Testicular Sex Cord–Stromal Tumors

What is Testicular Sex Cord–Stromal Tumors?

Most solid lumps or growths in the testicles (95%) are types of germ-cell tumors, which are largely split into two categories: seminomatous or nonseminomatous tumors. The remaining 5% of these lumps or growths in the testicles are from a group called testicular sex cord-stromal tumors (SCSTs). These are uncommon but usually non-cancerous, and they form from the tissues in the testicles that support the cells and produce hormones. More information on seminomatous and nonseminomatous tumors can be found on our website at the given links.

SCSTs can include different types such as Leydig and Sertoli cell tumors, adult- and juvenile-type granulosa cell lumps, gonadoblastomas, fibroma-thecomas, and mixed-type stromal tumors. The most frequent type of SCST is the Leydig cell tumor, making up more than 90% of these cases. Even though SCSTs are only a small part of all testicular cancers, they have unique characteristics and can be complex to diagnose and treat. So, they’re a significant area of interest for doctors. Fully understanding the causes, symptoms, diagnosis methods, and treatment options for SCSTs is important for improving patient outcomes.

What Causes Testicular Sex Cord–Stromal Tumors?

Sex Cord Stromal Tumors (SCSTs) are believed to form from changes in the normal tissue of the sex-cord or testis, though there aren’t many known risk factors tied to SCST development. This is different from germ cell tumors, which often correlate with undescended testes. Still, more research is needed to fully understand this. While genetics play a significant role in other types of testicular cancer, they account for less than 20% of the risk for most cancers.

SCSTs are sometimes linked to different genetic conditions. For instance:

– Leydig cell tumors: These have been tied to Klinefelter syndrome, a genetic condition affecting males, and other cancers like renal cell cancers and hereditary leiomyomatosis;
– Sertoli cell testicular neoplasms: These are associated with Carney complex, a rare genetic condition causing various benign tumors, and Peutz-Jeghers syndrome, a rare condition that causes abnormal pigmentation and polyps in the intestines;
– Gonadoblastomas: These may occur with conditions like cryptorchidism (undescended testes), gynecomastia (enlarged breast tissue in males), hypospadias (abnormally located urethral meatus), and male pseudohermaphroditism (having physical characteristics of both sexes);
– Sertoli-Leydig cell tumors and
paratesticular sarcomas: These may be linked to DICER1 syndrome, a rare inherited condition that increases the risk of developing benign tumors and certain types of cancer.

Further, SCSTs have also been associated with mutations in the adenomatous polyposis coli (APC) gene and familial adenomatous polyposis syndrome, an inherited condition that increases the risk of colorectal cancer.

Risk Factors and Frequency for Testicular Sex Cord–Stromal Tumors

Testicular cancer is not very common, and it only makes up 1% of male tumors. One subtype of testicular cancer, called Sex Cord-Stromal Tumors (SCSTs), is responsible for about 5% of adult testicular cancer cases. This rate increases to 8% when considering testicular cancers in children. Within SCSTs, the most common type is the Leydig cell tumor, making up over 90% of SCSTs.

• Despite being rare, about 1% to 2% of all testicular cancers are Leydig cell tumors.
• These tumors mainly affect adults between the ages of 30 and 35.
• In children, Leydig cell tumors are most common between the ages of 5 and 10.

Age, race, ethnicity, and geography are all factors that can affect the likelihood of developing SCSTs:

• The most common age group affected by SCSTs is those aged 20 to 34, accounting for half the cases. Males who haven’t yet reached puberty have slightly higher chances of getting these tumors.
• Race and ethnicity play a role too. White males have 4 to 5 times higher incidence than Black and Asian Americans, with American Indians’ risk falling between. Black Americans tend to have a more severe type of the disease, which may worsen their outcomes.
• The risk for this type of cancer is highest in the United States and Europe. On the other hand, it’s lowest in Africa and Asia.

Finally, research suggests that Leydig cell tumors are possibly more common than initially believed. They might make up 14% to 22% of all samples removed during surgery due to testicular malignancy.

Signs and Symptoms of Testicular Sex Cord–Stromal Tumors

Sex cord-stromal tumors (SCSTs) of the testes have similar symptoms to germ cell tumors. Patients often notice a non-painful lump in their testicles, possibly accompanied by some local swelling or discomfort. They may also have gynecomastia, or enlargement of the breasts. About a quarter of adults with these tumors experience hormone-related symptoms. Importantly, typical markers of testicular germ cell cancers do not usually increase in SCSTs.

The three most common and clinically significant SCSTs are Leydig, Sertoli, and granulosa cell tumors. Each type has certain characteristic features. Here, giving brief overview of each:

• Leydig cell tumors: The most frequent type of SCST and are often found in men between the ages of 30 and 35. However, they can also develop older men. Symptoms might include gynecomastia, loss of libido, erectile issues, and infertility. In addition, the tumors can produce hormones leading to masculinization or feminization.
• Sertoli cell tumors: The second most common type of SCST, but only account for about 0.1% of testicular tumors, known to occur without any hormone-related symptoms. Though, some patients can experience symptoms like gynecomastia, erectile issues, and impotency.
• Granulosa cell tumors: These tumors are rare and typically occur men around 42 years old. The tumor is divided into two types: adult granulosa cell tumors and juvenile granulosa cell tumors. Symptoms typically include gynecomastia.

Other rare types of testicular SCSTs include signet ring stromal tumors, myoid gonadal stromal tumors, gonadoblastomas, and testicular fibromas. These generally appear as benign masses within the testes.

Overall, a good number of SCSTs are rare but can have significant clinica implications. If one notices changes in their testicles or experiences hormone-related symptoms, they are adviced to consult a healthcare provider for an examination.

Testing for Testicular Sex Cord–Stromal Tumors

The initial evaluation begins with a thorough history and physical examination, with careful examination of the testicles. The doctor will be looking for any signs of enlarged male breasts (gynecomastia) and any abnormal changes in sexual development. After this, some routine tests may be done, such as checking blood levels for certain hormones and markers that might suggest illness, like follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol. Also, the doctor will check for tumor markers (biological substances that indicate the presence of cancer) related to germ cell tumors like alpha-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). However, these markers won’t be elevated in sex cord-stromal tumors, a type of testicular tumor.

There are several imaging techniques for evaluating testicular issues:

A testicular ultrasound is commonly used to evaluate and diagnose testicular lumps and growths. This method is safe, cost-effective, can be done more than once, and does not involve harmful radiation exposure. The accuracy of this procedure for diagnosing testicular tumors is nearly 100%. It helps to identify and differentiate between different issues like fluid-filled sacs around the testicle (hydroceles), cysts in the epididymis (spermatoceles), and inflammation of the testicles. But, ultrasound can’t distinguish between sex cord-stromal tumors and germ cell tumors, so a tissue sample examination is also needed for a correct diagnosis. An ultrasound may be indicated for issues like unexplained infertility, early puberty, gynecomastia, and one-sided testicular swelling or hardness.

Leydig cell tumors, a type of testicular tumor, are seen on ultrasound as a distinct, darker mass separate from the surrounding tissue. They often show a pattern of increased blood flow around the edge. Large cell calcifying Sertoli cell tumors have dense calcium deposits inside them. Another type of testicular tumor, Sertoli cell tumors, may look similar to seminomas on ultrasound because both tend to show increased blood flow around the edge. But, usually, a tissue sample examination is needed to distinguish between these two tumors. When diagnosed, granulosa cell tumors appear as darker solid masses on ultrasound, with clear borders and an average size of slightly over 2 cm.

Scrotal multiparametric magnetic resonance imaging (MRI) shows potential in differentiating between cancerous testicular tumors and benign sex cord-stromal tumors. Cancerous germ cell tumors usually appear larger and more variable in size and shape on T2-weighted imaging, show more restriction in the diffusion of fluids, show less contrast enhancement in the venous phase, and have lower apparent diffusion coefficient values (a measure of water diffusion within tissue). MRI can be a useful tool in cases of indeterminate testicular masses when ultrasound findings are inconclusive.

Contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis can be used to identify any spread of cancer to other parts of the body. If brain involvement is suspected, an MRI of the brain is recommended.

Treatment Options for Testicular Sex Cord–Stromal Tumors

A surgery called radical inguinal orchiectomy is the main treatment for all solid lumps in the testicle. This surgery helps to accurately determine the type of the lump and is often a complete cure. It also helps to lower the amount of the disease in the area. It’s usually not a good idea to do a biopsy (take a small sample) before surgery, because this can spread the disease, and often surgery is required anyway.

The majority of sex cord-stromal tumors (SCSTs), which make up about 90% of these lumps, are not harmful and don’t spread. Therefore, they can be treated simply with the surgery mentioned above. However, for SCSTs that may spread, like Leydig cell, Sertoli cell, and adult granulosa cell tumors, another procedure called a retroperitoneal lymph node dissection (RPLND) is recommended. RPLND is used to verify if the cancer has spread to the lymph nodes in the back of the abdomen and is very important for patients whose disease has spread or those with certain risk factors but no visible spread yet.

High-risk factors are signs that the cancer is more likely to spread or become severe. These include changes in the size or appearance of cells, evidence of lymph node involvement, rapid cell division (mitosis), large tumor size, spread of cancer into the lymph vessels and blood vessels, death of cancer cells (necrosis), and invasion or spread of the tumor into surrounding margins. Other factors, such as spread into the lymph and blood vessels, and tumor-related hormonal symptoms can also be high-risk factors, particularly for granulosa cell tumors.

RPLNDs are the best way of identifying tiny areas of cancer spread and correctly determining the stage of the disease. Poor response rates to radiation and chemotherapy for SCSTs have led to the recommendation of surgical removal of these spots whenever feasible, along with additional chemotherapy.

Leydig cell tumors are generally cured with radical inguinal orchiectomy surgery alone. If the tumor is small, can’t be felt, and detected with ultrasound only, there is a chance to save the testis with testis-sparing surgery. The survival rate appears to be similar between testis-sparing surgery and radical inguinal orchiectomy. To be considered for testis-sparing surgery, the tumor should be less than 2.5 cm, and the patient should not have any abnormal levels of hormones.

For spreading Leydig cell tumors, RPLNDs are recommended because neither chemotherapy nor radiation seems to be effective against them. The disease often spreads within 2 years following the main surgery, affecting sites such as the lymph nodes in the back of the belly, chest and neck, as well as organs like the lungs, liver, and bones. For widely spread disease, new drugs are being tested, but their effectiveness is still unclear.

SCSTs in men are difficult to judge if they are likely to spread or not. Patients with fewer than 2 high-risk factors demonstrated a 5-year survival rate of 98%, contrasting with 45% for those with more than 2 such factors. If a patient has a higher likelihood of hidden disease, complete imaging should be conducted to detect early spread, with early consideration given to RPLND or surgery for metastases.

Sertoli cell tumors and granulosa cell tumors are typically treated with radical inguinal orchiectomy as the main treatment. For metastatic (spread) diseases, the tumors may be removed with surgery, along with chemotherapy after surgery.

Tumor genetic profiling may lead to the discovery of new drugs. For instance, Leydig cell tumors and adrenocortical cancers share similar features. There have been reports of patients with widespread unresectable disease being treated with mitotane, a medication used in the treatment of adrenocortical cancer.

Estrogen-producing Leydig cell tumors can cause long-lasting infertility in males, even after their removal. This infertility is due to long-term effects on the hypothalamus-pituitary axis and direct effects on the testes. Early detection and treatment can help maintain spermatogenesis and protect future fertility.

In conclusion, surgery remains the mainstay of treatment for solid testicular masses. Further treatment and monitoring strategies depend on the type of tumor and its potential for spreading. For some patients, it’s important not just to treat the disease, but also to preserve fertility.

What else can Testicular Sex Cord–Stromal Tumors be?

It’s crucial for doctors to be accurate when diagnosing Sex Cord-Stromal Tumors (SCSTs) due to their varied features and symptoms. They must distinguish these tumors from other testicular growths, such as germ cell tumors and secondary growths, to correctly diagnose and treat the patient.

Leydig Cell Tumors:

When it comes to diagnosing Leydig cell tumors, doctors should consider other conditions like:

• Leydig cell hyperplasia
• Lymphoma
• Plasmacytoma
• Adrenal or testicular tumors that occur in males with a specific condition called congenital adrenal hyperplasia
• Sertoli cell or germ cell tumors

A staining technique using something called inhibin alpha can help doctors tell Leydig cell growths apart from germ cell tumors, but not Sertoli cell tumors. Certain protein markers such as calretinin, NKX3.1 and P501S are also used to pinpoint the type of tumor.

Sertoli Cell Tumors:

Differential diagnoses for Sertoli cell tumors include conditions like:

• Juvenile granulosa cell tumors
• Leydig cell tumors
• Seminomas
• Mixed Sertoli-Leydig cell growths

To identify Sertoli cell tumors, doctors look for positive stain results for markers such as cytokeratin, WT-1, and inhibin, while also checking for negative results for markers like PLAP and SALL4. Sertoli tumors can look similar to juvenile granulosa cell tumors so the characterization of their appearance is also important in differentiating between the two.

There are also other types of tumors that can appear in the rete testis and paratesticular areas. These include lesions produced by mesothelial cells, epithelial cells and soft tissues, with adenomatoid tumors being quite common. Testicular lymphoma is also a differential diagnosis to keep in mind, especially in older men.

What to expect with Testicular Sex Cord–Stromal Tumors

The outlook for patients diagnosed with Stage I Leydig cell tumors is generally quite good. The possibility of surviving these tumors one year after diagnosis is 98%, and after five years, it’s still quite high at 91%. On the other hand, Sertoli cell tumors are a bit more dangerous, with survival rates of 93% after a year and 77% after five years.

In one study, 38 men were successfully treated simply by surgically removing the tumor. None of them developed any further spread of the disease even after seven years. This led to the conclusion that patients with few or no high-risk factors can be safely monitored without additional surgery to remove lymph nodes (RPLND). However, early lymph node removal could be beneficial for selected patients who have more high-risk factors or are diagnosed with Stage IIa disease, as well as for all cases of Sertoli cell tumors that aren’t otherwise specified.

Patients with a type of tumor called gonadoblastoma generally have an excellent outlook, especially if the tumor is surgically removed before it becomes malignant or cancerous. Even when the disease advances and starts to spread, chemotherapy with platinum-based drugs can cure more than 90% of the cases. The outlook for patients with metastatic SCSTs, excluding gonadoblastoma, isn’t as good. Although some can live for quite a long time, typically patients live only 1 to 2 years after the diagnosis of spread, with about two-thirds passing away within 2 years after the diagnosis.

Possible Complications When Diagnosed with Testicular Sex Cord–Stromal Tumors

Complications can arise from sex cord stromal tumors (SCSTs), both due to the disease itself and its treatment. These tumors are usually less aggressive than germ cell tumors, but there’s still a possibility that the cancer might spread. This could lead to complications in far-off organs like the lungs, liver, or bones.

Surgery is commonly used to treat these tumors. However, it carries risks like infection, bleeding, and potential harm to surrounding structures. This could affect fertility and hormone function. Studies show that men who undergo removal of a testicle due to SCSTs tend to have a higher rate of low testosterone levels compared to those with germ cell cancers (42% vs 10%). Therefore, these patients will likely need testosterone replacement therapy after surgery and should have regular checks of their hormone levels.

Furthermore, patients that undergo chemotherapy or radiation therapy might experience body-wide side effects, like nausea, tiredness, and an increased risk of developing other types of cancer. The side effects of chemotherapy and radiotherapy are usually similar to those commonly associated with these treatments, but they can often be effectively managed using modern medications. It’s crucial to have patients checked regularly to monitor for a return of the cancer and to manage these complications effectively.
Common Complications:

• Complications in organs far from the original tumor such as lungs, liver, or bones due to cancer spread
• Infection from surgical treatment
• Bleeding during surgery
• Potential damage to surrounding structures affecting fertility and hormone functions
• Lower testosterone levels after surgery in males
• Nausea due to chemotherapy or radiation therapy
• Fatigue from chemotherapy or radiation therapy
• Increased risk of other types of cancer from chemotherapy or radiation therapy

Recovery from Testicular Sex Cord–Stromal Tumors

After undergoing surgery for SCSTs, the post-surgery care and rehab is extremely important for optimal recovery and long-lasting health. People with SCSTs usually need regular check-ups, especially during the first two years following the diagnosis and treatment. This careful monitoring is critical due to the fact that most patients with Leydig cells and other potentially harmful SCSTs, which have the ability to spread into other areas, tend to do so within this initial 2-year period.

These check-ups should include a full physical examination, a detailed hormone profile, and checks for signs of testicular cancer. Additionally, CT scans of the chest, abdomen, and pelvis should be conducted every 6 months for the initial 2 years after diagnosis.

After surgery, patients need close supervision for possible complications such as infection, bleeding, and proper wound healing. Effectively managing pain and providing supportive care is crucial during the immediate post-surgery phase. It’s also important to consider potential impacts on fertility and hormone function, often requiring consultations with specialists in reproductive health and hormone medicine.

Rehab after treatment for SCSTs may involve physical therapy to regain strength and mobility. Psychological support is also crucial to help patients deal with the emotional stress of their diagnosis and treatment. Comprehensive care plans that encompass these elements can greatly improve the life quality and recovery outcomes for patients recovering from SCSTs.

Preventing Testicular Sex Cord–Stromal Tumors

It is essential to spread awareness and provide education to tackle Sex-cord stromal tumors (SCSTs), a group of rare types of testicular cancer. Doing so serves two purposes – prevention and education. If people know what to look for, like certain signs and symptoms of testicular tumors including SCSTs, they can seek medical help earlier. This early detection can then lead to prompt treatment. Spreading this information can be done through awareness campaigns at schools, workplaces, and hospitals, highlighting the significance of regularly checking oneself and seeking immediate doctor’s advice for any unusual changes.

Patients should also remember that improvements in cancer treatment are happening all the time. In most cases, SCSTs have a very positive treatment outcome because it’s not common for this type of tumor to be aggressive or to spread to other parts of the body. But for that to be true, quick diagnosis, treatment, and regular check-up appointments are crucial.

Moreover, it’s vital that healthcare providers continually educate themselves about the newest guidelines for diagnosing and treating these rare tumors. This makes sure they can correctly identify the SCSTs and manage them appropriately. By aiming for increased awareness and knowledge, doctors can more effectively monitor their patients for this condition and thus reduce the impact of SCSTs on both patients and the overall healthcare system.