may be identified, consisting of PAS-positive material similar to that seen in the basement membrane of the tubules.
DIFFERENTIAL DIAGNOSIS
• Painful childhood testicular masses:
– Epididymitis/orchitis; bacterial, mumps
– Henoch–Schönlein purpura (usually no mass)
– Incarcerated/strangulated hernia
– Testicular or paratesticular tumor
– Testis trauma: Contusion, hematocele
– Torsion (testicle, testicular or epididymal appendage); more common after puberty
• Painless childhood testicular masses:
– Adenomatoid tumor of testis or epididymis
– Adrenal rest tumors
– Cystic dysplasia of the testis
– Chylocele: Usually associated with filariasis
– Fibrous pseudotumor of the tunica albuginea
– Hydrocele, primary or due to trauma, torsion, tumor, epididymitis; hydrocele of cord
– Hernia
– Lipoma of the cord
– Polyorchidism
– Rhabdomyosarcoma (RMS) (bimodal age 3–4 and adolescence)
– Scrotal edema (insect bite, nephrotic syndrome, acute idiopathic scrotal edema)
– Spermatocele (epididymal cyst)
– Testicular cysts
– Testicular tumors:
GCTs: YST, teratoma, seminoma, embryonal, choriocarcinoma, mixed tumors
Gonadal stromal tumors: Leydig tumor, Sertoli cell, granulosa cell tumors
Metastatic tumors
Hamartoma, carcinoid, and neurofibroma
Testis tumor of adrenogenital syndrome
Leukemia or lymphoma
– Varicocele
TREATMENT
GENERAL MEASURES
• TSS for most lesions in prepubertal children
• Prepubertal testicular teratomas, and Leydig and Sertoli cell tumors are benign; orchiectomy or TSS is curative and no additional therapy is indicated.
• YST or other malignant tumor; radical orchiectomy and observation if low stage
• PT-RMS require specific RMS management
MEDICATION
First Line
• Chemotherapy for all GCTs stage II or greater
– Bleomycin, etoposide, cisplatin
SURGERY/OTHER PROCEDURES
• Inguinal approach for primary lesion in all patients regardless of age
• RPLND
– Postchemotherapy for residual retroperitoneal mass
Rare given the rarity of metastatic disease and exquisite sensitivity to chemotherapy
– Staging RPLND in all boys >10 yr with PT-RMS regardless of staging imaging and those <10 yr with abnormalities on staging imaging
ADDITIONAL TREATMENT
Radiation Therapy
As indicated for PT-RMS depending on stage and histology
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Prepubertal teratoma is uniformly benign
• GCTs (5)
– 100% 6-yr overall survival for Stages I–III
– 91% 6-yr overall survival for Stage IV
COMPLICATIONS
Long-term complications after chemotherapy
FOLLOW-UP
Patient Monitoring
• Routine follow-up not necessary for teratoma
• Surveillance for malignancy based on stage of disease and adjuvant therapy
Patient Resources
Urology Care Foundation: Testicular cancer in children. http://www.urologyhealth.org/urology/index.cfm?article=37
REFERENCES
1. Agarwal PK, Palmer JS. Testicular and paratesticular neoplasms in prepubertal males. J Urol. 2006;176:875–881.
2. Pohl HG, Shukla AR, Metcalf PD, et al. Prepubertal testis tumors: Actual prevalence rates of histologic types. J Urol. 2004;172:2370–2372.
3. Schultz KA, Schneider DT, Pashankar F, et al. Management of ovarian and testicular sex cord-stromal tumors in children and adolescents. J Pediatr Hematol Oncol. 2012;34 (suppl 2):S55–S63.
4. Wood HM, Elder JS. Cryptorchidism and testicular cancer: Separating fact from fiction. J Urol. 2009;181:452–461.
5. Schlatter M, Rescorla F, Giller R, et al. Excellent outcome in patients with stage I germ cell tumors of the testes: A study of the Children’s Cancer Group/Pediatric Oncology Group. J Pediatr Surg. 2003;38(3):319–324.
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Paratesticular Tumors
• Reference Tables: TNM: Testis Cancer
• Rhabdomyosarcoma, Pediatric
• Scrotum and Testicle, Mass
• Testis Cancer, Adult General Considerations
• Testis Cancer, Nonseminomatous Germ Cell Tumors, General
• Testis, Cancer, General
• Testis, Leydig Cell Tumor
• Testis, Sertoli Cell Tumor
• Testis, Teratoma, Mature and Immature
• Testis, Tumor and Mass, Pediatric, General Considerations Images 
• Torsion, Testis and Testicular Appendages
CODES
ICD9
• 222.0 Benign neoplasm of testis
• 239.5 Neoplasm of unspecified nature of other genitourinary organs
• 608.89 Other specified disorders of male genital organs
ICD10
• D29.20 Benign neoplasm of unspecified testis
• D49.5 Neoplasm of unspecified behavior of other genitourinary organs
• N50.8 Other specified disorders of male genital organs
CLINICAL/SURGICAL PEARLS
• Scrotal US can generally distinguish a tumor from other causes of testicular swelling or pain and discriminate between a testicular and paratesticular mass.
• While infant and prepubertal boys with a testicular mass and normal serum tumor markers may be treated with attempted testis sparing surgery (TSS), peripubertal boys should be managed with a radical inguinal orchiectomy.