by Trevor A. Flood, MD FRCPC, updated on August 30, 2019.
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 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.
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. 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. Sperm then passes through ducts within the prostate to empty into the urethra and exit out the tip of penis.
Seminoma is a cancer that develops from the germ cells in the seminiferous tubules. The other types of germ cell tumours are known as the non seminomatous germ cell tumours. This includes yolk sac tumour, embryonal carcinoma, teratoma, and choriocarcinoma. Germ cell tumours are commonly referred to as testicular cancer.
The distinction between seminoma and non seminomatous germ cell tumours is important because they have different clinical features and treatment options.
When the tumour cells are only seen on the inside of the tubules, the disease is called germ cell neoplasia in situ (GCNIS). This disease was previously called intratubular germ cell neoplasia (ITGCN).
GCNIS is considered a pre-cancerous disease because it can turn into a cancer over time. A germ cell tumour develops once the tumour cells break out of the tubules and enter the surrounding tissue. The process of tumour cells breaking out of the tubules and into the surrounding tissue is called invasion. GCNIS can turn into any type of germ cell tumour over time.
The tumour cells in a seminoma are arranged usually in sheets. 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. The seminoma cells have pale cytoplasm and square nuclei.
Germ cell tumours are usually detected as a result of signs and symptoms that a person is having. A germ cell tumours commonly causes the testicle to appear swollen and feel tender. Occasionally a lump can be felt on physical exam. An ultrasound will frequently be performed to help determine if the changes in the testicle are because of a germ cell tumour. 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 the cancer. If there is a high likelihood that of a germ cell tumour, the patient is often treated by surgery. Surgery involves removing the affected testicle through a process called radical orchiectomy. Once removed, your testicle will be sent to the pathology department of your hospital where it will be processed and analyzed.
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 greatest dimension. Tumour size may be important for tumour stage (please see Pathologic stage below).
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 with prognosis and is used to determine the tumour stage (see Pathologic stage below).
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. Once the cancer 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 to find germ cell neoplasia in situ in tumours that also show an invasive seminoma. If your pathologist sees germ cell neoplasia in situ, it will be included in your report.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph contains waste and immune cells moves around the body through lymphatic channels.
Tumour 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).
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.
In a seminoma, 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.
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 a 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.
All lymph nodes are surrounded by a capsule. Extranodal extension means that the metastasized tumour cells have broken through the capsule and into the tissue that surrounds the lymph node.
Extranodal extension can be associated with an increased risk that the cancer will come back.
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 worse prognosis.
Seminoma is given a tumour stage between 1 and 4 based on size of the tumour, the extent of tumour extension, and the presence of lymphovascular invasion.
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.
Seminoma is given a metastatic stage of 0 or 1 based on the presence of tcells 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.
Areas of the testis outside of the tumour will be carefully examined for spermatogenesis and atrophy.
Spermatogenesis describes the normal production of spermatozoa from germ cells. The presence of spermatogenesis means that the testicular tissue outside of the tumour was functioning normally.
Atrophy (or atrophic) is a word 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.
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.