A mixed germ-cell tumour is a type of cancer. In males, most mixed germ-cell tumours start in the testicles but they may be found anywhere in the body. Mixed germ-cell tumours usually occur in young adults and are rarely seen in prepubertal children or adults older than 50 years of age.
This tumour starts from germ cells, which are normally found in the testicles. Germ cells are considered ‘primitive’ cells because they are capable of turning into almost any other type of cell. This type of tumour is called ‘mixed’ because it is made up of two or more types of germ-cell tumours.
The types of germ-cell tumour that may be found in a mixed germ-cell tumour include: seminoma; embryonal carcinoma; yolk sac tumour; choriocarcinoma; and teratoma. Doctors divide germ-cell tumours into two groups, seminomatous and non-seminomatous, and mixed germ cell tumours are considered a type of non-seminomatous tumour.
This article will help you read and understand your pathology report for mixed germ cell tumour of the testis. A similar tumour also called a mixed germ cell tumour involving the ovary will not be described in this article.
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.
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.
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.
If your doctor suspects that you have a germ-cell 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. Many germ-cell tumours produce specific tumour markers, which can be detected in your blood and can help in the detection of this 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 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.
By definition, all mixed germ-cell tumours are made up of two or more types of germ-cell tumours and the features described in your report will depend on the number and types of germ-cell tumours seen in the tissue sample when it is examined under the microscope.
Most mixed germ-cell tumours include a component of seminoma (see definition below). Other types of germ-cell tumours are: embryonal carcinoma; yolk-sac tumour; choriocarcinoma; and teratoma (see definitions below). Your pathology report should include the types of germ-cell tumours seen, as well as the percentage of each type within the whole tumour. For example, a report may state “mixed germ-cell tumour, 50% seminoma, 30% embryonal carcinoma, and 20% teratoma.”
Seminoma is the most common type of germ-cell tumour. When examined under the microscope, seminoma tumour cells are 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.
Embryonal carcinoma is an aggressive type of germ-cell tumour that frequently spreads to other parts of the body. The name ‘embryonal carcinoma’ reflects the appearance of the tumour cells, which resemble the cells normally seen in a developing embryo. The tumour is made up of large and abnormal-looking tumour cells. Pathologists describe these cells as atypical. The tumour may be monomorphic (cells look very similar to each other), or pleomorphic (show great variability from cell to cell). The tumour cells may be arranged in large groups called nests or sheets. They may also connect together to form finger-like structures described as papillary, or round groups called glands. Many mitotic figures (dividing tumour cells) are usually seen.
A teratoma is a type of germ-cell tumour that has started to change into more specialized, or well developed, cell types. Up to half of all mixed germ-cell tumours will include a component of teratoma. Pathologists divide teratomas into two groups: immature and mature. Immature teratomas are made up of cells normally found in the developing embryo. In particular, it is very common to find embryonic nervous tissue, such as developing brain, in an immature teratoma. In contrast, a mature teratoma is made up of more developed cells that are normally found in adults.
Mature teratoma often have a variety of different tissue types and it is common to see tissue from the digestive tract, lungs, thyroid, bones, and skin in a mature teratoma. Rarely, a cancer can arise from inside a mature teratoma. Pathologists call this a somatic malignancy. The type of cancer depends on the tissue from which the cancer started. For example, a cancer that starts within thyroid tissue would be a type of thyroid cancer, such as papillary thyroid carcinoma. Unlike mature teratomas that arise in the ovary, all teratomas in the testicle are considered cancerous and have the potential to spread to other parts of the body.
Yolk-sac tumour is the most common type of testicular tumour in young children, but it is found in less than half of mixed germ-cell tumours in adults. 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.
Choriocarcinoma is the least common type of germ-cell tumour found in a mixed germ-cell tumour. The tumour is made up of three types of specialized cells: syncytiotrophoblasts; cytotrophoblasts; and intermediate trophoblasts. These cells are typically only seen in choriocarcinoma and pathologists look for them in order to make the diagnosis. Choriocarcinoma is an aggressive type of germ-cell tumour that commonly spreads to other parts of the body.
Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis and to determine the specific 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.
All mixed germ-cell 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 mixed germ-cell tumour. If your pathologist sees GCNIS, it will be included in your report.
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.
All mixed germ-cell 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).
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).
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 mixed germ-cell 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.
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.
The pathologic stage for mixed germ-cell 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 mixed germ-cell tumour
Mixed germ-cell 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.
Nodal stage (pN) for mixed germ-cell tumour
Mixed germ-cell 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.
Metastatic stage (pM)
Mixed germ-cell 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.
Your pathologist will carefully examine areas of the testis outside of the tumour for two important microscopic features: spermatogenesis and atrophy.
Some mixed germ-cell tumours 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.