What is Yolk Sac Tumors?

Yolk sac tumors, also known as primitive endodermal tumors or endodermal sinus tumors, are a type of cancer that originates from early, undeveloped cells. These tumors share similarities with the tissue of the yolk sac, which is a part of the early development of an unborn child.

Typically, this type of cancer is a variety of germ cell tumor. Germ cell tumors usually develop in the reproductive organs, but can sometimes appear in other parts of the body where they are labeled as extragonadal germ cell tumors. The most routine type of testicular tumor seen in young children under the age of 3 is a yolk sac tumor, and it’s often called infantile embryonal carcinoma when it occurs in this age group. Luckily, in such young children, these tumors are often treatable and offer a good chance of recovery.

Compared to young children, adults find that yolk sac tumors are regularly mixed with other kinds of germ cell tumors like teratoma and embryonal carcinoma. The presence of multiple types in adults makes the condition more complex to manage.

What Causes Yolk Sac Tumors?

The exact cause of yolk sac tumors is not clearly known. However, some research hints that changes in certain genes may play a role in the development of these tumors. They found that a gene called RUNX3 could be excessively ‘switched off’, a process known as hypermethylation. Also, another gene named GATA-4 could be overly ‘active’, a situation referred to as overexpression. These gene alterations might contribute to the formation of yolk sac tumors.

Risk Factors and Frequency for Yolk Sac Tumors

Yolk sac tumors are uncommon and can occur in either sex. They can be found in the ovaries, testicles, and other parts of the body. They’re often seen in young children.

Yolk sac tumors in males tend to occur in two age groups: children under the age of 3 and adults who have passed through puberty.
In children, yolk sac tumors are the most common type of tumor in the testicles, making up about 30% of all germ cell tumors in this age group. The average age of diagnosis is 18 months. Children typically have just yolk sac tumors, and they generally have a good outlook.
In adults, yolk sac tumors often appear as mixed germ cell tumors and are usually seen in the second to third decades of life.

In females, yolk sac tumors are also rare but do occur in the ovaries. They make up 15% of all ovarian germ cell tumors and usually appear early in life, rarely after the age of 40. The average age of diagnosis is 19 years, with 40% of patients diagnosed before puberty.
About 60% of the ovarian yolk sac tumors are only yolk sac tumors, while 40% are mixed with other germ cell tumors.

Signs and Symptoms of Yolk Sac Tumors

Yolk sac tumors can exhibit different signs and symptoms depending on where they are located.

In the case of testicular yolk sac tumors, both children and adults usually have a visible and palpable lump in their testicle, but they typically don’t experience any pain. It is rare for this type of tumor to spread to other parts of the body, happening in less than 10% of cases. In adults, testicular yolk sac tumors often accompany other types of germ cell cancer, like embryonal carcinoma, choriocarcinoma, teratoma, and seminoma.

Ovarian yolk sac tumors, on the other hand, often result in symptoms such as sudden abdominal pain and distention. In many cases, a pelvic lump can be felt when the abdomen is examined. These tumors tend to grow very fast, with symptoms appearing in less than a week in most cases.

People with ovarian yolk sac tumors may also experience:

Fatigue
Upset stomach
Back pain
Pain during sex
Constipation
Changes in menstrual bleeding, such as heavier or irregular bleeding
Weight loss accompanied by abdominal swelling

Ovarian yolk sac tumors spread quickly, not only invading the structures around the ovaries but also potentially reaching the lymph nodes.

Testing for Yolk Sac Tumors

Diagnosing yolk sac tumors involves several steps including looking at your medical history, doing a physical examination, conducting imaging studies like CT scans or MRIs and carrying out blood tests.

On a CT scan or MRI, yolk sac tumors generally appear as a large solid cystic mass with internal bleeding.

Another valuable tool in diagnosing yolk sac tumors is a test called immunohistochemical staining. This test checks for a substance called alpha-fetoprotein (AFP) which is usually present in almost all cases of yolk sac tumors.

However, AFP isn’t only found in yolk sac tumors, it can also occur in other types of cancer like liver cancer. Therefore, while the presence of AFP might indicate a yolk sac tumor, it’s not definitive proof because its overall sensitivity is as low as 60%, meaning it may not always detect the disease.

In cases where various types of germ cell tumors are present with small areas of yolk sac tumors, biopsy findings might not show yolk sac tumors. Even though yolk sac tumors may only constitute small cancerous areas within a larger tumor, a positive stain for AFP can confirm the existence of yolk sac tumors within other germ cell tumors. An example of this could be in teratomas where the biopsy may only reveal teratoma, but an elevated AFP level indicates that yolk sac tumor is present too.

The substance AFP can be tested in several bodily fluids like tumor tissue, blood, spinal fluid, urine, and amniotic fluid.

When the yolk sac tumor is only present in a small area, it might be difficult to detect AFP through the staining test. This is because the staining process can be inconsistent and often varies throughout the tissue; strong staining isn’t seen in every tumor. However, in this situation, yolk sac tumors might be identified using substances called cytokeratin or glypican-3, as cytokeratin is present in almost all cases. Another fluid test frequently positive in yolk sac tumors is one which detects placental alkaline phosphatase.

Treatment Options for Yolk Sac Tumors

Yolk sac tumors can be quite dangerous if left untreated, potentially leading to death. Nowadays, the most common treatment for yolk sac tumors is a combination of surgery and chemotherapy. Treatments such as cisplatin, etoposide, and bleomycin have generally shown positive results in many patients.

When treating yolk sac tumors in the testicles, the choice of treatment often depends on the stage of the cancer and the age of the patient when they were diagnosed. It’s common for most children with yolk sac tumors to be diagnosed at stage 1. In most cases, the removal of the testicle (orchiectomy) and chemotherapy are recommended, and sometimes, certain lymph nodes also need to be removed. Most children with the spread or recurrence of the cancer can be successfully treated with a specific chemotherapy plan.

In contrast, yolk sac tumors in the ovaries, particularly in post-menopausal women, often require more intense treatment. If such a tumor is detected in its early stages, it is usually recommended to surgically remove the cancer and follow up with chemotherapy.

Kinds of treatments can vary based on the stage of testicular yolk sac tumors.

Stage 1 disease can often be cured with surgery that removes the testicle, with the next steps dependent on individual cases. These might include regular checkups and scans to watch for any recurrence of cancer, removal of certain lymph nodes, and a short course of chemotherapy to decrease the chance of cancer returning.

In some cases, chemotherapy is recommended when a specific blood marker known as alpha-fetoprotein remains high after surgery, despite there being no signs of a mass.

Surgery is also the first step in patients with stage 2 disease. After surgery, whether additional treatment is needed can depend on the levels of tumor markers in the patient’s blood and the impact on lymph nodes. Patients with high tumor markers after surgery are often treated with additional cycles of chemotherapy.

Stage 3 patients are often treated with a combination of surgery and chemotherapy, usually several cycles of specific chemotherapy drugs. For those whose cancer does not respond to standard chemotherapy, a higher dose of chemotherapy and a bone marrow transplant might be necessary.

For ovarian yolk sac tumors, surgery is almost always required, followed by chemotherapy. The type of surgery, either radical or conservative, depends on the patients’ future fertility wishes and whether one or both ovaries are involved. Additionally, a more extensive procedure is recommended in patients where the cancer has spread to other organs. Afterward, most patients would need at least three cycles of chemotherapy, and a suitable regimen would typically include bleomycin, etoposide, and cisplatin.

There are several other types of tumors that can display similar symptoms to certain conditions and it’s important to distinguish between them. Here are key variations among them:

Clear Cell Carcinoma: This type of cancer tests positive for cytokeratin, cytokeratin 7, and epithelial membrane antigen. On the other hand, it tests negative for glypican-3 and alpha-fetoprotein.
Sertoli-Leydig Cell Tumor: This tumor tests positive for inhibin, calretinin, and steroidogenic factor 1 (SF1). However, it tests negative for AFP and glypican 3.
Juvenile Granulosa Cell Tumor: This type of tumor shares several characteristics with the yolk sac tumor but it tests positive for inhibin and negative for SALL4, AFP, and glypican 3.
Metastatic Hepatocellular Carcinoma: Whether or not this is present can also depend on the patient’s clinical history. It tests negative for Sal-like protein 4 (SALL4), which is strongly positive in yolk sac tumors.
Dysgerminoma/Seminoma: This condition tests positive for placental alkaline phosphatase (PLAP), CD117, and octamer-binding transcription factor 4 (Oct-4).
Embryonal Carcinoma: This type of cancer tests positive for placental alkaline phosphatase (PLAP), cytokeratin, CD30, and Oct-4.
Granulocytic Sarcoma: This condition tests positive for CD117, leukocyte common antigen (LCA), and myeloperoxidase (MPO).
Melanoma: This type of cancer tests positive for S-100.
Lymphoma: This condition tests positive for leukocyte common antigen (LCA).
Yolk Sac Tumors: These tumors test negative for CD117, CD30, S-100, leukocyte common antigen (LCA), myeloperoxidase (MPO), and Oct-4.

These tests help doctors to accurately identify the type of tumor a patient may have.

What to expect with Yolk Sac Tumors

Your age at the time you’re diagnosed doesn’t affect your chances of recovery from yolk sac tumors. However, if your AFP (a protein that increases in your blood when certain cancers are present) levels are high, this is a bad sign for your prognosis, or how likely you are to recover. Like with any cancer, it’s crucial to figure out the stage of the tumor – or how far it’s spread – as soon as possible. Tumors that are found early, when they haven’t spread much, have a better chance of being successfully treated than those that are found later, when they’ve spread further.

Possible Complications When Diagnosed with Yolk Sac Tumors

Complications from yolk sac tumors can stem from the tumor itself or the treatment used to combat the tumor.

The tumor’s complications are directly influenced by its location and size. Another issue tied to the tumor is metastasis, which is the spread of cancer to other parts of the body. Unfortunately, many patients may not exhibit symptoms until the cancer is in its later stages.

Treatment complications can cover a range of things including side effects from chemotherapy, problems arising during surgery, and issues once surgery is completed.

Potential Complications: