Mark R. Anderson, MD, MSc
Sherry S. Ross, MD
BASICS
DESCRIPTION
• In contrast to adults, testicular tumors in children are often benign including teratoma, dermoid, and epidermoid cyst.
• The majority of malignant germ cell tumors in children are yolk sac tumors
• Differentiate testicular mass from scrotal wall and paratesticular mass with scrotal US.
• The most common causes of scrotal swelling or mass in pediatrics include hernias (organ protrusion required) and hydrocele (likely communicating in younger children), with lesions such as varicocele (see incidence section), scrotal wall swelling (insect bite or nephrotic syndrome), with testicular neoplasms less common (peak incidence at 2 yr old and adolescence).
• Though very rare, most common malignant paratesticular tumor is rhabdomyosarcoma.
EPIDEMIOLOGY
Incidence
• Testicular tumors (tumor-registry data not presented due to reporting bias toward yolk sac):
– Total 0.5–2/100,000 males; 2% of
Teratoma (well differentiated): ∼66%
Yolk sac (endodermal sinus) tumor 15%
Stromal tumors: ∼15%
Gonadoblastoma: 1%
Lymphoma testicular primary: Rare
Epidermoid cysts: <1%
Prevalence
N/A
RISK FACTORS
• Cryptorchidism: Postpubertal germ cell tumors
• Congenital adrenal hyperplasia (CAH): In boys often presents with precocious puberty. Adrenal rests, commonly present along the spermatic cord and in the testicular hilum, may hypertrophy in patients with CAH, leading to testicular nodules that are clinically indistinguishable from testicular tumors.
• Kleinfelters syndrome
• Family history of testicular cancer
• More common in white men than black men
Genetics
• Gonadoblastoma is associated with gonadal dysgenesis and a 45XO/46XY karyotype.
• Yolk sac tumors: Abnormalities: 1p, 6q, 3p
• Large-cell calcifying Leydig tumor is associated with Peutz–Jeghers syndrome and Carney complex.
• No clear genetic etiology exists for teratoma, Leydig cell tumor, and granulosa cell tumor.
PATHOPHYSIOLOGY
• Non–germ cell and germ cell tumors originate from the celomic epithelium and primordial germ cells, respectively
• Totipotent germ cells can evolve into seminoma or embryonal carcinoma
• Embryonal carcinoma is capable of differentiating into embryonic structures, such as mature (peds) or immature (adults) teratomas and extraembryonic structures such as yolk sac and choriocarcinoma tumors.
• Seminoma (dysgerminoma) is a primitive germ cell neoplasm that cannot further differentiate (unusual in childhood, except with gonadal dysgenesis).
• Teratoma: Monodermal (epidermoid cyst) or multiple histologic types present (nerve, cartilage, intestinal epithelium, etc.). Benign and no prepubertal metastasis
• Yolk sac tumors characterized by Schiller–Duval bodies (glomerulus in appearance, contain AFP)
• Leydig tumors which can secrete testosterone are malignant 10% of time. (Reinke crystals—40%, increased mitotic figures absent in peds), Sertoli (10% malignant) can secrete estrogen or testosterone, and granulosa cells (75% diagnosed within 1 mo of birth) have a common embryologic origin from a mesenchymal stem cell
• Gonadoblastomas are small benign tumors found in patients with gonadal dysgenesis, including those who have at least a portion of the Y chromosome. Although benign have high risk of malignant transformation.
• 15–20% of all RMS arise from the genitourinary system.
– Most common genitourinary sites are the prostate, bladder, and paratesticular (vagina and uterus are relatively unusual sites).
– Survival rates vary with site (vagina and paratesticular have a better prognosis than bladder/prostate primaries).
• 2 main histologic types of RMS
– Embryonal RMS is the most common subtype of RMS and accounts for most of the genitourinary tumors.
– Alveolar RMS occurs more commonly in the trunk and extremities than in GU; worse prognosis than embryonal tumors
• Epididymitis usually not infectious in pediatrics; likely due to refluxing fluid from urethra. Obtain urinalysis and culture. If infected need renal ultrasound to rule out ectopic ureter.
• Varicocele pathogenesis not known. Body habitus (tall, thin), genetics (risk increased if brother or 1st-degree relative has varicocele), or intrinsic venous anomalies (“nutcracker” by SMA, left renal vein insertion), and rarely central outflow obstruction from tumor.
• In neonates and young children “hernia” will be used to describe a communicating hydrocele with a “hernia sac” present though no organ protrusion present: Patent process vaginalis
ASSOCIATED CONDITIONS
• Hernia: Prematurity
• Testicular tumor: Undescended testicle (UDT), gonadal dysgenesis, precocious puberty in non–germ cell tumors (NGCT).
• Hernia: 1–5% newborns, 3-fold increase in preterm infants, 15% bilateral, clinical synchronous hydrocele 20% ; asymptomatic patent process vaginalis present ∼66% of time.
• Varicoceles: ∼0% <10 yr old, increasing to 15% through puberty into adulthood
• Paratesticular tumors: Very rare, bimodal—mo & adolescence
• Epididymitis: Less common than adults
GENERAL PREVENTION
• Unclear if orchidopexy reduces risk in undescended testicles
• USPSTF: Against routine screening for testicular cancer in asymptomatic adolescent and adults including routine testicular self-exams.
• American Cancer Society suggests that men with family history do monthly self-exams.
• American Urological Association (AUA): Monthly self-exams for all young men.
DIAGNOSIS
HISTORY
• Painless testicular mass (testicular tumor)
• Acute onset of pain (torsion, epididymitis)
• Symptoms of precocious puberty (non–germ cell testicular tumors)
• Subacute achy pain (varicocele)
• Past history of UDT
• Flank pain from kidney obstruction secondary to enlarged retroperitoneal nodes
PHYSICAL EXAM
• Systematic exam identifying intrascrotal structures (testicular mass vs. intrascrotal mass)
• Testicle should be smooth and firm and within 20% size of contralateral testicle (use orchiometer or ultrasound measurements)
• Epididymis: Posterolateral adjacent to testicle
• Hydrocele transilluminates (communicating if fluid manipulated back into abdomen)
• Solid masses do not transilluminate
• Varicoceles (“bag of worms”)
– If does not diminish when supine/under manual pressure may be due to tumor
• Lymph nodes: Lymphoma or metastasis
• Breast exam, signs of virilization (consider adrenal tumor) for NGCT tumors
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Order tumor markers immediately, but post orchiectomy markers determine staging
• AFP: Elevated postnatal up to 8 mo; AFP >1,000 ng/mL almost always due to yolk sac tumor (vs. teratoma) at any prepubertal age; only 15% of yolk sac tumors have AFP <100 ng/mL under age of 5.
– AFP <100 ng/mL and >5 yo suspect teratoma
– AFP never elevated in pure seminoma, choriocarcinoma, or teratoma
• β-HCG always elevated with choriocarcinoma (rarely pediatric), <10% of pure seminomas, and never elevated in pure teratoma
– Rarely falsely elevated (increases with marijuana use or LH cross-reactivity)
• Embryonal and yolk sac: May secrete both AFP/HCG
• Half lives: HCG ∼24 hr, AFP ∼5–7 days, LDH ∼4–5 days
• Testosterone/estrogen levels for NGCT
• LDH: Elevated if large tumor burden
Imaging
• Scrotal ultrasound very helpful (use color Doppler) for any scrotal or testicular concern
• No reliable sonographic features that can distinguish benign from malignant testis tumors
• Anechoic cysts trend toward benign
• Epidermoid cyst “onion skin” appearance
• Paratesticular RMS appears large, hypervascular and ipsilateral testicle may not be visualized
• Testicular microlithiasis not associated with increased risk of cancer
• Indeterminate lesions on US that resemble testicular neoplasm include tubular ectasia of the rete testis, inflammation, infarction, fibrosis, and traumatic hematoma.
• CT scan of abdomen and chest can be done before or after orchiectomy but reactive lymph nodes may appear postoperatively
Diagnostic Procedures/Surgery
Biopsy not indicated. The diagnostic procedure of choice is the radical orchiectomy.
Pathologic Findings
See Section I and II “Individual Tumor Types”
DIFFERENTIAL DIAGNOSIS
• Painful scrotum:
– Torsion (testicle, testicular, or epididymal appendages); more common after puberty
– Epididymitis/orchitis; bacterial, mumps
– Fournier gangrene
– Henoch–Schönlein purpura (usually no mass)
– Incarcerated/strangulated hernia
– Testis trauma: Contusion, rupture; hematocele
– Tumor (pain infrequent unless traumatized or rapidly growing; see below)
• Painless mass:
– 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
– Paratesticular rhabdomyosarcoma (bimodal age 3–4 and teens)
– Scrotal edema (insect bite, nephrotic syndrome, acute idiopathic scrotal edema)
– Spermatocele (epididymal cyst): Uncommon
– Testicular cysts
– Testicular tumor: Germ cell tumors: Yolk sac carcinoma, teratoma, seminoma, embryonal cell carcinoma, choriocarcinoma; Gonadal stromal tumors: Leydig, Sertoli cell, granulosa cell.
– Metastatic tumors: Unusual in childhood
– Mixed germ cell and stromal tumor (gonadoblastoma)
– Hamartoma, carcinoid, and neurofibroma
– Testis tumor of adrenogenital syndrome
– Leukemia or lymphoma
– Varicocele: Fullness and not a firm mass; changes with position
TREATMENT
GENERAL MEASURES
• If concern for tumor obtain tumor markers pre- and postoperatively (1–4 wk)
• Discuss sperm banking, especially if chemotherapy needed
• Do not make incision through scrotum (inguinal incision only)
• Use long tag nonabsorbable suture when ligating cord to help with lymph node dissection in future if necessary
• Open inguinal fascia so cord ligated as cephalad as possible
• International Germ Cell Cancer Collaborative Group (IGCCCG) staging:
– Stage 1: Limited to testis, markers normalize in the half-life. Normal markers at diagnosis require normal imaging and a negative ipsilateral retroperitoneal node dissection.
– Stage 2: Microscopic residual disease is present in the scrotum or high in spermatic cord (<5 cm from proximal end). Markers elevated after appropriate half-life interval. Tumor rupture or scrotal biopsy prior to complete orchiectomy.
– Stage 3: Retroperitoneal lymph node involvement. Nodes >4 cm by CT are considered metastases. Nodes 2–4 cm need biopsy to document nodal metastases.
– Stage 4: Distant metastases
MEDICATION
First Line
• Chemotherapy for all yolk sac tumor stage II or greater or other germ cell tumor
• Platinum-based as for other nonseminomas (cisplatin, etoposide, and bleomycin); see Section I: “Testis, Cancer General”
• Rhabdomyosarcoma: Adriamycin and dactinomycin chemotherapy
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Testis preservation with benign lesions most common in children as opposed to adults.
• Prepubertal testicular teratomas, Leydig and Sertoli cell tumors are benign; orchiectomy or testicular-sparing surgery is curative and no additional therapy is indicated in benign lesions.
• Yolk sac tumor or other malignant tumor; radical orchiectomy and observation if low stage
• Retroperitoneal lymph node dissection (RPLND):
– Postchemotherapy with residual mass.
– Rarely indicated: 90% of yolk sac tumors are stage 1 at presentation.
– 60–80% of paratesticular RMS are stage I at diagnosis. Patients >10 yr have a higher risk for retroperitoneal relapse and should undergo ipsilateral RPLND before chemo.
ADDITIONAL TREATMENT
Radiation Therapy
Used in rhabdomyosarcoma
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Prepubertal teratoma is uniformly benign
• 90% of yolk sac tumors are stage I at presentation;85% 6-yr survival in stage 4 patients
• Paratesticular RMS: Variable survival rates; modern surgical technique, and chemotherapy 90% overall survival in most patients.
COMPLICATIONS
• Chemotherapy toxicity
• Iatrogenic secondary cancers
• Infertility
• RPLND: Retrograde ejaculation, lymphocele
FOLLOW-UP
Patient Monitoring
Testicular and paratesticular cancer varies. Refer to NCCN guidelines@www.nccn.org
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Reference Tables: TNM: Testis Cancer
• Testis Cancer, Adult General Considerations
• Testis, Cancer Nonseminomatous Germ Cell Tumors, General
• Testis, Teratoma, Mature and Immature
• Testis, Tumor and Mass, Adult, General Considerations
• Testis, Tumor and Mass, Pediatric, General Considerations
CODES
ICD9
• 186.9 Malignant neoplasm of other and unspecified testis
• 608.89 Other specified disorders of male genital organs
• 171.6 Malignant neoplasm of connective and other soft tissue of pelvis
ICD10
• C62.90 Malig neoplasm of unsp testis, unsp descended or undescended
• N50.8 Other specified disorders of male genital organs
• C49.6 Malignant neoplasm of conn and soft tissue of trunk, unsp
CLINICAL/SURGICAL PEARLS
• The presence or absence of pain or tenderness alone cannot reliably rule in or out benign vs. malignant processes in the scrotum.
• Acute onset of testicular pain in a child is most likely torsion, and emergent evaluation is indicated, early surgical intervention; do not delay surgery for imaging.
• Painless testicular mass is highly suspicious for tumor and should be confirmed with imaging.