Elizabeth V. Dray, MD
Marcus L. Quek, MD, FACS
BASICS
DESCRIPTION
• Endodermal sinus tumors (yolk sac tumors [YSTs]) are germ cell tumor (GCT) that resembles cells of allantois, yolk sac, and mesenchyme
– AKA endodermal sinus tumors, Teilum tumor, orchioblastoma, juvenile embryonal
• Bimodal age distribution
– Children <3 yr, young adults
• Staging
– Adults: Per TNM staging for non seminomtous germ cell tumors (NSGCT) (See Section VI: Reference tables: TNM: Testis Cancer)
– Children: Children’s Oncology Group Staging
Stage I: Tumor limited to the testis, completely resected by high inguinal orchiectomy with negative margins. No clinical, radiographic or histologic evidence of disease beyond the testis. Tumor markers negative after appropriate half-life decline.
Stage II: Microscopic residual disease present in the scrotum or spermatic cord (<5 cm from proximal end). Tumor markers elevated after appropriate half-life. Tumor rupture or scrotal biopsy prior to completion orchiectomy.
Stage III: Retroperitoneal lymph node involvement (LN >4 cm on CT).
Stage IV: Distant metastases.
• 85% of children present with stage I disease, compared to 35% of postpubertal cases
EPIDEMIOLOGY
Incidence
• Children
– Incidence of pediatric testis tumors is 0.5–2 per 100,000.
– YST comprise 62% of all testicular tumors in childhood based on AAP tumor registry.
• Adults
– In US, ∼8,820 new cases of testicular cancer would be diagnosed and 380 men would die of this disease in 2014.
– Lifetime risk of developing testis cancer is ∼1 in 270, and the lifetime risk of dying of testicular cancer is 1 in 5,000
– Pure YST is extremely rare, but found in 42% of mixed GCTs.
Prevalence
N/A
RISK FACTORS
• General risk for testicular cancer
– Cryptorchidism
– Klinefelter’s syndrome.
– Family history.
– Male infertility
– Low birthweight, young maternal age, young paternal age, multiparity, breech delivery
– Infant hernia.
– Height-taller men
– Testicular microlithiasis
Genetics
Heredity unknown
PATHOPHYSIOLOGY
• Associated with gains in chromosome 12p in adults, RUNX promotor methylation on chromosome 1p in children (1)
• ITGCN precursor lesion in adults, unclear relationship in children.
• Lymphatic and hematogenous spread
– Up to 20% of children present with lung metastases compared to 4–6% of adults
ASSOCIATED CONDITIONS
• Adults
– Cryptorchidism
Later age at orchiopexy associated with higher relative risk of cancer.
Risk also increased with intra-abdominal testis and bilateral cryptorchidism.
• Children
– Disorders of sex development
DIAGNOSIS
HISTORY
• Presents as painless testicular mass
– May also present as retroperitoneal mass in mediastinal GCT
– Incidentally associated with trauma in <10% of cases.
PHYSICAL EXAM
• Painless testicular mass
– 15–50% have associated hydrocele
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum tumor markers
– β-hCG never elevated in pure YST.
– 90% of YST produce AFP
Also produced by liver and GI tract.
Half-life 5–7 days.
AFP often elevated in infants. Normal adult levels not reached until 8 mo of age.
Imaging
• Scrotal US
– Hyperechoic or heterogenous mass with increased blood flow on Doppler
Note: In children, anechoic cystic lesions with normal AFP suggestive of benign mass, can attempt testis-sparing surgery.
• CT chest/abdomen/pelvis with PO and IV contrast
– For staging in all age groups.
Diagnostic Procedures/Surgery
Inguinal orchiectomy with high ligation of spermatic cord within 1–2 wk of presumed diagnosis.
Pathologic Findings
• Gross
– Endodermal sinus tumors appear firm, yellow-white mass
• Microscopic
– Resemble cells of allantois, yolk sac, mesenchyme arranged in glandular, papillary, or microcytic pattern with hyaline globules.
– Schiller–Duval bodies characteristic finding
– Stains positive for AFP.
DIFFERENTIAL DIAGNOSIS
• Adults: See Section I “Testis, Tumor and Mass, Adult, General Considerations”
• 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
– 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
• Adults
– Management I handled as for nonseminomatous GCT: Section I “Testis Cancer, Nonseminomatous Germ Cell Tumors, General.”
• Children (2,3)
– Inguinal orchiectomy curative in 80% of children with stage I disease
– Adjuvant chemotherapy recommended for stage II–IV disease.
MEDICATION
First Line (4)
• Chemotherapy: Bleomycin, etoposide, cisplatin (BEP)
– Carboplatin may have equivalent outcomes compared to cisplatin with decreased ototoxicity and nephrotoxicity.
Second Line
• Etoposide, ifosfamide, cisplatin (VIP)
– High-dose chemotherapy regimens for treatment failures.
SURGERY/OTHER PROCEDURES
• In children: LN >2 cm and <4 cm in size at diagnosis should undergo excisional or interventional radiologybiopsy biopsy to confirm histology.
• Postchemotherapy residual retroperitoneal disease should undergo retroperitoneal lymphadenectomy.
ADDITIONAL TREATMENT
Radiation Therapy
No role for radiation in endodermal sinus tumor.
Additional Therapies
• Sperm banking should be offered prior to chemotherapy in adolescents and adults.
– Fertility-sparing procedure for prepubertal boys are controversial, but include Testicular sperm extraction (TESE) and cryopreservation of testicular tissue
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Adults: See “NSGCT”
• Children
– Survival for all stages approaches 100% at 6 yr.
– 20% of children with stage I disease will relapse during surveillance; however, excellent cure rates with chemotherapy.
COMPLICATIONS
• Chemotherapy toxicity
– Bleomycin: Pulmonary fibrosis
– Cisplatin: Ototoxicity, nephrotoxicity, neuropathy.
– Etoposide: Pancytopenia
• Infertility
FOLLOW-UP
Patient Monitoring
• Children
– CXR, CT or MRI, AFP, and history and physical exam monthly for 3 mo, then at 6 mo postoperatively, and subsequently every 6 mo for 36 mo.
Note: Imaging guidelines evolving in light of increasing awareness of the impact of radiation on pediatric populations.
Patient Resources
• Urology Care Foundation: Testicular cancer in children. http://www.urologyhealth.org/urology/index.cfm?article=37
• Children’s Oncology Group. http://www.childrensoncologygroup.org
REFERENCES
1. Kato N, Tamura G, Fukase M, et al. Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants. Am J Pathol. 2003;163(2):387–391.
2. Ahmed HU, Arya M, Muneer A, et al. Testicular and paratesticular tumor in prepubertal populations. Lancet Oncol. 2010;11(5):476–483.
3. Ross JH, Rybicki L, Kay R, et al. Clinical behavior and a contemporary management algorithm for prepubertal testis tumors: A summary of the Prepubertal Testis Tumor Registry. J Urol. 2002;168:1675–1679.
4. Wu HY, Snyder H. Pediatric urologic oncology: Bladder, prostate, testis. Urol Clin North Am. 2004;31(3):619–627.
ADDITIONAL READING
• Carver BS, Sheinfeld J. Germ cell tumors of the testis. Ann Surg Oncol. 2005;12(11):871–880.
• National Comprehensive Cancer Network Guideline Recommendations. http://www.nccn.org/clinical.asp (Accessed August 21, 2014).
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, Endodermal Sinus Tumors (Yolk Sac Tumors) Image 
• Testis Cancer, Nonseminomatous Germ Cell Tumors, General
• Torsion, Testis and Testicular Appendages
CODES
ICD9
• 186.9 Malignant neoplasm of other and unspecified testis
• 608.89 Other specified disorders of male genital organs
• 752.51 Undescended testis
ICD10
• C62.90 Malig neoplasm of unsp testis, unsp descended or undescended
• N50.8 Other specified disorders of male genital organs
• Q53.9 Undescended testicle, unspecified
CLINICAL/SURGICAL PEARLS
• Endodermal sinus tumor is the most common GCT of childhood.
• Inguinal orchiectomy with high ligation of spermatic cord mainstay of therapy.
• Excellent prognosis for all stages in children.