Learn about your pathology report:

Yolk-sac tumour of the testicle

What is a yolk-sac tumour?

Yolk-sac tumour is a type of cancer. In males, the tumour often starts in the testicle where it is part of a group of cancers known as germ-cell tumours. Yolk-sac tumour is the most common type of testicular tumour in young children and it typically responds well to chemotherapy.

Germ cells are specialized cells that are normally found in the testicles. They are considered ‘primitive’ cells because they are capable of turning into almost any other type of cell. Other types of germ-cell tumours include seminoma, embryonal carcinoma, and choriocarcinoma.

A ‘pure’ yolk-sac tumour is a tumour that is made up entirely of yolk-sac tumour cells and no other types of germ-cell tumours. While pure yolk-sac tumours do occur in children, it is much more common for a yolk-sac tumour to develop with at least one other type of germ-cell tumour as part of a mixed germ cell tumour.

This article will help you read and understand your pathology report for yolk-sac tumour of the testicle. A similar tumour also called a yolk-sac tumour involving the ovary will not be described in this article.

The male reproductive tract

Testicles and scrotum

The testicles, or testes, are part of the male reproductive system. A man has two testicles, which are egg-shaped organs that when fully matured measure approximately 5 cm in the greatest dimension. The testicles are each suspended by a structure called the spermatic cord, which is composed of connective tissue and muscle. The testicles are covered in a fleshy sac of skin called the scrotum. The scrotum hangs between the legs and beneath the penis. After puberty, the testicles are responsible for making sperm. The testicles also produce testosterone, which is a male sex hormone.

Seminiferous tubules

The tissue within the testicles is made up of hundreds of tiny tubes called seminiferous tubules. The seminiferous tubules are lined by millions of specialized cells called germ cells. Germ cells are responsible for the production of sperm (spermatozoa), which occurs through a process called spermatogenesis. The sperm produced within the seminiferous tubules travels through a series of ducts to eventually reach a coiled structure called the epididymis.

Epididymis

An epididymis sits on top of each testicle. Immature sperm are stored and mature within the epididymis. During ejaculation, sperm is pushed from the epididymis and into the vas deferens which is a tubular structure residing within the spermatic cord. The vas deferens eventually joins with the seminal vesicle of the prostate to form the ejaculatory duct. The sperm then passes through ducts within the prostate to empty into the urethra and exit out the tip of the penis.

male genital tract

How is the diagnosis of yolk-sac tumour made?

If your doctor suspects that you have a germ-cell tumour such as a yolk-sac tumour, they may draw blood and analyze it for proteins made by the tumour and released into your blood. These proteins are called tumour markers. Yolk sac tumours almost always produce alpha-fetoprotein (AFP).

Biopsies of germ-cell tumours such as yolk-sac tumour are rarely performed because of the risk of spreading cancer to other parts of the body. If there is a high likelihood that the tumour is a germ-cell tumour, most individuals are offered surgery to remove it. Once removed, the tumour will be sent to a pathologist for examination under the microscope.

Microscopic features

When examined under the microscope yolk-sac tumours can show a wide range of microscopic features. The tumour cells often connect together to form open spaces called cysts. Other patterns include large, solid groups of cells, glands, and finger-like papillary structures. A unique pattern only seen in yolk-sac tumours involves finger-like papillary structures, with a large central blood vessel, surrounded by a clear space. Pathologists describe these structures as Schiller-Duval bodies.

yolk sac tumour testicle

Immunohistochemistry

Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis and to see if any other types of germ-cell tumours in the tissue sample. The results of this test will depend on the types of germ-cell tumours seen in the sample because each tumour type produces specialized proteins that can be seen inside the tumour cells.

Yolk-sac tumour is typically positive for the following immunohistochemical markers:

  • SALL4
  • Glypican-3
  • Alpha-fetoprotein (AFP)

Yolk-sac tumour is typically negative for the following immunohistochemical markers:

  • OCT3/4
  • CD30
  • Human chorionic gonadotrophin (hCG)
  • Placental-like alkaline phosphatase (PLAP)

Germ-cell neoplasia in situ

All yolk-sac tumours start inside very small channels called seminiferous tubules. When the tumour cells are still inside the seminiferous tubules, the disease is called germ-cell neoplasia in situ (GCNIS). GCNIS can turn into any type of germ-cell tumour over time.

When the tumour cells break out of the tubules and enter the surrounding tissue, the disease is then called a germ-cell tumour. The process of tumour cells breaking out of the tubules and into the surrounding tissue is called invasion. It is common for pathologists to see GCNIS in the tissue surrounding a germ-cell tumour. If your pathologist sees GCNIS, it will be included in your report.

What to look for in your report after the tumour is removed

Tumour size

These tumours are measured in three dimensions, but only the largest dimension is typically included in the report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in the greatest dimension. Larger tumours are more likely to grow into surrounding structures (see Tumour extension below), and as result are associated with a worse prognosis.

Tumour extension

All yolk-sac tumours start in the seminiferous tubules but they may grow into any of the structures described below. The process of a tumour growing into any of these structures is called tumour extension. Tumour extension into the tunica vaginalis, hilar soft tissue, spermatic cord, or scrotum is important because it is associated with a worse prognosis and is used to determine the tumour stage (see Pathologic stage below).

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph contains waste and immune cells and moves around the body through lymphatic channels. Cancer cells can use blood vessels and lymphatic channels to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic channel. This process is called lymphovascular invasion. Lymphovascular invasion increases the risk that tumour cells will be found in a lymph node or metastasize to a distant part of the body, such as the lungs. Lymphovascular invasion is also used to determine the tumour stage (see Pathologic stage below).

lymphovascular invasion

Margins

A margin is any tissue that has to be cut by the surgeon in order to remove the tumour from your body. For most testis specimens, the most important margin is the spermatic cord.

When examining a yolk-sac tumour, a margin is considered ‘negative’ when there are no cancer cells at the cut edge of the tissue. A margin is considered ‘positive’ when there is no distance between the cancer cells and the edge of the tissue that has been cut. A positive margin is associated with a higher risk that the tumour will come back (recur) in the same site after treatment.

Margin

Lymph nodes and lymph-node metastasis

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour cells. Lymph nodes on the same side as the tumour are called ‘ipsilateral’, while those on the opposite side of the tumour are called ‘contralateral’.

Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour cells are often called ‘positive’ while those that do not contain any tumour cells are called ‘negative’.

The examination of lymph nodes is important because this information is used to determine the pathologic nodal stage (see Pathologic stage below) and because finding cancer cells in one or more lymph nodes is associated with a worse prognosis.

Lymph node

Pathologic stage (pTNM)

​​The pathologic stage for yolk-sac tumour is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for yolk-sac tumour

Yolk-sac tumour is given a tumour stage between 1 and 4 based on the location of the tumour, the extent of tumour extension into surrounding tissues, and whether there is lymphovascular invasion.​

  • Tis: Tumour cells are only seen inside the seminiferous tubules. There is no invasive tumour seen. This is the same as germ cell as neoplasia in situ.
  • T1: The tumour is only seen in the testis. It does not extend into any of the surrounding tissue.
  • T2: The tumour is only seen in the testis, and lymphovascular invasion is seen, or the tumour extends into the hilar soft tissue, epididymis, or tunica albuginea.
  • T3: The tumour extends into the spermatic cord.
  • T4: The tumour extends into the scrotum.​

Nodal stage (pN) for yolk-sac tumour

Yolk-sac tumour is given a nodal stage of 0 to 3 based on the number of lymph nodes with tumour cells, the size of the largest lymph node with cancer cells, and the presence of extranodal extension.

  • Nx: No lymph nodes were sent for pathologic examination.
  • N0: No cancer cells are seen in any lymph nodes examined.
  • N1: Cancer cells are seen inside no more than five lymph nodes, and none of the lymph nodes are larger than 2 cm.
  • N2: Cancer cells are seen in more than five lymph nodes, but none of the lymph nodes are over 5 cm, or extranodal extension is seen.
  • N3: Cancer cells are seen in a lymph node over 5 cm.​

Metastatic stage (pM)

Yolk-sac tumour is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example a bone). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

Changes in the testis outside of the tumour

Your pathologist will carefully examine areas of the testis outside of the tumour for two important microscopic features: spermatogenesis and atrophy.

  • Spermatogenesis: Spermatogenesis is the normal production of sperm from germ cells. The presence of spermatogenesis means that the testicular tissue outside of the tumour is functioning normally.
  • Atrophy: Atrophy or atrophic are terms pathologists use to describe tissue that has decreased in size and function. Atrophy in the testis means that the seminiferous tubules are no longer producing normal sperm.

Scar or regressed-germ cell tumour

Some germ-cell tumours such as yolk-sac tumour decrease in size or even disappear entirely before the tumour is removed. This process is called regression. If the process of regression is complete, your pathologist may only see a scar where the tumour used to be when your tissue is examined under the microscope. In this situation, your pathologist will not be able to provide any more details about the types of germ cell tumours present prior to regression.

In another situation, your pathologist may only see an early form of cancer called germ cell neoplasia in situ. The finding of germ-cell neoplasia in situ within a scar suggests that a germ-cell tumour was there previously but has now regressed.

by Jason Wasserman MD PhD FRCPC (updated November 19, 2021)
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