John L. Phillips, MD, FACS
Vladimir A. Valera, MD, PhD
BASICS
DESCRIPTION
• Testicular teratomas (TTs) are germ cell tumors (GCTs) which form somatic tissues in varying stages of maturity (ie, differentiation)
– Mature (M) = well-differentiated endoderm, mesoderm, and/or ectoderm germ cell (GC) layers
– Immature (I) = fet al or embryonal GC layers
• Most common GCT in childhood
• Adult TT, mature and immature: Consider as malignant
• Pediatric TT, mature and immature: Behave in general as benign lesions
EPIDEMIOLOGY
Incidence
• 8,820 cases of testicular cancer in the US in 2014
• 5.2 cases 100,000 men
• Adults: 2nd to 4th decade
• Mature: Immature types 10:1 (1)
• Pure teratoma (T) in 5% of adult GCTs but 35–40% of pediatric GCT
• T + GCT (ie, mixed) more common in adults (up to 50% of cases)
• Pure T more common in children
• T found in retroperitoneum in
– 22% stage IIa
– 1/3 of patients after chemo for NSGCT (2)
Prevalence
• US has 195,000 survivors of testicular cancer
• 5-yr survival
– 99% when confined to testis
– 96% for stage II
– 40% 4-yr survival with malignant transformation of teratoma (3)
RISK FACTORS
• Same for all GCTs
– Cryptorchidism
– Klinefelter syndrome
– Cannabis use controversial
– Family history
– Testicular atrophy/maldevelopment
– DDT exposure (see http://www.cancer.gov/cancertopics/causes/testicular/pesticides0408 Accessed August 22, 2014)
Genetics
• Isochromosome 12p
• Adult tumors hypotriploid
• pRB expressed in epithelial component
PATHOPHYSIOLOGY
• GC tumor model
– Initiation possibly in utero
– Intratubular GC neoplasia unclassified (ITGCNU) undergoes progression
– Differentiation of malignant embryonal GCs into mature teratoma thus mixed elements may occur
– Adult and not pediatric TT genetically unstable
– Adult and not pediatric TT has transforming capability
• Dermoid cysts are different in that they may differentiate from nonmalignant GCs
ASSOCIATED CONDITIONS
• Infertility and oligospermia
• Cryptorchidism
• Gynecomastia
GENERAL PREVENTION
• Self-exam for early diagnosis and treatment
• Possibly early orchidopexy for undescended testicle
DIAGNOSIS
ALERT
Identify symptoms of metastatic disease.
HISTORY
• The most common symptom at the time of diagnosis is painless swelling or enlargement of the testis.
• Scrotal injury
• Cryptorchidism
• Symptoms of metastatic disease may include:
– Weight loss
– Inanition
– Abdominal distention
– Joint, neck, or back pain
– Sweats, lethargy
PHYSICAL EXAM
• Most common: Painless scrotal mass
– Assess for tenderness, mobility, fixation
• Abdominal exam
• Breast exam
• Lymph node evaluation
• Document normal contralateral testis
DIAGNOSTIC TESTS & INTERPRETATION
ALERT
Markers must be drawn prior to orchiectomy.
Lab
• Tumor markers
– α-Fetoprotein (AFP) (10%, can be made seen if hepatoid differentiation has occurred)
– β-hCG (only elevated if chorio- or seminomatous elements present)
– LDH
– CEA (rare, can be seen if GI tissues present)
• Complete metabolic profile
– Electrolytes
– Liver function tests
• Complete blood count
• PT/INR
Imaging
• Ultrasound is critical in assessing for intratesticular mass, typically hypoechoic
• Microlithiasis in contralateral testis should be documented and followed; role of biopsy is controversial, more common in Europe
• Chest x-ray or better chest CT
• Abdomen–pelvis CT scan with and without contrast (if creatinine normal)
• PET scan not usually indicated; may have a role in the postchemotherapy setting
Diagnostic Procedures/Surgery
• Inguinal orchiectomy, radical, is standard of care for a solid testicular mass in adults
• Stage patient per TNMS
– Document tumor markers: Important for staging
– Document presence of nonteratomatous elements: Important for treatment algorithm
Pathologic Findings
• Large (5–10 cm), multinodular, heterogenous (solid, cartilaginous, cystic)
• May contain teeth, hair, bone, cartilage
• Cystic areas mixed with solid
• Mature teratoma
– Mixture of elements of ectoderm (eg, hair), endoderm (eg, GI), and mesoderm (eg, bone)
• Immature teratoma
– Neuroepithelium with embryonic features,
– Poorly formed cartilage
– Primitive glandular structures
– High grade if mitotically active
• Dermoid cysts
– Truly benign, no atypia or mitoses
– Keratin, hair, dermatoectoderm
DIFFERENTIAL DIAGNOSIS
• These are a delineation of testicular masses only. For a complete listing of intrascrotal and testicular masses see Section I: “Scrotum and Testicle Mass”
• Benign lesions
– Epididymitis/orchitis: Bacterial, STD/STI, mumps, TB
Often delayed testicular cancer diagnosis due to treatment of presumed epididymitis
– Testicular trauma: Usually blunt; contusion, rupture; usually associated hematocele
– Torsion (testicle or appendages)
– Incarcerated/strangulated hernia
– Cysts (simple, tunica albuginea, epidermoid)
– Adrenal rest tumors: In general benign, but can contribute to infertility in patients with congenital adrenal hyperplasia
– Fibrous pseudotumor of the tunica albuginea: Painless fibrous mass often associated with prior history of trauma or infection
– Adenomatoid tumor of testis or epididymis
– Other rare benign lesions: Angioma, fibroma, leiomyoma, hamartoma, carcinoid, neurofibroma
• Malignant lesions
– Testicular primary tumors (seminoma and nonseminomatous GCT)
– Leukemia involving testis—testis can be a site of solitary recurrence of leukemia posttreatment (sanctuary site). Biopsy can be utilized to confirm diagnosis in a patient with history of leukemia.
Treatment can be testis sparing with radiation, though contralateral testis should be treated as bilateral disease can be present.
– Lymphoma involving testis—usually represents extension from extratesticular sites, rarely can represent a primary lymphoma site (1% of lymphoma cases); can present bilaterally 1/3 of the time; mostly involves older men >60 yr; constitutional symptoms commonly present (fever, chills, night sweats, weight loss).
– Metastatic solid tumors: More common—prostate, lung, GI tract; more rare—kidney, malignant melanoma, pancreas, bladder, and thyroid
– Adenocarcinoma of the rete testis: Arises in the testis collecting system, high-stage presentation, poor response to chemotherapy and radiation, with median survival of 1 yr.
– Mesothelioma of tunica vaginalis: Rare, similar to the more common pleural histology, associated with asbestos exposure
– Paratesticular sarcomas: Rhabdomyosarcoma, malignant fibrous histiocytoma (most common soft tissue sarcoma in late adult life)
TREATMENT
GENERAL MEASURES
• Radical orchiectomy for adult solid testicular mass
– Staging and then treatment based on histology and stage
– Treat most aggressive subelement
• Chemo for high-stage disease followed by retroperitoneal lymph node dissection (RPLND)
• Prior to systemic therapy, discuss sperm banking
MEDICATION
First Line
• Teratomas are not chemosensitive
• Platinum-based chemotherapy used in teratoma only to treat the non-teratomatous elements, eg, embryonal, choriocarcinoma
• RPLND is only treatment to address teratoma in retroperitoneum, esp. after chemo
Second Line
N/A
SURGERY/OTHER PROCEDURES
• RPLND important in teratoma
– Primary (no prior treatment)
20% of stage I teratomas have retroperitoneal (retroperitoneum) disease and the retroperitoneum nodes should be resected
– Secondary (after chemotherapy/RT)
20–30% of residual retroperitoneum masses after chemotherapy in NSGCT may harbor teratoma and should be resected
– Tertiary (ie, “growing teratoma syndrome”)
Recurrent retroperitoneal teratoma after RPLND may occur after incomplete resection or recurrent differentiated tumor
Retroperitoneal lymph node reresection best option if feasible
ADDITIONAL TREATMENT
Radiation Therapy
• Teratomas are not radiosensitive
• In stage I seminomatous GCT, radiation to the retroperitoneum may be used for patients at risk of occult stage II disease but must be monitored for retroperitoneum teratoma
Additional Therapies
Discuss sperm banking before treatment
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Excellent with low stage & complete resection
– 95–100% cure rate in adults
– 100% cure rate in children
• Fair to poor if metastatic/incomplete resection
– 86% 2-yr survival for retroperitoneal disease only
– 40% 2-yr survival for retroperitoneal + multiple sites
COMPLICATIONS
• Infertility
– Preorchiectomy oligospermia
– Post-RPLND loss of emission (infertility)
• Chemotherapy toxicity
– Platinum: Renal
– Bleomycin: Pulmonary toxicity and fibrosis (watch for ARDS)
– Etoposide: Myelosuppression
FOLLOW-UP
Patient Monitoring
• Surveillance not good option in primary teratoma because of occult GC elements in retorperitoneum
• If markers elevated, look for occult nonteratoma elements or, rarely, GI elements within teratoma.
• NCCN guidelines for teratoma after RPLND
– Year 1–2
Chest x-ray (CXR) + markers q3mo
CT abdomen/pelvis baselines and q6mo
– Year 3–4
CXR + markers q3–6mo
CT annual
– Year 4–6, 6+
CXR + markers q6–12mo
CT biannual
Patient Resources
• National Cancer Institute. www.cancer.gov/cancertopics/types/testicular
• Testicular Cancer Awareness Foundation. www.testicularcancerawarenessfoundation.org
• Teratoma Support Foundation. www.Teratoma.weebly.com
REFERENCES
1. Pohl HG, Shukla AR, Metcalf PD, et al. Prepubertal testis tumors: Actual prevalence rate of histological types. J Urol. 2004;172:2370–2372.
2. Sheinfeld J, Motzer RJ, Rabbani F, et al. Incidence and clinical outcome of patients with teratoma in the retroperitoneum following primary retroperitoneal lymph node dissection for clinical stages I and IIA nonseminomatous germ cell tumors. J Urol. 2003;170:1159–1162.
3. Comiter CV, Kibel AS, Richie JP, et al. Prognostic features of teratomas with malignant transformation: A clinicopathological study of 21 cases. J Urol. 1998;159:859–863.
ADDITIONAL READING
• Beck SD, Foster RS, Bihrle R, et al. Long-term outcome for patients with high volume retroperitoneal teratoma undergoing post-chemotherapy surgery. J Urol. 2009;181:2526–2532.
• Simmonds PD, Lee AH, Theaker JM, et al. Primary pure teratoma of the testis. J Urol. 1996;155:939–942.
• Vaughn DJ, Flaherty K, Lal P, et al. Treatment of growing teratoma syndrome. N Engl J Med. 2009;360:423–424.
See Also (Topic, Algorithm, Media)
• Growing Teratoma Syndrome
• International Germ Cell Cancer Collaborative Group (IGCCCG)
• Reference Tables: TNM: Testis Cancer
• Testis Cancer, Pediatric, General Considerations
• Testis Cancer, Seminoma
• Testis Cancer, Nonseminomatous Germ Cell Tumors, General
• Testis, Teratoma, Mature and Immature Images 
• Testis, Tumor and Mass, Pediatric, General Considerations
CODES
ICD9
• 186.9 Malignant neoplasm of other and unspecified testis
• 222.0 Benign neoplasm of testis
• 752.51 Undescended testis
ICD10
• C62.90 Malig neoplasm of unsp testis, unsp descended or undescended
• D29.20 Benign neoplasm of unspecified testis
• Q53.9 Undescended testicle, unspecified
CLINICAL/SURGICAL PEARLS
• Teratomas are resistant to chemotherapy and radiotherapy.
• Metastatic embryonal germ cell tumor may mature into teratoma in adult cases. Therefore, mature teratomas in adults should be treated aggressively.
• Immature and mature teratomas in children are benign.
• Pure teratomas do not secrete AFP (but may harbor GI elements that do).
• Pure teratomas do not secrete β-hCG (but may harbor choriocarcinomatous or seminomatous elements that do).
• Postchemo RPLND has double the rate of teratomas than RPLND for stage I tumors.