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SPINE Semester 2 > Male Genitourinary tract Pathologies > Flashcards

Male Genitourinary tract Pathologies Flashcards

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1
Q

What are the key three zones of the prostate gland?

A

Peripheral zone - 70%
Transition zone -5%
Central zone - 25% - around ejaculatory duct

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2
Q

What region of the prostate gland enlarges the most with age?

A

Transitional zone (BPHP)

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3
Q

Which region of the prostate gland is most commonly affected in cancer?

A

Peripheral zone

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4
Q

What is the key function of the prostate gland?

A

Male male repoductive
Role in seminal fluid production - 30 weeks
If a fibro-muscular stroma around the prostate for muscular contraction during ejecaulation
Stoma contains emissions of seminal fluid prior to ejaculation

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5
Q

What drives the response of the prosatate?

A

Testosterone crosses the cell membrane and is reduced by 5-alpha reductase to DHT.
DHT is more potent -> binds to androgen receptors (which displaces from HSP).
(Note testosterone can also bind directly but is less potent)
Dimerises and phosphorylates-> acts as transcription factor on androgen response element
Leads to increased prostate growth, survival and inc PSA.

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6
Q

Androgen receptor is a major therapeutic target in what prostate diseases?

A

BPH
Prostate Cancer

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7
Q

What are the key parts of the androgen receptor?

A

N-terminal domain - contains Activator of function domain (regulated by other proteins to reg transcription)
DNA binding domain
Ligand binding domain

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8
Q

What is the function of the 5-alpha reductase enzyme?

A

Reduces testosterone to its more potent form DiHydro Testosterone (DHT).

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9
Q

What are the key symptoms of prostate disease?

A

Decreased urinary flow - in older men 60yrs> - inc frequency, dec stream, dec volume

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10
Q

How does prostate disease lead to decreased urinary flow?

A

Enlargement of the prostate
- compression of the intraprostatic urethra
- impaired urine flow
- increased risk or UTI
- acute retention of urine requiring urgent relief by catheterisation

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11
Q

What are the key epidemiology and morphology features of prostatisis?

A

Inflammation/infection of the prostate gland
Common
Anywhere in the gland
Morphology - Inflammatory infiltrate

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12
Q

What are the key epidemiology and morphology features of BPH?

A

75% of M over 70yrs
Occurs in the periurethral transition zone
Morphology : nodular hyperlasia of glands and stroma

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13
Q

What is the key epidemiology and morphology of prostatic carcinoma?

A

Commonest male cancer - peak 60-75
Occurs in the peripheral zone
Morphology - infiltrating adenocarcinoma

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14
Q

Where does prostatic cancer metastasise to?

A

Lymph nodes
Bone
Liver
Lung

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15
Q

What is the normal histology of the prostate gland?

A

Stroma with glands
Glands are lined by simple columnar or pseudostratified columnar epithelium
Stoma may have thick smooth muscle to aid expulsion from glands.

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16
Q

What are the histological features of prostatitis?

A

Increased size of cytoplasm of glandular cells
Increased inflammatory cells in the stroma

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17
Q

What are the histological features of BPH?

A

Increased cytoplasm of glandular cells
Overlapping of glands - without clear stroma between them.

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18
Q

How does the incidence of BPH vary with age?

A

20% in 40yrs (typically asymptomatic from autopsy)
70% in 60yrs
90% in 80yrs.
S curve increase with age

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19
Q

What is the medical treatment for BPH?

A

Finasteride
Binds to 5-alpha reductase inhibitor - prevents the conversion of testosterone to DHT
Reduces (NOT stop) activity at androgen receptors.

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20
Q

What are the surgical treatments for BHP?

A

Retroscope into urethra

TURP (trans-urethral resection of the prostate) - wire loop heated by electric current

HoLEP - Holmium Laser Enucleation of the Prostate -> new not widespread

Caution: risk of bleeding

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21
Q

What are the key risk factors for prostate cancer?

A

Age = main
Genetics - FH, particularly in 1stDR <50yrs
Rave - 3x African/Carribbean, lower is Japan/China
Diet - red meat increased, soya = protective.

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22
Q

What can PSA levels be effected by?

A

Prostate biospy
DRE
Ejaculation
BPH
Prostatitis
Intense exercise

(high risk of false positives)

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22
Q

What is the key diagnostic test of prostate cancer?

A

PSA blood test - AR regulated gene produced by prostatic ductal epithelium - normal upper limit 3-4ng/ml.

Digital rectal exam - for nodularity, enlargement, rigidity, masses.

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23
Q

What are the limitations of PSA blood test?

A

Non specific to prostate cancer
20% of patient will be missed
66% raised PSA and not prostate cancer
Some prostate cancers grow very slowly -> overdiagnoses

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24
What second line investigation from positive DRE and PSA is done for suspected prostate cancer?
Trans rectal ultra sonography biopsy Is very invasive -> frustrating for patients with false-positive PSA tests.
25
What scale is used to stratify prostate cancer?
Gleason Pattern Scale Adding the two most typical grades to calculate the Gleason score
26
What is theWhat are the different stages of a Gleason Grade in prostate cancer?
1 - small unfirm glands 2 - more stroma between glands 3 - infiltartion of cells from glands at margin 4 - irregular massess of neoplastic cells with few glands 5 - lack of or occasional glands, sheets of cells
27
What are the key features of bony mets from prostate gland?
Direct - stromal invasion into pelvic side wall Lymphatics - to sacral, iliac and paro-aortic Bloods to bone (pelvis, lumboscaral femur) Mets are osteosclerotic NOT osteonecrotic -> difficult to treat and painful
28
What are the different treatment approaches for prostate cancer?
Watchful waiting - may not progress, to frail for treatment, avoid side effects of drugs/surg.
29
What are the surgical treatment for prostate cancer?
Radical Prostatectomy Major operation - must be deemed fit for surgery Keyhole or robot-assisted Orchiectomy - remove testes -> reduce androgen production
30
What are some potential complications of a radical prostatectomy?
Infertility Erectile dysfunction Impotence Urinary incontinence
31
What are the key chemotherapy Zoladex used in prostate cancer?
LRHR agonist (chemical castration) = Zoladex/Gosalerine LRHR is released from hypothalamus -> activates PG to release LH -> targets testis to release testosterone. Increase LRHR signs leads to desensitization to signal -> leads to suppression. This reduces the testosterone and DHT available to bind to AR.
32
How does Casodex/Bicalutamide treat prostate cancer?
Potent AR inhibitor -> binds to AR -> AR can move into nucleus but not longer able to activate gene expression This leads to tumour shrinkage. Requires 50-200mg daily
33
What is the caution with the use of Casodex use in prostate cancer?
With long term use 2-3yrs becomes an agonist of AR -> leads to increased growth Independent of AR cells populations develop -> become primary population as dependent cells killed off -> survival advantageous.
34
How does the androgen receptor become Casodex resistant?
Promiscus /outlaw - Ligand binding domain mutation Allows other hormoens to bind to AR - multiple potential agonists (oestrogens, progesterone, glucocorticoids and casodex) Mutations - T877A Hypersensitivity - increased number of androgen receptors.
35
What treatment is used for replases of prostate cancer?
Taxanes/Docetaxal -> targets cell division nad microtubules Common in combination with prednisolone for relief of bone pain, inflammation and nausea.
36
What are the next generation antiandrogens? (Enzalutamide)
Reserved for patients with mestastasis, CRPC disease. Inc survival 4 months Stops testosterone binding to andorgen receptor, also stop migration into the nucleus. Still some resistance
37
How does Abiraterone Acetate (zytiga) treat prostate cancer?
Prevents testosterone biosynthesis Inhibits CYP17 -> prevents conversion of progestens to andorgens However can lead to mineralocorticoid excess, decrease cortisol hence high ACTH Must be treated with prednisolone/dexamethasone to lower ACTH
38
What is the site of sperm production?
Seminferous tubules in the testes Spermatagonia -> along the basement membrane of the germinal epithelium. Supported by sertoli cells and leydig cells.
39
What is the function of sertoli cells?
Epithelial supporting cells of the seminiferous tubules Are tall simple columnar, from BM to lumen Surround germ cells -> provide nutrients, and phagocytose excess cytoplasm
40
What is the function og leydig cells?
Support spermatogenesis in the testes Local production of testosterone in response to LH
41
What is cryptorchidism?
Development lesion -> undescended testicles seen in 5% newborn. Small seminiferous tubules as high temp = low sperm = replaced by sertoli cells = inc cancer risk Usually resolve or surgical descend pre puberty
42
What is the key pathology of hydrocele?
Intrascrotal swelling of serous fluid in tunica vaginalis Acute -rapid production due to damage/infection and inflammation Congenital Secondary inflammation - infection, underlying testis or epididymis lesion, tumours
43
What is a haematocele?
Intrscrotal haemorrhage in the tunica vaginalis Cause - trauma, neoplasm Minor - anti-inflams, antibiotics, ice pack Major - emergency surgery
44
What is a variocele?
Enlargement of blood vessels to the testes (more common in left) 1 in 7 men Primary -> no underlying cause Secondary -> venous obstruction such as kidney tumour causing back pressure Risk - may raised intrascrotal temp causing subfertility
45
What is orchitis?
Inflammation of the testes
46
What is mumps orchitis?
Acute infection (paramyoxivirus) in children Adults Vascular dilation and oedema with lymphocyte infiltrate Risk of ischaemia and necrosis of seminiferous tubules Rare = sub fertility
47
What is idiopathic granulomatous orchitis?
Chronic of unknown cause Firm testicular enlargement Managed with pain relief
48
What is STI orchitis?
Syphyllis - treponema pallidum (rare) Gonorrhea, chlamydia Causes inflammation of the testis.
49
What are the key features of a testicular torsion?
Most common in males under 25yrs Twisting of cord cuts off blood supply and prevents venous drainage Medical emergency - 6hrs to save the testicle. Can be sudden without trauma.
50
What are the common causes of testicular atrophy?
Progressive atherosclerotic narrowin of blood supply in old age End stage orchitis Cryptorchidism Hypopituitarism Malnurihsed Irridiation Prolonged administration of anti-androgens Alcoholism Kleinfelter syndrome
51
What is the epidemiology of testicular tumours?
Most common cancer in young men Highly treatable if detected early
52
What are the different classifications of testicular tumours?
1. Germ cell tumours 2. Sex cord-stromal tumours
53
What are the different types of germ cell tumours in the testes?
Seminomatous tumours - (spermatocytic) seminoma - more immature cells Non-seminamatous - embryonal, yolk sac, choriocarcinoma, teratoma - more mature cells, further differentiated into sperm
54
What are the different types of sex cord stromal tumours?
Leydig cell tumours Sertoli cell tumour
55
What are the main risk factors for testicular cancer?
Undescended tests Kleinfelter syndrome (XXY) Genetic - FH and polymorphism Xq27 Race - caucasian Enviro -
56
What are the key symptoms of testicular cancer?
Painless unilateral enlargement of the testis Secondary hydrocele Symptoms from mets (bone and lungs) Retroperitoneal mass Gynaecomastia
57
What are the locations of the testicular tumours?
58
What are the key features of a seminoma?
Most common germ cell tumour Peak 30-50yrs Enlarged tests - Homogenous white solid tumour replaces testes mass 10% secrete hCG 25% c-KIT activating mutation
59
What are the histological features of a seminoma of the testes?
Large neoplastic cells Vacuolated cytoplasm Stroma has variable lymphocytic infiltrate Positive cor c-KIT expression
60
What are the key features of an embryonal carcinoma?
Most common in 20-30yrs Very aggressice Pleomorphic epithelial cells Hyperchromatic nuclei Necrosis is very common Very pluripotent in nature - can de-differentiation Stain positive for Oct4 Negative for c-KIT expression
61
What are the features of yolk sac tumour?
Most common testicular tumour in infants and child up to 3yrs Painless Low risk of metastases Responds very well to chemotherapy
62
What are the features of teratomas?
Group of complex testicular tumours with various cellular and organoid components from more than one germ layer. Infants and children ->2nd most common Rare in adults.
63
What is the pathology of a teratoma?
Epithelial lined cystic structures Glands, cartilage, muscle, immature strome gut, muscle like etc Lots of different cell differentiations lines Gross - cystic and haemorrhagic
64
What are the features of mixed testicular tumors? Common types
60% are moxed Teratoma and embryonal Yolk sac, seminoma, embryonal Embryonal with teratoma Prognosis based on most progressive
65
What are the key features of Leydig tumours?
Produce androgens and oestrogens 20-60yrs Benign - 10% invasive
66
What are the key features of sertoli tumour?
Hormonally silent Small nodules 10% are invasive most are benign
67
What are the different stages of testicular cancer?
Stage 1 - in testes only Stage 1s - raised markers in blood after surgery Stage 2 - spread to nearby lymph or pelvis Stage 3 - spread to lymph nodes or other organs
68
What is the key treatment for tesitcular cancer?
Surgical removal of testicle Seminomas - + single chome and short radio Non-seminomous - follow up, short chemo Stage2/3 - 3/4 chemo and surg for mets
69
What is the typical chemotherapy regime used for testicular cancer?
IV central line at day clinic Bleomycin Bleomycin, Etoposide, Cisplatin (BEP)

SPINE Semester 2 (31 decks)

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