Seminoma



What is seminoma?

Seminoma is a type of testicular cancer. The tumour develops from specialized germ cells normally found in a part of the testicle called the seminiferous tubules. Seminoma is part of a group of tumours called germ cell tumours. The other types of germ cell tumours are called non-seminomatous germ cell tumours. The distinction between seminoma and non-seminomatous germ cell tumours is important because they have different clinical features and treatment options.

The male reproductive tract

The testicles, or testes, are part of the male reproductive system. A man has two testicles, which are egg-shaped organs that 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.

male genital tract

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 that is produced within the seminiferous tubules travels through a series of ducts to eventually reach a coiled structure called the epididymis.

An epididymis sits on top of each testicle. It is within the epididymis that immature sperm are stored and allowed to mature. 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.

Germ cell neoplasia in situ

All seminomas 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). Once the tumour cells break out of the tubules and enter the surrounding tissue, the disease is called seminoma. The process of cancer 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 seminoma. If your pathologist sees GCNIS, it will be included in your report. GCNIS can turn into any type of germ cell tumour over time.

What are the symptoms and how is this diagnosis made?

Most seminomas cause the testicle to appear swollen and feel tender. Occasionally a lump can be felt on a physical exam. An imaging test called an ultrasound may be performed to look inside the testicle. In addition, your doctor may draw blood and analyze it for proteins made by the tumour and released into the blood. These proteins are called tumour markers. Many germ cell tumours produce specific tumour markers which can be detected in your blood and can help in the detection of the cancer.

Biopsies of germ cell tumours are rarely performed because of the risk of spreading cancer to other parts of the body. If there is a high likelihood that of a germ cell tumour, most patients are offered surgery to remove the tumour. The specific type of surgery performed is called a radical orchiectomy. Once removed, the tumour will be sent to a pathologist for examination under the microscope.

When examined under the microscope, the tumour is made up of large cells arranged in groups called sheets. The body or cytoplasm of the tumour cells usually appears clear. The sheets are separated by thin strips of connective tissue, called fibrous septae. The tumour cells are surrounded by lymphocytes which are normal immune cells.

Seminoma

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

The testes sit outside of the body and are covered by the scrotum. Within the scrotum, each testis is surrounded by two thin layers of tissue. The layer closest to the seminiferous tubules is called the tunica albuginea. The layer in between the scrotum and the tunica albuginea is called the tunica vaginalis.

The millions of seminiferous tubules in the testis join together in a structure called the rete testis which then exits the testis through a structure called the epididymis. The rete testis and epididymis meet in an area of the testis called the hilar soft tissue. After leaving the testis, the epididymis connects with a long tube called the spermatic cord which leads out of the scrotum.

All seminomas start in the seminiferous tubules but they may grow into any of the structures described above. 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 move around the body through lymphatic channels. Cancer cells can use blood vessels and lymphatics 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. 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 seminoma, a margin is considered ‘negative’ when there are no tumour cells at the cut edge of the tissue. A margin is considered ‘positive’ when there is no distance between the tumour cells and the cut edge of the tissue. 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. Tumour 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 tumour cells from the tumour to a lymph node is called metastasis.

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. Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour cells.

Lymph node

Pathologic stage (pTMN)

​​The pathologic stage for seminoma 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 submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for seminoma

Seminoma 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 the presence of 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 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 seminoma

Seminoma 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 5 lymph nodes and none of the lymph nodes are larger than 2 cm.
  • N2 – Cancer cells are seen in more than 5 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)

Seminoma 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.

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

Scar or regressed germ cell tumour

Some seminomas decrease in size or even disappear entirely before the tumour is removed from the body. 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 through the microscope.

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 seminoma was there previously but has now regressed.

by Trevor A. Flood, MD FRCPC (updated September 18, 2021)
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