What is Nonseminomatous Testicular Tumors?
Testicular tumors are the most common solid organ cancer in men between the ages of 15 and 35. Even though they only make up about 0.5% to 1% of all solid cancers in men (or about 10,000 cancer cases every year) in the US, the good news is they have a great survival rate; most men live at least five years after being diagnosed.
There are three main types of testicular cancer: germ cell tumors, sex cord-stroma tumors, and extragonadal tumors. Germ cell tumors, which are divided further into two main types: seminomas and non-seminomas based on their microscopic appearance. Seminomas are the most common type, but non-seminomatous germ cell tumors (NSGCT) are found nearly as often. NSGCT are the most likely type of testicular cancer to spread to other parts of the body. They typically affect the lungs, liver, central nervous system, and bone, in that order.
About one-third of patients with NSGCT will have cancer that has spread, or metastasized, at the time they are diagnosed. NSGCT are further divided into different types, including yolk sac tumors, embryonal cell carcinomas, choriocarcinomas, and teratomas. Seminomas that have specific components, known as syncytiotrophoblasts, are also treated as non-seminomatous tumors. The treatment plan depends on the specific type and stage of the cancer.
In the past, testicular cancers led to 11% of all cancer deaths in men between 25 and 34, and only 64% of men survived at least five years after being diagnosed. But now, after treatment with surgery and chemotherapy, the overall outlook is much better, with about 96% of men living at least five years after diagnosis.
What Causes Nonseminomatous Testicular Tumors?
Testicular cancer is often linked to a condition called testicular dysgenesis syndrome. Risk factors for testicular cancer can include undescended testicles, a birth defect of the urethra, reduced sperm production leading to infertility, a family history of testicular cancer, hernias in the groin area during childhood, underdeveloped testicles during childhood, a type of cell abnormality in the testicles called germ cell neoplasia in situ (GCNIS), and a history of cancer in the other testicle.
Genetics is the most significant risk factor, with a much higher likelihood of testicular cancer in direct relatives (brothers and sons) of men with germ cell cancers. Research on families and twins indicates that testicular cancers may be inherited in approximately half of close relatives. This makes it more likely for testicular germ cell tumors to be inherited than breast, colorectal or ovarian cancers.
GCNIS, previously known as intratubular germ cell neoplasia, is usually the first sign of almost all testicular germ cell tumors, accounting for about 90%. Half of the individuals known to have GCNIS will develop testicular cancer within the next five years.
These abnormal cells originate from early germ cells, dormant cells that transform during fetal development or early childhood. They remain inactive until puberty, when an increase in certain hormone levels can stimulate their development. However, how exactly GCNIS transforms into testicular cancer is not entirely understood. The rising number of testicular tumors and other male reproductive disorders, like infertility, indicate that they might arise due to “testicular dysgenesis.” This condition results from a combination of environmental and lifestyle factors and genetic susceptibility.
Germ cell tumors appear more commonly in certain groups, such as individuals with mixed biological sex characteristics, hormone insensitivity syndromes, Klinefelter’s syndrome, and Down syndrome.
The occurrence of germ cell tumors in families, the drastic difference in the rate of testicular cancers between black and white Americans, and identified genetic risk factors support the role of genes in testicular cancer. Certain gene variations are also associated with an increased risk of testicular cancer.
A link has been observed between long-term marijuana use (for more than 10 years) and testicular cancer.
Exposure to estrogen during pregnancy, like from the drug diethylstilbestrol (DES) or certain pesticides, has been proposed as a possible cause for testicular cancers, but research results are still unclear.
Testicular microlithiasis, a condition where small calcium deposits are found in the testicles, is more common in men with germ cell cancers. However, this condition is much more common than testicular cancer, making it ineffective as a screening tool for this type of cancer.
Risk Factors and Frequency for Nonseminomatous Testicular Tumors
Testicular cancer is the most common form of cancer affecting young men. Interestingly, this disease is most common among white men, less common in African-Americans, and rapidly increasing among Hispanic populations. Over the last 40 years, the age-adjusted incidence of testicular cancer has almost doubled. Why the rate is hiking remains unknown, but it’s suggested that our environment may have become more harmful. More cases of germ cell tumors are being found in the early stages, owing likely to increased awareness and early diagnosis. Meanwhile, less than 15% of men are found to have advanced-stage disease when diagnosed. For men with a certain cell abnormality known as GCNIS, the chance of developing invasive germ cell cancer stands at about 50% within 5 years.
Having undescended testicles (cryptorchidism) can increase the risk of developing testicular cancer up to six times in the affected testicle. However, this risk can fall to two to three times if the condition is corrected before puberty. There’s only a slightly increased risk of developing cancer in the normally descended opposite testicle. If a man has a first-degree relative afflicted with germ cell cancer, he has a higher risk of also developing testicular cancer, and at an earlier age. Men with a personal history of testicular cancer have about a 12 times higher risk of developing a new cancer in the opposite testicle. Despite this elevated risk, only about 2% of these men will develop a new cancer over 15 years.
The global incidence of testicular cancer is rising, with the highest rates observed in Scandinavian countries like Norway and Denmark, as well as in Germany, Switzerland, and New Zealand. The fastest rates of increase are seen in Southern Europe and South America. In the US, although the incidence of testicular cancer is on the rise, the growth is starting to slow down. The current overall risk of a man developing testicular cancer in the US is roughly 6 in 100,000, and the annual rate of increase is about 0.8%.
Signs and Symptoms of Nonseminomatous Testicular Tumors
Checking for testicular non-seminomatous germ cell tumors involves taking a careful medical history and doing a detailed physical check-up. Doctors look for any unusual features in the testicles, as well as information on conditions at birth or family history of testicular cancer. The presence of a solid mass in either of the testicles will be treated as a potential tumor unless proven otherwise. Doctors also need to look for signs that the cancer has spread to other parts of the body.
Non-seminomatous germ cell tumors may lead to male infertility because of reduced sperm counts, poor sperm movement, or abnormal sperm shapes. This is associated with abnormal sperm production and is reported in up to 35% of patients. Therefore, doctors should also check the testicles of male infertility patients for possible masses.
People with localized disease usually have a painless swelling or lump in one of the testicles. Other symptoms include dull pain in the scrotum, severe pain, or trauma to the testicle leading to discovery of the lump during a check-up or imaging procedure. A thorough testicular examination will help spot a firm intra-testicular mass.
To tell apart lesions inside and outside of the testicles, doctors examine and gently roll each testicle. In some cases, fluid buildup (hydrocele) can make it hard to examine the testicle adequately, and ultrasound imaging will be needed to look for a testicular lesion more accurately. Uncommonly, testicular cancer patients may show signs of advanced disease. Notably, about 5% of men with testicular cancer have breast enlargement (gynecomastia) due to high levels of HCG hormone. Therefore, men with gynecomastia should have their testicles checked for masses and vice versa.
Patients with a significantly larger or swollen testicle are likely to have an inflammation of the testicle and epididymis (epididymo-orchitis), especially if the testicle is red or painful. If the supposed inflammation is painless or does not improve with antibiotics, it should be seen as potentially cancerous.
Additional wide-ranging symptoms may include loss of appetite, tiredness, and weight loss. Patients with cancer spread to the lungs might have a cough, coughing up blood, or difficulty breathing. Swollen lymph nodes in the neck or above collarbones can occur when the cancer spreads through the lymphatic system. Retroperitoneal (behind the abdominal cavity) spread can lead to back pain, varicocele (swelling of testicular veins), or swelling in the legs due to compression of testicular blood vessels. Digestive symptoms such as nausea, vomiting, or bleeding can occur in patients with spread behind the duodenum (part of the small intestine). When diagnosed early and treated promptly, testicular NSGCT has an excellent prognosis since it responds well to a combination of chemotherapy, radiation, and surgery.
Testing for Nonseminomatous Testicular Tumors
Before receiving any treatment, including surgery for testicular tumors, certain blood tests would be conducted to check the levels of specific substances known as tumor markers, such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactic dehydrogenase (LDH). These markers can help determine if non-seminomatous testicular germ cell tumors, a form of testicular cancer, are present.
AFP levels could rise in up to 70% of people with these types of tumors. If AFP levels are high in someone diagnosed only with seminoma, another form of testicular tumor, it means that other types of cancerous cells might have been missed. HCG, another tumor marker, is produced by certain types of cells in these tumors, while LDH is a nonspecific tumor marker, meaning it isn’t specific to any one type of cancer, and can be an indicator of large or aggressive tumors.
Ultrasound, an imaging test, is the initially recommended method for identifying testicular tumors. The combination of physical examination and ultrasound can diagnose testicular cancer with nearly 100% accuracy. A mass within the testicle that is less bright than surrounding tissue, solid, and has blood flow to it, as seen on an ultrasound, could indicate cancer. Doctors will need to discuss the potential impacts of the disease and its treatment with the patient, which can include infertility. Thus, sperm banking might be proposed in some cases.
For diagnosis, surgical removal of the testicle through the groin, known as an orchiectomy, is typically performed. Though a biopsy can also diagnose cancer, it sometimes leads to the spread of the disease.
CT scans of the abdomen and pelvis using contrast, a type of dye that helps improve the images, are important to detect any spread of the cancer to the lymph nodes. For patients showing high levels of HCG, a CT of the brain may be conducted to look for potential metastatic lesions or areas where the cancer has spread.
Patients don’t need a needle biopsy, a procedure that uses a needle to withdraw a small amount of tissue for testing, of a possible testicular tumor, as this could lead to the cancer spreading in unusual ways. If a biopsy is needed in rare situations, it can be done by making a cut in the groin area with control of the blood supply to the testicle. If cancer is presumed based on the preliminary results, the testicle is typically removed.
Treatment Options for Nonseminomatous Testicular Tumors
The go-to surgical treatment for testicular cancer with no signs of spreading beyond the affected testicle depends on a procedure called radical orchiectomy. This operation is carried out via the groin area and allows the doctor to remove the whole tumor and analyze it more precisely. In stage I of the disease (where the cancer is still localized to the testicle itself), this treatment can be curative for 75% of patients. So utmost caution is exercised while removing the tumor to avoid spreading any cancer cells to the lymphatic system.
Medical professionals may recommend a biopsy (a test carried out to examine tissue or cells) of the unaffected testicle in some cases, particularly if the patient has an increased risk of developing a cancerous condition known as Germ Cell Neoplasia In Situ (GCNIS); for example, a history of having an undescended testicle.
Careful investigation, including medical imaging and pathology tests, is needed for growths inside the testicle. While a full removal of the testicle might not be necessary for benign (non-cancerous) conditions or for low-volume cancerous tumors, fertility preservation such as sperm banking should be encouraged early on, especially before any chemotherapy, which can affect fertility.
In some cases, a doctor may recommend active surveillance; this involves closely following a patient’s condition without giving any treatment unless symptoms appear or change. This strategy relies on frequent check-ups, blood tests, and imaging tests after the initial surgery to remove the testicle, and is used mainly to avoid the side effects of chemotherapy or radiation therapy.
Chemotherapy is typically reserved for certain type of testicular cancer, such as non-seminomatous germ cell tumors (NSGCT). Apart from various side-effects such as numbness or weakness, kidney problems, loss of hearing, memory problems, and decreased sexual desire, chemotherapy can also affect a patient’s fertility.
Operating on the lymph nodes in the abdominal area, known as a retroperitoneal lymph node dissection, is largely common in the U.S. for managing low-stage non-seminomatous germ cell tumors. This procedure could pinpoint patients who may benefit from postoperative chemotherapy, although it does come with potential complications, such as ejaculatory problems and erectile dysfunction. The decision to opt for this method may vary according to the stage and risk factors associated with the patient’s condition.
Chemotherapy after surgery may be recommended for patients who show a high risk for the recurrence of the disease, given the relapse rate in stage I of non-seminomatous germ cell tumors stands at approximately 64%. This relapsed group would likely be considered high-risk for metastatic disease (cancer spreading to other parts of the body). In contrast, active surveillance, operation for the removal of lymph nodes, or chemotherapy treatment may be suggested for patients with initial stage I tumors, depending on the risk factors such as size and degree of cancer development.
Overall, the treatment for testicular cancer can be formulated based on its stage and the patient’s overall health. Later stage tumors may need a more intensive therapeutical approach as compared to early-stage tumors, while active surveillance could be a reasonable option for regular monitoring of the disease in low-risk patients. The importance of regular check-ups and early detection in managing testicular cancer cannot be overstressed. Furthermore, the treatment guidelines set by organizations like the American Urological Association and NCCN can be a good resource for understanding the treatment strategies and follow-up care for testicular cancer.
Lastly, extragonadal tumors, or germ cell tumors outside the testicles, are a rare occurrence. The original cause of these kinds of tumors is not explicitly known. Two prevalent theories suggest that these tumors develop from germ cells that have misplaced location during formation or due to reverse migration of germ cells from the testis. The treatment for such tumors largely depends on the surgical removal of tumors followed by chemotherapy. However, the prognosis rate for such tumors is relatively low, making it all the more essential to go through regular check-ups, early diagnosis, and prompt treatment.
What else can Nonseminomatous Testicular Tumors be?
The following are medical conditions that may be diagnosed:
- Epididymo-orchitis (inflammation of the testicle and the tube at the back of the testicle)
- Hematocoele (accumulation of blood within the scrotum)
- Hernia (abnormal exit of tissue or an organ through the wall of its original cavity)
- Hydrocoele (abnormal fluid buildup in the scrotum)
- Orchitis (inflammation of one or both testicles)
- Spermatocele (fluid-filled sac in the epididymis that houses the sperm)
- Syphilitic gumma (lesions caused by advanced syphilis)
- Testicular seminoma (a type of testicular cancer)
- Testicular torsion (an emergency condition where the spermatic cord becomes twisted)
- Varicocoele (enlargement of veins within the scrotum, similar to varicose veins)
What to expect with Nonseminomatous Testicular Tumors
Patients who have undergone chemotherapy, radiation therapy, or both, have a higher chance of experiencing heart-related conditions and developing other forms of cancer. They may also be at risk of hypogonadism, a condition which causes low levels of sex hormones.
When diagnosing patients with testicular germ cell tumors (a form of testicular cancer), doctors use several factors to categorize patients into low, intermediate, and high-risk groups. The factors include the type of cells involved in the tumor, the presence or absence of cancer spread to other organs (visceral metastasis), and levels of specific proteins (tumor markers) in the blood after the removal of a testicle.
Being in the low-risk group typically means a good prognosis (outcome). For instance, 56% of the patients with this form of testicular cancer have a good prognosis with 89% not showing any disease within 5 years and 92% surviving after 5 years. The low risk is defined as cancer located only in the testicle or the area behind the abdomen (retroperitoneal) without any visceral metastases and with low levels of specific proteins (tumor markers) like AFP, HCG, and LDH.
Intermediate-risk tumors account for 28% of all non-seminoma germ cell tumors, with a 5-year survival rate of 75%, and 80% survival rate after 5 years. This category includes cases with cancer found in the testicle or behind the abdomen with intermediate levels of tumor markers.
High-risk tumors typically have a poor prognosis. Only 41% of patients are disease-free after five years, and only 48% survive five years. High risk tumors are usually those with cancer spread to the area between the lungs (mediastinal), without visceral metastases, or have very high levels of tumor markers.
In terms of survival statistics by stages of cancer, stage I has a 98% chance of not having the disease after 5 years. For stages IIA and IIB, it’s a 92% disease-free rate, while stage IIC shows a 92% survival rate over 5 years. For stage III, the survival rate varies with risk level: 92% for low-risk, 80% for intermediate risk, and 48% for high risk.
Possible Complications When Diagnosed with Nonseminomatous Testicular Tumors
Complications are typically seen when non-seminoma germ cell tumors (NSGCT) spread to the area behind the abdominal cavity and distant tissues. Problems that may arise as a result of the treatment have already been outlined above, these include retrograde ejaculation (where semen enters the bladder instead of exiting the penis), incontinence at the neck of the bladder, infertility, and mass effects, which can cause pressure and pain. Additionally, other complications may occur based on which organs are affected.
Common Complications:
- Spread of NSGCT to distant tissues
- Retrograde ejaculation
- Incontinence at the neck of the bladder
- Infertility
- Mass effects causing pressure and pain
- Additional complications related to affected organs
Recovery from Nonseminomatous Testicular Tumors
All patients are encouraged to participate in various support groups following diagnosis and treatment. If a patient is expected to receive chemotherapy, radiation, or surgery, they should be informed about potential fertility problems and possible complications that may arise from their treatment. It is also important to discuss how to handle these complications, should they occur.
Preventing Nonseminomatous Testicular Tumors
The testes, the main reproductive organs in males, are found in the scrotum. They are crucial in fertility as they produce sperm. Through a process called testicular self-examination, men (or their doctor) can check each testicle one at a time to feel for any unusual lumps or bumps. This can help detect testicular cancer, a disease which can usually be cured if spotted and treated early on. Most of the time, a testicle with a lump will need to be taken out. Other ways of diagnosing and understanding the stage of the cancer may involve several kinds of imaging tests.
Some people with testicular cancer might experience symptoms like a lump in their testicle that generally does not hurt, a feeling of weight in the scrotum, or nausea and vomiting if the cancer has spread elsewhere in the body.
A particular type of testicular cancer, known as non-seminomatous germ cell tumors, has a high survival rate, with over 95% of individuals diagnosed being cured. It’s important for everyone, including those in healthcare and the public, to know about testicular cancer as early detection can play a vital role in managing this type of cancer.
