HISTO: Urological pathology Flashcards
What are urinary calculi?
Crystal aggregates that form in the renal collecting ducts
May be deposited anywhere in the urinary tract
How common are renal calculi? Who is most affected?
Lifetime incidence 15%
M:F 3:1
What are the three most common types of urinary calculi?
- Calcium Oxalate (Weddellite) – 75%
- Magnesium Ammonium Phosphate (Struvite) – 15%
- Uric Acid – 5%
What are three aetiologies of calcium oxalate calculi?
Absorptive hypercalciuria – excessive gut calcium absorption
Renal hypercalciuria – impaired proximal renal tubule absorption of calcium
Hypercalcaemia – primary hyperparathyroidism, rare
What are triple stones? Why do they form?
Magnesium ammonium phosphate stones = ”triple stones”
Form as a consequence of infection with urease-producing organisms e.g. Proteus sp.
Ammonia alkalinises urine –> precipitation of magnesium ammonium phosphate salts
What form can triple stones take?
Can become very large –> “Staghorn Calculi”
When do uric acid stones form?
Uric acid stones may form in patients with hyperuricaemia e.g.
- Gout
- Rapid cell turnover
BUT most patients do not actually have hyperuricaemia or increased uric acid excretion in urine so believed to occur due to (3) tendency to produce slightly acidic urine.
What are the complications of urinary calculi?
If large:
- Obstruction,
- risk of infection,
- chronic renal failure
When do urinary calculi cause colic? What locations?
When small stones that drift out of the kidney may become impacted in…
- Pelvi-ureteric junction (PUJ)
- pelvic brim
- vesico-ureteric junction (VUJ)
Name 3 benign renal neoplasms.
- Papillary adenoma
- Angiomyolipoma
- Renal oncocytoma
Define renal papillary adenoma.
Benign epithelial kidney tumour composed of papillae and / or tubules
By definition, 15mm or less in size + well-circumscribed
What genetic abnormalities are renal papillary adenomas associated with?
- Trisomy 7,
- Trisomy 17,
- Loss of Y chromosome
When are papillary adenomas more commonly diagnosed?
Frequent incidental finding in nephrectomies and at autopsy
What is this benign renal tumour?
Papillary adenoma
What is this benign renal tumour?
Renal oncotyoma
- Pink, oncocytic cells – full of mitochondria
What is this benign renal tumour?
Angiomyolipoma
What is renal oncocytoma?
- Benign epithelial kidney tumour composed of oncocytic cells
- Well-circumscribed
What is the aetiology of renal oncocytoma?
- Usually sporadic
- Can be seen in Birt-Hogg-Dubé syndrome
Birt-Hogg-Dubé syndrome (BHD) = hereditary condition associated with multiple benign skin tumors, lung cysts, and an increased risk of renal lesions (cysts, benign tumors, and kidney cancer.)
Which benign renal tumour is associated with BHD syndrome?
Renal oncocytoma
What are renal angiomolipomas?
•Benign mesenchymal kidney tumour composed of thick-walled blood vessels, smooth muscle and fat
What are angiomyolipomas derived from? What is their aetiology?
Derived from perivascular epithelioid cells
Mostly sporadic. Can be seen in tuberous sclerosis.
What are the complications of angiomyolipomas?
Usually an incidental finding but larger tumours (>4cm) can cause:
- flank pain
- haemorrhage
- shock
Name three types of malignant renal neoplasms.
Renal cell carcinoma
- Clear cell
- Papillary
- Chromophobe
Nephroblastoma
What is renal cell carcinoma? How common is it?
Malignant + epithelial renal tumour
2% of all cancers worldwide, more common in developed countries
List 4 risk factors for RCC.
- Smoking
- Hypertension
- Obesity
- Long-Term Dialysis
- Genetic Syndromes – von Hippel Lindau
How does RCC present?
- 50% present with painless haematuria
- Detected incidentally on imaging
- Some present with metastatic disease
What are the main subtypes of RCC and which is most common?
- Clear Cell Renal Cell Carcinoma (70%)
- Papillary Renal Cell Carcinoma (15%)
- Chromophobe Renal Cell Carcinoma (5%)
Remaining 10% are various rare subtypes
What genetic abnormality is seen in clear cell RCC?
loss of chromosome 3p
What is a clear cell RCC composed of? Describe its gross appearance.
Epithelial kidney tumour composed of nests of clear cells set in a delicate capillary vascular network
Golden yellow tumour with haemorrhagic areas
What genetic mutations are seen in papillary RCC?
- trisomy 7,
- trisomy 17
- loss of Y chromosome
What is the difference between papillary adenoma and papillary RCC?
Main difference is size
- Papillary aenoma <15 mm
- Papillary RCC >15mm
Both have similar mutations.
What are papillary RCCs subdivided based on?
Morphology
Two types:
- Type 1 = well defined, show genetic loss consistently, single layer of smaller flat cells
- Type 2 = heterogenous , may be further subdivided in the future; worse prognosis; multilayering/stratification of cells is characteristic
What is the gross histology of papillary RCCs?
Grossly appears as a fragile, friable brown tumour
(papillary adenomas = well circumscribed)
What is the gross histology of chromophobe RCC?
Grossly appears as a well-circumscribed solid brown tumour
What are the histological chromophobe RCCs? What genetic abnormalities exist?
Epithelial kidney tumour composed of sheets of large cells that display distinct cell borders, reticular cytoplasm and a thick-walled vascular network
Shows variable genetic aberrations
“plant-like” defined cell borders
What is the prognosis for RCC? What is the most important prognostic factor?
Most important prognostic factor - stage and grade (ISUP Nuclear Grade (1-4) applies to clear cell and papillary renal cell carcinoma)
5-year survival for RCC = 60%
What is the Leibovich risk model?
Clear Cell Renal Cell Carcinoma risk progression index
Stratifies into low risk, intermediate risk, high risk
What is a Wilm’s tumour? What three components does it consist of?
Nephroblastoma = malignant triphasic kidney tumour of childhood:
Consists of:
- Blastema (small round blue cells)
- Epithelial cells
- Stromal cells
How does nephroblastoma present? What is the prognosis?
Second most common childhood malignancy
Typically presents as an abdominal mass in children aged 2-5 years old
95% of cases show favourable histological features with excellent prognosis
What are urothelial carcinomas also known as?
TCC - transitional cell carcinoma
They are a group of malignant epithelial neoplasms arising in urothelial tract
- Bladder
- Renal Pelvis
- Ureters
What are two risk factors for TCC/urothelial carcinoma?
- Smoking
- Aromatic amines (probably from a step in their production and not the actual amines)
How do urothelial carcinomas present?
Most present with haematuria
What are the three types of urothelial carcinomas?
- Non-Invasive Papillary Urothelial Carcinoma
- Infiltrating Urothelial Carcinoma
- Flat Urothelial Carcinoma in-situ
Describe the appearance of non-invasive papillary carcinomas. How are they divided into low vs high grade i.e. what is it based on?
frond-like growths (low grade on left, high grade on right)
Divided into low grade and high grade (WHO 2004) based on nuclear atypia
True or false: Low grade non-invasive papillary urothelial tumours have a low risk of progression to invasive disease.
True =<5%
High grade tumours carry a higher risk of progression to invasive disease
What mutations are present in non-invasive papillary urothelial carcinomas?
Unstable and carry various genetic abberations including:
- RB
- TP53
What is an infiltrating urothelial carcinoma?
Urothelial tumour displaying invasive behaviour
What is treatment of infiltrating urothelial carcinomas based on?
Treatment based on depth of invasion
- Lamina propria
- Muscularis propria
Describe the appearance of flat urothelial carcinoma in situ (CIS). What is the prognosis?
May be invisible or appear as a reddish area
Flat urothelial lesion with unequivocal high grade features - high risk of progression
What is BPH? How common is it?
Benign enlargement of prostate as a consequence of increase in cell number
Very common – symptomatic in 25% of men by age 80 and histologically present in 90% of men by age 80
What is the aetiology of BPH? What is treatment based on?
Increased oestrogen levels in blood, which rises with age, may induce androgen receptors and stimulate hyperplasia
Treatment based on:
- alpha blockers
- 5⍺-reductase inhibitors
- transurethral resection
What are the clinical features of BPH?
Presents with “Lower Urinary Tract Symptoms”
- Frequency
- Nocturia
- Urgency
- Hesitancy
- Poor flow
- Terminal Dribbling
Rarely: urinary tract infection, acute urinary retention or renal failure
What is shown?
BPH - nodule of normal glandular and stromal parts of the prostate which is expanding and growing on its own
What is the most common malignant tumour in men?
Prostatic adenocarcinoma - malignant epithelial prostate tumour
How common is prostatic adenocarcinoma?
25% of all male cancers
1 in 8 men will develop it in their lifetime
What are some risk factors for prostatic adenocarcinoma?
- Red meat consumption
- 5-10x risk increase if first degree relative is also affected
What does prostatic adenocarcinoma arise from? What mutations are implicated?
Arises from Prostatic Intraepithelial Neoplasia (PIN)
Mutations in PTEN, AMACR, GST-pi, p27 and more…
What are the presenting features of prostatic aenocarcinoma?
- Usually asymptomatic; usually diagnosed on biopsy following raised serum prostate-specific antigen or digital rectal examination
- May have lower urinary tract symptoms
- Rarely may present with metastatic disease e.g. pathological fracture
What is the most powerful prognostic factor for prostatic adenocarcinoma?
Gleason score - influences treatment decisions
Describe how the Gleason score is calculated and the significance of a high score.
Expressed as x + y = z
- Add two most common patterns (or most common pattern + worst pattern in biopsy setting)
- Patterns range from 1-5
- 1 and 2 rarely if ever diagnosed so scores typically range from 6-10
Higher scores correlate with aggressive behaviour
- High volume tumours scoring 8-10 in particular
- Grade grouping used as well
Prostatic Adenocarcinoma – Gleason Grades 1, 2 and 3
Distinct glands of the prostate are present and still resemble glands
Prostatic Adenocarcinoma – Gleason Grade 4
There is fusion and cribiform glands
Prostatic Adenocarcinoma – Gleason Grade 5
Diagnosed by either:
- pattern 4 with necrosis
- OR sheets of tumour cells with no formation of glands
What is the most common type of testicular tumour? Who is most affected?
Testicular germ cell tumours account for 90% of testicular tumour - they are tumours of the testis arising from germ cells
Typically arise in men aged 20-45
What are the risk factors for testicular germ cell tumours?
- Undescended testis (3-5x increased risk)
- Low birth weight / small for gestational age
What is the aetiology/pathophysiology of testicular germ cell tumours?
Malignant tumours arise from Germ Cell Neoplasia in-situ
- Process likely begins in foetal life
- Amplification of i12p
What are the clinical features of testicular GC tumours? What % present with metastasis symptoms?
Present as painless lump
10% present with symptoms related to metastasis
- Back pain – drainage is para-aortic so if affected will cause back pain
- Cough
- Dyspnoea
What subtype of GC tumour is shown?
Seminoma - most common subtype, mostly clear cells
What subtype of GC tumours is shown?
Embryonal carcinoma -anaplastic tissue, high grade appearance
What subtype of GC tumour is shown?
Post-pubertal teratoma - this tumour is trying to produce keratin, there are some glandular parts and cartilage i.e. trying to produce various tissues from the germinal layers. Therefore, metastases may look very different
What subtype of GC tumour is shown?
Yolk sac tumour - varying appearance but here small cells are seen with a lace-like growth pattern
What subtype of GC tumour is shown?
Choriocarcinoma
- Made up of cytotrophoblast cells (clear) and syncytiotrophoblastic cells (multinucleate cells)
- Both need to be present to diagnose choriocarcinoma
Which treatment are testicular GC tumours sensitive to?
Highly sensitive to platinum-based chemotherapy regimes
Prognosis excellent - 5 year survival is 98% in most countries
Name 3 testicular non-germ cell tumours.
- Lymphoma - older men, 5% of all testicular tumours
- Leydig cell tumour - 3% of all testicular tumours
- Sertoli cell tumour - 1% of all testicular tumours
State whether each of these testicular tumours is benign/aggressive:
- lymphoma
- leydig cell tumour
- sertoli cell tumour
- Lymphoma - highly aggressive, poor survival rates
- Leydig cell tumour - benign usually
- Sertoli cell tumour - 90% benign
List 4 different paratesticular conditions.
- Epididymal cyst
- Epididymitis
- Varicocele - dilated venous plexus
- Hydrocele - fluid between layers of tunica vaginalis
- Adenomatoid tumour - small tubules lined by mesothelial cells
What are the most common causes of epididymitis?
Usually related to:
- C. trachomatis or N. gonnorrhoeae in men under 35;
- E. coli in men over 35
List 4 different penile diseases.
- Lichen sclerosus/balanitis xerotica obliterans - inflammatory condition that causes phimosis
- Zoon’s balanitis - inflammatory condition that causes red areas
- Condylomas
- Peyronie’s disease
- Penile carcinoma
What is the cause of condylomas?
HPV 6 and 11
What is Peyronie’s disease?
Scarring , inflammation, thickening of corpus cavernosa
What are the risk factors for penile carcinoma?
- Smoking,
- HPV,
- chronic Lichen Sclerosus
Rare, affects elderly men
List 4 urethral diseases.
- Urethritis - N. gonorrhoeae, C. trachomatis
- Prostatic Urethral Polyp - papillary lesion in prostatic urethra
- Urethral Caruncle - common lesion at urethral meatus in women
- Urethral Carcinoma - rare, more common in women
- Malignant Melanoma - rare
What cell type are most urethral carcinomas?
squamous cell carcinomas
List 4 scrotal diseases.
- Epidermoid Cyst – invagination of skin, common
- Scrotal Calcinosis - rare; may be related to old epidermoid cysts
- Angiokeratomas - benign vascular lesions
- Fournier’s Gangrene
- Scrotal squamous cell carcinoma - very rare, historical interest; chimney sweep
What is Fournier’s gangrene?
Necrotising fasciitis that affects the genital, perineal, or perianal regions of the body
Mortality 15-20%
What are the subtypes of testicular GC tumours?
- Seminoma
- Non-seminoma
- Embryonal carcinoma
- Post-pubertal teratoma
- Yolk sac tumour
- Choriocarcinoma
