Week 4 - Testicular Cancer Flashcards
What is gynecomsatia?
Enlargement of breast tissue in men due to hormonal imbalance
(i) Where are the checkpoints in the cell cycle (1.5 marks)
AND
(ii) What are they monitoring (1.5 marks)?
3 checkpoints in cell cycle
G1-S (1/2 mark) transition that the cell organelles have been replicated and that the cell has enough organelles to divide. (1/2 mark)
G2-M (1/2 mark) transition that the DNA has been replicated appropriately and accurately. (1/2 mark)
Exit M (1/2 mark) phase transition that the chromosomes have attached to the mitotic spindle. (1/2 mark)
Alexi has to give informed consent before the operation for the consent to be valid.
What three things must be verified?
3 marks
· The patient must have capacity (Competence).
· The patient must be offered adequate information (Adequate Disclosure).
· The patient’s decision must be non-coerced/voluntary (Non-Coercion/Voluntariness)
Define gynecomastia?
1 mark
Benign enlargement of breast tissue in males (if enlarged breasts and no mention of this being in males then ½ mark)
Explain why self-examination of the testis is important for male health?
2 marks
It familiarizes a man with the normal size, shape, and weight of his testicles and the area around the scrotum. (1 mark)
This allows him to detect any changes from normal at an early stage. (1 mark).
How many testicular cases were diagnosed in 2011?
2200
In which age group is testicular cancer most common?
Young Men between 25-49 years
How many testicular cases were diagnosed in 2015?
2300
In which ethnicity is testicular cancer most common?
Caucasian
Which groups are more high risk for developing testicular cancer?
- Baby boys born with undescended testicles (3-5% of boys) - increases risk by 4-10x
- Baby boys born with an indirect inguinal hernia
- Family history of testicular cancer (family dad - 4-6x, brother 6-8x)
- Using marijuana - 70% more likely and linked to more aggressive testicular cancer
- Smoking (12 year pack history - twice)
- Height (190-194cm - twice, 195cm+ - 3x, less than 170cm - decrease risk by 20%)
Signs and symptoms of testicular cancer
A firm, usually painless mass or lump on the testicle (some cancerous masses can be painful - 25-50%)
Growth or swelling of the testicle
Abnormality in shape or consistency of one testicle compared to the other
Associated with abdominal pain occuring with above symptoms
Asymptomatic at presentation in 10% of cases
What are the 2 functions of the testes?
- Produce the male gametes or spermatozoa
- Produce male sex hormones - testosterone which stimulates the accessory male sexual organs and causes the development of the masculine extra genital sex characteristics
Name two roles of the lymphatic system
1 mark
Any 2 from
· It is responsible for the removal of interstitial fluid from tissues
· It absorbs and transports fatty acids and fats as chyle from the digestive system
· It transports white blood cells to and from the lymph nodes into the bones
· The lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated.
What is mild bilateral gynaecomastia?
Enlargement of male breast tissue on both sides
What is an undescended right testicle?
‘As a child Alex had an undescended right testicle which had been repaired by an orchidopexy surgical intervention when he was 2 years old’
Testicle which hasn’t moved into the scrotum
What is an orchidopexy surgical intervention?
‘As a child Alex had an undescended right testicle which had been repaired by an orchidopexy surgical intervention when he was 2 years old’
Surgery to move the undescended testicle into the scrotum
What does variegated consistency mean? (describing the tumour)
‘On physical examination the GP finds a 4cm non-tender mass in the right testis, the temperature was normal, testicular sensations were absent on the affected side. When the GP used a light, the light did not pass through the mass and had a variegated consistency’
Has streaks, marks or patches of different colours
What does organomegaly mean?
Abnormal enlargement of organs
What is an homogenous intratesticular mass?
‘Alex has an ultrasound of his right testis, which shows a homogenous intratesticular mass with low echogenicity compared to the left testis’
Mass in the testicles that exhibits essentially the same physical properties at every point throughout the mass
What does low echogenicity
mean?
‘Alex has an ultrasound of his right testis, which shows a homogenous intratesticular mass with low echogenicity compared to the left testis’
A mass in the testicles which exhibits essentially the same physical properties at every point throughout the mass
What does radical orchiectomy mean?
‘The oncologist explains to Alex the examination findings and that it is likely that he has testicular cancer and that surgery is recommended. Alex underwent a radical orchiectomy of the right testis and retroperitoneal lymph node dissection’
Removal of one or more testicles
What is an retroperitoneal lymph node dissection?
‘The oncologist explains to Alex the examination findings and that it is likely that he has testicular cancer and that surgery is recommended. Alex underwent a radical orchiectomy of the right testis and retroperitoneal lymph node dissection.’
Removal of the retroperitoneal lymph nodes
What is a non-seminomatous germ cell tumour?
’ The histopathologists’ diagnose a Stage I nonseminiomatous germ cell tumour. Alex is given advice on testicular self-examination and is told that he will be followed by surveillance for a 1 year and that his prognosis is good.’
One of the main groups of germ cell tumours
These types of germ cell tumors usually occur in men between their late teens and early 30s.
A type of cancer that begins in cells that form sperm or eggs. There are several types (4) of nonseminoma tumors, including embryonal carcinoma, malignant teratoma, choriocarcinoma, and yolk sac tumor. These tumors are usually made up of more than one type of cancer cell. Although nonseminomas occur most often in the testicles or ovaries, they can occur in other tissues, such as the brain, chest, or abdomen. This happens when cells that have the ability to form sperm or eggs are found in other parts of the body.
What is the median age of diagnosis?
33
How does the incidence of testicular cancer now compared to mid 1970s?
Doubled
What is the incidence of testicular cancer in White males?
6.6 per 100,000
What is the incidence of testicular cancer in hispanic males?
4.8 per 100,000
What is the incidence of testicular cancer in Native American males?
4.5 per 100,000
What is the incidence of testicular cancer in Asian males?
1.9 per 100,000
What is the incidence of testicular cancer in African American males?
1.4 per 100,000
What are the properties of indirect hernias?
- Transverses inguinal canal
- Same course of spermatic cord
- Enter inguinal canal at the deep inguinal ring
- Lateral to the inferior epigastric vessels
- Can pass into the scrotum or labia major
- Congenital/injury
What are the properties of direct hernias?
- Bulge through weakened fascia of abdominal wall
- Directly behind the superficial inguinal ring
- Medial to the inferior epigastric vessels
- Rarely enter the scrotum
- Common in elderly men with weak abdominal muscles
Mutations in which 2 genes appear to increase the risk of developing testicular cancer?
KITLG (KIT ligand or stem cell factor SCF)
SPRY4 (protein sprouty homolog 4)
What kind of a receptor is KIT?
Tyrosine Kinase
How do KIT and Kras link?
So the binding of the KIT ligand with the KIT tyrosine kinase receptor activates different signalling pathways and one of them is Ras and MAP kinases
Where do the germ cells originate?
Primordial germ cells migrate from the yolk sac to the gonadal ridges
For testicular cancer, these germ cells have already got the mutations
They divide repeatedly and migrate through the gut into the developing gonads at 4.5 weeks
Are the mutations in testicular cancer acquired or spontaneous?
Acquired
The germ cells have the mutations already
Where is the spermatozoa made?
In the seminiferous tubules
Where is sperm stored?
In the epididymis
What type of testicular cancer accounts for 95% of all cases?
Germ cell testicular cancer
What percentage of cases does germ cell testicular cancer account for?
95%
What are the two main types of germ cell testicular cancer?
Seminomas
Non-seminomas
What is the mean age of someone with a seminoma germ cell testicular cancer?
35 years
What is the mean age of someone with a non-seminoma germ cell testicular cancer?
25 year years
Younger patients
More malignant
Where do seminomas germ cell tumours derive from?
Germinal epithelium
Where do non-seminomas germ cell tumours derive from?
Endoderm - closest to the yolk sac
Do seminomas and non seminomas have the same pre-cursors?
Yes
What can you tell about Alex’s haematocrit and platelet count?
Haematocrit 42.5% (normal 38.8-50%) Platelets 213000 (normal is 150000-440000 per cubic ml of blood)
They are both normal
What does the Alpha Fetoprotein (AFP) levels indicate?
2628ng/ml (<400ng/ml)
The AFP levels were really high
AFP is not normally found in testicular tissue
AFP is also rare in seminomas but found in several non-seminomas so helps differentiate between the two
What do the Beta-human chorionic gonadadotrophin levels indicate?
49.525 IU/L(<5 IU/L)
Not normally found in adult testicular tissue
Beta HCG is usually elevated in non-seminomas and only in 7% of seminomas
Again helps differentiate between non-seminomas and seminomas
What do the levels of lactate dehydrogenase indicate here?
979 IU/L
100-250 IU/L
General Tumour Marker
It is usually found in the anaerobic respiration metabolic pathway
This is usually found in tumours as the vasculature around the tumour cannot sustain aerobic respiration in the tumour as it grows, so it switches to anaerobic respiration
How does testicular cancer spread?
Through the lymph nodes
Not through the blood
Lymphogenous dissemination
Where does the lymph from the testes drain to?
Para-aortic lymph nodes
Where does the lymph from the scrotum (skin, tunical vaginalis) drain to?
Superficial inguinal lymph nodes
Where are the para-aortic lymph nodes found?
Retroperitoneal lymph nodes
Anterior to T11 to L4 vertebral bodies concentrated at L1-L3
What does it mean to stage a cancer?
Stage of a tumour indicates how far advanced the tumour has become
Whether it has metastasised
Whether it has spread beyond the testicle
What is Stage 1 Testicular Cancer?
Contained in the testicle
What is Stage 2 Testicular Cancer?
Lymph node spread but no distant metastases
What is Stage 3 Testicular Cancer?
Spread to lymph nodes in the thorax
What is Stage 4 Testicular Cancer?
Spread to another organ e.g. lungs
What is the primary landing site for lymph node metastases or cancer spread?
Lymph nodes in the retroperitoneum
Region is up near the kidneys
Is grading and staging of cancers universal to all cancers?
No
Each cancer has it’s own staging and grading system
There is even a difference between prostate and testicular cancer
What is the treatment for low stage, low risk NSGCT?
Surveillance
Retroperitoneal lymph node dissection (RPLND)
What is the treatment for low stage medium risk NSGCT?
Retroperitoneal lymph node dissection (RPLND)
Short course chemotherapy
Surveillance
What is the treatment for intermediate stage NSGCT?
Retroperitoneal lymph node dissection (RPLND)
Chemotherapy
What is the treatment for advanced stage high risk NSGCT?
Chemotherapy:
Cis-Platinum
Etoposide (DNA interacts with topoisomerases)
Bleomycin
What percentage of NSGCTs are cured?
> 90% are cured
Even Stage IV have a 5 year survival rate of 70-80%
What are the treatments for NGCSTs?
Surveillance
Radical orchiectomy
Retroperitoneal lymph node dissection
Chemotherapy
What variables are considered for treatment in seminomas?
Age
Personal preference
Likely compliance with surveillance
What variables considered for treatment in non-seminomas?
Risk factors
Pathological characteristics
Age
Personal preferences
Likely compliance to surveillance
What kind of chemotherapy is used for seminomas?
Chemotherapy: carboplatin alone
1 or 2 cycles
What kind of chemotherapy is used for non-seminomas?
Chemotherapy: BEP
Bleomycin, etoposide and cisplatin
How often does the Department of Health recommend that you self-examine?
Once a month
Preferably after a bath or shower
Relaxed
In a warm place
What is the process of self-examining?
Once a month
After a warm bath or shower when the scrotal sac is warm and relaxed
- Check each testicle separately using one or two hands
- Roll each testicle between thumb and forefinger checking the entire surface is free from lumps
- Become familiar with the epididymis (collecting tube that runs behind the testicle) - this is normal and not a new growth. Lumps in the epididymis are normal and almost invariably benign
- Men should be encouraged to see their doctor immediately if they find any new lumps
Main symptoms of testicular cancer
A lump or swelling in the testicle (not painful)
Pain in a testicle or scrotum
An enlarged testicle
A heavy feeling in the scrotum
What symptoms might present if the cancer has spread?
Dull ache in the groin, abdomen or back
Shortness of breath
Tenderness in the breast
A lump on the side of your neck (not painful)
Pain in the stomach
What is the function of testosterone?
Stimulates the accessory male sexual organs
Causes the developmentt of the masculine extra-genital sex characteristics
Which part of the testicle is the tunica?
It is the skin that covers the testicle inside the scrotum
2 parts: Tunica vaginalis (outer) Tunica albuginea (inner)
What runs behind the testicle?
The vas deferent and epididymis
What do the lobules of the testicles contain?
Seminiferous tubules where the spermatozoa are produced
Where is sperm produced?
Seminiferous tubules
Where is sperm stored?
Epididymis
What is the rate testis?
The seminiferous tubules open up into a series of uncoiled, interconnected channels called the rate testis
Connect to the epididymis then the vas deferens
What does the spermatic cord do and what does it contain?
Holds the testicle inside the scrotum
Contains the vas deferent, blood vessels, lymph vessels and nerves
What is the spermatic cord made of?
Tough connective tissue and muscle
What does the spermatic cord contain?
Contains the vas deferent, blood vessels, lymph vessels and nerves
What is the route of lymph fluid in the testicles?
Through vessels in the spermatic cord, then into either the para-aortic or Superficial inguinal lymph nodes
Both are retroperitoneal lymph nodes (back of abdomen near kidneys)
What are the main 4 subtypes of non-seminomas?
Embryonal carcinoma
Choriocarcinoma
Yolk sac carcinoma
Teratoma
What are the markers for germ cell cancers?
AFP
Beta HCG
Lactose dehydrogenase
Why are ultrasounds helpful for diagnosis of testicular cancer?
What are the steps for an ultrasound here?
Clear gel is placed on the scrotum
Helps to determine if the lumps are solid or fluid filled, also if they are inside or outside of the testicle
Explain how Testicular Germ Cell Tumour (TGCT) is acquired from childhood
Usually the oncotic mutations accumulate before the rapid growth period of puberty
TGCT derives from abnormally arrested fatal gonocytes
Gonocytes are the earliest undifferentiated sex cell, initially not in the gonads
At birth, gonocytes reside within the centre of the seminiferous cords, in a state of mitotic arrest (G0 in the cell cycle)
After birth, the monocytes need to differentiate and undergo spermatogenesis to form spermatozoa at the basement member of the seminiferous tubules during puberty
Spermatozoa are then stored in the epididymis
Gonocytes can be arrested abnormally in many different ways so the disease can be caused by a lot of different mutations and gonocytes are highly pluripotent so they are capable of differentiating into a lot of different types of cells
As the gonocytes have been arrested abnormally, at puberty they do not form proper spermatogonia
The gonocytes also accumulate genetic adaptations and mutations throughout childhood before the onset of puberty
This becomes germ cell neoplasia in situ (GCNIS) in childhood and young adulthood
This emerges as invasive TGCT in the young adult
In a few words, where does TGCT (Testicular germ cell tumour) derive from?
Abnormally arrested fetal gonocytes
Where do the gonocytes start off?
In the centre of the seminiferous cords in mitotic arrest
When do the gonocytes accumulate their oncotic mutations?
During childhood before puberty
They are in mitotic arrest from birth until the onset of puberty
When are the gonocytes in mitotic arrest?
They are in mitotic arrest from birth until the onset of puberty
What is spermatogenesis?
Gonocytes to spermatogonia to spermatozoa at the basement membrane of the seminiferous tubules during puberty
What is stored in the epididymis?
Spermatozoa
What is incorrectly formed TGCT?
Spermatogonia which has knock on effects
What is the name for the tumour that is before TGCT?
Germ cell neoplasia in situ (GCNIS)
