Male repro pathology Flashcards
1
Q
Overview of pathology in the body
A
2
Q
Describe the structure of the prostate gland
A
- The prostate gland surrounds the neck of the blafder and urethra, weight about 20g and is enclosed in a fibrous capsule
- Peripehral one = 70%
- Transitional zone = 5% - Gradually enlarges with age
- Centrla zone = 25%
prostate cacers arise almost exclusively from the peripheral zone
prostate surrounds urehtra
3
Q
Whta si the funciton of the prostate
A
- Prostate is a part of the male repro system
- Mjaor role in seminal fluid production
- products constitute to abotu 30% semen
- Surroundign the prostate is the fibro-muscular stroma = muscular contraction during ejaculation. This ocntains thick sheet of CT and a layer of smooth muscle surroundign the entire prostate gland. This stroma is invovled in the emission of seminal fluid prior to ejaculation
4
Q
The prostate is an AR regulated organ- what does this mean
A
- Testosterone dirves the AR (andorgen receptor) growth/function
- Higher levels of testosterone and AR lead to higher activity
- AR is a major therapeutic target in prostate diseases - BPH, Prostate cancer
5
Q
What symptom can prostate disease cause commonly
A
- Urinary prolems, incidence increases particularly with age (beyond 60years).
- Most prostatic diseases caus eenlargement of the prostate:
- Compression of the intraprostatic portion of urethra
- impaire durien flow
- Increased risk of urinary infections
- Acute retention of urine requiring urgent relief by catheterisation.
- Due to prostate gand surroundign the bladder neck and urethra.
6
Q
What is prostatitis, and pathology
A
- COmmon partiuclarly asymptomatic
- Anys ite of the prostate gland
- inflammatory infiltrate
- Slight to moderate elevation of Prostate specfic antigen
7
Q
Benign prostatic hyperplasia - what is it
A
- 75% of men over 70
- Periurethral transition zone
- Nodular hyperplasia of glands and stroma
- Slight to moderate elvation of serum prostate specific antigen
8
Q
Prostatic carcinoma - what is it, where in prpstate, morphology
A
- Commonest mal cancer, peak 60-75
- In peripheral zone
- Infiltrating adenocarcinoma
- Slight to gross elevation (depends on stage). May be normal
- Mets - Lymph nodes, bone, liver, lung
9
Q
A
Benign prostate gland with basl cell and secretory cell layer
10
Q
Normal prostate on left, whats on right
A
Prostatitis
11
Q
Normal prostate on left, whats on right
A
BPH
12
Q
BPH TREATMENT
A
- Finasteride medication - competitive and specific inhibitor of Type II 5α-reductase, a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone
- Main method of alleviating enlarged prostate is via surgery. Involves inserting a small instrument called resectoscope into urethra.
- Trans-Urethral Resection of Prostate (TURP0 - wire loop heated by electric current is used to remove excess tissue from prostate
- HoLEP - Holmium Laser Enucleation of prostate - Uses laser rather than heated loop - very new. =- not get widespread .
- Careful for risk of bleeding for men on blood thinning medications.
13
Q
Aetiology of Prostate cancer
A
Unknown but susbtantial proportion is dependent on androgens. Most tumorus arise in peripheral zone.
- Age - major risk fator
- Genetics - FH disase (2-3fold if 1st deg relative diagnosed <50)
- Race - Race - 3 fold risk for African or caribbea men comapred to caucasian, risk in china and japan is lower
- Diet - Some studies shown possible assoications of increased risk with red meat and soya is protective.
- Epidemiological studies have shown environmental impact (ie, moving from japan (low) to USA (high) shows families adopt same incidence within 2 generations.
14
Q
Diagnosis options of prostate cancer
A
- DRE
- Prostate specific antigen (PSA) blood test - measure effectivenes sof Tx too
- Trans rectal ultra sonography (TRUS) biopsy - follow up form psoitive DRE and PSA test
- Gleason Grade - Stratifyign prostate cancer)
15
Q
Digital rectal exam in diagnosis Prostate cancer - findings and drawbacks
A
- Key intiial diagnostic step
- “normal” prostate is smooth to the touch. An experience urologist can quickly identify many pathologies by feel: Prostate enlargement, irregular nodules, rigidity, masses
- Immediate, very quick, cheap test, once a mass is identified additional tests can occur
- Drawbacks - Men get embarassed by this method. Mass as already reached certain size to be detected by touch
16
Q
Prostate specific antigen (PSA) blood test
A
- PSA is 34KDA serine protease (KLK3gene) primarily produced by prostatic duct epithelium - AR regulated gene
- Abnormal prostate - Increased AR = increased PSA
- PSA ELISA test used in clinical use since 1987 and is most important current tumour marker for prostate cancer
- PSA Levels can be affected by - prostate biopsy, DRE, Ejaculation, BPH, Prostatitis, intense exercise.
- Measured in serum whcih iusually has uppe rlimit set at 3-4ng/ml for nromal serum PSA. PSA “correlated” with clinical and pathologic tumour stage.
- We use PSA to monitor effectiveness of treatment -“is drug working”
17
Q
PSA in diagnosis - the limitations
A
- ~20% of patients with prostate cancer will be missed by PSA testing (have normal PSA). 2/3rd of patients with raised PSA may not have prostate cancer
- Benign Prostatic Hyperplasia or prostatitis or urinary infection may lead to raised PSA level - All very common
- Prostate cancer is a paradox: some tumours will grow VERY slowly and NEVER progress yet some will rapidly become lethal – autopsies reveal up to 50% of ALL men have some level of unknown prostate cancer at the time of death.
- PSA screening (done in USA but not in UK) usefulness?? Over diagnosing slow growing tumours?
- Common phrase – many men “die with prostate cancer rather than of prostate cancer” BUT still single biggest cause of cancer death in men as well…!!!
18
Q
Trans Rectal Ultra Sonography (TRUS)/ biopsy
A
- Follow up from positive DRE and PSA test
- US allows imaging of prostate
- Biopsy may be taken at same time if needed
- Quite invasive technique
- “Frustratign” for patients with false positive PSA tests
19
Q
Gleason grade (Stratifying Prostate Cancer)
A
- The Gleason score is determined by adding the 2 most typical grades
- Fro example, the most common grade of the cells in a tissue sample may be grade 3 cells, dollowed by grade 4 cells. The Gleason score for this sample would be 7
20
Q
Prostatic Bone Metastases
A
Spread of prostatic carcinoma may be:
- Direct - Stromal invasion, through prostatic capsule, into seminal vesicle, bladder bas,e or pelvic side wall
- Lymphatics - to sacral, iliac and para-aortic nodes
- Blood to bone 9pelvic, lumbosacral spine, femur), lungs and liver
Clinical Features:
- Many men are unaware of their prostate cancer, or may have tumour diagnosed and remain aymptomatic. This situation can last for years
- Other men have tumour that will rogress and potentially fatal.
- Bone mets often present as lcoalised bone pain, back pain and from vertebral mets being common intiial manifestation of the tumour.
21
Q
“Watchful waiting’ in prostate cancer
A
- Some prostate cancers do not progress or spread so waiting can be ideal
- May have been present for decades growing very slowly.
- If the patient has no symptoms they they may opt for no treatment but closely monitered for changes.
- Patient suffers none of the side effects of surgery or drugs
- If the sitation changes then treatment can behin immediately.
- SOme patient too elderly/frail for treatment
22
Q
Surgery - Radical prostatectomy
A
- Although only small organ - thsi is major operation, can have major blood loss and area surroudnign prostate is packed with nerves. patient must be deemed fit enough
- Keyhold surgeyr by hand - surgeon makes 5/6 small incisions and removes prostate using thin,, lgihted tube with small camera on tip and special surgicla tools.
- Robot-assisted surgery - surgeon used three robotic arms (one for camera and two for surgical tools) to do operation. “da vinci” robot. Less infection, less blood loss, faster healing, less time in hospital.
- This will lead to infertility but other risks can be erectile dysfunction, impotence and urinary incontinence
23
Q
Chemotherpay for prostate cancer
A
24
Q
Hallmarks of cancer
A
25
Q
Androgen Deprivation Therapy
A
- Orchiectomy (surgical castration)
- LHRN agonists (chemical castration) - Lueinizing homrone-releasing hormone (lNRH) agonists are drugs that lower amount of testosterone amde by testicles Eg zoladex
- Doesnt interact with AR, Lowers testosterone/DHT levels.
26
Q
Lh inhibition - Goserelin (Zoladex) in prostate cancer treatment
A
- Goserelin is a synthetic decapeptide hormone analogue of LHRH.
- Thecontinuousagonistpresenceleads to DECREASED levels of LHRH Receptor levels
- Goserelin acts as a potent inhibitor of pituitary LH secretion when administered
- The result is sustained suppression of LH and serum testosterone levels.
- Initial “testosterone flare” observed initially but this settles down and LH decreases
28
Q
CRPC (castrate resistant prostate cancer) - Prostate cancer can “escape” drug treatment
A
Ligand Binding Domain mutation – resistance mechanism
- Allows OTHER hormones to bind to AR: *allows multiple agonists to activate AR*
- Oestrogens, Progesterone, Glucocorticoids
- Antagonists can become AGONISTS…. E.g. 1st gen anti-androgen flutamide became a strong agonist with T877A mutation
- T877A Allows conformational change of the receptor to activate genes
30
Q
Mechansims of castrate reisstant prostate cancer
A
33
Q
Enzalutamide in prostate cancer
A
For patients with metastasis, CRPC disease (reisstant)
35
Q
Prostate cancer and patients journey
A
36
Q
Testis - describe
A
- Testis – major role in reproduction
- Involved in seminal fluid and sperm
- production
- Each testis descends from the posterior abdominal wall
- The spermatic cord is also on the posterior side
- The epididymis is a convoluted tubular structure
- Main storage for newly formed sperm
37
Q
Seminiferous Tubules
A
- Seminiferous tubules are the site of sperm production
- Spermatagonia, reside along the basement membrane of the germinal epithelium
- Function as stem cells for sperm production.
38
Q
Sperm production / development
A
39
Q
Setoli cells in Testis
A
- Sertolicells-theepithelialsupporting cells of the seminiferous tubules. They are tall simple columnar cells, which span from the basement membrane to the lumen.
- Theysurroundtheproliferatingand differentiating germ cells forming pockets around these cells, providing nutrients, and phagocytosing excess spermatid cytoplasm.
42
Q
Cryptorchidism
A
- Inapprox5%ofnewbornsthetestesremain undescended – termed cryptorchidism
- Undescended testes are usually surgically descended prior to puberty
- If they remain undescended the semiferous tubules remain small and leads to decreased spermatogenesis. Ultimately the spermatogonia are replaced by sertoli cells
- Undescended testes also have an increased risk of developing tumours
43
Q
Hrydocele
A
- Intrascrotal swelling of serous fluid within Tunica Vaginalis
- Tunica vaginals - serous sac that contains testicle and sections of the body and tip of the epididmis. It is the serous membranous coverign of the testis
- Types -
- Acute inflammation - rapid production, damage, infection, ifnlammation
- Congenital anomaly
- Secondary inflamamtion - undelrying testis or epididymus lesion, infection, orhcitis, tumours
44
Q
Haematocele
A
- Intrascrotalhaemorrhageofbloodintothe Tunica Vaginalis
- Causes - Trauma. Neoplasm
- Can be minor – anti-inflammatories, antibiotics,ice pack
- Can be major – emergency surgery
- Not so funny when children hit you where it hurts and this happens – very low risk
- Footballaccidentstory..!
45
Q
Varicocele
A
- Varicosity of the pampiniform plexus of veins of the spermatic cord
- Effects1in7men
- Primary varicocele – no underlying cause. More common on the left testis
- Secondaryvaricocele–venous obstruction – e.g. tumour of the kidneys
- Varicocele may raise the intrascrotal temperature effecting spermatogenesis and causing subfertility.
49
Q
Sperm granuloma
A
- Uncommonchronicinflammation
- Lesion is caused by a mass of extravasated sperm that leads to inflammation in the epididymis
- Typicallyoccurinmenfollowingvasectomy due to changes in pressure, the sperm leaks and forms a lump at the cut vas deferens site
- Can be very painful but usually clear up over time
- In some instances a urologist can investigate further (minor exploratory surgery)
52
Q
Clinical features testicular cancer
A
Tumours present with
- Painless unilateral enlargement testis
- Secondary hydrocele
- Symptoms from mets
- Retroperitoneal mass
- gynaecomastia
53
Q
Location of testicular tumours - options
A
56
Q
Seminoma pathology
A
57
Q
Embryonal Carcinoma
A
- Embryonalcarcinomasoccurmostlyinthe20-to30-yearagegroup.
- These tumours are more aggressive than seminomas.
- Pleomorphic epithelial cells
- Hyperchromatic nuclei
- Necrosis is very common
- Very pluripotent in nature (immature cells capable of de-differentiation)
- Stain positive for Oct4 stem cell marker as well as CD30 and cytokeratins
- Negativeforc-KITexpression
58
Q
Yolk Sac Tumour
A
- The most common testicular tumour in infants and children up to 3 years of age. Very good prognosis.
- Painless mass with very low chance of metastases on presentation
- In adults the pure form of this tumour is rare; instead, yolk sac elementsfrequently occur in combination with embryonal carcinoma.
- A true success story – before development of chemotherapy this was a very lethal disease – not anymore
59
Q
Choriocarcinoma
A
- Highlymalignant
- Very rare as a “pure” tumour
- Small in size but very common to have haemorrhagic and necrotic sites
• 2 cells types are present
- Syncytiotrophoblastic cells – large with hyperchromatic nuclei
- Cytotrophophoblastic cells – regular cells with defined borders, uniform nucleus
61
Q
Teratoma
A
- The designation teratoma refers to a group of complex testicular tumours having various cellular or organoid components from more than one germ layer
- Pure forms of teratoma are fairly common in infants and children, second in frequency only to yolk sac tumours.
- In adults, pure teratomas are rare, constituting 2% to 3% of germ cell tumours. However, the frequency of teratomas mixed with other germ cell tumours is approximately 45%.
