Congenital Disease

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Congenital Disease Tumours of Kidney and Bladder

• Dr. Barbara Dunne

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Congenital Anomalies of Kidney

• Agenesis
• Hypoplasia
• Ectopic
• Horseshoe kidney

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Cystic Diseases of Kidney

• Hereditary /Developmental
• Acquired
• Miscellaneous

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Cystic Diseases of Kidney- Hereditary

• Adult Polycystic Kidney Disease
• Autosomal Dominant- APKD1 on chrom 16
• Usually progress to chronic renal failure
• Can get cysts in liver (40) and in circle of
  willis (up to 30)

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• Cut section of adult polycystic kidney disease
• Cysts of various sizes
• Some containing fluid and blood clot

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Polycystic liver
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Cystic Diseases of Kidney- Hereditary

• Infantile Polycystic Kidney Disease
• Autosomal recessive
• Renal failure in infancy
• Congenital Hepatic Fibrosis

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Cystic Disease of Kidney- Developmental

• Cystic Renal Dysplasia
• Sporadic
• Associated with ureteropelvic abnormality
• Can be unilateral or bilateral

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Cystic Diseases of Kidney

• Medullary Cystic Disease
• Medullary Sponge Kidney- adults
• Familial nephronophthisis- medullary cystic
  disease (FN-MCD complex)- childhood

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Cystic diseases of Kidney- Acquired

• Dialysis asssociated is the commonest
• Multiple cysts but kidneys normal size

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Cystic diseases of Kidney-misc

• Simple Cyst
• Common finding at autopsy
• Variable size
• Lined by cuboidal epithelium

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Renal neoplasms- Benign

• Adenoma (papillary adenoma)
• lt5mm - bland papillary structures
• common- seen in up to 1/3 autopsies

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Renal neoplasms- Benign

• Oncocytoma
• 3-5 of renal tumours
• Tan/ mahogany brown with central scar

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Renal neoplasms- Benign

• Oncocytoma
• Nests of oncocytic (pink) cells
• Important to differentiate from carcinoma- lack
  of atypia

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Oncocytoma
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Renal neoplasms- Benign

• Metanephric adenoma
• Closely packed tubules/papillae
• Can grow to a large size

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Metanephric adenoma
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Renal Cell CarcinomaEpidemiology

• Overall 12th commonest cancer in males and 17th
  commonest cancer in females
• 2-3 times more common in men
• Peak age in 6th and seventh decade
• Commoner in developed countries

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Renal Cell CarcinomaAetiology

• Tobacco smoking
• Arsenic compounds, asbestos , cadmium and
  pesticides
• ? Risk with ? BMI
• Long term haemodialysis

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Renal Cell Carcinoma Symptoms

• Haematuria, flank pain, mass
• Weight loss, anorexia, fever
• Paraneoplastic endocrine syndromes
• ? Epo, ? ca , ? renin, prolactin
• Hepatic Dysfunction
• Amyloidosis

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Renal Cell Carcinoma

• Clear cell (conventional ) 75
• Papillary7-15
• Chromophobe3-5
• Collecting Duct Carcinoma-lt1
• RCC unclassified eg sarcomatoid
• Others eg urothelial

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Clear Cell CarcinomaGenetics

• 95 sporadic most have somatic 3p deletions
• 5 familial
• Von- Hippel Lindau disease (VHL)
• RCC, haemangioblastomas, phaeochromocytoma
• Germline 3p25-26 deletions
• Loss of pVHL protein

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Function of pVHL

• Involved in cell cycle regulation and
  angiogenesis
• HIF1a stimulates VEGF, PDGFb, TGFa
• pVHL degrades HIF1a
• When pVHL absent- HIF1 a accumulates-tumorigenesi
  s is facilitated
• VEGF is potential target for treatment in RCC

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Classic renal cell carcinoma
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Classic renal cell carcinoma
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Renal Cell Carcinoma

• Clear cell (classic) 75
• Papillary7-15
• Chromophobe3-5
• Collecting Duct Carcinoma-lt1
• RCC unclassified eg sarcomatoid
• Others eg urothelial

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Papillary Renal Cell Carcinoma-Genetics

• Sporadic
• vast majority
• Trisomy 7, 17, loss of chromosome Y
• Hereditary (HPRC)
• Multiple bilateral tumours
• Mutations of MET oncogene 7q31

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Papillary renal cell carcinoma
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Renal Cell Carcinoma

• Clear cell (conventional ) 75
• Papillary7-15
• Chromophobe3-5
• Collecting Duct Carcinoma-lt1
• RCC unclassified eg sarcomatoid
• Others eg urothelial

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Chromophobe renal cell carcinoma
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Collecting duct carcinoma
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Renal Cell Carcinoma

• Clear cell (conventional ) 75
• Papillary7-15
• Chromophobe3-5
• Collecting Duct Carcinoma-lt1
• RCC unclassified eg sarcomatoid
• Others eg urothelial

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Sarcomatoid renal cell carcinoma
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Renal Cell Carcinoma- Spread of Disease

• Haematogenous spread via renal vein/IVC
• ? Lungs
• ? Bone
• ? Liver
• Direct spread through capsule into adjacent
  organs

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Urothelial carcinoma of renal pelvis
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Staging of Renal Carcinoma

• pT1- lt 7cm, limited to kidney
• pT2-gt7cm, limited to kidney
• pT3-adrenal/perinephric/major vein invasion
• pT4- Beyond Gerotas fascia

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Nephroblastoma (Wilms Tumour)

• 2-5 year olds
• 90 sporadic
• 10 associated with syndromes
• WAGR-WT1 mutations, 11p13
• Beckwith-Wiedemann-WT2 mut, 11p15

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Wilms tumour
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Non-epithelial renal neoplasm

• Angiomyolipoma
• Benign
• Sporadic (80)
• or
• Associated with tuberous sclerosis(20)
• autosomal dominant, caused by LOH at TSC1(
  9q34) or TSC2 (16p13)

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Congenital Anomalies of Bladder

• Diverticulum (can also be acquired)
• Exstrophy- failure of closure of anterior wall of
  bladder
• Anormality of vesicoureteral junction
• Vesical fistulas (to vagina, rectum, uterus)
• Persistant urachas

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Bladder Carcinoma- Epidemiology

• 2nd commonest cancer in the UK
• Malefemale ratio 31
• Predominantly 5th, 6th and 7th decade

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Aetiology of bladder carcinoma

• Occupational- aniline dyes, chlorinated HC
• Cigarette smoking
• Drugs eg phenacetin, cyclophosphamide
• Chronic irritation eg Shistosoma haematobium
  squamous ca
• Most are non- familial

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Types of Bladder Carcinoma

• Urothelial/transitional cell carcinoma-90
• Squamous Cell -5
• Adenocarcinoma- 2
• Other-3
• small cell carcinoma
• spindle cell carcinoma
• lymphoepithelioma-like carcinoma
• nested variant of TCC
• micropapillary carcinoma

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Types of Urothelial Carcinoma

• Non-invasive-papillary (pTa)
• ca in-situ (pTis)
• Invasive TCC
• pT1- invasion of submucosa
• pT2- invasion of muscle
• pT3- beyond muscle
• pT4- invades other organs

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Natural History of Bladder Carcinoma

• Superficial TCC
• 95 5 year survival
• frequent recurrences
• 10-20 risk of disease progression
• Carcinoma in-situ
• gt50 risk of disease progression
• Muscle invasive TCC
• 35 5 year survival

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Mesenchymal Lesions in Bladder

• Leiomyoma
• Leiomyosarcoma
• Post-operative spindle cell nodule
• Inflammatory pseudotumour

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Thank You