Nonseminomatous Testicular Tumors

Updated: Oct 31, 2017
  • Author: Alexander D Tapper, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Overview

Background

Testicular cancer is relatively uncommon in the United States, with approximately 8800 cases per year, making up 0.5% of all new cancer diagnoses in the United States. [1]  The overall incidence of testicular tumors worldwide ranges from 0.2-10.3 cases per 100,000 persons. Roughly 0.4% of males will be diagnosed with testicular cancer at some point during their lifetime. [1]  

Testicular tumors may arise in males of nearly any age but are most often seen in men 20-34 years old.  Most often these tumors are germ cell in origin, with a small percentage being sex cord/stromal tumors. Tumor histology (see Histologic Findings) and tumor stage (see Staging) are of primary importance in determining the prognosis of testicular tumors. This review 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

There are three main types of primary testicular neoplasms: germ cell tumors, sex cord–stromal tumors, and extragonadal tumors. Germ cell tumors, which are the most common, are classified histologically as either seminoma or nonseminoma.

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 8850 new cases predicted to occur in 2017 in the United States. [2] 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 per 100,000 men. Birth cohort was strongly associated with relative risk of testicular cancer, and peak age at diagnosis decreased for each successive birth cohort. [3] The incidence of testicular cancer has continued to increase over the past 10 years, rising on average 0.8% each year. Based on 2010-2014 data, the incidence is approximately 5.7 cases per 100,000 men. [1]

Testicular cancer is most frequently seen in non-Hispanic white men. The lowest incidence is in African-American men. 

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, particularly southern Europe and Latin America. In contrast, the increase in rates has begun to slow in countries such as Australia and the United States [4]

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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 cryptorchidism (undescended testis), personal history of testicular cancer, family history of testicular cancer, intratubular germ cell neoplasia (ITGCN), and gonadal dysgenesis. Other risk factors may include childhood inguinal hernias and any other cause of testicular atrophy.

Cryptorchidism is one of the most significant risk factors for testicular cancer. Almost 10% of men with testicular cancer have a history of undescended testicle. [5]  

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 in those who underwent orchidopexy at age 13 years or older was 5.40. [6] Therefore, orchidopexy performed before puberty appears to reduce the likelihood of testicular cancer later in life.

Additionally, ITGCN is thought to be a common precursor of most testicular germ cell neoplasms. Roughly 90% of testicular tumors are associated with adjacent ITGCN. Furthermore, men with known ITGCN have an approximately 50% risk of cancer developement in 5 years. [5]

 

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Pathophysiology

As mentioned above, as many as 90% of germ cell tumors are associated with ITGCN. ITGCN appears to result from arrested maturation of gonocytes. These cells fail to differentiate into spermatogonia, and maintain their ability to differentiate into both germinal and somatic tissues. [5, 7]

NSGCTs are germ cell tumors that contain embryonal stem cells. These may be differentiated into extraembryonic tissues or somatic elements. Most NSGCTs are composed of a mixture of these elements, though they can be present in pure forms.

The four histologic classifications of NSGCTs are as follows:

Mixed histology tumors have some combination of the above tumors and may have a component of seminomatous tumor present as well.  As such, 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 as a painless testicular mass 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. Roughly one third of patients diagnosed with NSGCT will present with disseminated disease. [7]

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. 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 patient's occupational, chemical exposure, and smoking history should be obtained.

In the physical exam, both testicles should be carefully evaluated. 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. Any palpable firmness within the testicular parenchyma should raise suspiscion for malignancy and prompt further workup. 

Differentiation of the scrotal contents should be found with careful palpation. The epididymis, attached to the posterolateral aspect of the testicle, is frequently the site of induration or cysts. These conditions should be identifiable during the physical examination. Additionally, testis tumors can cause a reactive hydrocele, limiting the ability to perform a complete exam.  

Whenever the physical examination reveals any deviation from a palpably normal testicle, scrotal ultrasonography should be performed. Scrotal ultrasonography is also necessary if inability to perform an adequate evaluation is a concern.  

During the general physical examination, special attention should be given to the following:

  • Gynecomastia, which is a finding in 5% of testicular cancer cases
  • Supraclavicular adenopathy, which may be a finding in advanced disease
  • Lung examination in patients with widespread lung metastases may reveal areas of decreased breath sounds, or these patients may present with hemoptysis, dyspnea, or cough.
  • Abdominal examination should be performed to assess for visceral or bulky lymphatic involvement.
  • In patients with risk factors for altered lymphatic drainage (see Relevant Anatomy, below) careful examination of the inguinal lymph nodes should be performed.

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

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Indications

Radical orchiectomy is the gold standard in management of suspected testicular neoplasms, as it has both diagnostic and therapeutic benefits. Trans-scrotal biopsy or a scrotal approach to orchiectomy should never be performed in cases of suspected neoplasm, as it can cause contamination of the scrotum and alter patterns of lymphatic spread of tumor as well as complicate subsequent management.

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Relevant Anatomy

Testicular lymphatics relate to the embryonic origin of the testis. The male gonad forms near the kidney and descends through the inguinal canal to the scrotal sac. The right and left gonadal arteries arise from the abdominal aorta at approximately the level of the second lumbar vertebra. Additional blood supply derives from the deferential and cremasteric arteries. The right gonadal vein derives from the inferior cava, while the left gonadal vein derives from the left renal vein.

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, lymphatic drainage 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. As such, a radical orchiectomy should be performed 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 ipsilateral inguinal nodes.

In patients who have undergone prior herniorrhaphy, orchiopexy, or other alteration in lymphatic drainage, radiation treatment, if indicated, should include the contralateral inguinal region with contralateral testis shielding.

Lastly, while these cancers spread predominantly through lymphatic pathways, choriocarcinoma is known to metastasize hematogenously.

 

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Contraindications

Radical (inguinal) orchiectomy is the gold standard of care for suspected testicular neoplasms and 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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Prognosis

The prognosis for patients with NSGCT is ultimately dependent on clinical staging and subsequent risk stratification using histology, primary tumor site, post-orchiectomy tumor marker nadir, and imaging including a minimum or chest x-ray and CT scan of the abdomen and pelvis.  

Using the risk stratification system established by the International Germ Cell Cancer Collaborative Group (IGCCCG) in 1997, patients are categorized into good, intermediate, or poor prognostic categories. [8] Rates of disease-free survival at 5  years are roughly 90%, 75%, and 50% for good-, intermediate-, and poor-risk groups, respectively. 

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