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Repro/GU > 233/234/235 renal and urothelial pathology, cancer > Flashcards

233/234/235 renal and urothelial pathology, cancer Flashcards

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1
Q

What is the most to least common morphology of urothelial cancers?

A

transitional&raquo_space; squamous > adenocarcinoma

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2
Q

What is the most to least common location of urothelial cancers?

A

bladder&raquo_space; upper tract > urethra

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3
Q

What are the environmental risk factors for urothelial cancer?

A

smoking, analgesic abuse, exposure to aryl amines

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4
Q

What are the medical risk factors for urothelial cancers?

A 
UTIs/indwelling catheters/stones
Balkan nephropathy (multifocal pelvis/ureter tumor)
Prolonged cyclophosphamide/ifosfamide use
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5
Q

What are the genetic risk factors for urothelial cancer?

A

lynch II variant of HNPCC (upper tract tumors)

Loss of segments of chromosome 9

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6
Q

What molecular and phenotypic characteristics distinguish between high and low grade urothelial carcinoma?

A

low-grade: proliferative, non-invasive, loss of 9q

high-grade: invasive, defects in pRB, p53, etc.

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7
Q

What are the major signs and symptoms of urothelial carcinoma?

A

hematuria, irritative voiding, flank pain, palpable mass, mucosuria (specific to adenocarcinoma)

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8
Q

What is the gold standard for work up of suspected bladder cancer?

A

cystoscopy

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9
Q

Where has T1 grade urothelial cancer invaded?

A

into the lamina propria
T2+ invades into muscular layers
usually need to re-TURBT to ensure that it is actually T1

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10
Q

What is the treatment for low stage (CIS, Ta, T1) urothelial carcinomas?

A

trans-urethral resection (TURBT), surveillance, intravesical BCG (stimualtes immune response to fight tumor)
intravesical chemotherapy
Lifestyle modifications

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11
Q

What is the treatment for higher stage (T2-4) urothelial carcinomas?

A

radical cystectomy (usually total, can be partial)
platinum-based chemotherapy (cisplatin-based), chemoradiation, RE-TURBT
+ ileal conduit or neobladder after cystectomy

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12
Q

Where do patients with bladder cancer need surveillance in addition to the bladder?

A

upper tract surveillance (more frequent for higher grade)

Patients with upper tract UCC also require surveillance for bladder cancer

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13
Q

What is the treatment for upper tract cancers?

A

radical nephroureterectomy, segmental ureteral resection, distal ureterectomy and reimplantation

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14
Q

Where do posterior urethral tumors drain?

A

pelvic lymph nodes

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15
Q

Where do anterior urethral tumors drain?

A

inguinal lymph nodes

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16
Q

What type of cancer is associated with posterior urethral involvement?

A

transitional cancer

harder to remove, worse prognosis

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17
Q

What type of cancer is associated with anterior urethral involvement?

A

squamous cancer

usually discovered earlier, better prognosis

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18
Q

What structures constitute the urothelial system?

A

kidney, ureter, bladder, proximal urethra

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19
Q

What is the “field cancerization” concept and how does it apply to the recurrence pattern seen in transitional cell carcinoma of the urothelial system?

A

changes to one area of the urothelium can affect the entire urothelium

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20
Q

What are the major risk factors for urothelial cancers?

A

smoking, chronic inflammation

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21
Q

What are the two most common presenting symptoms in patients with urothelial carcinoma?

A

hematuria, de novo urgency

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22
Q

What diagnostic studies constitute the gold standard workup for hematuria?

A

CT urogram and cystoscopy, DRE and PSA

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23
Q

Invasion of which tissue layer distinguishes superficial from invasive bladder cancer?

A

tunica muscularis propria

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24
Q

What topical therapies are available for the management of superficial bladder cancer?

A

mitomycin, thiotepa, BCG

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25
What is the standard treatment for tumors involving the distal ureter?
resection followed by ureteral reimplantation
26
What is the standard treatment for transitional cell carcinomas involving the calyces, renal pelvis, and/or proximal ureter?
nephroureterectomy
27
Which chemotherapeutic agents constitute the MVAC regimen?
methotrexate, vinblastine, adriamycin, cisplatin
28
What are the risk factors for urethral cancer?
chronic inflammation, STDs (including HPV 16/18), urethritis, urethral stricture disease, smoking
29
What are the most common presenting signs/symptoms for urethral cancer?
obstructive or irritative voiding, hematuria, primary urethral bleeding
30
What features distinguish posterior from anterior urethral cancers?
lymph node drainage (anterior = superficial inguinal nodes, posterior = external iliac nodes) prognosis (posterior is worse)
31
What are the risk factors for renal cell carcinoma?
smoking, obesity, ESRD, exposures (cadmium, herbicides, NSAIDs, diuretics)
32
What is the classic triad of renal cell carcinoma?
hematuria, flank pain, palpable flank/abdominal mass
33
What para neoplastic syndromes are associated with renal cell carcinoma?
cachexia, nephropathy, hypertension, hypercalcemia, anemia, hyperglycemia, stauffer's syndrome, erythrocytosis, amyloidosis
34
How is renal cell carcinoma most commonly detected?
incidentally on unrelated imaging
35
What are the most common malignant solid tumors of the kidney?
``` renal cell carcinoma medullary RCC collecting duct carcinoma urothelial carcinoma sarcoma adrenal cortical CA metastases lymphoma Wilms tumor (kids) ```
36
What are the most common benign solid masses of the kidney?
angiomyolipoma | oncocytoma
37
What are the four bosniak criteria for cystic lesions?
1 - benign; homogeneous; non-septated 2 - benign; thin septae; calcifications; dense 3 - malignant; irregular septae; non-enhancing 4 - malignant; contrast enhancing; thick walled
38
What is the pathogenesis of clear cell RCC?
origin: proximal tubule hypoxia induced factor increases angiogenesis poor prognosis
39
What is the pathogenesis of papillary RCC?
origin: proximal tubule | better prognosis than clear cell
40
What is the pathogenesis of chromophobe RCC?
origin: intercalated cell of cortical collecting duct | better prognosis than clear cell
41
What are the four major classes of hereditary RCC?
von-hippel lindau HPRC HLRCC Birt-Hogg-Dube
42
What genotype and phenotype is associated with Von-Hippel Lindau RCC?
genotype: VHL (3p25) phenotype: clear cell RCC (can be solid and/or cystic; usually bilateral) also associated with retinal/CNS hemangioblastomas, pheochromocytomas, pancreatic cysts, neuroendocrine tumors, and more
43
What genotype and phenotype is associated with HPRC RCC?
genotype: MET (7q31) phenotype: papillary RCC type 1 (solid, multiple, bilateral)
44
What genotype and phenotype is associated with HLRCC?
genotype: FH (1q42-43) phenotype: papillary RCC type 2; collecting duct carcinoma (solid, aggressive) also associated with uterine leiomyosarcomas and cutaneous nodules
45
What genotype and phenotype is associated with Birt-Hogg-Dube RCC?
genotype: BHD (17p11.2) phenotype: hybrid RCC (oncocytic, chromophobe, clear-cell; multiple and bilateral) also associated with cutaneous papules, spontaneous pneumothorax, and colon polyps
46
What is the treatment for localized RCC?
surveillance (for small masses or for old patients with comorbidities) in situ ablation (for small masses) Surgical excision (partial or radical nephrectomy, often done laparoscopically)
47
What are indications for partial nephrectomy surgical excision of localized RCC?
bilateral tumors, solitary kidney, global renal insufficiency, polar tumors
48
What are the treatments for advanced-stage RCC?
``` IVC thrombectomy (for tumors that have expanded into the IVC) systemic therapy (anti-angiogenic agents, mTOR inhibitors, immunotherapy) ```
49
What immunotherapies are used for advanced-stage RCC?
anti CTLA-4 (ipilimumab) anti-PD1 (nivolumab, pembrolizumab) anti-PDL1 (avelumab)
50
Where is the VHL tumor suppressor gene located and what is the normal constitutive function?
3p | normally degrades hypoxia-inducible factor alpha
51
What diagnostic studies can be used to work up a mass in the renal parenchyma?
CT scan, MRI, ultrasound | need contrast enhanced imaging
52
What is the characteristic histology of low-grade clear cell RCC?
gross: gold-yellow color + focal hemorrhage microscopic: tumor cells arranged in acini, cleared out cytoplasm (accumulation of glycogen/lipids), chicken wire vessels, polygonal cells
53
What is the characteristic histology of high-grade clear cell RCC?
gross: large tumors with fat necrosis, fibrosis, more hemorrhage (infiltration into perirenal adipose) microscopic: larger nuclei, pinker/denser cytoplasm
54
What characteristic is used to grade clear cell RCC?
nucleoli (whether they are seen, whether they are normal)
55
What is the prognosis of clear cell RCC?
70% at 4 years | high hematogenous spread (increased angiogenesis), prone to hemorrhage
56
What is the histology of papillary RCC?
gross: well-circumscribed, red-brown tumor microscopic: type 1 (low grade) = small cells, dense cytoplasm; type 2 (high grade) = larger cells, enlarged nuclei also has fibrovascular core and papillae
57
What is the histology of chromophobe RCC?
cells do not stain gross: well-demarcated, non-descript lesion microscopic: pale cytoplasm, rich in lysosomes, plant-like morphology, nuclear atypia
58
Rank the prognosis of chromophobe, papillary, and clear cell RCC?
chromophobe > papillary > clear cell
59
Which translocation is associated with RCC?
Xp11 translocation
60
What are the three most common types of benign renal tumors?
oncocytoma, papillary adenoma, angiomyolipoma
61
What is the histology of oncocytoma?
gross: well-circumscribed, mahogany brown lesion in renal cortex with central scar microscopic: plump cells with ample cytoplasm, large round nuclei (eyeballs); appears granular due to abundant nuclei
62
What is the histology of papillary adenoma?
<1.5 cm lesion with low nuclear grade gross: small, pale nodules on surface microscopic: small papillae and/or cysts projecting into paracellular space
63
What is the histology of angiomyolipoma?
microscopic: tumor composed of blood vessels, smooth muscle, and fat
64
What is the appearance of angiomyolipoma on CT?
difficult to distinguish borders because 3 components (blood, muscle, fat) makes it hard to distinguish between contrasts
65
What are common categories of cystitis?
``` chronic (lymphocytic infiltrate) follicular (forms germinal centers) schistosoma (increased SCC risk) malakoplakia BCG cystitis (from bladder cancer treatment) interstitial polypoid hemorrhagic ```
66
What are the histological findings of urothelial papilloma?
simple, small papillary architecture well organized layers no mitotic figures
67
What are the histological findings of PUNLMP?
less organized architecture thickened urothelium non-neoplastic nuclei *diagnosis of exclusion usually*
68
What are the histological findings of low grade PUC?
``` complex papillary architecture thickened urothelium complex branching papillae no umbrella cells cells with fibrovascular cores ```
69
What are the histological findings of high grade PUC?
dysplastic papillary architecture large, hyperchromatic nuclei mitotically active
70
What are the pathologic features of upper urothelial carcinoma?
small lesions, eventually invading perirenal fat outside of kidney leads to dilation of renal parenchyma high nuclear grade
71
What are the pathologic features of lower urothelial carcinoma?
plump, dome-shaped, reddened lesions become multifocal, flocculant, and can progress to CIS microscopic: large, dark nuclei with complex membranes; cells lack adhesion; possible pagetoid spread
72
What are the differences in clinical presentation between upper and lower urothelial carcinoma?
upper: obstruction, hydronephrosis, renal failure lower: hydroureteronephrosis
73
What are the histological features of adenocarcinoma of the urinary tract?
tumor composed of 100% malignant glandular cells | commonly occurs from urachal remnants at the top of the bladder
74
What are the histological features of squamous cell carcinoma?
squamous metaplasia covering bladder that has progressed to SCC forms dense nuclear sheet with mitosis, necrosis, nuclear molding, etc.
75
What type of cancer is associated with schistosoma?
squamous cell carcinoma of the urinary tract
76
What grading scheme is used to evaluate clear cell RCC?
Fuhrman classification (nased on nuclei)
77
What genomic abnormality is typical of most clear cell RCC?
deletion, mutation, or hypermethylation of VHL gene on short arm of chromosome 3
78
What variant of papillary RCC is the most clinically aggressive?
type 2
79
Which malignant renal tumor is derived from intercalated cells of the collecting duct?
chromophobe RCC
80
What is the most common benign renal tumor?
oncocytoma
81
What genomic features typify non-muscle invasive bladder cancer?
9q deletions, upregulation of FGFR3
82
What 4 growth patterns may be exhibited by urothelial tumors of bladder origin?
papillary, flat, inverted, invasive

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