The Urinary Tract: Tumors of The Urinary Tract Flashcards
1
Q
What is autosomal dominant polycystic kidney disease? (ADPKD)
A
A group of congenital diseases that are characterized by numerous cysts within the renal parenchyma
2
Q
What is the epidemiology of ADPKD?
A
1 in 500 to 1000 individuals
3
Q
What is the pathogenesis of ADPKD?
A
Mutations in the polycystic kidney disease 1 gene (PKD1/polycystin-1) on the short arm of chromosome 16 (85%)
OR
Mutations in PKD2 (15%)
–> ALtered mechanosensation by tubular cilia and altered calcium flux –> Altered tubular epithelial growth and differentiation –> Abnormal extracellular matrix, cell proliferation, and fluid secretion –> CYST, glomerular vascular damage and interstitial inflammation/fibrosis
4
Q
What is the morphology of ADPKD? (3)
A
- Bilaterally enlarged kidneys (each weighs up to 4.5kg)
- The external contours of the kidneys are distorted by numerous cysts (up to 5cm in diameter)
- The cysts are filled with fluid, which may be clear, turbid or hemorrhagic
5
Q
What is ARPKD?
A
Autosomal recessive polycystic kidney disease –> affects children
Rare
6
Q
What is ARPKD characterized by?
A
Cystic transformation of collecting ducts
7
Q
What is the pathogenesis of ARPKD?
A
Mutation in the PKHD1 gene (coding for a putative membrane receptor protein called fibrocystin)
8
Q
What is the morphology of ARPKD kidneys?
A
Numerous small cysts in the cortex and he medulla
Songe like appearance
9
Q
What is ARPKD associated with?
A
Associated with congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts
The mutation in PKHD1
10
Q
Where is renal cell carcinoma derived from?
A
Renal tubular epithelium (predominantly in the cortex)
11
Q
What is the epidemiology of Renal cell carcinoma?
A
Most common malignant tumor of the kidneys
Accounts for 2 to 3% of all cancers in adults
12
Q
What is the age population target of RCC?
A
60 to 70s
13
Q
What is the male to female ration of RCC?
A
2:1
14
Q
What are the risk factors of RCC? (5)
A
- Smoking
- Obesity and hypertension
- Occupational exposure
- Acquired polycystic disease as a complication of chronic dialysis
- Genetic factors
15
Q
What kind of occupational exposure leads to RCC?
A
Exposure to candium
16
Q
What are the classifications of renal cell carcinomas? (3)
A
3 main types:
1. Clear cell carcinoma
2. Papillary renal cell carcinoma
3. Chromophobe renal carcinoma
17
Q
What is the most common subtype of renal cell carcinomas?
A
Clear cell carcinoma –> 65% of RCC
18
Q
What is the pathogenesis of Clear cell carcinomas?
A
Sporadic or familial forms
19
Q
What is the sporadic pathogenesis of Clear cell carcinomas?
A
Adult males (average age is 60) as a single tumor in the upper pole of the kideny
20
Q
What is the major risk factor of sporadic tumors in clear cell carcinoma?
A
Smoking
21
Q
Who do familial clear cell carcinomas of RCC affect
A
Arise in younger adults and are often bilateral
22
Q
What disease is the familial clear cell carcinoma associated with?
A
Von Hippel-Lindau (VHL) dsease
23
Q
What is the pathogenesis of familial clear cell carcinoma?
A
- Individuals with VHL disease
- Inherit a germline mutation of the VHL gene on chromosomal band 3p25 and lose the second allele by somatic mutation
- Increased IGF-1 or degradation of HIFs
- Promotes growth or stimulation of the expression of VEGF and PDGF
- Proliferation of RCC
24
Q
What % of RCC is Papillary renal cell carcinomas?
A
Accounts for 10 to 15% of RCC
25
What are Papillary renal cell carcinomas like?
1. Shows papillary pattern
2. Multifocal and bilateral and appear as early-stage tumors
3. Sporadic or familial forms
26
What is the pathogenesis of papillary renal cell cracinomas?
1. Duplication of chromosome 7 or Activating mutations of MET in germline
2. Overexpression of MET gene
3. Abnormal growth in the proximal tubular epithelial cell precursors of the papillary carcinomas
27
What % of RCC is Chromophobe renal carcinomas?
5%
28
Where does chromophobe renal carcinoma arise from?
Intercalated cells of collecting ducts
29
What is the pathogenesis of Chromophobe renal carcinomas?
Multiple losses of entire chromosomes: 1, 2, 6, 10, 13, 17 & 21)
30
What is the gross morphology of clear cell carcinomas? (2)
1. Solitary and large (3 to 15cm)
2. Arise anywhere in the cortex
31
What is the cut surface of clear cell carcinomas? (2)
1. Yellow to orange to Gary-white, with prominent areas of cystic softening or hemorrhage
2. The margins of the tumor are well defined
32
What is the range of clear cell carcinomas? Examples? (4)
Range from low grade to high grade:
1. Tumor cells may extend to calyces, pelvis or ureter,
2. May invade renal vein and grow within the vessels
3. Extending as far as the inferior vena cava and into the right side of the heart
4. Direct invasion into the perinephric fat and adrenal gland
33
What is the microscopy of clear cell carcinomas? (tumor cells)
1. Large and polygonal
2. Show distinct cell membranes
34
What is the microscopy of clear cell carcinomas? (the cytoplasm)
Clear in most cells (presence of abundant glycogen and neutral lipids)
35
What is the microscopy of clear cell carcinomas? (the nuclei)
Usually: small, round to slightly oval and regular
Sometimes: enlarged, hyperchromatic and pleomorphic nuclei
36
What is the microscopy of clear cell carcinomas? (the stroma)
Highly vascularized
37
What is the gross morphology of papillary renal carcinomas?
1. Bilateral and multiple
2. Show necrosis, hemorrhage, and cystic degeneration (less vibrantly orange-yellow because of their lipid content)
38
What is the microscopy of papillary renal cell carcinomas? (3)
1. Various degrees of papilla formation with fibrovascular cores (foamy histiocytes)
2. The cells may have pink cytoplasm (common) or clear cytoplasm (less common)
3. Neutrophil infiltration in the fibrovascular cores
39
What is the gross morphology of chromophobe renal carcinoma?
1. Well-circumscribed, not encapsulated & tan to light brown
2. Occasionally central scar (15%)
40
What is the microscopy of chromophobe renal carcinomas? (the cells)
The cells are clear, flocculent cytoplasm with very prominent and distinct membranes
41
What is the microscopy of chromophobe renal carcinomas? (the nuclei)
The nuclei are surrounded by halos of clear cytoplasm (irregular giving rise to a raisonoid)
42
What is the staging technique used for RCC?
Robson's staging
43
What are the clinical presentations of RCC? (7)
1. Macroscopic hematuria
2. Flank pain
3. Palpable mass
4. Fever
5. Polycythemia
6. Weight loss
7. Paraneoplastic syndromes
44
What are examples of paraneoplastic syndromes that could present in the RCC? (3)
Hypercalcemia, hypertension, Cushing syndrome
45
When are the primary RCC tumors found in most people?
In many patients, the primary tumors remain silent and are only discovered after their metastasis and have produced symptoms
46
What are RCCs characterized by regarding clinical presentation?
The triad:
1. Painless hematuria,
2. Palpable abdominal mass,
3. Dull flank pain
47
What is Wilms tumor?
The most common renal neoplasm of childhood (between 2 and 5 years of age)
48
What is WAGR syndrome?
A syndrome that presents with Wilms tumor, aniridia, genital abnormalities, and mental retardation
48
Patients with which 3 syndromes are at a greater risk for Wilms tumor?
WAGR syndrome
Denys-Drash syndrome
Beckwith-Wiedemann
49
What is Denys-Drash syndrome?
Gonadal dysgenesis and renal abnormalities, both of which are associated with abnormalities of Wilm's tumor 1 gene, located on 11p3
50
What is the difference between WAGR and DDS when it comes to genetic abnormalities?
Patients with WAGR syndrome demonstrate loss of genetic material of WT1, whilst patients with DDS harbor a dominant negative inactivating mutation in a critical region of the gene
51
What is Beckwith-Wiedemann syndrome?
Enlargement of individual body organs, kidney, liver, or tongue --> Imprinting abnormalities at the WT2 locus (11p15.5), principally involving the IGF-2 gene
52
What is the gross morphology of Wilms tumor?
Large, solitary, well-circumscribed mass
53
What is the cut section morphology of Wilms tumor?
Soft, homogenous, and tan-to-grey, with occasional foci of hemorrhage, cystic degeneration, and necrosis
54
What is the microscopy of Wilms tumor? (3)
Triphasic combination of:
1. Blastemal, immature epithelial and stromal elements
2. Epithelila "differentiation" usually takes the form of abortive tubules or glomeruli
3. Stromal cells "undifferentiation" are usually smooth muscle or fibroblasts
55
What is the age population of bladder cancer?
50 to 80 years old
56
What is the male to female ratio for bladder cancer?
Male: female
3:1
57
What is the prognosis of bladder cancer like?
Variable prognosis --> depends on the grade and stage of the tumor
58
What are the 3 main types of bladder cancer?
Urothelial (transitional cell) carcinomas
Squamous cell carcinoma
Adenocarcinoma
59
What is the most common bladder cancer?
Urothelial carcinomas (90% of bladder cancer)
60
What are the risk factors of urothelial carcinomas?
1. Cigarette smoking
2. Various occupational carcinogens
3. Drugs and radiation therapy
61
What kind of occupational carcinogens can increase the risk of urothelial carcinomas?
Naphtylamine
Azo dyes
62
What kind of drugs increase the risk of urothelial carcinomas?
Cyclophosphamide
63
What are the two distinct ways from which urothelial carcinoma can arise?
1. Papillary carcinomas grow in slender, finger-like projections from the inner surface of the bladder towards the hollow center without growing into the deeper bladder layer (non-invasive papillary cancers and tend to have a good outcome)
2. Flat carcinomas do not grow toward the hollow part of the bladder at all. If a flat tumor is only in the inner layer of the bladder cells, it is known as a non-invasive flat carcinoma or flat carcinoma in situ
64
What is the pathogenesis of urothelial carcinomas?
1. Normal urothelium
2. Depetions of tumor suppressor genes on 9p and 9q --> mutations in telomerase, FGFR3
3. Formation of superficial papillary tumor
4. TP53 mutations
5. Progression to invasive disease
OR
1. Normal urothelium
2. Loss of p53 (mutation of TP53)
3. CIS or dysplasia with loss of genes on chromosome 9
4. High-grade muscle-invasive urothelium carcinoma
5. Metastasis
65
What is the grading system of Urothelial carcinomas?
Grade 1: papilloma
Grade 2: papillary urothelial neoplasm with low malignant potential
Grade 3: Low-grade papillary urothelial carcinoma
Grade 4: High-grade papillary urothelial carcinoma
66
What are squamous cell carcinomas?
3 to 7% of bladder carcinomas
More common in countries where urinary schistosomiasis is endemic like Africa, the Middle East and the island of Corsica (France)
67
How does squamous cell carcinoma arise?
Arises in a background of squamous metaplasia (normal bladder surface is not lined by squamous epithelium)
Shows extensive keratinization (associated with chronic bladder irritation and infection)
68
What are the risk factors of squamous cell carcinomas?
1. Chronic cystitis
2. Schistosoma hematobium infection
3. Longstanding nephrolithiasis
69
What is the prognosis of squamous cell carcinomas?
A poor prognosis with a 5 year survival rate of 7 to 50%
70
What is the pathogenesis of schistosoma-associated bladder cancer? (4)
1. Schistosoma ova deposited in the bladder
2. Provoke intense inflammatory reaction, associated wth the production of oxygen-derived free radicals
3. May induce genetic mutations or promote the production of carcinogenic compounds
4. Leading to malignant transformation
71
What is adenocarcinoma of the bladder?
Rare case, accounts for only 1% of bladder cracinomas
Suggested to arise from intestinal metaplasia of the urothelium
72
What are the two general types of adenocarcinomas in the bladder?
1. Arising from the urachus (urachal adenocarcinoma --> 1/3 of cases)
2. Arising from the bladder itself (2/3 of cases)
73
What is the histology of adenocarcinomas of the bladder?
Purely gland forming
Invasive form characterized by mucinous, signet ring cell, hepatoid, or mixed
74
What are the risk factors of adenocarcinomas of the bladder?
1. Non-functioning bladder
2. Chronic irritation
3. Obstruction
75
What are the clinical presentation of bladder carcinomas?
1. Painless hematuria
2. Dysuria
3. Lower abdominal pain
76
How do you diagnose bladder carcinomas?
Abdominal CT scan
Bladder biopsy --> usually performed with cystoscopy
Cystoscopy
IVP
Urinalysis
Urine cytology
77
What is cystoscopy?
Examining the inside of the bladder with a camera
78
What is IVP?
X-ray pictures of the ureter and the bladder to ceck for cancer
79
What would you look at with urinalysis?
Physical color, microscopic and chemical appearance
80
What is urine cytology? How does this help diagnose balder carcinoma?
Examination of the cells in the urine
CIS tumor cells lack cohesiveness --> leads to the shedding of malignant cells in urine
81
