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Nonseminomatous Testicular Tumors

  • Author: David M Hoenig, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Mar 04, 2016
 

Background

Testicular cancer is relatively uncommon in the United States, with approximately 8500 cases per year. The overall incidence of testicular tumors worldwide ranges from 0.2-10.3 cases per 100,000 persons. Such tumors may arise in males of nearly any age and may be of germ cell or non–germ cell origin. Tumor histology (see Histologic Findings) and tumor stage (see Staging) are of primary importance in determining the prognosis of testicular tumors. This article addresses the demographics, histology, prognosis, and treatment of nonseminomatous germ cell tumors (NSGCTs).

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History of the Procedure

The treatment of testicular cancer has developed in earnest over the past half century. Before 1970, testicular tumors carried a mortality rate that approached 50%, whereas recent studies have reported that the cure rate using multimodal therapy exceeds 90%. Improved understanding of the histology, mechanisms of tumor spread, and tumor markers, combined with the improved quality of radiographic imaging for accurate staging, have greatly contributed to the management of testicular cancer. The combination of refinements in surgical intervention and the application of effective combination chemotherapy has emerged as a paradigm for the successful use of multimodal therapy for solid tumors.

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Problem

Testicular cancer has three main types: germ cell tumors, non–germ cell tumors, and extragonadal tumors. Germ cell tumors, which are the most common, are classified as either seminoma or nonseminoma, based on histology. Of the three main types of testicular cancer, nonseminomatous germ cell tumors (NSGCTs) are second only to seminomas in terms of frequency. This discussion explores the incidence, risk factors, diagnosis, treatment options, and prognosis of NSGCTs.

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Epidemiology

Frequency

US incidence

Testicular cancer is relatively uncommon, with approximately 8720 new cases predicted to occur in 2016 in the United States.[1] The peak incidence is in men aged 20-34 years. Testicular cancer is the most common solid tumor in this otherwise young, healthy, and productive age group.

Between 1973 and 1995, the incidence of testicular cancer in the United States increased 51%, from 3.61 to 5.44 per100,000 men. Birth cohort was strongly associated with relative risk of testicular cance, and peak age at diagnosis decreased for each successive birth cohort.[2] Rates for new testis cancer cases have continued to increase over the past 10 years, rising on average 0.8% each year. Based on 2008-2012 data, the incidence is approximately 5.6 cases per 100,000 men.[3]

The rate of NSGCTs specifically also appears to have increased. In addition, the incidence of NSGCTs among active servicemen in the military almost doubled from 1988-1996.[4] NSGCTs are less common in African-American males than in white males.

International incidence

Worldwide, testicular cancer has the highest incidence in northern Europe, with the highest rates in Norway and Denmark. Rates continue to increase in most countries worldwide, especially in southern Europe and Latin America, but rates have been slowing in northern Europe, the United States, and Australia.[5]

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Etiology

Factors that alter the differentiation of the primordial germ cell, resulting in the presence of an embryonal stem cell, can increase the risk of NSGCT. Risk factors include a history of testicular cancer in the contralateral testis, cryptorchidism (undescended testis), gonadal dysgenesis, prenatal exposure to high estradiol levels, exposure to chemical carcinogens, trauma, and orchitis. Other risk factors may include childhood inguinal hernias and any cause of testicular atrophy.

In 2005, a 25-year follow-up study of 44,864 Swedish men suggested that elevated serum cholesterol levels may increase the risk of testicular cancer.[6] Further validation studies are required to evaluate these findings in other populations.

One of the most significant risk factors for testicular cancer is cryptorchidism. In addition, the age at which orchidopexy (an operation to bring the testicle down into the scrotum) is performed appears to play a significant role. A 2007 study reported a 2.23 relative risk (in comparison with the general Swedish population) of testicular cancer in patients who underwent orchidopexy before age 13 years, while the relative risk among those who underwent orchidopexy at age 13 years or older was 5.40.[7] Therefore, among boys with cryptorchidism, orchidopexy performed before puberty appears to reduce the likelihood of testicular cancer later in life.

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Pathophysiology

NSGCTs refer to the germ cell tumors that contain embryonal stem cells. These may be differentiated into extraembryonic tissues or somatic elements. Most tumors are composed of a mixture of these elements.

The four histologic classifications of NSGCTs are as follows:

Mixed tumors are those with some combination of those histologies. Tumors with both seminomatous and nonseminomatous elements are classified as NSGCTs because the NSGCT component most accurately reflects the response to treatment and overall prognosis.

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Presentation

The classic presentation of a testicular tumor is a painless, swollen, hard testis in an otherwise healthy man in the third or fourth decade of life. The presentation can vary depending on the amount of disease, clinical stage, and the presence of metastases at the time of referral.

Some patients present with a swollen painful mass in the scrotum that may be dismissed as infectious or inflammatory in nature, potentially resulting in a detrimental delay in starting treatment for NSGCT. Whenever the physical examination reveals any deviation from a palpably normal testicle, scrotal ultrasonography should be performed.

In all patients in whom testicular tumors are suspected, obtain a complete history and perform a complete physical examination. The history should include specific questions regarding possible risk factors for testicular cancer. Questions about cryptorchidism, trauma, and mumps orchitis are useful. Likewise, the occupational, chemical exposure, and smoking history of the patient should be obtained.

During the general physical examination, special attention should be given to the presence of gynecomastia, which is a finding in 5% of testicular cancer cases. Supraclavicular adenopathy may be a finding in advanced disease. Lung examination in patients with widespread lung metastases may reveal areas of decreased breath sounds. Abdominal examination should be performed to assess for visceral or bulky lymphatic involvement.

The contralateral testis must be examined for possible abnormalities. The testicles should be readily palpable in the scrotum. The contour of each testicle should be smooth and the consistency uniform. Any size discrepancy between the two testicles should be assessed and noted.

Differentiation of the scrotal contents should be found with careful palpation. The epididymis, attached to the posterior aspect of the testicle, is frequently the site of induration or cysts. Patients may discover such abnormalities during self-examination, prompting them to seek medical attention. These conditions should be identifiable during the physical examination. If the inability to perform an adequate evaluation is a concern, scrotal ultrasonography must be performed to aid in the diagnosis.

Finally, a neurologic examination should be conducted. This is important to evaluate for possible brain metastasis.

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Indications

Surgery is indicated not only for the initial treatment of nonseminomatous germ cell tumors (NSGCTs) but also for diagnosis.

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Relevant Anatomy

Testicular lymphatics relate to the embryonic origin of the testis. The male gonad initially forms near the kidney and descends through the inguinal canal to the scrotal sac. The right gonadal vein derives from the inferior cava, while the left gonadal vein derives from the left renal vein. Additional blood supply derives from the artery of the vas and the cremasteric arteries.

Testicular lymphatics follow the vessels of the spermatic cord through the inguinal canal and into the retroperitoneum. Testicular cancer spreads predominantly and initially through lymphatic routes. On the right, the cancer landing zone is between the aorta and the inferior vena cava; on the left, it is on top of and lateral to the aorta. Within the retroperitoneum, there can be a crossover from the lymphatics draining the right toward those of the left.

Scrotal skin lymphatics are different from testicular lymphatics and drain into the inguinal nodes. Perform all orchiectomies for solid masses through an inguinal route to avoid tumor spillage into the inguinal drainage basin. If a patient undergoes scrotal exploration, subsequent therapy may necessitate hemiscrotectomy and radiation treatment of the inguinal nodes.

In patients who have undergone prior herniorrhaphy, orchiopexy, or other alteration in lymphatic drainage, extend their radiation field to include the contralateral inguinal region with contralateral testis shielding.

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Contraindications

Radical (inguinal) orchiectomy has no contraindications, other than potential anesthetic risks and uncontrolled bleeding diathesis. In such high-risk patients, preoperative clearance and preparation may be required, but radical orchiectomy should still be performed at the earliest opportunity.

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Contributor Information and Disclosures
Author

David M Hoenig, MD Chief of Urology, Long Island Jewish Medical Center

David M Hoenig, MD is a member of the following medical societies: American Urological Association, Endourological Society

Disclosure: Received honoraria from Best Doctors Inc for consulting.

Coauthor(s)

Thomas H Rechtschaffen, MD Consulting Staff, Department of Urology, A Family Urology Practice, PC

Disclosure: Nothing to disclose.

Janice Angela Santos-Cortes, MD Assistant Professor of Urology at Columbia University, Division of Urology at Mount Sinai Medical Center (Miami Beach)

Janice Angela Santos-Cortes, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Urological Association, Society of Urologic Oncology, Society of Women in Urology, Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

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Table. Serum tumor markers
Stage LDH hCG (mIU/mL) AFP (ng/mL)
S0 Normal or below normal Normal or below normal Normal or below normal
S1 < 1.5 times the reference range < 5,000 < 1,000
S2 1.5-10 times the reference range 5,000-50,000 1,000-10,000
S3 >10 times the reference range >50,000 >10,000
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