A Leydig cell tumor is a tumor that starts from Leydig cells in the testicle. Leydig cells normally make testosterone, the main male hormone. A Leydig cell tumor belongs to a group called sex cord-stromal tumors. These tumors develop from the testicle’s supporting and hormone-producing cells rather than the cells that make sperm. Most Leydig cell tumors are noncancerous and can be cured with surgery. Fewer than 1 in 10 behave like a cancer and spread to other parts of the body.
This article explains what a Leydig cell tumor is, how the diagnosis is made, and what the findings in a Leydig cell tumor pathology report mean. It also explains the features the pathologist looks for to judge the chance that the tumor will spread.
Leydig cell tumors make up about 1 to 2 in 100 testicular tumors in adults and a slightly higher share in boys. They are the most common type of testicular sex cord-stromal tumor. Leydig cell tumors occur at two main ages. The first is in boys between 5 and 10 years old, and the second is in men between 30 and 60 years old. Leydig cell tumors are often small and may be found by chance on an ultrasound done for another reason, such as infertility.
The cause of most Leydig cell tumors is not known. A small number are linked with inherited conditions. The best known is hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), which is caused by an inherited change in a gene called FH. People with HLRCC have a higher risk of noncancerous muscle tumors of the skin and uterus and of a type of kidney cancer. Leydig cell tumors are not related to germ cell neoplasia in situ (GCNIS), the early change that leads to most testicular cancers in adults.
Many Leydig cell tumors cause no symptoms and are found by chance. Others make hormones, such as testosterone or estrogen, which can cause symptoms. Symptoms of a Leydig cell tumor can include:
The diagnosis of a Leydig cell tumor usually begins with an ultrasound of the scrotum, which shows a solid mass inside the testicle. Blood tests may include hormone levels such as testosterone and estrogen. The blood tumor markers used for germ cell tumors, AFP and hCG, are normal in Leydig cell tumors. Doctors sometimes use an MRI when the ultrasound is unclear because Leydig cell tumors can have a typical appearance on MRI.
The tumor is removed by surgery. For a larger tumor, the whole testicle is removed in an operation called a radical orchiectomy. For a small tumor, the surgeon may remove only the tumor and leave the rest of the testicle, which is called testis-sparing surgery or partial orchiectomy. During testis-sparing surgery, the pathologist may examine the tumor while the patient is still in the operating room, using a test called a frozen section. This helps the surgeon decide whether to leave the rest of the testicle in place.
A pathologist then examines the tumor under the microscope. Leydig cell tumors consist of sheets of large, round cells with abundant pink cytoplasm. Some cells contain a golden-brown pigment called lipofuscin. In about 3 in 10 tumors, the cells contain small, rod-shaped structures called Reinke crystals, found only in Leydig cells. Pathologists usually use special stains to confirm the diagnosis.
Immunohistochemistry uses antibodies to show which proteins cells make. In a Leydig cell tumor, pathologists use immunohistochemistry to confirm the diagnosis and to separate it from other testicular tumors. The stains used vary between laboratories, but typical results in a Leydig cell tumor include:
Not every tumor needs all these stains, and when the diagnosis is clear under the microscope, pathologists may use only a few.
A Leydig cell tumor is not given a histologic grade. Instead, the pathologist looks for specific features linked to a higher chance that the tumor will spread. Your Leydig cell tumor pathology report may list some or all of these features:
No single feature proves that a Leydig cell tumor will spread. Most Leydig cell tumors that have spread show more than two of these features, and a tumor with none of them is very unlikely to spread. Your care team uses the number of features present to plan follow-up.
The pathologist measures the Leydig cell tumor and reports its greatest dimension in centimeters. Most Leydig cell tumors are small. Size matters because a Leydig cell tumor larger than 5 cm is more likely to spread.
Lymphovascular invasion means Leydig cell tumor cells were seen inside a blood vessel or lymphatic channel. These vessels carry blood and fluid away from the testicle, so tumor cells inside them have a route to spread. Your report will describe lymphovascular invasion as present, not identified, or cannot be determined. Lymphovascular invasion is uncommon in Leydig cell tumors, and when present it is one of the features linked with malignant behavior.
A margin is the cut edge of tissue removed during surgery. After a radical orchiectomy for a Leydig cell tumor, the most important margin is the end of the spermatic cord. After testis-sparing surgery, the most important margin is the edge of normal testicle around the tumor. Your report will describe the margins in one of these ways:
Genetic testing for a Leydig cell tumor focuses on whether the tumor may be linked with an inherited condition. No biomarker in a Leydig cell tumor currently predicts response to a particular drug.
Some laboratories test Leydig cell tumors for a protein called fumarate hydratase (FH) using immunohistochemistry. The FH gene makes the FH protein. Your report may describe FH in one of these ways:
An FH-deficient result does not by itself mean you have HLRCC, because the change may have happened only in the tumor. To confirm an inherited change, you need a separate genetic test on blood or saliva. If your result shows FH loss, your doctor may recommend a referral to a genetics service, because relatives may also benefit from testing. Our Biomarkers and Genetic Testing section explains genetic testing in more detail.
Some Leydig cell tumor reports include a pathologic stage using the TNM system in the 8th edition of the AJCC Cancer Staging Manual. This is the same system used for testicular germ cell tumors. A tumor limited to the testicle without lymphovascular invasion is pT1. Lymphovascular invasion, or growth into the hilar soft tissue, epididymis, or through the tunica vaginalis, makes the stage pT2. Growth into the spermatic cord is pT3, and growth into the scrotum is pT4. For Leydig cell tumors, features linked to malignant behavior provide more useful information than stage alone.
The prognosis for most people with a Leydig cell tumor is excellent. More than 9 in 10 Leydig cell tumors are noncancerous and are cured by surgery alone. Overall, more than 90 in 100 people are alive five years after surgery.
The outlook is very different for the small number of Leydig cell tumors that spread. These tumors usually spread to the lymph nodes at the back of the abdomen or to the lungs. Leydig cell tumors that have spread respond poorly to chemotherapy and radiation therapy, and most people with spread of the tumor die of the disease. This is why the features linked with malignant behavior matter for follow-up.
After confirming a Leydig cell tumor, the next steps depend on how many features linked to malignant behavior are present. For a tumor with none of these features, surgery is usually the only treatment needed. Follow-up may include physical examinations and imaging.
For a tumor with several features linked with malignant behavior, the care team may recommend a CT scan of the chest, abdomen, and pelvis and closer follow-up. Surgery to remove the lymph nodes at the back of the abdomen, called a retroperitoneal lymph node dissection, may also be considered. This surgery can sometimes cure a Leydig cell tumor that has spread only to these nodes.
Hormone levels are often checked after surgery. Your care team can tell you whether symptoms caused by extra hormones, such as breast tenderness, are expected to improve after the tumor is removed. Testis-sparing surgery may help preserve fertility and testosterone production in younger men.