Testicular cancer

Definitions & Key takeaways

Testicular cancers are malignant tumors that form in one or both testes. They usually present as a mass that's often detected in the early stages. Major types of testicular cancer include germ-cell testicular cancer and non-germ-cell testicular cancer. Germ cell testicular cancers come from germ cells that normally develop into sperm.

Their five main subtypes include seminomas, teratomas, yolk sac tumors or endodermal sinus tumors, choriocarcinoma or placental tissue tumors, and embryonal carcinomas. Non-germ cell testicular cancers come from the Sertoli cells or the Leydig cells which can secrete excess sex hormones. Risk factors for developing testicular cancer include cryptorchidism, Klinefelter syndrome, and in-utero exposure to pesticides and synthetic sex hormones. Treatment of testicular cancer involves surgery, chemotherapy, and radiotherapy.

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Introduction0:00–0:20

Testicular cancers are malignant tumors that form in one or both testes. They usually present as a mass that’s often detected in the early stages since they are on an organ that’s easily accessible during physical examination.
Thus, they typically have a good prognosis.The testes are a pair of male reproductive glands the size of small plums, that are located in the scrotum.

Physiology0:20–2:40

The testes themselves are covered on the outside by the tunica albuginea, a white, fibrous layer. If we slice a testis open and look inside, sorry for the cringe moment, we can see septa that partition each testis into lobules.
Each lobule contains up to four seminiferous tubules, where sperm is synthesized.Now let’s zoom in on a single seminiferous tubule, which is the “sperm factory”.
A seminiferous tubule has a thick wall of epithelial cells that surround a fluid-filled lumen, a bit like a garden hose.
The wall of the tubule is made up of two kinds of cells: at the periphery, there’s the germ cells known as spermatogonia, which are the primordial sperm cells that begin dividing over and over in puberty, and give rise to male gametes.
Next to them are Sertoli cells which are large cells that extend from the margin all the way to the lumen of the tubule.
Sertoli cells are supportive cells that provide nutrients to developing sperm cells, and contribute to the blood-testis barrier by only allowing certain molecules, like testosterone, into the seminiferous tubules.
Outside the tubule, there’s connective tissue with capillaries, as well as Leydig cells - another supportive cell which produces testosterone, which is a hormone necessary for the proper development of sperm.During fetal development the entire body derives from three layers called germ layers; the ectoderm, mesoderm and endoderm.
These germ layers are made of germ cells that migrate out and differentiate into all of the different types of tissues. Some very special germ cells stay as germ cells, meaning that unlike the cells that differentiate, these germ cells retain their ability to turn into other cell types.
They are like ancient little shapeshifters. Normally, during development these germ cells head to the testicles in males or ovaries in females\, where they remain for decades, eventually developing into sperm or eggs, respectively.If any of these testicular cells start to divide uncontrollably it can either form a benign tumor, meaning that it doesn’t invade nearby tissue or spreads to other parts of the body, or it can be a malignant tumor which means it can penetrate the tunica albuginea and spread to nearby tissue and even to other organs via the bloodstream or lymphatic system.

Pathophysiology2:40–3:16

Now let’s go back to the seminiferous tubule and look into the germ cells. Once they start dividing uncontrollably inside the tubules, they give rise to germ cell tumors.
There are five main types of germ cell tumors. Starting with the most common one, seminomas.

Seminoma3:16–3:56

These are made of germ cells that multiply without differentiating into other types of cells. Under the microscope the germ cells are big with central nuclei surrounded by the clear cytoplasm, which kind of looks like a fried egg.
These cells group into lobular forms that are surrounded by fibrous tissue which separates it from the healthy tissue. Fibrous tissue almost always contains lymphocytes, which is helpful in diagnosis.
Seminomas can also secrete placental alkaline phosphatase, or PLAP PALP, which is an enzyme normally secreted by the placenta.The second type are yolk sac tumors, also called endodermal sinus tumors, which are the most common germ cell tumors in children and can be very aggressive.

Yolk sac tumors3:56–4:31

They are made of the germ cells that differentiate into yolk sac tissue. Under the microscope they form Schiller-Duval bodies, which are rings of malignant cells around the central blood vessel.
These cells can also secrete alpha-fetoprotein or AFP, which is normally secreted by the yolk sac and fetal liver, and resembles albumin, a transport protein of the blood.The third type are teratomas, where “terato” means monster and “oma” is a tumor.

Teratomas4:31–5:32

They are named this way because they could contain all types of tissues including hair, eyes, teeth, bones and neurons. Kind of like Frankenstein’s monster that’s got bits of this-and-that stitched together.
Now there are two types of teratomas. The first is mature cystic teratoma that looks like a cyst with fully developed tissue inside, like skin, hair, nails etc.
It usually appears in children, and is usually benign, but when they appear in adults they tend to be malignant. The other type is immature teratoma which usually appears in adults, and unlike the mature cystic type, it has undifferentiated tissue that resembles embryonic structures, like undeveloped muscle cells from the mesoderm.
It tends to be malignant and metastasizes quickly. The fourth type is the choriocarcinoma and it’s made out of germ cells that turn into syncytiotrophoblast and cytotrophoblast, 2 types of cells that help form the placenta.

Choriocarcinoma5:32–6:37

These tumors are small but very malignant so they tend to invade nearby tissues, like blood vessels, causing frequent bleeding.
They can even spread beyond the testicles via blood stream. These tumors grow quickly and often outgrow their blood supply, leading to areas of ischemia and necrosis.
Under the microscope these tumors contain two types of large cells, cytotrophoblasts with central nuclei and pale cytoplasm, and syncytiotrophoblasts that have multiple nuclei and darker cytoplasm.
The syncytiotrophoblast cells can secrete high levels of a hormone called human chorionic gonadotropin, or hCG, which is normally secreted by the placenta.
High levels of hCG could sometimes be detected by a positive pregnancy test in biological male individuals.And the fifth type is the embryonal carcinoma and it’s made of germ cells that turn into embryonic pluripotent stem cells that form clumps called embryoid bodies.

Embryonal carcinoma6:37–7:10

They are usually small and painful, but very aggressive, and just like choriocarcinoma, they tend to invade nearby tissue and blood vessels, then spread beyond the testicles.
Under the microscope germ cells are large and tend to form a tubular or alveolar like structures while sites of bleeding and necrosis can also be seen.Okay, let’s switch gears and talk about cancers that arise from the support cells in the testicles.

Sex cord-stromal tumors7:10–8:42

These are called non-germ cell tumors or sex cord-stromal tumors. Sex cord refers to the embyogenic structures that develop into the seminiferous tubules of the testicles, and stromal cells are the connective tissue of any organ.
These arise from sertoli cells inside the tubules, or Leydig cells outside of them. Sertoli cell testicular tumors are rare, small, usually benign, and don’t produce any hormones.
Under the microscope tumor cells are well differentiated, have pale cytoplasm and originates inside the seminiferous tubules.
On the other hand, the Leydig cell tumors can be hormonally active, meaning they could secrete both male and female sex hormones.
Excess male sex hormones, like testosterone, can cause premature puberty in young males, while in adults they usually cause no symptoms.
Excess female sex hormones, like estrogen, can cause a feminization and delayed puberty in young biologically male individuals.
In adults they can cause gynecomastia or enlargement of breasts, feminine hair distribution, erectile dysfunction, testicular atrophy and loss of libido or sexual drive.
Under the microscope, classically there would be Reinke crystals, which are pink, rod like crystals believed to be made out of excess proteins inside the cytoplasm of Leydig cells.The most important risk factor for developing testicular cancer is cryptorchidism, where “crypto” means hidden and “orchi” is testicles.

Risk Factors8:42–9:41

This happens when the testicles develop inside the abdominal cavity, but fail to descend to the scrotum or get stuck in the inguinal canal, leading to undeveloped or even abnormally developed testicles.
Second risk factor is Klinefelter syndrome, where biological male individuals inherit more than one X chromosome leading to small, undeveloped testicles.
Also, in utero exposure to some environmental factors like pesticides or synthetic sex hormones found in contaminated food and water increase the risk as well.
There are also some genetic risk factors, like having a mutation in the genes that encode ligands for tyrosine kinase receptors, which are important for maintaining normal cell processes, like apoptotic cell death.Symptoms are usually subtle, as testicular cancer most often presents as a small, painless lump.
The Testicle can also be swollen or firm to the touch. Sometimes a sharp or dull pain can be felt both in the testicles and lower abdomen.

Symptoms9:41–10:08

Tumors that secrete hormones like hCG can cause gynecomastia, testicle atrophy, loss of libido or erectile dysfunction. Complications may arise when the malignant tumor starts invading nearby tissue.
Once it invades a blood vessel it can enter the bloodstream and metastasize to other organs, most commonly the lungs. This leads to symptoms like dyspnea, or shortness of breath, cough and hemoptysis, or coughing of blood.

Complications10:08–10:41

Another way for the cancer cells to metastasize is by the testicular lymphatic system that drains into retroperitoneal lymph nodes.
Metastasis to these lymph nodes lead to symptoms like lower back pain. Diagnosis usually starts by discovering a lump on the testis during a physical examination.
An ultrasound can help differentiate it from cysts, and mark the size and border of the mass. An imaging with CT or MRI scan can be done to look for evidence of metastasis.

Diagnosis10:41–11:37

Then a blood test can be done to measure levels of some tumor markers like PLAP, hCG,or AFP. Lactate dehydrogenase, or LDH, could also be measured as a tumor marker but it’s not specific to testicular cancer since it could be released by any damaged tissue in the body.
Biopsy should not be performed because the lymph from the scrotum is drained by the superficial inguinal lymph nodes and not the retroperitoneal ones.
So cutting into the scrotum would open an additional route for the cancer cells to escape and metastasize.Treatment of testicular cancer involves surgery, chemotherapy and radiotherapy.
Surgical removal of the whole testicle through the inguinal canal called, inguinal orchiectomy is the procedure of choice because it has lower chances of tumor cells spreading.
After the removal a pathological work up can be done to determine the histologic type of the tumor and also if it has a benign or malignant nature.

Treatment11:37–12:24

Chemotherapy and radiotherapy can be added after surgery if the tumor has spread. Measuring levels of PLAP, hCG, AFP and LDH before and after procedures could be useful in assessing the effects of the therapy and potential relapses.All right, as a quick recap...
Germ cell testicular cancers come from germ cells that normally develop into sperm. The five main types include seminomas, teratomas, yolk sac tumors or endodermal sinus tumors, choriocarcinoma or placental tissue tumors and embryonal carcinomas.
Non germ cell testicular cancers come from the Sertoli cells or the Leydig cells which can secrete excess sex hormones. Risk factors for developing testicular cancer include cryptorchidism, Klinefelter syndrome and in utero exposure to pesticides and synthetic sex hormones.

Review12:24–13:03

seminomas, teratomas, yolk, Sac, tumors, or endodermis sinus, tumors choriocarcinoma, or placental tissue tumors. And, and Brian old, carcinomas Nom germ-cell testicular.
Cancer come from the sertoli cells or the lady cells which can secrete excess sex, hormones risk factors for developing testicular, cancer include cryptorchidism, Klinefelter syndrome and in utero exposure to pesticides and synthetic sex hormones.