Understanding how testicular germ cell tumours are diagnosed is crucial for young men, as this cancer most commonly affects males in their teens through 30s, and early detection can make a significant difference in successful treatment outcomes.

Introduction: Who Should Seek Diagnostic Testing

Testicular germ cell tumours are the most common cancer in males between the ages of 15 and 35, though they can occur at any age.^[1] While these cancers are rare overall, affecting about 1 in 250 men during their lifetime, knowing when to seek medical evaluation is essential for early detection and successful treatment.^[6]

You should consider seeking diagnostic evaluation if you notice a painless lump or swelling in your testicle. This is the most common symptom of testicular cancer.^[3] Other signs that warrant a doctor’s visit include a feeling of heaviness in your testicles, scrotum, or the area between your anus and testicles (called the perineum), or a dull ache in these areas.^[24] Sometimes men notice swelling or changes in the size of a testicle without any pain at all.

It’s important not to delay seeking medical attention even if the lump is painless. Many young men feel embarrassed discussing concerns about their testicles, but doctors deal with these issues regularly and are there to help. Getting checked could potentially save your life, as testicular germ cell tumours are highly treatable when caught early.^[20]

Regular self-examination is recommended, especially for teenagers and young adults. You should become familiar with what your testicles normally feel like so you can notice any changes.^[20] If you notice anything unusual during a self-exam, schedule an appointment with your doctor promptly. Men with certain risk factors, such as an undescended testicle (a condition called cryptorchidism), a family history of testicular cancer, or a personal history of testicular cancer in one testicle, should be especially vigilant about monitoring for changes.^[10]

Classic Diagnostic Methods

When you visit a doctor with concerns about a possible testicular tumour, they will use several different approaches to determine whether cancer is present and what type it might be. These diagnostic methods help distinguish testicular germ cell tumours from other conditions and identify the specific characteristics of any cancer found.

Physical Examination

The diagnostic process typically begins with a physical examination. Your doctor will perform what’s called a digital examination, which simply means they use their hands to carefully feel your testicles, scrotum, and the surrounding area.^[3] They’re checking for lumps, swelling, or any unusual masses. The doctor will also examine your abdomen and may check your neck for swollen lymph nodes (small glands that are part of your immune system), as cancer can sometimes spread to these areas.

Ultrasound Imaging

If a lump or mass is detected during the physical exam, the next step is usually an ultrasound of the testicles. Ultrasound is a painless test that uses sound waves to create pictures of the inside of your body.^[12] This imaging test is particularly useful for testicular evaluation because it can show whether a lump is solid (which might be cancer) or filled with fluid (which is usually not cancer). The ultrasound helps your healthcare team get more detailed information about any suspicious masses and helps them determine whether the findings look like they could be cancerous.^[1]

Blood Tests for Tumour Markers

Blood tests play a crucial role in diagnosing testicular germ cell tumours. These tests measure the levels of certain proteins in your blood called tumour markers.^[12] Three specific markers are important for testicular cancer: alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH).

These markers should be measured before any testicle is removed, as they provide important information about the type of tumour and help with planning treatment.^[10] Different types of germ cell tumours produce different patterns of these markers. For example, pure seminomas (one type of testicular germ cell tumour) never produce AFP, so if AFP levels are elevated, it indicates the presence of a non-seminoma component even if the tissue appears to be pure seminoma under the microscope.^[10] About 40% to 60% of men with non-seminomas have elevated levels of AFP or beta-hCG.^[10]

The levels of these tumour markers are also important for determining prognosis. Higher marker levels after the cancerous testicle has been removed can indicate a more serious situation and help doctors decide on the best treatment approach.^[10] These markers continue to be useful throughout treatment and follow-up, as rising levels can be an early sign that cancer has returned.

Additional Imaging Studies

Once testicular cancer is confirmed or strongly suspected, additional imaging tests may be ordered to determine if the cancer has spread beyond the testicle. A computed tomography scan (CT scan) creates detailed three-dimensional images of your body and is commonly used to examine the abdomen, pelvis, and chest.^[12] This helps doctors see if cancer has spread to nearby lymph nodes or to distant organs like the lungs.

Magnetic resonance imaging (MRI) is another imaging technique that may be used in certain situations.^[12] It uses magnets and radio waves instead of radiation to create detailed pictures of soft tissues in your body. Some medical centres may also use other types of scans depending on individual circumstances.

Surgical Diagnosis and Biopsy

Unlike many other cancers where a small tissue sample (biopsy) is taken before treatment, testicular cancer diagnosis usually involves removing the entire affected testicle through a surgical procedure called an orchiectomy.^[13] This is because taking just a small sample could potentially spread cancer cells. The removed testicle is then sent to a laboratory where a specialist doctor called a pathologist examines the tissue under a microscope to confirm the diagnosis and determine exactly what type of germ cell tumour is present.

The pathologist will identify whether the tumour is a seminoma, a non-seminoma, or a mixed type containing both components.^[5] Non-seminomas can include several different cell types, such as embryonal carcinoma, yolk sac tumour, choriocarcinoma, and teratoma. Some tumours contain a mixture of different types of cells. This detailed information about the tumour type is essential for determining the best treatment plan.

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or compare different treatment approaches for testicular cancer. To participate in a clinical trial, patients must meet specific criteria that are carefully defined by the research protocol. Understanding these requirements helps patients and doctors determine whether a clinical trial might be an appropriate option.

Standard Diagnostic Requirements

Before enrolling in a clinical trial for testicular germ cell tumours, participants typically need to have their cancer confirmed through the standard diagnostic methods described earlier. This includes having tissue from the orchiectomy examined and classified by a pathologist to confirm the diagnosis and determine the exact type of tumour.^[4]

Tumour marker blood tests (AFP, beta-hCG, and LDH) are also standard requirements for clinical trial participation. These baseline marker levels help researchers understand the characteristics of each patient’s cancer and monitor how well treatments are working during the study.^[10] Some trials specifically enrol patients based on their tumour marker levels or other prognostic factors.

Staging Assessments

Clinical trials often require precise information about the stage of cancer, meaning how far it has spread in the body. This requires the imaging studies mentioned earlier, such as CT scans of the chest, abdomen, and pelvis.^[10] The staging information helps researchers group patients with similar disease characteristics together, which allows them to better evaluate how well different treatments work for specific situations.

Many clinical trials use the International Germ Cell Cancer Consensus Group (IGCCCG) classification system, which divides patients into different risk groups based on factors like where the tumour started, where it has spread, and the levels of tumour markers.^[10] For instance, patients with seminomas that have only spread to abdominal lymph nodes or lungs are considered to have a good prognosis, while those with more extensive spread may be categorized differently.

Additional Testing Requirements

Depending on the specific clinical trial, additional diagnostic tests may be required. These might include more detailed genetic or molecular analysis of the tumour tissue to look for specific characteristics that the experimental treatment is designed to target. Some trials studying testicular germ cell tumours have examined genetic features like chromosome abnormalities, as gains of chromosome arm 12p are nearly universal in these cancers.^[6]

Clinical trials may also require tests to evaluate your overall health and organ function before you can participate. This ensures that participants are healthy enough to safely receive the experimental treatment being studied. These assessments might include kidney function tests, heart function tests, hearing tests, and other evaluations depending on the specific treatments being tested.