Testicular lymphoma is a rare form of testicular cancer. Primary testicular lymphoma (PTL) is a rare form of non-Hodgkin lymphoma (NHL) that originates in the testicles (testes) and mostly affects men over the age of 50. Lymphomas that originate in other parts of the body can also spread to the testes — this type of lymphoma is sometimes referred to as secondary testicular lymphoma.

Primary testicular lymphoma makes up only 1 percent to 2 percent of all NHLs and 5 percent of all testicular tumors. Early-stage PTL has a five-year survival rate as high as 76 percent with treatment, whereas advanced disease has a lower survival rate of 47 percent with treatment.

What Is Testicular Lymphoma?

Primary testicular lymphoma is an extranodal form of lymphoma (meaning that it occurs outside of the lymph nodes) originating in the testicles. Lymphoma is a type of blood cancer that is related to leukemia, myeloma, and myeloproliferative neoplasms (MPNs). Lymphomas form from lymphatic tissue, which includes the lymph nodes, spleen, thymus, bone marrow, and other organs. Most cases of lymphoma are non-Hodgkin lymphoma, which has many subtypes.

The most common subtype of NHL seen in PTL is diffuse large B-cell lymphoma (DLBCL), which accounts for 78 percent of cases. Follicular lymphoma and Burkitt lymphoma, the next most common types of NHL that cause testicular lymphoma, can also rarely be seen in children and adolescents. There are many other subtypes of NHL, and any of them can occasionally be primary or secondary testicular lymphoma.

What Causes Testicular Lymphoma?

Testicular lymphoma is caused by genetic mutations of lymphocytes, a type of white blood cell. Certain genetic mutations can cause cells to become abnormal so that they grow and divide more rapidly, leading to cancer.

Cancer-causing mutations that occur in lymphoma can be genetic (inherited) or acquired. Risk factors for developing lymphoma include age, exposure to radiation and cancer-causing chemicals, and infection with certain viruses, such as the Epstein-Barr virus.

Signs and Symptoms of Testicular Lymphoma

Testicular lymphoma can have a variety of symptoms, also seen in other types of lymphoma. This type of cancer usually first appears as swelling or a mass in the testes and scrotum (the skin that contains the testicles). Testicular lymphoma may be unilateral (affecting only one testicle) or bilateral (affecting both testicles). Testicular lymphoma affects the testicles and scrotum with symptoms affecting the groin, but it can also produce systemic symptoms (symptoms that affect the whole body). If lymphoma has spread beyond the testicles or originated elsewhere in the body, it can produce signs and symptoms in other parts of the body. These symptoms depend on where tumors or enlarged organs are.

Symptoms in the testicles and scrotum include swelling of the testicles or scrotum, which is usually painless. Painless lumps, or masses, felt in the scrotum or the testicle may also be a symptom.

Systemic signs and symptoms include:

• B symptoms, which include unexplained fever, unexplained weight loss, and drenching night sweats
• Swollen or enlarged lymph nodes (lymphadenopathy) in the groin, armpits, or neck
• Fatigue
• Frequent infections

Localized symptoms from the spread to different parts of the body can include:

• Chest — Pain or pressure, shortness of breath, and difficulty breathing
• Abdomen — Swelling, pain, loss of appetite, nausea, and vomiting
• Lymph nodes in and around the groin — Edema (swelling from excess fluid) in the legs
• Central nervous system (the brain and spinal cord) — Headaches, changes in personality, difficulty thinking, and seizures

Diagnosis and Staging of Testicular Lymphoma

Diagnosis of testicular lymphoma begins with a thorough medical history and physical exam of the entire body. Additional diagnostic tests include imaging, blood tests, and tests performed on cancer tissue. A biopsy (the removal of all or part of a tumor for analysis) is not usually performed in cases of suspected testicular cancer. Because there's a risk of “seeding” cancer cells — allowing them to spread throughout the body — the entire affected testicle is typically removed to analyze the tumor and determine the type of cancer.

Ultrasound and Other Imaging Tests

An ultrasound, or sonogram, uses sound waves to determine whether masses in the scrotum are solid or filled with fluid. Ultrasound is generally one of the first tests a doctor uses to diagnose tumors of the scrotum and testes.

Other imaging tests, such as X-rays, computed tomography (CT) scans, positron emission tomography (PET) scans, and magnetic resonance imaging (MRI), may also be used to detect the spread of lymphoma.

Blood Tests

A complete blood count is one of the most important blood tests for lymphoma. Other blood tests for testicular cancer include tests for blood levels of specific tumor markers such as alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase.

Staging Testicular Lymphoma

Determining how far cancer has spread in the body is important for staging lymphoma and other types of testicular cancers.

Lymphoma is usually staged using the Lugano classification system, and testicular cancer is usually staged using the TNM system. The way that the stages are named and the specific criteria for each stage vary between the two systems. The general criteria include the size and location of tumors and whether cancer has spread to other organs. The stage and subtype of testicular lymphoma are used to develop an effective treatment plan and estimate the prognosis (outlook) of the cancer.

Treatment of Testicular Lymphoma

The primary treatment for any testicular cancer, including testicular lymphoma, is surgery to remove the affected testicle. In addition to surgery, other treatments can include a combination of chemotherapy, targeted drug therapy, and radiation. The best treatment plan for PTL depends primarily on the subtype of lymphoma involved. Other factors such as age, other medical conditions, and personal preferences can also influence treatment.

Surgery

Different types of surgery may be done to remove the lymphoma. A radical inguinal orchiectomy surgery involves removing one or both testicles and attached structures (the epididymis and spermatic cord). Retroperitoneal lymph node dissection may also be performed to remove lymph nodes deep inside the abdomen. Removing lymph nodes can be an important part of treatment because lymphoma usually spreads through the lymph nodes.

Chemotherapy

Chemotherapy works by preventing cancer cells from growing and dividing into more cancer cells. Specific chemotherapy regimens for testicular lymphoma are chosen based on the subtype of lymphoma.

The most commonly used chemotherapy treatment for DLBCL and other aggressive B-cell lymphomas is called R-CHOP. R-CHOP combines the targeted immunotherapy drug rituximab (Rituxan) ​​​​​with a chemotherapy regimen of cyclophosphamide (sold as Cytoxan); doxorubicin (also known as hydroxydaunorubicin and sold as Adriamycin); vincristine sulfate (formerly sold as Oncovin); and prednisone.

Targeted Therapy

Targeted therapy can include immunotherapy with monoclonal antibodies, treatment with small-molecule drugs, and chimeric antigen receptor T-cell (or CAR T-cell) therapy. Rituximab is frequently used to treat testicular lymphoma. The antibody attaches to specific proteins found on the surface of cancer cells to help the immune system attack and destroy them. Rituximab specifically targets the CD20 protein.

Radiation

Radiation therapy for testicular lymphoma involves external beam radiation (similar to an X-ray) performed after surgery to kill any remaining cancer cells in the remaining testicle and lymph nodes. Radiation may also be used to treat other parts of the body if the lymphoma has spread.

Central Nervous System Prophylaxis

Prophylactic (preventive) treatment is an important part of testicular lymphoma treatment to prevent relapse or spread to the central nervous system (CNS). CNS prophylaxis may include radiation, chemotherapy, or other treatments, and it is usually used for more advanced stages.

Methotrexate is frequently used in people with testicular lymphoma to prevent the spread of cancer cells to the spinal cord and brain. Intrathecal injection (into the fluid around the spinal cord) is a common route of administration for CNS prophylaxis with methotrexate. Drugs such as rituximab do not cross into the CNS from the bloodstream.

Prognosis of Testicular Lymphoma

The prognosis of testicular lymphoma depends on many factors beyond its type and stage. Some factors predict a poor outcome regardless of treatment, including:

• Older age (over 70)
• Advanced stage at diagnosis
• The presence of B symptoms
• Spread to other parts of the body
• Large tumor size
• Lymphoma in the left testicle
• Elevated blood levels of lactate dehydrogenase and beta-2 microglobulin

The International Prognostic Index is also used to help determine the prognosis of non-Hodgkin lymphoma, including testicular lymphoma.

PTL is generally a very aggressive type of cancer and has a much higher five-year survival rate when it is diagnosed at an early stage. The survival rate also increases with appropriate treatment.

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