Testicular cancers are classified based on their cell of origin: seminomatous, nonseminomatous, Leydig, Sertoli, choriocarcinoma, embryonal, teratoma, and yolk-sac derivatives. Seminoma and non-seminomatous lesions are frequently grouped as germ cell tumors and are notable for their responsiveness to chemotherapy in comparison to the other types. Seminoma accounts for about a third of all testicular germ cell malignancies and is one of the most treatable cancers with a survival rate of 98% to 99% in early-stage disease.
While the overall incidence of testicular germ cell tumors is low, at only 1% to 2% of all male malignancies; it remains the most common cancer in the 15 to 35 year age group.
The exact etiology of seminoma is unknown. The most current theory is that environmental endocrine disrupters exert estrogenic and/or antiandrogenic activities, contributing to the arrested development of the gonocyte. The disease probably develops as carcinoma in situ during a short phase of intrauterine growth. One widely accepted theoretical concept is Testicular Dysgenesis syndrome (TDS). TDS groups germ cell tumors, impaired spermatogenesis, cryptorchism, and hypospadias based on reports that they share some common risk factors, hypothesized to originate during fetal life. An increased incidence is reported during the past several decades. Roughly 10% of all patients with germ cell tumors had a personal history of cryptorchidism.
A patient with an undescended testicle has at least four times the risk for carcinoma compared to a normal testicle. This risk is increased regardless of the age at repair. Patients with Trisomy 21 are 50 times more likely to have testicular cancer. There is evidence of a recessive gene inheritance in familial testicular cancer. In a Japanese population, this association was linked to the HLA class II allele DRB1*0410, and in a United Kingdom study, it seemed to be associated with a homozygous allele of the GSTP1 locus and expansion of (CAG)n repeats.
Testicular germ cell tumors (GCT) are the most common solid malignancies affecting young males (age 15 to 45 years). It is ten times more common in males of northern European ancestry and five times more common in all whites compared to others. The overall prevalence of seminoma generally increases with age.
Testicular seminoma originates in the germinal epithelium of the seminiferous tubules. The disease is thought to result from the proliferation of immature spermatogonia. Arrested gonocyte maturation with persistence of embryonic features and correspondingly increased genomic instability is the most probable model for the pathogenesis of CIS. The transition from the precursor lesion to invasive cancer is associated with a gain of the short arm of chromosome 12, Isochromosome i(12p), likely involving KRAS2 and possibly NANOG (pseudogenes). The exact mechanism is unknown. However, there is also an increased frequency of isozymes of 7, 15, 19 and X in seminoma.
Exposure to various factors in adolescence and adulthood appears linked to the development of testicular cancer. Firefighters and aircraft maintenance personnel and farmers exposed to organochloride pesticides appear to have an increased risk of developing testicular cancer. Case-control studies have revealed significant associations between seminoma and levels of cis-nonachlor, trans-nonachlor, oxychlordane, and total chlordane.
Ochratoxin A, a substance less well-studied, naturally occurs in the mold in grains, coffee, nuts, and spices that have recently been linked to testicular cancer.
Patients usually present with an asymptomatic testicular mass which may be associated with infertility. Testicular pain from malignancy is relatively rare but still should be included in the differential diagnosis.
On physical exam, there is usually a unilateral, firm to hard palpable mass in the scrotum which is localized to the testis. This may be associated with a hydrocele that would preclude palpation, so testicular ultrasonography may be needed to identify the mass. Metastatic disease, although rare, can present initially with lymphadenopathy in the retroperitoneum and the anterior mediastinum. Even massive metastatic disease can be produced from a non-palpable testicular malignancy.
Typically, testicular ultrasonography shows an intratesticular mass that is relatively hypoechoic and homogeneous. As the mass increases in size, it may become less homogeneous due to hemorrhage and necrosis.
The initial evaluation is by testicular ultrasonography. A CT scan of the abdomen and pelvis is the initial staging modality, but it may fail to identify retroperitoneal nodes in 15% to 20%. A chest CT is usually recommended only when there is an abnormal chest x-ray first. PET scanning is not usually part of the initial workup but may be useful in tracking activity and growth in residual masses following definitive chemotherapy.
Several laboratory values may be useful in following tumor burdens. These include AFP, B-HCG, and LDH. Alpha-fetoprotein (AFP) elevation indicates at least some nonseminomatous disease and those patients are then treated as nonseminomas, germ cell patients. LDH may be used to follow the overall seminomatous tumor burden. Beta-human chorionic gonadotropin (HCG) is present in 5% to 10% of seminoma patients; these usually demonstrate the syncytial cytotrophoblastic subtype. Such elevations tend to be associated with metastatic disease, but the beta-HCG elevation by itself has no connection with overall survival.
As noted earlier, a plain chest film may reveal metastatic disease, and chest CT is only indicated to evaluate abnormalities on the plain abnormalities. Ultrasound is the typically the most useful diagnostic method for follow-up of metastatic masses.
Staging: the TNM system:
In the numerical system:
Management (National Comprehensive Cancer Network - NCCN Guidelines)
Stage 0 Seminomas: Carcinoma in situ (CIS) where the levels of tumor markers like HCG and AFP are not elevated. Treatment may not be needed as long as there are no signs that the CIS is growing or turning into invasive cancer. (The diagnosis is typically made via a biopsy.) If CIS is treated, it is with an orchiectomy (to remove the testicle) or with testicular radiation.
If tumor marker levels are high, then the cancer is not stage 0, even when only CIS is found in the testicle, and there are no signs of cancer spread. These cases are treated like stage I cancers. CT scan of the abdomen and pelvis is required to verify the extent of the malignancy in such cases.
All of the following cancers are treated initially with initial radical orchiectomy. After surgery, there may be several treatment choices as follows:
Stage I Seminomas:
Stage II A:
Stage II B and C:
Small tumors are often watched with CT scans to see if they grow. If they do, further treatment is needed. If the tumors are detected on a PET scan, surgery or a different chemotherapy is indicated.
Stage IV refers to cancer that has spread to any other organ.
There are several treatment options available to these patients, but surgery, a radical orchiectomy, is almost always the primary intervention. The surgical approach usually requires an incision in the groin with the removal of the entire testicle and most of the spermatic cord. This is called a radical inguinal orchiectomy and is both therapeutic and a part of the staging procedure. A scrotal incision approach should be avoided in any orchiectomy or surgical testicular exploration where a malignancy is suspected.
Most men do not have a significant decrease in testosterone or low testosterone symptoms of sexual dysfunction with the removal of a single testicle. The procedure is not usually a cause of infertility, and 25% of men with testicular malignancies are already infertile before getting a testicular cancer diagnosis.
Sperm counts may increase after removal of the cancerous testicle. Reconstructive surgery with a prosthetic testicle is an option which may be exercised with the primary operation delayed until active treatment is done or completely declined. Retroperitoneal lymph node dissection is more complex and invasive. It is used for staging and is usually open, but laparoscopic approaches are being developed. Complications include immediate problems, such as infection or bowel blockage, and loss of the ability to ejaculate. For these reasons, retroperitoneal lymph node dissections are rarely done for seminoma except possibly for growing, residual abdominal masses not responding to other treatments. Radiation or chemotherapy generally is indicated for the management of positive lymph nodes.
Pelvic nodes are anatomically near to L1-L4 sympathetic roots of the superior hypogastric plexus. When oncologically possible, they should be surgically spared, at least unilaterally, to preserve ejaculatory function.
Contrary to non-seminomatous germ cell tumors, retroperitoneal lymph node dissection (RPLND) is not indicated in seminomas.