AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Pure choriocarcinoma of the testis is the exception to most of the rules established for testicular seminoma and all other forms of nonseminomatous germ cell tumors (NSGCT). Like other germ cell tumors (GCT), choriocarcinoma is diagnosed in men of a young age range. Unlike other cancers, choriocarcinoma metastasizes by hematogenous routes, the testicular primary is often small or even "burned-out," and the mortality rate is high. In most reports, the tumor responds poorly to radiation and chemotherapy. Surgery is usually limited to radical orchiectomy for tissue diagnosis.

Pathophysiology

Choriocarcinoma recapitulates placental tissue development. For unknown reasons, it metastasizes early via hematogenous routes to the lung, liver, and brain, among others.

Frequency

United States

Testicular GCTs are rare, occurring in only 1-2% of all male malignancies and in 1 out of 250 men by age 65 years. However, these tumors represent the most common malignancy in men aged 15-35 years. Incidence rates are 3.7 cases and 0.9 cases per 100,000 per year for white people and black people, respectively. GCTs have several subtypes and frequencies, including seminoma 40%, embryonal tumor 25%, teratocarcinoma 25%, teratoma 5%, and choriocarcinoma (pure) 1%.

International

The incidence of testis cancer has increased worldwide from the early 1960s to the mid 1980s. Nonwhite populations have a lower incidence than white populations. The highest rates are in Denmark (8.4 cases per 100,000 per y) and Switzerland (6.2-8.8 cases per 100,000 per y), and variation exists across Europe. Because of its rare incidence, no differences in international rates of pure choriocarcinoma are known.

Race

No racial differences in choriocarcinoma have been reported.

Age

• Ramon y Cajal (1987) reported a case of pure choriocarcinoma in the oldest patient recorded, aged 63 years. The patient died of aspiration shortly after starting chemotherapy, and reporting the efficacy of treatment in this age group was impossible. The second oldest patient reported was aged 50 years.
• In a literature review of 10,000 cases of germinal testicular cell tumors, Ramon y Cajal found 54 (0.5%) cases of pure choriocarcinoma. The tumors occurred mostly in men aged 20-30 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Unlike classic seminoma or mixed GCTs, pure choriocarcinoma is more likely to present with symptoms from metastatic disease and is the most common element observed in brain metastases.
• The local tumor itself may be small and not cause symptoms.

Physical

• Most testicular GCTs cause scrotal swelling, with a palpable mass. Testicular pain with or without radiating pain to the groin and abdomen is possible but is more consistent with epididymitis.
• Choriocarcinoma is different in that the local tumor may be small or nonpalpable.
• Widely metastatic testicular GCTs, including choriocarcinoma, may also present with a "burned-out" local testis lesion consisting of fibrous scar with absent or minute amounts of viable tumor.
• Physical examination findings from lung, liver, and/or brain metastases may be more pronounced than an abnormal finding on testicular examination.

Causes

• Patients with a history of cryptorchidism have a 10-40 times higher risk of testis cancer. The risk is higher for the abdominal versus the inguinal location of the undescended testis.
• • An abdominal testis is more likely to be seminoma, while a testis surgically brought to the scrotum by orchiopexy is more likely to be an NSGCT.
  • Orchiopexy allows for earlier detection by physical examination but does not alter the risk of GCT.
  • Ten percent of patients with a GCT have a history of cryptorchidism.
  • In a series of 125 patients with a history or clinical evidence of cryptorchidism and testis tumor, 3 (2%) were pure choriocarcinoma, which is similar to the overall incidence of choriocarcinoma among GCTs.
• Genetic changes in the form of amplifications and deletions are observed predominantly in the 12p11.2-p12.1 chromosomal region.
• • Gain of 12p sequences is associated with invasive growth of seminomas and nonseminomas.
  • In contrast, spermatocytic seminoma shows a gain of chromosome 9, and most infantile yolk sac tumors and teratomas show no chromosomal changes.
• Other risks include trauma, mumps, and maternal estrogen exposure.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Chronic epididymitis
Non–germ cell testicular tumor, Leydig
Syphilitic gumma

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Alpha-fetoprotein (AFP) is secreted by yolk sac elements, and its elevation is consistent with NSGCT. Choriocarcinoma could be a component of such a tumor, but AFP is within the reference range in pure choriocarcinoma.
• Human chorionic gonadotropin (HCG) is a glycoprotein with the same alpha unit as thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Therefore, the beta subunit must be assayed. Beta-HCG has a 24-hour half-life and is secreted by syncytiotrophoblast cells within the tumor. Beta-HCG is usually markedly elevated in pure choriocarcinoma.
• Liver enzyme profile to include lactic acid dehydrogenase (LDH): LDH elevation may indicate bulky or advanced disease; however, the sensitivity and specificity are limited compared to beta-HCG and AFP. Rising levels after treatment may indicate relapse. Elevation of the remaining liver function tests may correlate with metastatic liver disease.
• Placental alkaline phosphatase (PLAP): PLAP is elevated in some patients with seminoma and advanced disease; however, smoking and several other tumors also cause elevations; therefore, this marker is uncommonly used.

Imaging Studies

• Scrotal ultrasound
• • Any male with a palpable testicular mass should undergo scrotal ultrasound imaging. Other indications for ultrasound may include acute scrotal pain, hydrocele, or other nonspecific scrotal pain, swelling, or mass.
  • Choriocarcinoma is associated with hemorrhage and necrosis and may appear more cystic, inhomogeneous, and calcified than a seminoma.
• Abdominal CT scan of the abdomen and pelvis with IV and oral contrast
• • In all other forms of testis GCT, CT scan can be used to identify metastatic disease to the retroperitoneal lymph nodes, most commonly, and it understages approximately 15-20% of patients thought to be stage I.
  • With pure choriocarcinoma, metastatic disease via hematogenous routes may skip the retroperitoneal lymphatics.
• CT scan of the brain
• • Choriocarcinoma is associated with brain metastases. In a review of 242 patients with metastatic germ cell testis cancer being treated in a multi-agent chemotherapy protocol, Vugrin (1979) found 38 cases of brain metastases. Among patients with pure embryonal carcinomas, 13% had brain metastases compared to 83% of patients with pure choriocarcinomas. Furthermore, choriocarcinomas tended to have multiple brain metastatic sites with cerebellar involvement.
  • In almost all cases, pulmonary metastases preceded or coincided with brain metastases.
• Chest radiograph: Chest CT scan is only indicated for an abnormal finding on chest radiograph; however, choriocarcinoma has a high metastatic rate, and CT scan of the chest is usually indicated.
• Bone scan
• • In an autopsy study by Bredael (1982), GCTs had bony metastases at autopsy, including seminoma 56%, mixed choriocarcinoma 35%, teratocarcinoma 30%, and embryonal carcinoma 24%; however, 0 out of 6 cases of pure choriocarcinoma had bone metastases.
  • In pure choriocarcinoma, a bone scan can probably be omitted in the absence of bone pain.

Histologic Findings

Gross findings include a small hemorrhagic nodule with some grayish-white viable tumor at the periphery. Histology shows that choriocarcinoma contains both syncytiotrophoblastic cells and cytotrophoblastic cells in intimate association (see Image 1).

Syncytiotrophoblastic cells are responsible for beta-HCG production.

Staging

American Joint Committee on Cancer and the International Union against Cancer

Testicular cancer staging system

• Primary tumor (T)
• • pTx - Primary tumor cannot be assessed.
  • p0 - No evidence of primary tumor
  • pTis - Intratubular germ cell neoplasia
  • pT1 - Tumor limited to the testis and epididymis, no vascular/lymphatic invasion, may invade the tunica albuginea, no invasion of the tunica vaginalis
  • pT2 - Tumor limited to the testis and epididymis, vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of the tunica vaginalis, invades beyond the tunica albuginea or into the epididymis
  • pT3 - Tumor invades the spermatic cord with or without vascular/lymphatic invasion.
  • pT4 - Tumor invades the scrotum with or without vascular/lymphatic invasion, invades the scrotum
• Regional lymph nodes (N)
• • Clinical
  • • Nx - Nodes not assessed
    • N0 - No regional lymph node metastasis
    • N1 - Lymph node mass or multiple lymph node masses less than or equal to 2 cm in greatest dimension
    • N2 - Lymph node mass or multiple lymph node masses greater than 2 cm but less than or equal to 5 cm in greatest dimension
    • N3 - Lymph node mass greater than 5 cm in greatest dimension
  • Pathologic
  • • pN0 - No evidence of tumor in lymph nodes
    • pN1 - Lymph node mass less than or equal to 2 cm in greatest dimension, 5 or fewer nodes positive
    • pN2 - Lymph node mass greater than 2 cm but less than 5 cm in greatest dimension, more than 5 nodes positive, evidence of extranodal extension of tumor
    • pN3 - Lymph node mass greater than 5 cm in greatest dimension
• Distant metastases (M)
• • M0 - No evidence of distant metastases
  • M1a - Nonregional nodal or pulmonary metastases
  • M2b - Nonpulmonary visceral metastases
    
    Table 1. Serum Tumor Markers (S)
    
    

    S	LDH		HCG (mIU/mL)		AFP (ng/mL)
    Sx	Not assessed		Not assessed		Not assessed
    S0	£N*	and	Normal	and	Normal
    S1	<1.5 x N	and	<5000	and	<1000
    S2	1.5-10 x N	or	5000-50,000	or	1000-10,000
    S3	>10 x N	or	>50,000	or	>10,000

    *N=upper limit of reference range for the LDH assay

    Table 2. Stage Grouping

    Stage grouping	T	N	M	S
    Stage 0	pTis	N0	M0	S0
    Stage I	T1-T4	N0	M0	Sx
    Stage IA	T1	N0	M0	S0
    Stage IB	T2-4	N0	M0	S0
    Stage IS	Any T	N0	M0	S1-S3
    Stage II	Any T	Any N	M0	Sx
    Stage IIA	Any T	N1	M0	S0-S1
    Stage IIB	Any T	N2	M0	S0-S1
    Stage IIC	Any T	N3	M0	S0-S1
    Stage III	Any T	Any N	M1	Sx
    Stage IIIA	Any T	Any N	M1a	S0-S1
    Stage IIIB	Any T	Any N	M0-M1a	S2
    Stage IIIC	Any T	Any N	M0-M1a	S3
    …	Any T	Any N	M1b	Any S

    Additional staging systems are well discussed by Prow, 1998.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Metastatic NSGCTs are highly sensitive to cisplatin-based chemotherapy, with cure rates of approximately 80% for advanced disease and nearly 100% for early stage disease. Furthermore, numerous randomized clinical trials conducted for NSGCT have identified efficacious chemotherapy regimens that reduce toxicity. Risk-adapted protocols are also available to tailor treatment regimens toward patients with good, moderate, or poor risk factors.

Pure choriocarcinoma, an extremely rare variant comprising less than 1% of NSGCT, is not as sensitive to chemotherapy as mixed NSGCT. The authors' exhaustive search of major textbooks and the literature revealed no clear guidelines as to how to treat these patients. Most case reports describe patients presenting with advanced metastatic disease, with varying responses to chemotherapy. In general, standard chemotherapy for poor-risk NSGCT is the initial therapy. However, these patients may require salvage regimens and may benefit from referral to a major cancer center to be treated under protocols that can involve cyclical regimens or dose escalation with growth factor/stem cell support. Cases responsive to chemotherapy may require additional surgical debulking.

• Standard chemotherapy for good-to-poor–risk NSGCT - Bleomycin, etoposide, cisplatin (BEP) for 4 cycles
• Additional agents - Vinblastine, ifosfamide

Surgical Care

Radical inguinal orchiectomy

• Preoperative details
• • Serum tumor markers must be drawn preoperatively because they fall rapidly postorchiectomy. Other staging tests can be performed preoperatively or postoperatively.
  • Due to the rapid doubling time of a potential choriocarcinoma, testis tumors are often scheduled for surgery rapidly to avoid upstaging.
  • Most patients with testicular choriocarcinoma are young and healthy and only require routine preoperative preparation.
  • Semen donation for subsequent fertility should be discussed if the contralateral testis function is in question; however, many patients have poor semen quality that improves after orchiectomy.
  • Cosmetic testicular prostheses are not widely available due to the recent problems with silicone implants used primarily in breast augmentation; however, Mentor Urology is conducting trials for saline testis implants.
  • If a patient presents with symptomatic metastatic lesions from a testis tumor, proceeding with platinum-based chemotherapy and delaying radical orchiectomy is reasonable. Radical orchiectomy is not a very morbid procedure, but it may potentially delay the initiation of chemotherapy.
  • Differentiation of seminoma versus NSGCT for advanced disease is not important at the outset of treatment because both groups receive the same regimen.
  • Although chemotherapy may result in disappearance of the testicular mass, orchiectomy is always indicated.
• Intraoperative details
• • Patients may be administered spinal, general, or (uncommonly) local anesthesia. The inguinal area is shaved and prepared in standard fashion.
  • An inguinal incision is made to allow exposure of the external and internal iliac canal.
  • The external iliac fascia is opened, exposing the spermatic cord and the internal iliac canal. The spermatic cord is controlled with a Penrose drain in tourniquet fashion to stop retroperitoneal lymphatic and venous drainage of tumor cells.
  • The testis is then delivered from the scrotum, and the vas deferens and spermatic arteries are ligated separately.
  • A long, nonabsorbable tie is left on the patient side of the spermatic cord to facilitate identification should retroperitoneal lymph node dissection become necessary, requiring dissection of the remaining spermatic cord structures from the abdominal exposure.
  • The external oblique fascia is reapproximated and the skin closed in standard fashion.
• Postoperative details
• • Radical orchiectomy is usually an outpatient procedure or is performed as a 23-hour admission often accompanied by the staging workup.
  • As follow-up, patients are staged and referred for the appropriate adjuvant therapies.
• Complications are rarely a problem but may include wound infection, inguinal skin numbness from injury to the genitofemoral nerve, hematoma, and standard anesthetic risks.

Consultations

A hematologist and/or oncologist should be consulted for chemotherapy in advanced cases.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Metastatic pure choriocarcinoma is treated with multi-agent chemotherapy with the same regimens as NSGCT, which are discussed in a separate article.

Standard chemotherapy for poor-risk and some good-to-moderate–risk patients includes 4 cycles of BEP (ie, bleomycin, etoposide, cisplatin). Additional agents in some regimens or for salvage include vinblastine and ifosfamide.

Most case reports show poor response to chemotherapy, and the literature/texts offer no clear treatment guidelines.

Drug Category: Antineoplastic agents

These agents inhibit cell growth and proliferation.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Prognosis

• In most reports, choriocarcinoma has a dismal prognosis.
• • Batala (1982) reported 0 out of 20 patients surviving 5 years; however, Requena (1991) reported a case of pure choriocarcinoma with metastases to the skin (rare), lung, and brain. This patient was treated with a 4000-rad dose to the skull and a multi-agent chemotherapy regimen, including platinum, vinblastine, and bleomycin (PVB) and lomustine, VP-16, and VePesid. The patient's beta-HCG normalized, and he was disease free at 2 years.
  • Lepidini (1997) reported a patient treated with multi-agent chemotherapy who was disease free at 43 months of follow-up.
• In 5 cases of pure choriocarcinoma with brain metastases, all patients died, and median survival was 1 month despite treatment with multi-agent chemotherapy.
• In a 9-year review of patients treated in multi-agent chemotherapy trials at Memorial Sloan-Kettering Cancer Center, Bosl (1983) reported 5 cases of pure choriocarcinoma and 2 long-term survivors.

Patient Education

• For excellent patient education resources, visit eMedicine's Men's Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Cancer of the Testicle and Testicular Self-Exam.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Scrotal masses should be evaluated with ultrasound if they are associated with the testicle.
• Malignancies of the paratesticular structures are very uncommon and should be evaluated based on the clinical findings.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Testicular choriocarcinoma has multinucleated syncytiotrophoblastic cells that drape over smaller cytotrophoblastic cells, which together appear to form a border along a blood-filled, villouslike space (upper right). Used with permission, from Ernstoff MS, Heaney JA, and Peschel RE, eds. Testicular and Penile Cancer. Malden, Mass: Blackwell Science, Inc, 1998, p20.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Azzopardi JG, Mostofi FK, Theiss EA. Lesions of the testes observed in certain patients with widespread choriocarcinoma and related tumors. Am J Pathol. 1961;38:207-225.
• Batata MA, Whitmore WF Jr, Chu FC. Cryptorchidism and testicular cancer. J Urol. Sep 1980;124(3):382-7. [Medline].
• Batata MA, Chu FC, Hilaris BS. Therapy and prognosis of testicular carcinomas in relation to TNM classification. Int J Radiat Oncol Biol Phys. Aug 1982;8(8):1287-93. [Medline].
• Beahrs O, Henson D, Hutter R. Handbook for staging of cancer. In: The Manual of Staging Cancer. 4th ed. Philadelphia, Pa:. JB Lippincott;1993:195-197.
• Bosl GJ, Geller N, Cirrincione C. Interrelationships of histopathology and other clinical variables in patients with germ cell tumors of the testis. Cancer. Jun 1 1983;51(11):2121-5. [Medline].
• Bredael JJ, Vugrin D, Whitmore WF Jr. Autopsy findings in 154 patients with germ cell tumors of the testis. Cancer. Aug 1 1982;50(3):548-51. [Medline].
• Fleming ID, Cooper JS, Henson DE, et al. AJCC cancer staging manual. 5th ed. New York, NY:. Lippincott-Raven;1997.
• Horstman WG. Scrotal imaging. Urol Clin North Am. Aug 1997;24(3):653-71. [Medline].
• Kodama M, Murakami M, Kodama T. Chronological transition of the age-adjusted incidence rates (AAIRs) of 20 major neoplasias from early 1960s to mid-1980s. Anticancer Res. Jan-Feb 1999;19(1B):779-87. [Medline].
• Lepidini G, Biancari F, D''Andrea V. Severe thrombosis after chemotherapy for metastatic choriocarcinoma of the testis maintaining complete remission for a long period. Scand J Urol Nephrol. Apr 1997;31(2):221-2. [Medline].
• Looijenga LH, Oosterhuis JW. Pathogenesis of testicular germ cell tumours. Rev Reprod. May 1999;4(2):90-100. [Medline].
• Mead GM. Chemotherapeutic Management of Metastatic Germ Cell Testis Cancer. Risk-Adapted Therapy/Poor Risk Patients. In: Vogelzang et al, eds. Comprehensive Textbook of Genitourinary Oncology. 2nd ed. Philadelphia, Pa:. Lippincott Williams & Williams;2000:1024-1031.
• Mostofi FK, Sesterhenn IA. Anatomy and pathology of testis cancer. In: Comprehensive Textbook of Genitourinary Oncology. Baltimore, Md:. Williams and Wilkins;1996.
• Parkin DM, Muir CS. Cancer Incidence in Five Continents. Comparability and quality of data. IARC Sci Publ. 1992;45-173. [Medline].
• Prow DM. Germ cell tumors: staging, prognosis, and outcome. Semin Urol Oncol. May 1998;16(2):82-93. [Medline].
• Ramon y Cajal S, Pinango L, Barat A. Metastatic pure choriocarcinoma of the testis in an elderly man. J Urol. Mar 1987;137(3):516-9. [Medline].
• Requena L, Sanchez M, Aguilar A. Choriocarcinoma of the testis metastatic to the skin. J Dermatol Surg Oncol. May 1991;17(5):466-70. [Medline].
• Richie JP. Neoplasms of the Testis. In: Campbell's Urology. 7th ed. Philadelphia, Pa:. WB Saunders Co;1998.
• Ro JY, Dexeus FH, el-Naggar A. Testicular germ cell tumors. Clinically relevant pathologic findings. Pathol Annu. 1991;26 Pt 2:59-87. [Medline].
• Saxman SB, Loehrer PJ. Chemotherapeutic Management of Metastatic Germ Cell Testicular Cancer. Overview of Initial Therapy for Metastatic Seminoma and Nonseminoma. In: Vogelzang et al, eds. Comprehensive Textbook of Genitourinary Oncology. 2nd ed. Philadelphia, Pa:. Lippincott Williams & Williams;2000:1010-1017.
• Swerdlow AJ. Epidemiology of testicular cancer. In: Principles and Practice of Genitourinary Oncology. Philadelphia, Pa:. Lippincott-Raven Publishers;1997.
• Ulbright TM. Germ cell neoplasms of the testis. Am J Surg Pathol. Nov 1993;17(11):1075-91. [Medline].
• Vugrin D, Cvitkovic E, Posner J. Neurological complications of malignant germ cell tumors of testis: biology of brain metastases (I). Cancer. Dec 1979;44(6):2349-53. [Medline].

Article Last Updated: Mar 24, 2006