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CPR100: Urinary tumours


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Kidney tumours - benign
Papillary adenoma, Angiomyolipoma, Oncocytoma
Papillary adenoma
Small, discrete tumour, Usually less than 5 mm in diameter
Papillary adenoma symptoms
Usually asymptomatic, Incidental finding in kidneys at autopsy (7-22%), Must be distinguished from renal cell carcinoma, otherwise it is of little clinical significance
Angiomyolipoma
Uncommon benign neoplasm, angio(blood vessel), Myo(smooth muscle), Lipo(Fat)
Angiomyolipoma origin
Originating from perivascular epithelioid cells
Angiomyolipoma Ix
Most cases diagnosed incidentally by imaging by CT demonstrating fat
Angiomyolipoma other features
Renal mass, Haematuria
Angiomyolipoma association
Associated with hereditary disease (Tuberous sclerosis), 25-50% of patients with this disease develop angiomyolipoma, Usually bilateral and multiple
Tuberous sclerosis
Autosomal dominant inheritance, Angiomyolipoma in kidney, liver, Astrocytic tumor in brain, Rhabdomyoma in heart
Angiomyolipoma Large tumours (more than 4 cm)
present with haemorrhage and can potentially be fatal, Tumour size often increases in pregnancy and increase risk of haemorrhage
Angiomyolipoma Histology
No capsule, Blood vessels ensheathed by smooth muscle cells, Clusters of adipose cells
Oncocytoma
Approximately 5-15% of renal neoplasms, Usually solitary
Oncocytoma origin
Thought to arise from intercalated cells of collecting ducts
Oncocytoma histology
Large eosinophilic cells with small round nuclei and large nucleoli
Kidney tumours – malignant
Renal cell carcinoma (clear cell type), Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Collecting duct carcinoma, Urothelial carcinoma, Nephroblastoma (Wilms tumour) childhood
Renal cell carcinoma
One of the top 10 cancers amongst male for incidence, clear cell type most common
Renal cell carcinoma types
Clear cell (70-80%), Papillary (10-15%), Chromophobe (5%), Collecting duct carcinoma (less than 1%), Urothelial carcinoma of renal pelvis (5- 10%)
Renal cell carcinoma RF
Smoking, cadmium, asbestos, Hereditary conditions
Renal cell carcinoma Hereditary conditions
Von Hippel Lindau syndrome, Hereditary papillary renal cancer syndrome, Hereditary leiomyomatosis and renal cell carcinoma syndrome, Birt-Hogg Dube syndrome
Renal cell carcinoma features
Classical triad: hematuria, loin pain, mass (10% of cases), Paraneoplastic syndrome, can have metastasis before symptoms appear (25% newly diagnosed with metastasis)
Paraneoplastic syndrome
Fever of unknown origin, Polycythemia
Spread of Renal cell carcinoma
Locally to adjacent organs, Blood borne via renal vein (Lungs and Bones are common sites) Lymphatic to regional lymph nodes
Renal cell carcinoma Prognosis
Average 5 year survival: Around 70%, Around 95% if no distant metastasis
Renal cell carcinoma, clear cell type
70-80% of all Renal cell carcinoma, About 5% of cases show sarcomatoid change
Renal cell carcinoma, clear cell type etiology
95% are sporadic (Associated with 3p deletions (VHL gene)), Rest of the cases associated with Von Hippel Lindau syndrome
Von Hippel Lindau syndrome
Autosomal dominant, 1 in 30,000 to 40,000, Defective VHL on 3p
Von Hippel Lindau syndrome Clinical features
Cerebellar hemangioblastoma, Cysts in kidney, liver, pancreas, Renal cell carcinoma
Renal cell carcinoma, clear cell type histology
Mostly clear cells, some have eosinophilic or granular cytoplasm, Delicate branching capillary network surrounding tumour cells
Papillary renal cell carcinoma
10 15% of all renal cell carcinoma
Papillary renal cell carcinoma origin
Thought to be arising from DCT
Papillary renal cell carcinoma etiology
Most cases are sporadic, Cytogenetic changes (Trisomy 7, 17, loss of Y), Can be associated with hereditary papillary renal cancer syndrome
hereditary papillary renal cancer syndrome
Autosomal dominant, Multiple bilateral tumours, Germline mutation of MET proto oncogene
Papillary renal cell carcinoma histology
Cuboidal or low columnar cells arranged in papillary formation, Foam cells common in papillary cores, Highly vascular stroma
Renal Cell Carcinoma
Around 5% of all renal cell carcinoma
Renal Cell Carcinoma origin
Thought to be arising from intercalated cells of collecting ducts (Same as benign oncocytoma)
Chromophobe Renal Cell Carcinoma Cytogenetics
Monosomies of different chromosomes
Chromophobe Renal Cell Carcinoma prognosis
Better prognosis than renal cell carcinoma, clear cell type and papillary renal cell carcinoma
Chromophobe Renal Cell Carcinoma Histology
Cells with prominent cell membranes and pale eosinophilic (pinkish) cytoplasm, Halo around nucleus
Collecting duct carcinoma
Less than 1% of carcinoma in kidney
Collecting duct carcinoma origin
Arise from collecting duct cells in medulla (Typical in medulla location)
Collecting duct carcinoma prognosis
Aggressive carcinoma with unfavourable outcome (Early metastasis, Around 50% patients die within 2 years)
Urothelial (Transitional cell) carcinoma of the renal pelvis
Around 5-10% of carcinoma in kidney
Urothelial (Transitional cell) carcinoma of the renal pelvis origin
Originate from urothelium (transitional cell) of renal pelvis, Range from benign papilloma to invasive urothelial (transitional cell) carcinoma --> Similar histology to counter parts in the urinary bladder
Urothelial (Transitional cell) carcinoma of the renal pelvis presentation
Usually small upon presentation (Haematuria, Block urinary outflow --> flank pain and hydronephrosis)
Urothelial (Transitional cell) carcinoma of the renal pelvis locations
Can be multiple involving renal pelvis, ureters and urinary bladder (All lined by urothelium (transitional cell), Infiltration of wall of pelvis and calyces is common
Nephroblastoma (Wilms tumour)
Most common primary renal tumour of CHILDHOOD, 20% of malignant childhood tumours
Nephroblastoma (Wilms tumour) incidence
Highest incidence between 2 and 5 years old, 95% of tumour before age of 10
Nephroblastoma (Wilms tumour) involvement
5-10% have bilateral kidney tumours -> Synchronous (simultaneously)/ Metachronous (one after the other)
Nephroblastoma (Wilms tumour) genetics
Deletions or mutations of WT 1 or WT 2 genes (WT: Wilms Tumour),
Nephroblastoma (Wilms tumour) Clinical presentation
Abdominal mass, Haematuria, Pain
Nephroblastoma (Wilms tumour) Mode of spread
Local to adjacent organs, usually late, Blood borne to lungs and liver, Lymphatic to regional lymph nodes
Nephroblastoma (Wilms tumour) Rx
Surgical resection +/ adjuvant chemotherapy and radiotherapy
Nephroblastoma (Wilms tumour) histology
Triphasic combination (3 components): Undifferentiated round cells (Blastemal) + Undifferentiated spindle cells (Stromal) + Columnar epithelial cells (Epithelial)
Tumors of the lower urinary tract
Urinary Bladder tumors (most common) > Ureter and urethra (less common) , vast majority are urothelial (transitional cell) tumors
UB Histology
Urothelium (umbrella + transitional) -> Lamina propria -> Muscularis propria
UB tumors
The vast majority (90%) are urothelial (transitional cell) tumors, Other tumours: Malignant Squamous cell carcinoma/ Malignant Adenocarcinoma
UB tumors epidemiology
Middle aged and elderly, Men to female (3:1)
UB tumors Clinical presentation:
Painless gross hematuria
Urothelial carcinoma occupational RF
aniline dyes, rubber, benzidine, 2 naphthalamine
Urothelial carcinoma other RF
Smoking, Analgesic nephropathy, Food additives, Herbal: Aristolochic acid, Stones
Benign Urinary bladder tumours
Urothelial papilloma, Inverted papilloma
Malignant Urinary bladder tumours
Papillary carcinoma Vs. Flat carcinoma, Non-invasive Vs. Invasive
Papilloma
Represent 1% of all bladder tumour, Typically single and small
Papilloma histology
Finger like papillae with central fibrovascular core, Lined by normal urothelium (transitional cells)
Papillary urothelial tumours (Non-invasive) Types
1. Papillary urothelial neoplasm of low malignant potential 2. Papillary urothelial carcinoma, low grade 3. Papillary urothelial carcinoma, high grade
Papillary urothelial tumours (Non-invasive) characteristics
Usually larger than papilloma, Thicker layer of urothelium (abnormal)
Urothelial Carcinoma Grading
High grade vs Low grade: Increased cellularity, Nuclear crowding, Disturbance of cellular polarity, Absence of differentiation from base to surface layers, Nuclear pleomorphism, High mitotic rate
Papillary urothelial carcinoma spread
Capable of spreading within the urinary system by implantation
Papillary urothelial tumours (Non-invasive)
Less than 10% of papillary urothelial carcinoma, low grade are invasive
Papillary urothelial tumours (Non-invasive) low grade
Less than 10% invasive
Papillary urothelial tumours (Non-invasive) high grade
Around 80% invasive
Flat noninvasive carcinoma (CIS: Carcinoma in situ)
Also known as urothelial carcinoma in situ, By default high grade
Flat noninvasive carcinoma characteristics
Cytological malignant cells within flat urothelium (No papillary frond), Commonly multifocal
Flat noninvasive carcinoma prognosis
50-75% progress to invasive cancer if untreated
Flat noninvasive carcinoma histology
Large dark irregular overlapping nuclei
Non-invasive prognosis
Non-invasive carcinoma do not metastasize by blood or by lymphatics and has a good prognosis -> Non invasive low grade papillary urothelial carcinoma has more than 95% 10 year survival rate
Invasive prognosis
Invasive carcinoma DO metastasize by blood and lymphatics to other organs and has a poor prognosis -> Invasive urothelial carcinoma, especially those invading into muscularis propria has only around 70% survival rate even after radical cystectomy (surgical removal of UB)
Invasive urothelial carcinoma staging
Determine depth of invasion: Lamina propria invasion (T1), Muscularis propria (detrusor muscle) invasion (T2, T3)
Invasive urothelial carcinoma grading
Low or High grade, Both papillary and flat type carcinoma can be invasive
Non invasive papillary neoplasm/ carcinoma, low grade Rx
Transurethral resection
lamina propria invasion (T1) Rx
Transurethral resection, Intravesicle instillation of BCG (Attenuated strain of tuberculous bacillus)
Invasive urothelial carcinoma with muscularis propria (T2) invasion Rx
Radical cystectomy (Surgical removal of UB)
Urine Cytology
Used for screening of urinary tumor and for follow up of patients after tumor resection by transurethral resection (Diagnostic sensitivity is low in cases of low grade urothelial carcinoma)
Bladder Cancer Kit
A test kit has been designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer.