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Urogenital Pathology Flashcards

1
Q

3 major features of glomerulonephritis, aetiology, treatment principle

A

Chronic, immune-mediated, major cause of ESRD

Often unknown aetiology and no specific therapy (supportive tx to slow progression)

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2
Q

Indications for renal biopsy (5)

A

Nephrotic syndrome, nephritic syndrome, isolated haematuria or proteinuria, renal failure, renal tubular dysfunction

For Dx, Px and Tx

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3
Q

Uses of LM, IF and EM on renal biopsy specimens

A

LM: visualise intrinsic cells and classify type of glomerular disease (H&E, PAS, PASM)

IF: Antigen detected by IF labelled Ab to identify protein deposition; Linear IF = anti-GBM, Granular IF = IC Disease

EM: ultrastructure of kidney , identify electron dense deposits

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4
Q

Heymann model vs Masugi model of GN

A 
Heymann = IC disease (inject bovine serum albumin to rabbit to induce IC formation)
Masugi = anti-GBM (inject rat kidney to rabbit to induce production of anti-rat kidney Ab)
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5
Q

Mechanism of IC and anti-GBM disease

A

IC: Type III hypersensitivity e.g. nephritic
anti-GBM: Type II hypersensitivity e.g. Goodpasture

  • -> both activate complement system to trigger chemotaxis and inflammation –> renal injury with progressive sclerosis (only a minority will resolve)
  • -> progressive due to sustained production of IC or persistence of antigen
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6
Q

Terminology of describing glomerular diseases (2)

A

Focal vs Diffuse (% abnormal glomeruli in kidney)

Segmental vs Global (affected part of the involved glomerulus)

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7
Q

Possible presentations of glomerular injury (4)

A
  1. Active glomerular disease with normal glomerulus
  2. Hypercellularity of mesangial, endocapillary or extracapillary (epithelial) proliferation
  3. Necrotising with disruption of capillary wall, haemorrhage into bowman’s space, fibrin deposits – reversible
  4. Sclerosis with collapse of portion of capillary tufts, adhesion to bowman’s capsule – irreversible
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8
Q

Classification of GN (3)

A

Primary
- Aetiology of primary GN often unknown - name disease by its best morphological characteristics

Secondary
- known systemic disease

Hereditary
- Alport’s, Thin membrane, Fabry’s disease

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9
Q

Poststreptococcal GN: epidemiology, IC or anti-GBM?, pathogenesis, clinical manifestation, pathology (3), prognosis, treatment and outcome

A

Secondary GN - Most commonly in children

IC disease, due to bacterial Ag following Grp A streptococcal infection
Manifests as acute nephritic syndrome

Pathology: “acute diffuse proliferative GN” (endocapillary proliferation) with IgG-C3 or isolated C3 IC
EM –> sub epithelial dense deposits (humps)

Prognosis: 95% spontaneous recovery with lesion cleared as antigen is displaced and returning to normal

Note: severe systemic infection can also cause diffuse proliferative GN

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10
Q

Crescentic GN: other name?, pathogenesis and examples (3), clinical manifestation, pathology (3), prognosis, treatment and outcome

A

Primary GN - “Rapidly progressive GN” –> medical emergency progressing to AKI

Can be due to any GN other than minimal change nephropathy

  • anti-GBM: Goodpasture syndrome
  • IC disease: Lupus nephritis, SBE, HSP
  • pauci-immune (-ve IF but +ve ANCA): Wegener’s granulomatosis, microscopic polyarteritis

Manifests as nephritic syndrome

Pathology: proliferation of epithelial cells forming crescents (>2 cell thick in Bowman’s capsule), leukocyte infiltration +/- necrotising lesion

Poor prognosis, outcome depends on early diagnosis and treatment to prevent irreversible injury
Tx: immunosuppression, plasmapheresis for GBM or ANCA

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11
Q

Goodpasture’s Syndrome: IC or anti-GBM, pathogenesis, clinical manifestation, pathology, prognosis, treatment and outcome

A

Severe Anti-GBM disease with Anti-BM Ab against the pulmonary and glomerular capillaries BM antigen (collagen IV - NC1 of COL4-alpha-3)

Manifests as haemoptysis (pulmonary haemorrhage) and acute renal failure

Pathology: Crescentic GN

Treatment with plasmapheresis, steroids and cyclophosphamide (+ tx of pulmonary haemorrhage)
Usually poor outcome

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12
Q

IgA Nephropathy (Berger Disease): epidemiology, IC or anti-GBM, pathogenesis, clinical manifestation, pathology, prognosis, treatment and outcome

A

Previously the most common GN worldwide (now overtaken by DM nephropathy)
IC disease by formation of IgA-C3 complexes due to the increased mucosal synthesis and decrease clearance of IgA

Manifests as nephritic syndrome (microscopic or gross haematuria) and more specifically, synpharyngitic haematuria - begins within 1-2 days of non-specific URTI –> subsides and then recurs periodically in the setting of viral infection

Pathology: focal proliferative pattern of mesangial hypercellularity with electron dense deposits at mesangium on EM; IgA-C3 and properdin deposits at mesangium on IF

Treatment by anti-hypertensives and steroids for proteinuria –> prognosis is persistence of IC leading to progressive sclerosis and ESRD (20% over 10 years)

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13
Q

Lupus Nephritis: IC or anti-GBM, pathogenesis, clinical manifestations, pathology, prognosis, treatment and outcome

A

IC disease due to the presence of auto-antibodies e.g. ANA, dsDNA, Smith, ENA

Manifests as either nephrotic or nephritic syndrome with other multisystem effects of SLE such as butterfly rash, cytopenia, arthritis, serositis etc.

Pathology: all types are possible (different hypercellularities, necrotising etc.) – “Full House” in IF with extensive electron dense deposits on EM

Treatment by immunosuppression (steroid and cyclophosphamide) and usual progression to ESRD

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14
Q

Minimal Change Nephropathy: epidemiology, type of disease, pathogenesis, clinical manifestations, pathology, prognosis, treatment and outcome

A

Most common in children, abrupt onset

Unknown type with unknown pathogenesis – possible due to T-cell dysfunction with cytokines causing GBM to lose negative charge –> selective proteinuria\

Manifests as nephrotic syndrome with normal renal function

Pathology: “Minimal change” on both LM and IF; fusion of podocytes on EM

May spontaneously resolve but treated with steroids usually, good outcome
<5% progress to CKD over 25 years (likely due to undetected focal segmental glomerulosclerosis)
- focal segmental GN can also be due to HIV, Heroin, Haematological (sickle cell anaemia)

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15
Q

Membranous Nephropathy: epidemiology, type of disease, pathogenesis (2), clinical manifestations, pathology, prognosis, treatment and outcome

A

Most common in adults (30-60 years), indolent course with sudden onset

IC disease due to primary or secondary causes

  • primary (>70%): PLA2R Ab (intrinsic antigen on podocyte)
  • secondary: Lupus Class V, HBV-related, Syphilis, Gold, ACEi, Penicillamine, Carcinoma
  • -> IC triggers complement activation on surface of podocytes to generate MAC leading to injury

Manifests as nephrotic syndrome

Pathology: thick GBM with sub epithelial “spike and dome” pattern on LM; granular IF (IgG-C3) and sub epithelial electron dense deposits on EM

Prognosis: 1/3 pattern (either resolved, persists or progresses) - steroid may slow progression

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16
Q

Diabetic Nephropathy: epidemiology, pathogenesis (3), clinical manifestations (3), pathology, prognosis, treatment and outcome, other effects of DM on kidneys

A

Most common cause of chronic nephropathy now

Manifests as nephrotic? type – proteinuria (microalbuminuria), HT, renal failure

Glomerulosclerosis due to non-enzymatic glycosylation of protein –> form advanced glycation products (AGE) which activates GFs –> increase membrane permeability to proteins
Arteriosclerosis due to AGE effect on efferent arterioles
Also affects renal papillae

Pathology of glomerulosclerosis: early stage - normocellular glomerulomegaly with thickened GBM on EM; intermediate stage - mesangial cellular and matrix expansion; advanced stage: mesangial nodular sclerosis with capillary aneurysms, IF-ve (Kimmelsteil-Wilson Disease)
Pathology of arteriosclerosis: benign hyaline pattern

Poor prognosis with progression to ESRD in 5-10 years; ACEi can be used for selective dilation of efferent arteriole to manage microalbuminuria

Other effects of DM: UTI (acute bacterial pyelonephritis), renal papillary necrosis

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17
Q

Amyloidosis: epidemiology, pathogenesis, pathology, diagnosis (3)

A

Often in elderly, due to monoclonal gammopathy

Deposition of fibrillary protein which replaces functioning tissue
Pathology: accumulation of amorphous material most often at mesangium, GBM and arterioles

Diagnosis: EM characteristics (c.f. general pathology), IHC stain for amyloid-p, Congo red stain with apple green birefringence

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18
Q

Nephrosclerosis: definition, associated risk factors, pathogenesis, pathology of atherosclerosis, pathology of hypertensive nephrosclerosis (benign and malignant)

A

Sclerosis of renal arteries and arterioles
Associated with increased age, DM and hypertension

Caused by endothelial injury and subsequent medial and intimal thickening (smooth muscle hypertrophy) of vessel walls leading to narrowing of lumen by hyalinisation

Atherosclerosis: large arterial wall thickening and loss of elasticity with lipid deposition/ cholesterol plaque/ inflammation and fibrosis

Hypertensive Nephrosclerosis:

  • Benign HT –> hyaline arteriosclerosis of renal arterioles with symmetrical renal atrophy and a finely granular kidney surface; ischemia leads to tubular atrophy and glomerular sclerosis in severe cases
  • -> causes mild proteinuria and variable GFR (rarely ESRD)
  • Malignant HT –> petechial haemorrhage (flea-bitten), fibrinoid necrosis of arterioles, hyperplastic arteriolitis
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19
Q

Thrombotic Microangiopathy: definition, pathology, primary TMA causes/ effects on kidney/ treatment (3), secondary TMA causes

A

Microangiopathic HA with thrombocytopenia due to endothelial injury and platelet activation and aggregation

Pathology: endothelial degeneration with intimal edema and haemorrhage, acellular occlusion and then thrombosis

Primary:
- shiga-toxin mediated HUS –> glomerular endothelial cells activated by toxin leading to damage, increased vasoconstriction and promotion of platelet activation; usually sudden onset of bleeding after diarrhoea, common cause of AKI in children requiring prompt dialysis; 25% renal insufficiency over 15-25 years

  • atypical HUS –> excessive activation of alternative complement pathway leading to microvascular injury and thrombosis (inherited mutations or acquired autoantibodies - rare); sudden onset with poorer prognosis than shiga HUS (20% fatality); plasmapheresis and Ab against MAC to control
  • TTP –> inherited or acquired deficiency of ADAMST13 leading to buildup of vWF multimers which are thrombogenic and activate platelets; sudden onset, more CNS related disorder and less kidney involvement; good prognosis with plasmapheresis

Secondary:
- malignant HT, scleroderma related

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20
Q

ANCA Vasculitis: pathogenesis, pathology

A

Anti-neutrophil cytoplasmic antigen Ab stimulating neutrophil infiltration of vessel wall
May affect small capillaries or extra-glomerular arteries

Pathology: cortical infarcts, inflammatory cells and fibrinoid necrosis in severe cases

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21
Q

Tubulo-interstitial nephritis (TIN): definition, general points (3)

A

Inflammatory diseases involving renal tubules and interstitium

Common conditions with known causes and mechanism
Poor correlation between clinical presentation and pathological findings
Can be acute or chronic

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22
Q

Acute Pyelonephritis: cause, risk factors (4), clinical manifestations, pathogenesis (2), pathology (3), treatment and prognosis, complications (4)

A

TIN due to bacterial infection, most common causative organism is E.coli (and then proteus and enterobacter)

Risk factors: obstruction (stone/ BPH etc.), urinary instrumentation e.g. indwelling catheter, DM (more susceptible to infections and neurogenic bladder dysfunction, congenital ureterovesical orifice defect leading to vesicoureteral reflux

Manifests as fever, chills, loin pain, dysuria, frequency, urgency (WBC casts in urine)

Pathogenesis: most commonly ascending infection from lower urinary tract (stasis/ incomplete voiding, reflux)
Less commonly from haematogenous spread
Usually unilateral

Pathology: Grossly, enlarged kidney with yellowish diffuse cortical small abscesses (liquefactive necrosis) – microscopically seen as polymorphs in tubules and interstitium (if more severe)

Treatment: Treat early with Ciprofloxacin or Nitrofurantoin –> reversible injury and may recover completely

Complications:
Minority may relapse in cases of reflux or obstruction and lead to development of chronic pyelonephritis
Papillary necrosis (coagulative necrosis of pyramid tips - renal papillae) in DM/ Obstruction/ Sickle Cell
Perinephric abscesses
Pyonephrosis if pus can’t drain

23
Q

Chronic pyelonephritis: clinical manifestations, pathogenesis (2), pathology

A

Important cause of CKD with gradual onset of renal insufficiency

Chronic obstructive nephropathy or Chronic reflux nephropathy in congenital VUR (very common cause of chronic pyelonephritis) - both either unilateral or bilateral

Pathology: recurrent inflammation and scarring leading to asymmetric kidneys with uneven scarring involving the pelvis or calyces –> papillary blunting and deformed calyces

24
Q

Tuberculosis Nephritis: pathogenesis, pathology

A

Rare nowadays
Haematogenous from primary focus

Pathology: Miliary or cavitatory lesions; Caseating granulomatous inflammations

25
Q

Drug-induced interstitial nephritis: causes and types of drugs, pathogenesis (2), clinical manifestations (4), pathology (3), treatment and prognosis

A

Most common TIN caused by many drugs e.g. penicillin, thiazide, NSAIDs, PPI, sulphonamide

Hypersensitivity reactions: Type 1 (IgE mediated) or Type 4 (T cell mediated) - dose-independent

Latent period prior to onset of fever, rash, eosinophilia and oliguria (lab results: haematuria and leukocyturia)

Pathology: swollen kidney and interstitial edema with interstitial infiltration by mononuclear cells and an abundance of eosinophils (eosinophilia)
Non-necrotising granuloma in the case of methicillin, thiazides (T cell reaction)

Drug withdrawal –> may take up to several months to recover

26
Q

Analgesic Nephropathy: cause, types of drugs, pathology (3), complications

A

Can be classified as another type of drug induced TIN
Rare nowadays, due to direct toxicity from drugs causing dose dependent reaction

Combined chronic use of ASA + paracetamol (oxidative injury)

Pathology: papillary necrosis, tubular atrophy and interstitial fibrosis

Complications: increase CA risk

27
Q

Acute Tubular Necrosis (ATN/ATI): clinical manifestations (6), pathogenesis (2), pathology (5), treatment and outcome

A

Most common cause of AKI (acute renal failure)

Oliguria and decreased GFR in some patients
Most common clinical manifestations are electrolyte abnormalities, acidosis, signs and symptoms of uraemia and fluid overload

Can be due to ischaemia or nephrotoxicity

  • Ischaemia: hypovolaemia caused by shock/ MI/ burns/ sepsis/ DIC/ gastroenteritis etc.
    • -> causes sublethal endothelial injury which increases endothelin and decreases NO –> infrarenal vasoconstriction to further decrease GFR and O2 delivery
  • Nephrotoxicity: drugs e.g. aminoglycosides, ethylene glycol, heavy metals, contrast agent
    • -> tubular injury leads to inflammation, sloughed cells and tubular backleak –> decrease urine output and decrease GFR

Pathology: Various tubular injuries (mainly at PT and TAL) - Blebbing and sloughing of brush border, detachment of tubular cells from basement membrane into urine (may cause obstruction if build up), interstitial edema and infiltration due to tubular backleak, formation of proteinaceous casts due to tubular cell necrosis
- may not correlate with severity of AKI

Treatment: removing inciting harmful event –> reversible lesion as TBM intact, recovery depends on severity of injury and capacity to proliferate (may have residual scar and partial loss of function)

28
Q

Obstructive Nephropathy: clinical manifestations (3), pathogenesis (3), pathology (2), outcome

A

Asymptomatic, Acute renal colic, AKI

Intraluminal: Renal stone
Mural
Extraluminal: BPH

Pathology: hydronephrosis and pyonephrosis

Leads to progressive loss of functioning parenchyma

29
Q

Immunologic Transplant Rejection: clinical manifestation (1), pathogenesis (2), pathology (2), treatment and outcome

A

Impaired RFT

Cellular and Humoral Immunity – T cell mediated binding to recognise donor kidney antigen expressed on MHC

Pathology: swollen kidney, tubulitis (infiltration of T cells and tubular cells)

Treatment: Immunosuppressant –> reversible lesions but chronic insult

30
Q

Simple Cyst: epidemiology, location, pathogenesis (4), clinical signficance

A

Most common adult renal cyst, usually at cortex
Can be single or multiple, no inherited mechanism

Caused by intratubular obstruction, defect in TBM matrix and compliance, altered cell growth and defective fluid secretion or absorption

No clinical consequence, most important is differentiation from renal tumour on imaging – features e.g. smooth contour, avascular

31
Q

Cystic Renal Dysplasia: epidemiology, pathogenesis

A

Most common child renal cyst

Caused by abnormal development of the kidney with abnormal structures e.g. cartilage, which is associated with obstruction during intra-uterine development
Non-functional kidney

32
Q

Adult polycystic kidney disease (ADPKD): inheritance, gene defect, pathogenesis, presentation, outcome, treatment

A

85% due to AD mutation in PKD1 gene for polycystin
Accounting for 10% of all CKD

Leads to ciliopathy with aberrant signalling pathways and abnormal cell proliferation or ion secretion

Presents usually at 40-50 years old with flank pain/ intermittent gross haematuria; may have other complications e.g. HT, UTI, aneurysm at circle of Willis

Kidney normal at birth but gradually enlarges due to diffuse formation of cysts leading to ESRD (at 50 years old)

Treatment: renal transplantation

33
Q

Juvenile polycystic kidney disease (ARPKD): inheritance, gene defect, pathogenesis, outcome

A

AR mutation in PKHD1 gene for fibrocystin (regulated polycystin-2 expression)

Leads to ciliopathy, strongly associated with liver abnormalities

Results in stillbirth or rapid progression to ESRD (at birth or in infancy)

34
Q

Dialysis/Acquired cystic disease

A

In 50% of patients on long-term dialysis

Tubular obstruction by interstitial fibrosis, oxalate crystals etc.

Increases the risk of RCC as non-functional kidney develops cortical adenoma

35
Q

Nephrotic vs Nephritic

A

Nephrotic:

  • glomerular injury due to cytokines
  • hypoalbuminemia (pitting edema), proteinuria (>3.5g/day), hyperlipidemia with fatty casts of Maltese crosses and oval fat bodies in urine
  • hypercoagulability (loss of ATIII) –> DVT and PE, HT (RAAS due to decreased ECF)

Nephritic:

  • glomerular injury due to neutrophils
  • HT (fluid retention from azotaemia), periorbital puffiness and edema, proteinuria (150mg - 3.5g/day) haematuria (inflamed glomeruli with dysmorphic RBC), oliguria/ azotaemia (decreased GFR)
36
Q

Tumour-like Lesions of the Kidney (2) - pathogenesis, presentation, pathology, treatment

A

Xanthogranulomatous Pyelonephritis

  • rare form of chronic granulomatous pyelonephritis due to recurrent bacterial infection caused by obstruction
  • Macroscopically: enlarged kidney with yellow nodules (mimics malignant tumour on imaging)
  • Microscopically: aggregation of foamy macrophages and atrophy/loss of functional parenchyma
  • Treat with nephrectomy
  • *Angiomyolipoma
  • Hamartoma (mass of disordered tissues)
  • Commonly sporadic but may be due to TUBEROUS SCLEROSIS – mutation in TSG (TSC1 and TSC2) which controls hamartin and tuberin –> leading to multi system hamartomas
  • Triad of mental retardation, seizures and skin lesions (and BLEEDING RISK)
  • Macroscopically: single or multiple masses
  • Microscopically: vessels, smooth muscle, fat (PEComa)
37
Q

Benign Tumours of the Kidney (3) - presentation, pathology, treatment

A

Renal papillary adenoma

  • usually asymptomatic, incidental finding
  • Macroscopically: single or multiple nodules of <1cm at cortex
  • Microscopically: papillary or tubules lined with cuboidal renal cell
  • Larger adenoma is precursor for RCC (>1.5 cm considered carcinoma or high-grade)

Oncocytoma

  • from intercalated cells of collecting ducts; loss of chromosome 1 and Y
  • usually asymptomatic but may be palpable and could manifest as haematuria
  • difficult to distinguish from RCC (can only determine based on metastasis or aggressive infiltrative properties)
  • Macroscopically: large dark brown mass with central scar and pseudo-capsule
  • Microscopically: nests/ tubules of eosinophilic cells with ABUNDANT MITOCHONDRIA and small round nucleus

Medullary Fibroma

  • common benign nodule <1cm in the medulla
  • non-functional, usually incidental finding
  • Macroscopically: white mass
  • Microscopically: hyalinised fibrous nodule
38
Q

Renal Cell Carcinoma: epidemiology, presentation/ clinical (6), pathogenesis (2), risk factors (5), pathology, staging/ grading, treatment and outcome

A

Most common CA of the kidney (85%), affecting those >60 years old and more prevalent in male

Presents with painless haematuria (in more than 50%), palpable renal mass and flank pain; metastasis most commonly to lung or bone
Paraneoplastic syndromes e.g. polycythaemia (5-10%), hyperCa
Left sided varicocele

Mostly sporadic cases with unknown aetiology, 5% hereditary e.g von-Hippel Lindau disease
Risk factors: smoking, obesity, HT, CKD (dialysis), exposure to cadmium

*Mutated VHLp in clear cell carcinoma (sporadic or familial) leads to impaired degradation of HIF-alpha which increases the transcription factors for VEGF and PDGF growth factors implicated in tumourigenesis

Pathology:

  • Macroscopically - heterogenous tumour (usually at upper pole of kidney, at cortex) with areas of haemorrhage, yellowish tissue and cystic areas; OFTEN EXTENDS TO RENAL VEINS
  • Microscopically - many histological types: MOST COMMON IS CLEAR CELL CARCINOMA (contain lipid and glycogen - cells can appear vacuolated if lipid-laden or can appear granular); others include papillary cell carcinoma, chromophobe cell carcinoma

Prognosis:

  • WHO grading
  • TNM staging: T1 <7cm, T2 >7cm, T3 extends to perinephric tissues or major veins, T4 beyond Gerota’s capsule
  • generally good prognosis

Treatment:

  • Surgery, VEGF inhibitor targeted therapy e.g. sorafenib, bevacizumab with IFN
  • 5 year survival >70%
39
Q

Transitional (Urothelial) Cell Carcinoma: prevalence, presentation (3), risk factors (1), pathology, staging/grading, outcome

A

10% CA kidney

Present with haematuria, obstruction and infection
Risk factors: smoking

Pathology:

  • multiple papillary tumours at renal pelvis
  • c.f. urinary tract pathologies

Prognosis:

  • staging: invasion of pelvi-calyceal wall
  • grading: degree of urothelial anaplasia
  • 5-year survival up to 90%
40
Q

Wilms Tumour

A

Most common renal tumour in children (5% of all child CA)

Present with abdominal mass, haematuria and fever

Most cases are sporadic (66%)
Genetic causes include WT1 inactivation - associated with various syndromes e.g. WAGR syndrome –> Wilms tumour, aniridia, GU anomaly, mental retardation; DDS (Denys-Drash syndrome); WT2 inactivation – BWS

Nephrogenic cysts (embryonic remnants are a precursor of Wilms)

Pathology:

  • Macroscopically: very large, pale grey and soft tumour (10% bilateral)
  • Microscopically: triphasic (blastemal, stromal, epithelial), immature tubules and glomeruli, fibrotic cells/ skeletal ms/ bone

Prognosis:

  • staging, size, anaplasia (large hyper chromatic nuclei, atypical mitosis)
  • 90% cure with treatment

Treatment:
- surgery, chemotherapy, radiation

41
Q

Tumour-like lesions of Urinary Tract (2)

A

Malakoplakia

  • rare form of chronic granulomatous cystitis (also xanthogranulomatous)
  • due to recurrent cystitis (most commonly found at bladder)
  • Macroscopically: “soft plaque”
  • Microscopically: Michaelis-Gutmann bodies (aggregated of defective foamy macrophages which have micro calcifications from intracellular deposits of Ca and Fe) – can be visualised by von Kossa stain on LM and has characteristic concentric targetoid appearance on EM

Metaplasia

  • replacement of urothelium by either squamous or glandular epithelium in the the background of insult
  • glandular metaplasia due to chronic cystitis leading to cystitis glandular cystica and then transform to metaplasia (increases risk of AdenoCA)
  • squamous metaplasia due to urinary calculi or schistosomiasis
  • reversible
42
Q

Benign tumours of urinary tract (1)

A

Papilloma

  • Urothelial papilloma –> exophytic (papillary)
  • Inverted papilloma –> endophytic (nodular) – COMPLETELY BENIGN (no increased risk of CA)
  • due to chronic inflammation
  • Macroscopically: single or multiple
  • Microscopically: benign cellular features e.g. less than 5 layers, no mitosis, uniform cytology including cell size and nuclear features; supported by vascularised slender stroma
43
Q

Urothelial Carcinoma (TCC): epidemiology, manifestation (3), pathogenesis (3), pathology and precursors (3), grading and staging, treatment (2)

A

Most common urinary tract CA (90%), more prevalent in male >50 years old

Presents with painless haematuria, dysuria and recurrent UTI

Caused by exposure to environmental carcinogens e.g. smoking, cyclophosphamide, industrial carcinogens such as benzidine, aryl amines
Also affected by genetics – mutation in HRAS and p53 genes are frequent
Schistosomiasis haematobium infection
(Field effect due to common malignant stem cell –> recurrence is inevitable)

Pathology:

  • single, often multi centric
  • non-invasive papillary tumour (precursor; pre-invasive; pTa) –> invasive papillary CA (>pT1)
  • flat carcinoma in situ (precursor; Cis) –> invasive flat or ulcerated CA (>pT1)

Grading: degree of cellular atypia

  • papilloma (2-5 layers, no atypia)
  • papillary urothelial neoplasm of low malignant potential (multiple layers, no atypia, rare basal mitosis)
  • low grade papillary urothelial CA (moderate pleomorphism, few mitosis, slight variation in shape and size) – often recur but infrequently invade
  • high grade papillary urothelial CA (obvious pleomorphism, loss of cell polarity, many mitosis) – associated with concurrent or subsequent recurrence of invasive urothelial CA after excision

(papillary can be low or high grade, flat is always high grade)

Staging:
- Ta = non-invasive papillary CA
- Tis = flat CA in situ
- T1 = invade lamina propria
- T2 = muscle involved -- important in guiding treatment plan (endoscopic resection/ TURBT vs. radical cystectomy)
- T3 = perivesical fat involved
- T4 = invade adjacent organs or fixed to pelvic side wall
N>1 or M1 = stage IV (advanced disease)

TCC is the only exception for tumour where it is still considered malignant when there is no stromal invasion

Treatment: transurethral resection (small localised), BCG immunotherapy (higher grade), radical cystectomy (>T2, refractory to BCG)
- periodic cystoscopy and urine cytology to monitor

44
Q

Other malignant tumours of urinary tract (3): cause, histology

A

Squamous Cell Carcinoma (5%)

  • extensive keratinisation
  • schistosomiasis/ urinary calculi –> squamous metaplasia (due to chronic inflammation)

Adenocarcinoma (3%)

  • identical histology to ADC of GI tract
  • urachal remnants
  • extensive glandular metaplasia from recurrent infection

Rhabdomyosarcoma

  • most common sarcoma in children
  • overall rare and aggressive tumour
  • differentiate towards primitive skeletal muscle
45
Q

Clinical Anatomy of the Prostate: zones (4), histology (2)

A

Peripheral zone - palpable during DRE, site of CA prostate
Transitional zone - glandular component of BPH
Periuretheral zone - stromal component of BPH
Central zone - free of BPH or CA

Histology:

  • glandular structures with INNER TALL COLUMNAR epithelium and OUTER FLATTENED epithelium of basal cells
  • copora amylacea: laminated proteinaceous secretory material forming hyaline masses in gland lumen
46
Q

Benign Prostatic Hyperplasia: epidemiology, pathogenesis (1), pathology, clinical manifestation (4), complications (1), diagnosis (1), treatment (3)

A

Most common cause of enlarged prostate in >50

Unknown aetiology leading to increased sensitivity of prostate tissue to DHT –> activation of FGF and TGF-beta leading to prostatic smooth muscle hypertrophy and glandular hyperplasia

Pathology:

  • nodular hyperplasia of glandular and stromal cells in transitional zone (median lobe)
  • Macroscopically: lobular GLANDULAR hyperplasia and FIRBOMUSCULAR hypertrophy
  • Microscopically: glandular structures with BASAL CELLS INTACT, hyperplasia of acini, hypertrophy of smooth muscle stroma (dark red), PAPILLARY PROJECTIONS

Manifests through obstruction symptoms of urinary tract e.g. frequency, dysuria, nocturia (+ haematuria)
Increase in PSA in 30-50%

Complications: obstructive uropathy (post renal azotaemia, cystitis, bladder distension and hydronephrosis)
NOT A RISK FACTOR FOR CA PROSTATE

Diagnosis: TRUS (transrectal ultrasound)

Treatment: alpha blockers (relax muscle) e.g. tamsulosin, 5-alpha reductase inhibitors e.g. finasteride, TURP (to reduce obstruction –> but may cause hypoNa, incontinence and retrograde ejactulation)

47
Q

CA Prostate: epidemiology, risk factors (3) and pathogenesis (3), precursor and pathology (4), clinical manifestation (2), complications (2), diagnosis (4), prognosis (3), treatment (3)

A

Most common cancer in adult male >65 (3rd most common HK?)

Risk factors: age, smoking, high fat diet
DHT dependent tumour

Genetics: TMPRSS2-ETS fusion gene leading to disrupted androgen receptor signalling (activation of gene expression despite therapy leads to castration-resistant CA); LOF of PTEN TSG leading to increase in PIK3/AKT signalling

Pathology:

  • moderately differentiated adenoCA
  • develops in the peripheral zone, seldom conspicuous
  • precursor = prostate intraepithelial neoplasia –> proliferation of atypical cells with basal cells still intact (same incidence, location and histology as CA)
  • glandular differentiation (90%)
  • microscopic: lack of basal cells, lack of branching and papillary infolding, clear/dark purple cells

20% clinically silent until advanced stage, similar symptoms to BPH

Complications: obstructive uropathy (seldom at early stage as it requires extension of tumour to the bladder baser peri-urethral zone); lower back or pelvic pain due to bony metastasis (osteoblastic)

Diagnosis: serum PSA (sensitive but not specific - c.f. causes of high PSA), DRE, TRUS + transrectal biopsy

Prognosis based on staging, grading and PSA
Staging:
- T1 = not detectable by DRE or imaging but found from biopsy
- T2 = detectable by DRE or imaging but confined to prostate
- T3 = grown outside the prostate and may have grown into the seminal vesicles (T3b)
- T4 = invade into adjacent tissues e.g. bladder, pelvic wall, rectum, urethral sphincter

Grading: Gleason system

  • 5 grades, score by adding up the 2 most prominent glandular patterns observed on biopsy
  • low grade (uniform small acini), intermediate (irregular larger glands to glandular complexes), high (lacks gland formation, just sheets)

Treatment:

  • early –> surgery, radiation
  • advanced –> hormonal castration e.g. LHRH agonist, chemo, radiation
  • “watchful waiting” –> CA can follow very indolent course and not have any clinical significance - overtreatment can lead to incontinence and erectile dysfunction
48
Q

Disorders of the Testis: congenital, vascular, inflammation

A

Congenital: cryptorchidism

  • failure of testicular descent from intra-abdominal position (unknown cause)
  • may descend spontaneously at 3 months
  • 90% unilateral
  • causes infertility (germ cell deficiency due to arrest in maturation, testicular atrophy)
  • increases risk of seminoma

Vascular: torsion

  • acute surgical emergency caused by trauma or cryptorchidism
  • acute testicular pain, haemorrhagic infarction, absent cremasteric reflex
  • spontaneous remission or orchidectomy if extensive infarction

Inflammation: epididymitis, orchitis

  • specific infections due to STD e.g. N gonorrhoeae, C. trachomatis or Systemic infections e.g. TB, mumps
  • non-specific infections secondary to UTI
49
Q

Testicular Tumours: presentation, classification, features of each class

A

Rare, present as painless mass in young males

Divided into germ cell tumours (95%) and sex-cord stromal cell tumours (5%)

Germ cell tumours: malignant

  • precursor: germ cell neoplasm in situ/ intratubular germ cell neoplasm
  • risk factors: cryptorchidism and gonadal dysgenesis e.g. Turner syndrome
  • further divided into seminoma and non-seminoma germ cell tumours

Sex-cord stromal cell tumours: benign

50
Q

Seminoma vs Non-seminoma: type, stage at presentation, spread, radio sensitivity, prognosis

A

Seminoma:

  • usually pure type
  • present at early stage
  • lymphatic spread
  • radiosensitive
  • 90% curable by surgery

Non-seminoma:

  • usually mixed type
  • present at late stage
  • haematogenous spread
  • radio resistant
  • variable prognosis after surgery and chemo, aggressive
51
Q

Seminoma: age at presentation, origin, pathology (3), tumour markers (2)

A

Most common germ cell tumour
Present in 40s

Originate from seminiferous tubule epithelium
Pathology:
- white, yellow “potato” +/- haemorrhage or necrosis
- large clear cells in sheets or tubules with lymphocytic infiltration
- granuloma

Tumour marker: hCG in 10% {placental alkaline phosphatase - PLAP (increases in smoking), CD117, Oct-4, C-kit}

52
Q

Non-seminoma GCT: age at presentation, origin, pathology, tumour markers

A

Embryonal CA:

  • present in 30s
  • 50% mixed
  • bulk tumour with haemorrhage and necrosis (variegated)
  • basophilic immature cells form sheets or primitive glands
  • tumour marker: negative if pure {PLAP, Oct-4, CD30}

Yolk sac tumour:

  • present <4
  • from endoderm
  • large variegated tumour
  • columns of epithelial cells forming papillary structures
  • Schiller-Duval bodies - resemble primitive glomeruli
  • tumour marker: AFP (tissue hyaline droplets and in serum) in 90%
  • better prognosis than other NSGCT

Choriocarcinoma:

  • present in 20s
  • originate from trophoblast
  • highly malignant
  • cytotrophoblast and syncytial trophoblastic proliferation
  • tumour marker: beta-HCG in 100%

Teratoma:

  • present at any age
  • 50% mixed
  • from trigeminal layers
  • differentiate along different somatic cell lines
  • mostly immature – malignant (mature are benign)
  • negative markers in pure type
53
Q

Sex-cord Stromal Tumours: functionality, colour, pathology

A

Rare, usually benign

Leydig cell tumour:

  • production of sex hormones –> gynaecomastia, sexual precocity
  • tan brown
  • eosinophilic cells, Reinke crystals

Sertoli cell tumour:

  • may produce hormone
  • white-yellow
  • form tubular structures
54
Q

Staging of testicular tumours

A

TNMS - S stands for serum tumour markers

3 stages;
I = testis, spermatic cord, epididymis
II = LN below diaphragm
III = LN above diaphragm

ACP (27 decks)

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