- precursor cells of germ cells which will produce gametes

- surgical procedure that moves an undescended testicle into the scrotum

Pathology of the Testis Flashcards by David Houghton

How common is testicular cancer?

1 - 1%
2 - 10%
3 - 20%
4 - 40%

1 - 1%

accounts for 1% of cancers in men
most common malignancy in men between 15-40 in western populations

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Although the aetiology of testicular cancer is not completely understood, intratesticular germ cell neoplasia (ITGCN), also known as carcinoma in situ (CIS) is the accepted precursor to testicular cancer. What is ITGCN?

germ cell is any cell that gives rise to gametes (sex cells)
uncontrolled, abnormal growth of cells or tissues in the testes
generally occurs in the post pubertal period

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What is carcinoma in situ?

cancer in which abnormal cells have not spread beyond where they first formed

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Cryptorchidism is when the testes do not descend down into the scrotum. Is this a major risk factor for testicular cancer?

yes
most important risk factor
increases risk by 4-8 time greater risk

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Cryptorchidism is when the testes do not descend down into the scrotum. Where are are the testes most likely to be located in this condition?

1 - abdominal
2 - inguinal canal
3 - bladder
4 - high scrotal

1 - abdominal =15%
2 - inguinal canal = 25%
4 - high scrotal = 65%

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What does hypospadias mean?

hypo = below
spadias = slit
urethra develops below where it normally exits the penis

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Hypospadias is when the urethra develops below where it normally exits the penis. What are the 3 parts of the penis called where the urethra could exit the penis?

1 - anterior = 50% of cases
2 - middle = 30% of cases
3 - posterior = 20% of cases

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How can patients present with testicular cancer?

painless swelling in testis (10% present with pain in scrotum)
dull ache or heaviness in lower abdomen
back pain – sign of lymph node extension of disease
cough, chest pain, SOB – suggestion of chest metastases
gynaecomastia – choriocarcinoma secreting beta-HCG

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Label the histology slide of the seminiferous tubules using the labels below”

seminiferous tubules
spermatocyte
leydig cells
sertoli cells
spermatid
spermatogonium

1 = spermatocyte
2 = spermatogonium
3 = leydig cells
4 = sertoli cells
5 = seminiferous tubules
6 = spermatid

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What are gonocytes?

precursor cells of germ cells which will produce gametes

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Cryptorchidism. which is where the testes have failed to descend is a common cause of testicular cancer which can then lead to hypogonadism. How can this then lead to testicular cancer?

1 - testes are exposed to trauma
2 - testes environmental conditions (temperature)
3 - poor blood supply
4 - vas deferens is blocked

2 - testes environmental conditions (temperature)

poor development of somatic cell in development (sertoli and leydig cells)
gonocytes (precursor of germ cells) have delayed development
delayed gonocyte development causes genetic abnormalities
gonocyte abnormalities can then lead to testicular cancer

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What is orchidopexy?

surgical procedure that moves an undescended testicle into the scrotum

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Is family history a risk factor for testicular cancer?

- increases risk by 4-8 fold

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What are the 2 main classification groups of testicular cancer?

1 - germ cell tumours (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

GCT = germ cell tumours
GCNIS = Germ cell neoplasia in situ

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

GCT can be further subdivided into Germ cell neoplasia in situ (GCNIS) and non-GCNIS. What is germ cell neoplasia?

precursor lesion for testicular germ cell tumours

- germ cells undergo neoplasia, which then leads to tumour formation

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

GCT can be further subdivided into Germ cell neoplasia in situ (GCNIS) and non-GCNIS. GCNIS is a precursor lesion for testicular germ cell tumours, where germ cells undergo neoplasia, which then leads to tumour formation. There are 2 subcategories of GCNIS; seminoma and non-seminomas. What are these?

seminoma = germ cells proliferate uncontrollably

- non seminoma = begin in sperm

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

1 - seminomatous = older men 30-45 or >60 y/o

2 - non-seminomatous = late teens and early 20s

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

There are 2 main types of cells involved in sex cord stromal tumours, what are these 2 cells of the seminiferous tubules?

1 - leydig cells (70%, so much more common)

2 - sertoli cells

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

There are 2 main types of cells involved in sex cord stromal tumours, leydig and sertoli cells. Tumours in which type of cells is more common?

1 - leydig cells (70%, so much more common)

2 - sertoli cells

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There are the 2 main classification groups of testicular cancer:

1 - germ cell tumours (GCT) (95% of testicular cancer)
2 - sex cord stromal tumours (5%)

non-seminomatous GCTs – mixture of histological subtypes

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There are 2 main types of germ cell tumours (GCT):

1 - seminomatous GCTs (originating in testes)
2 - non-seminomatous GCTs – mixture of histological subtypes

Within seminomatous there are 2 further classifications, what are they?

classical seminomas (95% of tumours)

- spermatocytic seminoma

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There are 2 main types of germ cell tumours (GCT):

1 - seminomatous GCTs (originating in testes)
2 - non-seminomatous GCTs – mixture of histological subtypes

Within seminomatous there are 2 further classifications:

classical seminomas (95% of tumours)
spermatocytic seminoma

What ages groups are more likely to get either of these seminoma tumours?

classical seminomas = 30-45 y/o

- spermatocytic seminoma = average 65y/o (RARE)

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Seminomatous germ cell tumours (GCTs) (originating in testes) are able to secrete what hormone?

1 - human gonadotrophin hormone
2 - LH
3 - FSH
4 - testosterone

1 - human gonadotrophin hormone

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There are 2 main types of germ cell tumours (GCT):

1 - seminomatous GCTs (originating in testes)
2 - non-seminomatous GCTs – mixture of histological subtypes

Within non-seminomatous there are 4 further classifications, what are they?

1 - Embryonal carcinoma
2 - Yolk sac carcinoma/tumour
3 - Choriocarcinoma
4 - Teratoma

There are 2 main types of germ cell tumours (GCT): 1 - seminomatous GCTs (originating in testes) 2 - non-seminomatous GCTs – mixture of histological subtypes What age do non-seminomatous GTCs generally occur in?

- late teens to early 30s

What are teratoma tumours?

- tumours derived from all 3 layers of trilaminar germ disk | - can contain tissue from anywhere in the body

There are 2 main types of germ cell tumours (GCT): 1 - seminomatous GCTs (originating in testes) 2 - non-seminomatous GCTs – mixture of histological subtypes Within non-seminomatous there are 4 further classifications: 1 - Embryonal carcinoma 2 - Yolk sac carcinoma/tumour 3 - Choriocarcinoma 4 - Teratoma There are 2 types of Teratoma, what are they and do they have the same prognosis?

1 - mature = more common but not as dangerous | 2 - immature = more likely to metastasis and invade

Embryonal carcinomas are a form of non-seminomatous germ cell tumours. What are embryonal carcinomas?

- tumours that develop from cells that are left over from the early stages of our development - grows rapidly outside of testes

Embryonal carcinomas are tumours that develop from cells that are left over from the early stages of our development. What % of non-seminomatous germ cell tumours are composed of embryonal carcinomas? 1 - 5% 2 - 20% 3 - 40% 4 - 90%

3 - 40% | - grow rapidly and invade

Yolk sac tumour are a form of non-seminomatous germ cell tumours. What are yolk sac tumours?

- a rare, malignant tumour of cells that line the yolk sac of the embryo

Yolk sac tumour are a form of non-seminomatous germ cell tumours that are a rare malignant tumour of cells that line the yolk sac of the embryo. What age do these tumours affect the most? 1 - babies 2 - children 3 - teenages 4 - older mem

2 - children | - most common form of testicular cancer in children

Choriocarcinoma are a form of non-seminomatous germ cell tumours. What are choriocarcinomas?

- cells that were part of the placenta in a normal pregnancy become cancerous

Choriocarcinoma are a form of non-seminomatous germ cell tumours, where cells that were part of the placenta in a normal pregnancy become cancerous. Are these dangerous?

- yes, highly malignant and fast growing

Choriocarcinoma are a form of non-seminomatous germ cell tumours, where cells that were part of the placenta in a normal pregnancy become cancerous. These are highly malignant and fast growing. What 3 places do they tend to spread to? 1 - lungs, bones, liver 2 - heart, bones, brain 3 - lungs, bones, eye 4 - lungs, bones, brain

4 - lungs, bones, brain

What are the 3 common tumour markers that are generally used in clinical practice? 1 - AFP, bHCG, LDH 2 - AFP, CK, LDH 3 - CK, bHCG, LDH 4 - AFP, bHCG, CK ``` AFP = Alpha Fetoprotein bHCG = Beta Subunit human chorionic gonadotropin LDH = Lactate dehydrogenase CK = creatine kinase ```

1 - AFP, bHCG, LDH RISE IN ANY OF THESE MARKERS IS PRESENT IN 60% OF PATIENTS WITH TESTICULAR CANCER

Lactate dehydrogenase (LDH) can be used to assess if cancer is present and monitor the presence of cancer treatment. What is LDH and why can it be used to monitor cancer?

- LDH is an enzyme that converts sugar into energy (pyruvate to lactate) - tumours have a high energy demand - enhanced glycolytic activity of the tumour and tumour necrosis due to hypoxia

Alpha Fetoprotein (AFP) is the most abundant plasma protein present in the foetus produced by yolk sac cells. Why is AFP elevated in cancer?

- regenerating/proliferation cells produce AFP | - high AFP suggests high cell turnover such as in cancer

Beta Subunit HCG (human chorionic gonadotropin) is a dimer consisting of a 145 amino acid beta-subunit that is unique to hCG and a 92 amino acid alpha-subunit. This is secreted by syncytiotrophoblasts of the placenta. The alpha-subunit is identical to that for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Why might B-HCG be raised in cancer?

- choriocarcinoma secrete beta-HCG | - if choriocarcinoma is present then beta-HCG levels will be high

Alpha Fetoprotein (AFP) is the most abundant plasma protein present in the foetus produced by yolk sac cells. AFP is elevated in cancer due to regenerating/proliferation cells producing high levels of AFP, so high AFP suggests high cell turnover such as in cancer. What % of non-seminomatous GCTs (NSGCTs) have a high level of AFP?

- up to 70% of cases | - good sensitivity to detect NSGCT cancers

Lactate dehydrogenase (LDH) can be used to assess if cancer is present and monitor the presence of cancer treatment. LDH is an enzyme that converts sugar into energy (pyruvate to lactate). Tumours have a high energy demand and high LDH shows enhanced glycolytic activity of the tumour and tumour necrosis due to hypoxia. Is LDH more accurate in Seminomatous or non-seminomatous germ cell tumours?

- seminomatous germ cell tumours | - can also be useful for assessing testosterone levels

If a patient presents to their GP with a mass in the testicles, what is generally the 1st line imaging approach?

- ultrasound - can see mass on top image - can see increased blood flow on ultrasound doppler scan in bottom image

When assessing for testicular cancer, why would a scan of the abdomen and pelvis, potentially followed by the chest, using a CT be used for?

- assess for metastases in the lymph nodes, liver and lungs

When assessing for testicular cancer, when would a CT/MRI be useful?

- identify for metastases of brain or bone if they are suspected

When investigating testicular cancer, should it be biopsied?

- no | - high risk of retroperitoneal spread

Once testicular cancer has been confirmed, what is the initial management plan? 1 - chemotherapy 2 - radiotherapy 3 - orchidectomy 4 - chemotherapy and radiotherapy

3 - orchidectomy - orchidectomy = surgery to remove the testis - take sperm bank donation prior to surgery

What does TNM stand for when staging testicular cancer?

- T = tumour size - N = nodal involvement - M = metastasis

When germ cell tumours metastasise where do they generally metastasise to?

- lungs | - posterior mediastinum

What 2 key factors determine the prognosis of a patient who has been diagnosed with testicular cancer?

1 - type of cancer (seminoma vs non-seminoma) | 2 - stage of cancer (TNM)

In a patient with stage 1 testicular cancer, what is the 5 year survival free rate? 1 - 25% 2 - 45% 3 - 75% 4 - 99%

4 - 99%

In a patient with stage 1 testicular cancer, the 5 year survival free rate is 99%. How are these patients normally managed?

- monitored | - sub groups should be screened for adjuvant therapy

In a patient with stage 1 testicular cancer, the 5 year survival free rate is 99%. There is a risk of relapse though. What is the risk of relapse in: - Seminomatous GCTs (SGTCs) - Non-seminomatous GCTs – (NSGTCs) - GCT = germ cell tumour

- SGTCs = within 3 years | - NSGTCs = within 2 years

In a patient with seminomatous germ cell tumour (SGTCs) what does an increasing size of tumour increase the risk of?

- relapse | - >4cm is high risk

In a patient with seminomatous germ cell tumour (SGTCs) what are the 2 key prognostic risk factors for relapse?

1 - size of the tumour 2 - invasion of the rete testis (network of small tubes in the testicle that helps move sperm cells (male reproductive cells) from the testicle to the epididymis. The epididymis is where the sperm mature and are stored)

What are the 3 treatment options for patients with non-seminomatous germ cell tumours? 1 - orchidectomy, adjuvant chemotherapy, retroperitoneal lymph node dissection 2 - radiotherapy and adjuvant chemotherapy 3 - orchidectomy and radiotherapy 4 - chemotherapy and radiotherapy

1 - orchidectomy, adjuvant chemotherapy, retroperitoneal lymph node dissection

In a patient with non-seminomatous germ cell tumours what is the most widely accepted adverse prognostic risk factor? 1 - size of the tumour 2 - age of the patient 3 - lymphovascular invasion 4 - location of tumour

3 - lymphovascular invasion

In a patient with non-seminomatous germ cell tumour, the most widely accepted adverse prognostic risk factor is lymphovascular invasion. If a patient has lymphovascular invasion what is the risk of relapse?

- 25-50%

What % of sex chord tumours, which are tumours that develop from the seminiferous tubules, which mainly involves leydig and sertoli cells become malignant? 1 - 10% 2 - 30% 3 - 50% 4 - 70%

1 - 10%

What are the 5 main prognostic factors of sex chord tumours, which are tumours that develop from the seminiferous tubules, which mainly involves leydig and sertoli cells?

1 - tumour size > 5 cm 2 - tissue necrosis 3 - moderate/severe nuclear atypia (abnormal cell appearance) 4 - angiolymphatic invasion infiltrating margins 5 - > 3 mitotic features per 10 high power fields