Renal Pathology Flashcards
Compare 2 patterns of pathogenesis of glomerular injuries (HSR type, Model, IF pathology, examples)
Pathogenesis: type III; type II
Reflect by: Heymann model; Masugi model
IF: granular; linear
Diseases: most GN; Goodpasture syndrome
Aetiology of glomerulonephritis (2+3+3+1)
Primary:
- nephrotic: minimal change disease, membranous nephropathy
- nephritic: IgA nephropathy, post-Streptococcal GN, Rapidly progressive / Crescentic GN
Secondary:
- Diabetic nephropathy, Lupus nephritis, Amyloidosis
Hereditary: Alport syndrome
MC nephrotic syndrome in children
Minimal change disease
Which GN presents with selective proteinuria?
Minimal change disease
GN pathology: diffuse effacement of podocyte foot processes
Minimal change disease
Treatment for minimal change disease
Steroid
MC nephrotic syndrome in adults
Membranous nephropathy
Which autoAbs (2) are associated with membranous nephropathy?
autoAb against PLA2R, THSD7A
Secondary causes for membranous nephropathy (5)
Infection (e.g. HBV, HCV, syphilis, malaria)
Malignancy
Autoimmune
Drugs (e.g. ACEI, penicillamine)
Heavy metals
Pathology of membranous nephropathy (4)
LM: diffuse GBM thickening
IF: granular pattern
EM: subepithelial deposits, spike and dome pattern
MC detected immunoglobulin and complement in IF for GN
IgG, C3
Compare nephrotic and nephritic syndrome (pathogenesis, presentations (6 vs 5))
Pathogenesis: ↑ permeability to glomeruli to plasma protein v.s. inflammation of glomeruli –> capillary wall injury –> decrease GFR
Presentations
- Nephrotic: proteinuria (>3.5g/day), hypoalbuminaemia, generalised oedema, hyperlipidaemia, hypercaogulability, hypertension
- Nephritic: proteinuria (0.15~3.5g/day), haematuria, oliuria / azotaemia, hypertenion, oedma
Prognosis of membranous nephropathy
1/3 resolve, 1/3 persist, 1/3 progress
Timing of GN: post-streptococcal GN vs IgA nephropathy
Post-streptococcal GN: 1~4 weeks
IgA nephropathy: 1~2 days
Pathology of post-streptococcal GN (4)
LM: diffuse capillary proliferation, leukocytic infiltration
IF: granular pattern
EM: subepithelial “humps”
Prognosis of post-streptococcal GN
95% spontaneous recovery
MC nephritic syndrome
IgA nephropathy
Pathogenesis of IgA nephropathy
production of mutated GD-IgA, which is not degraded, after mucosal infection –> recognised as foreign antigens & autoAb form –> IC form & deposit in mesangium
What is Henoch-Schonlein Purpura (HSP)?
systemic syndrome involving IgA nephropathy, purpuric rash…
Pathology of IgA nephropathy
mesangial deposition of IgA
3 types of crescentic GN
- Anti-GBM Ab-mediated
- IC-mediated
- Pauci-immune type (associated with ANCA)
Presentations of Goodpasture disease
haemoptysis, acute renal failure
Antibodies in Goodpasture disease
anti-a3(IV)NC1
(Ag found in basement membrane of alveoli & glomeruli)
Management of Goodpasture disease (2)
plasma exchange
immunosuppression
Vasculitis associated with crescentic GN (2)
microscopic polyangiitis
granulomatosis with polyangiitis
Pathology of crescentic GN (2)
crescents (extracapillary proliferation)
ruptures in GBM
MC glomerulonephropathy
diabetic nephropathy
Pathogenesis of diabetic nephropathy
hyperglycaemia –> glycation of protein at efferent arterioles (hyaline arteriosclerosis) –> ↑ pressure of glomeruli –> GBM thickening, mesangial expansion –> losing anionic charge & podocyte damage –> albuminuria
Pathology of diabetic nephropathy (4)
- Diffuse GBM thickening
- Diffuse mesangial expansion
- Nodular mesangial sclerosis (Kimmelstiel-Wilson lesion)
- mesangiolysis
Pathogenesis of lupus nephritis
cell damage –> ↑ anti-nuclear Ab –> IC formation & deposition
Most severe form (also MC) of lupus nephritis
diffuse proliferative
Causes of diffuse proliferative GN (2)
lupus nephritis, post-streptococcal GN
Pathology of lupus nephritis
“full house” IC by IF
MC genetic mutation for Alport syndrome (hereditary pattern)
COL4α5 (X-linked)
Presentations of Alport syndrome (4)
- nephritis
- sensorineural deafness
- lens dislocation, cataract
Pathology findings in urine for nephrotic syndrome
fatty casts
GN pathology: GBM thickening (2)
membranous nephropathy, diabetic nephropathy
GN pathology: subepitheial deposits (2)
membranous nephropathy, post-streptococcal GN (subepithelial “humps”)
GN pathology: spike and dome pattern
membranous nephropathy
GN pathology: mesangial abnormalities
- IgA nephropathy (mesangial deposits)
- Diabetic nephropathy
GN pathology: rupture in GBM
crescentic GN
GN pathology: “basketweave”/ “bread crumb” appearance
Alport syndrome
GN pathology: splitting of lamina densa
Alport syndrome
Aetiology of tubulo-interstitial nephritis (1+2+2+3)
- Acute tubular necrosis
- Acute pyelonephritis, Kidney tuberculosis
- Drug-induced TIN, analgesic nephropathy
- Obstructive nephropathy, radiation nephropathy, renal transplant rejection
Pathology of acute tubular necrosis (1+3)
Gross: pale enlarged kidney
Histology:
- granular casts
- interstitial oedema
- necrosis
Pathology of acute pyelonephritis (2)
- enlarged kiney, with yellow abscesses on kidney surface
- neutrophil infiltrate in tubules and interstitium
Pathology of kidney TB (2)
- multiple cavities with yellow necrotic materials
- extensive caseous necrosis, granulomas
Examples of drugs inducing GN
penicillin, septrin, NSAIDs, thiazides, cimetidine…
Pathology of drug-induced GN (3)
- mononuclear cell infiltrate
- Type I HSR: eosinophils
- Type IV HSR: non-necrotizing granuloma
What is analgesic nephropathy?
dose-depdent oxidative injury caused by combined chronic use of aspirin + paracetamol
Pathology of analgesic nephropathy (3)
papillary necrosis, tubular atrophy, interstitial fibrosis
MC adult renal cyst
Simple renal cyst
MC children renal cyst
cystic renal dysplasia
Pathogenesis of adult PKD
PKD1 mutation (AD) –> failure to produce polycystin –> ciliopathy –> aberrant signalling pathway –> abnormal cell proliferation –> multiple enlarging bilateral cysts
Presentations (3), complications (2), and associations (3) of adult PKD
Presentations:
- flank pain
- heavy, dragging sensation
- haematuria
Complications: hypertension, UTI
Associations: hepatic cysts, Berry aneurysm, MVP
Pathogenesis of juvenile PKD
PKHD1 gene mutation –> fail to produce fibrocystin (regular of polycystin)
Tumour-like lesion (1) and tumours (6) found in kidneys
- ## Xanthogranulomatous pyelonephritis
- Oncocytoma
- Papillary adenoma
- ## Angiomyolipoma
- RCC (MC)
- TCC
- Wilm’s tumour (MC in children)
Lifetime risk of prostate cancer
1:26
Risk factors for prostate cancer (3)
Ageing, smoking, hormone, genetics
Gene mutation for CA prostate
TMPRSS2/ERG fusion
Precursor lesion of CA prostate and its feature
prostate intraepithelial neoplasia (PIN)
(basal cells still intact)
How much proportion of CA prostate is palpable and what is its indication on staging?
25%, T2
Presentations of CA prostate (4)
(symptoms are often late findings)
- obstructive LUTS
- haematuria, haemospermia, early-onset erectile dysfunction
3 common sites of metastasis from CA prostate
bone, liver, adrenal
PSA normal range
<4
Grading score for CA prostate after biopsy. Describe in brief.
Gleason score, the sum of 2 most predominant histological patterns in prostate biopsy (=> Grade 1~5)
3 criteria in determining the staging of CA prostate
TNM, serum PSA, Gleason score
Management of CA prostate (3+3)
Local: active surveillance, radical prostatectomy, radiotherapy
Metastatic: surgical / medical castration, chemotherapy, androgen receptor targeted agents (ARTA)
Which type of carcinoma is MC for CA prostate?
adenocarcinoma
Which zone is CA prostate located at?
peripheral zone (so palpable in T2 but obstruct in late stage)
MC cause of enlarged prostate >50y
BPH
Pathogenesis of BPH
↑ sensitivity of prostate tissue to DHT –> stromal hyperplasia
Which zone is BPH located at?
transitional zone (so obstruct quickly)
DRE result for BPH (4)
smoothly enlarged, non-tender, >3 finger breath, anal tone intact
Complications of BPH (1+3+2)
Prostate level: bleeding / haematuria
Region level: AROU, recurrent UTI, bladder stone
Kidney level: hydronephrosis, obstructive nephropathy
!! ⨉ CA prostate
Imaging tools for BPH (3)
Plain AXR/KUB, transrectal ultrasound, cystoscopy
Pathology of BPH (3)
nodular hyperplasia
glandular and fibromuscular proliferation
basal cells still intact
Managmenet for BPH (1+2+3)
Conservative: lifestyle modifications
Medial:
1. alpha blocker (e.g. tamsulosin)
2. 5 α -reductase inhibitor (e.g. finasteride)
Surgical:
1. UroLift
2. Steam treatment
3. TURP (transurethral resection of prostate)
Aetiology & Treatment of xanthogranulomatous pyelonephritis
Aetiology: urinary tract obstruction –> recurrent bacterial infection
Treatment: antibiotics –> nephrectomy
Which benign renal neoplasm is difficult to differentiate from RCC? What can determine a neoplasm to be RCC?
Oncocytoma
non-distinguishable unless there is evidence of metastasis or infiltration into adjacent structures
Which renal tumour gives peritoneal bleeding as a common side effect?
Angiomyolipoma
Origin of angiomyolipoma
perivascular epithelioid cells (vessels, smooth muscles, fat)
Genetic disorder associated with renal angiomyolipoma (2 genes related) (hereditary pattern)
Tuberous sclerosis (TSC1, TSC2) (AD)
Risk factors for RCC (3+5)
Lifestyle: smoking, obesity, occupation (petrol)
Underlying conditions: HT, CKD, PKD, acquired cystic disease, renal transplant
Pathogenesis for von-Hippel-Lindau disease
VHL mutation (AD) –> impaired degradation of HIF α (hypoxia inducible factor) –> tumorigenesis
von-Hippel-Lindau disease presentations / tumour association
Haemangioblastoma, renal clear cell carcinoma, phaeochromocytoma, pancreatic neuroendocrine tumour, endolymphatic sac tumour [inner ear], liver cysts
Hereditary syndromes associated with RCC (4)
**von Hippel-Lindau syndrome
Hereditary leiomyomatosis & renal cell cancer (HLRCC)
Hereditary papillary renal carcinoma (HPRC)
Brit-Hogg-Dube (BHD) syndrome
Presentations of RCC (triads + 4 paraneoplastic)
- haematuria, flank pain, palpable renal mass
- anaemia, HHM, polycythaemia, HT
5 types of RCC
Clear cell carcinoma, Papillary cell carcinoma, Chromophobes carcinoma, Collecting duct carcinoma, Xp11 translocation carcinoma
Staging and grading (2) of RCC
- TNM staging
(T1: <7cm within kidney, T2: >7cm within kidney, T3: extend into perinephric tissues / major veins, T4: beyond Gerota’s fascia) - Fuhrman grading (nuclear size)
- WHO grading (nucleoli prominance)
Treatment for RCC (1+4)
Local: Partial / Radical nephrectomy
Metastatic: anti-VEGF-r (sunitinib, sorafenib, pazopanib, axitinib…)
MC primary renal tumour in children
Wilms tumour
Precursor lesion of Wilms tumour
nephrogenic rests / cysts
Hereditary syndromes (3) associated with Wilms tumour and their genes
(WT1) WAGR syndrome, Danys-Drash syndrome
(WT2) Beckwith-Wiedemann syndrome
Prognosis of Wilms tumour
90% cure with treatment
Pathology of Wilms tumour (gross and microscopic)
Gross: very large, pale-grey, soft tumour
Microscopic: triphasic (blastemal, stromal, epithelial)
Urinary bladder: aetiology of squamous metaplasia vs glandular metaplasia
squamous: schistosomiasis, stones
glandular: chronic cystitis
Types of bladder cancer (4)
Transitional cell carcinoma
Squamous cell carcinoma
Adenocarcinoma
Rhabdomyosarcoma
MC sarcoma in children
Rhabdomyosarcoma
Risk factors for bladder cancer (TCC vs SCC vs ADC vs Rhabdomycosarcoma) (4+2+1+1)
TCC: smoking, occupation, cyclophosphamide, genetics
SCC: schistosomiasis, bladder stone
ADC: chronic cystitis
Rhabdomyosarcoma: urachal remnants
Genetic risk factors for transitional cell carcinoma in urinary bladder (2)
p53, HRAS
Features of p53-dependent TCC bladder (2)
flat, more invasive
Imaging for bladder cancer (2)
Flexible cystoscopy +/- biopsy
CT urogram
TNM staging for TCC bladder (6)
Ta: non-invasive papillary carcinoma
Tis: non-invasive flat carcinoma in situ
T1: invading lamina propria
T2: invading muscularis propria
T3: invading perivesical fat
T4: invading adjacent structures
Which is the only tumour that is considered malignant even without stromal invasion?
Bladder cancer
What is field effect? What is the associated cancer?
Bladder cancer. Entire urothelium is affected by genetic changes that give rise to tumorigenesis –> recurrence is inevitable
WHO/ISUP grading for bladder cancer (4)
- Papilloma
- Papillary urothelial neoplasm of low malignant potential
- Low-grade papillary urothelial carcinoma
- High-grade papillary urothelial carcinoma
Management for bladder cancer (2)
Non-muscle invasive: TURBT (transurethral resection of bladder tumour)
Muscle invasive: radical cystectomy + urinary diversion
TNM staging for CA prostate (4)
T1: clinically undetectable
T2: palpable on DRE
T3: invade beyond prostatic capsule
T4: invade adjacent structures
Precursor lesion of germ cell tumours
germ cell neoplasm in situ (GCNIS)
Seminoma vs NSGCT (presents at…, spread, RT response)
Presents at: early stage ; late stage
Spread: lymphatic ; hematogenous
RT: sensitive ; resistant
4 types of NSGCT (age & origin)
Embryonal CA (30s), Choriocarcinoma (20s, trophoblast), Yolk sac tumour (<4, endoderm), teratoma (any, trigeminal layers)
Seminoma: age, origin, pathology (4), markers (2)
Age: 40s
Origin: seminiferous tubule
Pathology:
- white-yellow “potato”
- clear cells in sheets or tubules
- lymphocytes
- granuloma
Markers:
- PLAP
- Oct-4
Embryonal CA: pathology, markers (3)
Pathology: variegated tumour
Markers: PLAP, Oct-4, CD30
Tumour markers for choriocarcinoma and yolk sac tumour respectively
HCG; AFP
GCT vs Sex cord stromal tumours (prevalence, malignancy)
Prevalence: 95%; 5%
Malignancy: malignant, benign
What are the two types of sex cord-stromal tumour?
Leydig cell tumour, Sertoli cell tumour
Leydig cell tumour vs Sertoli cell tumour (colour, histology, hormonal activity)
Colour: tan-brown; white-yellow
Histology: eosinophils, Reinke crystals; tubular structures
Hormonal activities: yes (gynaecomastia, sexual precocity); varies
Staging for testicular tumour
TNMS Staging (S stands for serum tumour marker)
3 stages of testicular tumour
I: testis, spermatic cord
II: LN below diaphragm
III: LN above diaphragm
⨉ stage IV
Investigations for prostate cancer
PSA
PHI
Prostate biopsy (“Fusion biopsy”, transrectal / transperineal)
Multiparametric MRI prostate
What is Gleason score?
sum of 2 most predominant histological patterns in prostate biopsy
1 is most well-differentiated, 5 is most poorly differentiated
It is a key prognostic factor of CA prostate
Which RCC is associated with MET gene?
Papillary RCC
