Lymphoma of the Testicle: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
October 23, 2026

Lymphoma of the testicle is a cancer of immune cells called lymphocytes that is found in the testicle. When the lymphoma starts in the testicle, it is called primary testicular lymphoma. Almost all primary testicular lymphomas are diffuse large B-cell lymphoma (DLBCL). Testicular lymphoma is the most common cancer of the testicle in men over 60.

Testicular lymphoma behaves differently from both testicular germ cell tumors and from DLBCL that starts in lymph nodes. It tends to recur in the brain and the other testicle. For this reason, treatment usually includes steps to protect these sites as well as treatment of the lymphoma itself.

This article explains how doctors diagnose testicular lymphoma and what the results of a testicular lymphoma pathology report mean. It also explains how the findings shape the next steps in your care.

Who gets lymphoma of the testicle?

Lymphoma of the testicle usually affects older men, with most men diagnosed in their 60s or 70s. This is very different from testicular germ cell tumors such as seminoma, which mostly affect men under 45. Primary testicular lymphoma makes up only about 1 to 2 in 100 cases of non-Hodgkin lymphoma. It also occurs at a younger age in men with HIV.

Lymphoma that starts elsewhere in the body can also spread to the testicle. This is called secondary testicular lymphoma. In children, testicular lymphoma is rare. When it occurs, it is usually a different type, such as Burkitt lymphoma or a form of follicular lymphoma seen in children.

What causes lymphoma of the testicle?

The cause of primary testicular lymphoma is not known. Researchers believe the testicle plays a special role. The testicle is an immune-privileged site, meaning the immune system normally keeps its activity there to a minimum to protect developing sperm. The brain and the inside of the eye are also immune-privileged sites.

Lymphoma cells that grow in these sites share similar genetic changes, which may help them hide from the immune system. Because of this, the World Health Organization (WHO) classification, 5th edition (2022), groups primary testicular DLBCL with similar lymphomas of the brain and eye. This group is called large B-cell lymphomas of immune-privileged sites. This shared biology helps explain why testicular lymphoma tends to recur in the brain.

What are the symptoms of lymphoma of the testicle?

The most common symptom of testicular lymphoma is a painless, firm swelling of one testicle. The swelling often grows over weeks to months. Some men also have fevers, drenching night sweats, or weight loss without trying, which are called B symptoms. Lymphoma is the testicular cancer most likely to involve both testicles, either at the same time or later.

How is the diagnosis made?

The diagnosis of testicular lymphoma usually begins with a scrotal ultrasound showing a solid mass. Because the mass usually looks like any other testicular tumor, the whole testicle is removed through a cut in the groin in an operation called a radical orchiectomy. A pathologist then examines the testicle under the microscope.

Under the microscope, the lymphoma consists of sheets of large, abnormal lymphocytes. These cells first grow between the seminiferous tubules, the small tubes of the testicle that make sperm. As the lymphoma grows, it fills and destroys the tubules. The pathologist uses special stains to confirm the cells are lymphocytes and to distinguish lymphoma from seminoma, which can look similar.

Once lymphoma is confirmed, further tests check whether it has spread. These usually include a PET-CT scan and blood tests. Because testicular lymphoma often involves the brain, doctors often do a brain MRI and test the fluid around the brain and spinal cord. This fluid test is called a lumbar puncture. Some people also have a bone marrow biopsy.

Immunohistochemistry

Immunohistochemistry uses antibodies to show which proteins cells make. In testicular lymphoma, pathologists use immunohistochemistry to confirm the tumor is a B-cell lymphoma and identify its subtype. The stains used vary between laboratories, but typical results in testicular DLBCL include:

CD20 and PAX5. The lymphoma cells are positive for these proteins, confirming they are B cells.
CD10, BCL6, and MUM1. These three stains are used together in the Hans algorithm, described in the next section.
Ki-67. Ki-67 shows how many cells are dividing. In DLBCL, the result is usually high, often more than 60%, which reflects a fast-growing lymphoma.
OCT3/4 and SALL4. The lymphoma cells are negative for these proteins. Seminoma cells are positive, so a negative result helps rule out seminoma.

Not every case needs all of these stains, and the exact panel depends on the laboratory.

Cell of origin: GCB versus non-GCB

Diffuse large B-cell lymphoma is divided into two main groups based on the type of normal B cell it most resembles. Your testicular lymphoma pathology report may give the cell of origin as one of the following:

Germinal center B-cell type (GCB). The lymphoma resembles B cells found in the center of normal lymph node follicles. This type is uncommon in the testicle.
Non-germinal center B-cell type (non-GCB), also called activated B-cell type (ABC). The lymphoma resembles B cells activated by the immune system. Most primary testicular lymphomas are this type.

The cell of origin is usually estimated with the Hans algorithm, which combines CD10, BCL6, and MUM1 results. In DLBCL in general, the non-GCB type has a somewhat less favorable outlook with standard treatment. It is also the focus of several clinical trials.

Biomarker and molecular testing

Biomarker testing in testicular lymphoma looks for proteins and genetic changes that affect how the lymphoma is classified and treated. Some results appear in the pathology report, and others come later in a separate report.

CD20

CD20 is a protein on the surface of B cells. In testicular DLBCL, lymphoma cells are almost always CD20-positive. A positive result means treatment can include rituximab, an antibody that attaches to CD20 and helps the immune system destroy the lymphoma cells. A negative CD20 result is rare and would lead the care team to reconsider the diagnosis or the treatment plan.

MYC and BCL2

MYC and BCL2 are genes that control how fast cells grow and how long they live. They are tested in two ways, and your report may describe either or both:

Immunohistochemistry for MYC and BCL2 protein. When both proteins are expressed at high levels, the lymphoma is called double-expressor. Double-expressor DLBCL has a somewhat less favorable outlook with standard treatment, and it is common in testicular lymphoma.
FISH for MYC and BCL2 rearrangements. Fluorescence in situ hybridization (FISH) looks for a rearrangement, meaning a piece of the gene has broken off and joined another chromosome. A negative result, meaning no rearrangement was found, is the most common result in testicular lymphoma. When both MYC and BCL2 are rearranged, the diagnosis changes to high-grade B-cell lymphoma with MYC and BCL2 rearrangements, which may be treated differently.

MYD88 and CD79B

MYD88 and CD79B are genes that help send growth signals inside B cells. Changes in these genes are found in most primary testicular lymphomas, and they are typical of lymphomas of immune-privileged sites. They may be reported by next-generation sequencing (NGS). A result may say that a mutation was detected or not detected. These changes do not currently determine first treatment, but they help confirm the lymphoma type. They may also make a person eligible for clinical trials of drugs that block this growth signal.

Our Biomarkers and Genetic Testing section explains these tests in more detail.

Staging

Lymphoma of the testicle is not staged with the TNM system used for testicular germ cell tumors. Instead, it is staged using the Lugano classification (2014), which relies on PET-CT and other tests rather than the pathology report alone. The letter E means the lymphoma involves an organ outside the lymph nodes, such as the testicle.

Stage IE. The lymphoma is found only in the testicle.
Stage IIE. The lymphoma is in the testicle and in nearby lymph nodes, usually those at the back of the abdomen.
Stage III and IV. The lymphoma has spread to lymph nodes on both sides of the diaphragm or to distant organs. Lymphoma in both testicles or in the brain is treated as advanced disease.

Most men with primary testicular lymphoma have stage IE or IIE disease at diagnosis. The letters A and B may be added to show whether B symptoms are absent (A) or present (B).

What is the prognosis?

The prognosis for testicular lymphoma depends mainly on the stage and whether the brain and the other testicle are protected during treatment. Before preventive treatment became standard, older studies found that the lymphoma came back in the brain in up to 30 in 100 men. Without treatment to the other testicle, relapse there was also common.

Outcomes have improved with modern treatment. An international trial studied men with stage IE or IIE testicular lymphoma. At five years, about 74 in 100 had no relapse and about 85 in 100 were alive. A later trial added stronger treatment to protect the brain. In that trial, about 91 in 100 men had no relapse at five years, about 92 in 100 were alive, and no relapses in the brain were seen. Outcomes are less favorable for men with advanced-stage disease or lymphoma that started elsewhere and spread to the testicle.

Findings linked with a less favorable outlook include:

Advanced stage. Spread beyond the testicle and nearby lymph nodes, especially to both testicles, the brain, or other organs.
B symptoms. Fevers, night sweats, or weight loss.
Age over 70. Older men may not be able to receive full-strength treatment.
A high LDH level. Lactate dehydrogenase (LDH) is a blood test that is often elevated when more lymphoma is present.
A large tumor. A tumor larger than 10 cm is linked with a higher chance of relapse.

What happens after the diagnosis?

After lymphoma of the testicle is confirmed on the orchiectomy specimen, a hematologist or medical oncologist experienced in treating lymphoma usually plans care. The orchiectomy removes the lymphoma in that testicle, but further treatment is needed even for stage IE disease. Treatment usually has three parts:

Chemotherapy with rituximab. The most common combination is R-CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. It is usually given for six cycles.
Treatment to protect the brain. This is called central nervous system (CNS) prophylaxis. It may include high-dose methotrexate given through a vein, chemotherapy given into the fluid around the spinal cord, or both.
Radiation therapy to the other testicle. This lowers the chance the lymphoma will return there. Radiation to lymph nodes at the back of the abdomen may also be considered for stage IIE disease.

If the lymphoma comes back, the options are similar to those for other forms of DLBCL and are described in our diffuse large B-cell lymphoma article. Newer drugs targeting the MYD88 and CD79B signaling pathway, along with immunotherapy drugs called PD-1 inhibitors, are being studied in clinical trials. Your care team can tell you whether any trials are open to you.

Radiation to the other testicle stops sperm production, and chemotherapy can also affect fertility. Sperm banking can be discussed before treatment for men who may want children. Radiation can also lower testosterone levels over time, so these levels are checked during follow-up.

Questions to ask your doctor

Is this a primary testicular lymphoma, or did the lymphoma start somewhere else?
What type of lymphoma is it?
Is my lymphoma GCB or non-GCB?
Is my lymphoma a double-expressor for MYC and BCL2?
Was FISH testing done for MYC and BCL2 rearrangements, and what did it show?
Was next-generation sequencing done, and did it find MYD88 or CD79B changes?
What is my stage, and was my brain or the other testicle involved?
What is my LDH level?
How will my brain be protected during treatment?
Do I need radiation to my other testicle, and how will it affect my testosterone?
Should I bank sperm before treatment?
Are there clinical trials that are open to me?