Urological pathology Flashcards
1
Q
What is the histological structure of the wall of the renal pelvis, ureter, bladder and urethra?
A
- urothelium
- lamina propria
- muscularis propria (detrusor in bladder)
- adventitia (perivesical fat in bladder)
2
Q
What are the zones of the prostate gland?
A
- transition
- central
- peripheral
3
Q
Prostate gland produces alkaline secretion to neutralise acidic environment of vagina. Gland is made up of numerous acini (glands) + ducts lined by epithelial cells, embedded in a stroma composed of sm muscle cells + fibroblasts.
What do the prostatic acini do?
A
- secrete prostatic juice
- drain into the prostatic urethra via duct system
4
Q
What do the stromal cells contain?
A
- 5 a-reductase
- converts T -> DHT (more potent)
- maintaining suitable levels of androgens in prostate
5
Q
What are common causes of macroscopic (frank) haematuria?
A
-
UPPER TRACT:
- kidney cancer (renal cell carcinoma)
- stone in kidney or ureter
- trauma
-
LOWER TRACT:
- bladder cancer
- BPH
- infection (bacterial cystitis)
6
Q
For macroscopic haematuria, following a full history and examination, what investigations are useful to request?
A
- MSU for MC+S
- urine cytology
- flexible cystoscopy +/- biopsy
7
Q
What are LUTS?
A
- lower urinary tract symptoms
- frequency, urgency, nocturia, hestiancy, poor flow + terminal dribbling
- suggests problem in bladder or prostate
- important to realise that LUTS not specific for any particular pathology
8
Q
What are some causes of LUTS?
A
- BPH
- UTI
- urinary tract stones
- bladder cancer
- prostate cancer (LUTS are a late feature of this)
9
Q
What is the most common malignant tumour of the kidney?
A
-
renal cell carcinoma (RCC)
- most common type of RCC -> clear renal cell carcinoma
- RCCs are adenocarcinomas, arise from epithelia lining renal tubules
10
Q
What are the risk factors for development of RCC?
A
- male gender (4M:1F)
- inc age (most cases occur in over 50)
- smoking
- obesity
-
familial syndromes - Von Hippel Lindau sydndrome
- rare autosomal dominant genetic disease
- predisposes individuals to certain benign + malignant tumours incl RCC + phaeochromocytoma
11
Q
How is renal cell carcinoma graded?
A
Fuhrman grading system
- grade 1: tumour cell nuclei closely resembal normal -> less aggressive (better prognosis)
- grade 4: tumour cell nuclei larger + pleomorphic etc -> more aggressive (worse prognosis)
12
Q
How is renal cell carcinoma staged?
A
- TNM system
- size of the primary tumour important in determining the T stage
13
Q
What is the clinical presentation of RCC?
A
There is a triad, however it is uncommon in clinical practice:
- loin pain
- loin mass
- haematuria
Other common presentations of kidney cancer include:
- incidental finding on scan
- presentation w/ symptoms/signs of metastatic disease (lung or bone) eg. bone pain, SoB
- paraneoplastic syndrome eg. hypercalcaemia, erythrocytosis, amyloidosis
14
Q
What type are the majority of bladder cancers?
A
- urothelial carcinomas
- malignant tumour arising from urethelium
- transitional cell carcinoma is an old term
15
Q
Wht are risk factors for developing urothelial carcinoma?
A
- cigarette smoking
- industrial exposure to certain industrial dyes + solvents (eg arylamines)
16
Q
Bladder cancers are staged using the TNM system. What are key features of the TNM system regarding bladder cancer?
A
- superficial tumours are Ta or T1
- muscle invasive tumours are T2, T3, or T4
- CIS is Tis
17
Q
How do you clinically classify bladder cancer?
A
Three main groups:
- low-risk bladder cancer (superficial tumours Ta T1 + low grade)
- high-risk bladder cancer (muscle invasive T2 or worse + high grade)
- carcinoma in situ (CIS) - precancer
18
Q
Describe low-risk bladder cancers and their extent of invasion
A
- confined to mucosa or invade into lamina propria
- do not invade into muscularis propria (detrusor) or beyond
- often low grade
- tend to be composed of frond-like papillary growths
- papillary refers to finger-like projection (w/ fibrovascular core)
19
Q
How are superficial urothelial carcinomas (low-risk bladder cancers) managed?
A
- removed at cystoscopy by TURBT
- after removal:
- high chance tumour will recur
- low chance tumour will transform into high risk
Therefore, pts diagnosed w/ superficial urothelial carcinoma require regular check cystoscopies
20
Q
Describe high-risk (muscle-invasive) bladder cancer and how they differ to low-risk cancers
A
- invade into detrusor muscle or beyond
- tend to be solid rather than papillary
- almost always high grade
- have much worse prognosis than low-risk tumours
- more likely to spread to regional nodes + metastasise to distant sites
- radical treatment required for cure, often cystectomy (removal of bladder) +/- other organs eg. uterus
21
Q
Describe urothelial carcinoma in situ (CIS)
A
- flat lesion
- ureothelium contains cells that display nuclear features
- associated w/ malignancy (eg pleomorphism, mitoses etc)
- BUT no invasion through basement membrane
- form of precancer: left untreated, ~40% progress to muscle invasive cancer
- diagnosis of CIS bladder v serious due to chances of prog
22
Q
What is blue light cystoscopy?
A
- may be used to identify CIS
- ~1hr before cystoscopy, Hexyl aminolevulinate (HAL) inserted into bladder via a urinary catheter
- urologist performs cystoscopy using special cystoscope + blue light
- CIS cells absorb chemical + then fluoresce red in blue light
- background normal urothelial cells do not absorb chemical so do not fluoresce
- thus, urologist can identify areas of CIS bc they stand out
23
Q
How is urine cytology helpful in picking up CIS?
A
- highly atypical cells shed into urine
- abnormal urothelium loses its normal cohesiveness + begins to fall apart
- loss of urothelium -> intense LUTS (dysuria, inc freq)
- important to note that negative urine cytology does not exclude a significant pathology
24
Q
What is the molecular classification of bladder cancer?
A
- low risk (superficial) bladder cancers strongly associated w/ mutations in HRAS and FGFR3
- CIS + high-risk (muscle invasive) bladder cancers strongly associated w/ mutations in TP53 and RB1
25
What is BPH?
* overgrowth of prostatic tissue in **transition zone** of gland
* overgrowth of prostatic tissue -\> formation of large **nodules**
* nodules form due to **hyperplasia** of all cellular elements in prostate ie. epithelial cells, sm muscle cells + fibrous tissue
26
BPH is due to a subtle hormonal imbalance which occurs w/ age. What is this imbalance?
* oestrogen levels in blood increase with age
* vicious cycle set up as more stromal cells produce more potent androgens which induce more growth and so on
27
What is the most important complication of BPH?
* gradual compression of prostatic urethra
* causing urinary tract obstruction
* two components underlying development of obstruction:
* inc tone of sm muscle in prostate, making organ more contracted around urethra
* mechanical effect due to physical bulk of prostate
28
Wha timpact does BPH have on the bladder?
* **_gradually_** progressive bladder outflow obstruction
* in order to generate higher pressure required to eject all urine from bladder, bladder **detrusor** muscle undergoes **compensatory hypertrophy** (visible as trabeculations)
* eventually, detrusor '**decompensates**' + relaxes
* bladder begins to **dilate** until it's converted into a big flabby sac w/ little power over contraction
* pts w/ chronic urinary retention have a palpably enlaregd distended bladder (typically _painless_)
* in contrast, _acute_ urinary retention is _painful_
* if bladder outflow obstruction not relieved, **hydroureter** + **hydronephrosis** may develop on both sides of urinary tract
29
What is hydronephrosis?
* literally "water inside kidney"
* refers to distension + dilation of renal pelvis + calyces
* caused by obstruction of free flow of urine from kidney
* untreated -\> progressive **atrophy of renal parenchyma**
* **-\> progressive loss of renal fxn** in _both_ kidney
* development of chronic kidney injury
30
What is obstructive nephropathy (uropathy)?
* renal dysfunction
* due to obstruction to flow of urine
* BPH common cause of obstructive nephropathy in adults
31
What are possible complications of obstructed urinary tract?
* infection
* hypertension
32
How might BPH present?
* LUTS
* acute urinary retention
* urinary tract infection
* renal dysfunction (obstructive nephropathy)
BPH may also give rise to a significantly raised serum PSA level
33
What is the risk of prostate cancer?
likelihood of...
* **developing** = 1 in 3
* causing **problems** = 1 in 10
* **dying** = 2-3 in 100
34
What are risk factors for developing prostate cancer?
* increasing age
* afro-caribbean origin
* germline BRCA mutations
* Lynch syndrome
35
There are two distinct ways in which prostate carcinoma may present: latent prostate cancer or symptomatic prostate cancer.
What is _latent_ prostate cancer?
* inc # of men diagnosed when they have no symptoms
* eg. 50yo man asks GP for PSA test
* PSA is elevated -\> pt undergoes prostate biopsy
* -\> diagnose prostate cancer
36
Symptomatic prostate cancer refers to pts presenting w/ symptoms. These may be due to the primary tumour in the prostate (local) or due to effects of metastases.
What are local and metastatic symptoms that present first?
* symptoms due to **_metastatic_** disease typically occur first - eg. bony mets common in prostate cancer + may be mode of presentation eg. persistent back pain
* **_local_** symptoms eg. bladder outflow obstruction typically occur late - bc prostate cancer occurs in peripheral zone of prostate + so obstruction of urinary flow through prostatic urethra occurs late in natural history of disease
37
Which cancers most commonly metastasise to bone?
* breast
* lung
* prostate
* kidney
* thyroid
Remember, any cancer has theoretical potential to metastasise to bone. Bone mets are usually **osteolytic**, the one major exception to this is _prostate_ cancer, in which bone mets are typically **osteosclerotic**.
38
What is the pathology of prostate cancer?
* **adenocarcinomas** arising from **epithelial** **cells** lining acini or ducts of prostate gland
* asymptomatic premalignant lesion = **prostatic intraepithelial neplasia** (PIN)
* progression from PIN to adenocarcinoma is _not_ inevitable
* prostate cancer is often **multifocal**
* usually arises from **peripheral** zone of prostate
39
How is diagnosis of prostate cancer made?
* transrectal US-guided biopsy of prostate (TRUS)
* biopsies taken from 12 areas within gland
40
How is prostate cancer graded?
* **gleason scoring system**
* **_very important in helping determine most appt treatment + prognosis for patients_**
* tumour given two scores (1-5) according to microscopic appearance
* scores added together to give overall grade (2-10)
* in practice, nowadays only scores 3-5 are used, giving poss total of 6-10
* 6 (3+3) = indolent, good prognosis
* 7 (4+3/3+4) = intermediate prognosis
* 8+ = agressive, worse prognosis
41
How is prostate cancer staged?
* TNM system
* CT/MRI
* bone scan
42
What is the problem with treating _latent_ prostate cancers?
* *if* we treat _all_ prostate cancers we risk over-treating clinically insignificant prostate cancers
* *if* we _don't_ treat any prostate cancers we will under-treat potentially lethal cancers
There are a # of treatment options for latent prostate cancer which aim to cure th disease. The 'active surveillance' option attempts to minimise the chances of over-treating clinically insigniciant prostate cancers
43
What is a radical prostatectomy and its side-effects?
* **entire prostate removed**
* bladder is rejoined to **urethra**
* may be done as robotic procedure using a da Vinci robot
* **side-effects** include:
* urinary incontinence (5-15%)
* erectile dysfunction (30-100%)
* bladder neck obstruction (\<10%)
* death (\<1%)
44
What is radical radiotherapy and its side-effects?
* **external beam radiotherapy** (EBRT) or **brachytherapy**
* aim of **brachytherapy** -\> deliver high dose of radiation more _directly_ to prostate + reduce radiation damage to normal surrounding structures
* brachytherapy involves placement of permanent radioactive **seeds** into prostate gland
* seeds slowly release radiation over couple of months
* **side-effects** include:
* urinary incontinence (5%)
* erectile dysfunction (40-80%)
* long term bowel + bladder problems (5-10%)
45
What is involved in active surveillance?
* careful clinical monitoring
* repeat PCA
* repeat digital rectal examinations
46
What is the rationale behind active surveillance?
* many pts w/ low risk and low volume cancer have **clinically insignificant** or indolent cancer
* may **not** necessarily be causing them problems in lifetime
* provided these pts are appropriately **monitored** for disease progression + then offered more active treatment, the risk of over-treatment can be _reduced_ and the risks of side-effects of active treatment can be _deferred_ in order to maximise the **quality of life**
47
Which patients are suitable for active surveillance?
* relatively low PSA (\<10)
* **Gleason 3+3 cancer**
* those w/ only a **small proportion** of 12 core biopsies containing cancer
If subsequent biopsies show a large volume of cancer or there is Gleason 4 cancer present, radical therapy would be recommended
48
How is symptomatic prostate cancer treated?
* pts presenting w/ symptoms due to prostate carcinoma will almost always have **advanced** disease
* disease _not usually curable_
* so **palliative** treatments to control disease employed
* **_androgen deprivation_** used to slow tumour growth
* achieved by surgical castration (bilateral orchidectomy)
* or by pharmacological treatment (anti-androgens or LH-RH agonists)
49
Where do urinary tract stones most commonly arise?
* anywhere in urinary tract
* but most commonly: renal calyces + pelvis
* lifetime risk of stone formation = 10%
50
What are the most common types of renal calculi?
* **calcium oxalate**
* or mixture of calcium oxalate + **calcium phosphate**
51
Most patients w/ calcium stones have hypercalci**_uria_** but do not have hypercalc**_aemia_**.
What are the causes of **hypercalciuria**?
* **absorptive hypercalciuria** - overabsorption of calcium from gut
* **renal hypercalciuria** - defect in renal tubules, impairs renal tubular absorption of calcium in prox tubule
* **hypercalcaemia** - usually due to primary hyperparathyroidism (minority)
52
How might larger stones present clinically?
* tend to remain confined to kidney
* may form a **staghorn calculus**
* fills the entire renal pelvis + calyces
* stones may remain clinically silent or come to light when **haematuria** or recurrent UTIs are investigated
53
How do smaller stones present clinically?
* pass into ureter + cause **ureteric colic**
* if stone becomes impacted in ureter -\> *severe* pain
* agonising pain - sudden + colicky, lasts several mins
* originates in loin + radiates towards groin
Remember, most small stones _pass_ through the urinary tract **naturally** and so a 'watch and wait' policy is appropriate (as long as no complication supervenes)
54
A stone may become **impacted** in the urinary system causing obstruction.
What are the three most common places that ureteric stones become impacted?
* **pelviureteric junction** - large diameter of renal pelvis decreases to that of the ureter
* **pelvic brim** - as ureters arch over iliac vessels
* **vesicoureteric junction** - ureter narrows, *_most common place for impaction!_*
55
What are the complications of an impacted/blocked stone?
* stone blocks urine flow in one _half_ of urinary tract
* serious immediate complication = **UTI** -\> **pyelonephritis** -\> **sepsis**
* in medium to long-term, inc in pressure proximal to impacted stone causes **hydroureter** + **hydronephrosis**
* loss of kindey fxn on affected side = **unilateral obstructive uropathy**
* however, since only _one_ kidney affected, contralateral kidney able to maintain sufficient kidney fxn *(eg _bilateral_ obstruction secondary to BPH -\> _both_ kidneys affected!)*
* **hypertension** is another long term complication of ureteric obstruction
56
What is the **immediate** **emergency** treatment of urinary stone obstruction?
* **nephrostomy**
* involves insertion of tube through abdominal wall
* into renal pelvis through which urine can drain freely
* usually performed by radiologists under image guidance
57
What is the general management of an impacted urinary stone?
* **uteroscopy**
* +/- **laser lithotripsy**
* lithotripsy breaks up stone into small pieces which can then be removed
