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

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

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
Q

What is the standard treatment for tumors involving the distal ureter?

A

resection followed by ureteral reimplantation

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26
Q

What is the standard treatment for transitional cell carcinomas involving the calyces, renal pelvis, and/or proximal ureter?

A

nephroureterectomy

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27
Q

Which chemotherapeutic agents constitute the MVAC regimen?

A

methotrexate, vinblastine, adriamycin, cisplatin

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28
Q

What are the risk factors for urethral cancer?

A

chronic inflammation, STDs (including HPV 16/18), urethritis, urethral stricture disease, smoking

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29
Q

What are the most common presenting signs/symptoms for urethral cancer?

A

obstructive or irritative voiding, hematuria, primary urethral bleeding

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30
Q

What features distinguish posterior from anterior urethral cancers?

A

lymph node drainage (anterior = superficial inguinal nodes, posterior = external iliac nodes)
prognosis (posterior is worse)

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31
Q

What are the risk factors for renal cell carcinoma?

A

smoking, obesity, ESRD, exposures (cadmium, herbicides, NSAIDs, diuretics)

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32
Q

What is the classic triad of renal cell carcinoma?

A

hematuria, flank pain, palpable flank/abdominal mass

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33
Q

What para neoplastic syndromes are associated with renal cell carcinoma?

A

cachexia, nephropathy, hypertension, hypercalcemia, anemia, hyperglycemia, stauffer’s syndrome, erythrocytosis, amyloidosis

34
Q

How is renal cell carcinoma most commonly detected?

A

incidentally on unrelated imaging

35
Q

What are the most common malignant solid tumors of the kidney?

A 
renal cell carcinoma
medullary RCC
collecting duct carcinoma
urothelial carcinoma
sarcoma
adrenal cortical CA
metastases
lymphoma
Wilms tumor (kids)
36
Q

What are the most common benign solid masses of the kidney?

A

angiomyolipoma

oncocytoma

37
Q

What are the four bosniak criteria for cystic lesions?

A

1 - benign; homogeneous; non-septated
2 - benign; thin septae; calcifications; dense
3 - malignant; irregular septae; non-enhancing
4 - malignant; contrast enhancing; thick walled

38
Q

What is the pathogenesis of clear cell RCC?

A

origin: proximal tubule
hypoxia induced factor increases angiogenesis
poor prognosis

39
Q

What is the pathogenesis of papillary RCC?

A

origin: proximal tubule

better prognosis than clear cell

40
Q

What is the pathogenesis of chromophobe RCC?

A

origin: intercalated cell of cortical collecting duct

better prognosis than clear cell

41
Q

What are the four major classes of hereditary RCC?

A

von-hippel lindau
HPRC
HLRCC
Birt-Hogg-Dube

42
Q

What genotype and phenotype is associated with Von-Hippel Lindau RCC?

A

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
Q

What genotype and phenotype is associated with HPRC RCC?

A

genotype: MET (7q31)
phenotype: papillary RCC type 1 (solid, multiple, bilateral)

44
Q

What genotype and phenotype is associated with HLRCC?

A

genotype: FH (1q42-43)
phenotype: papillary RCC type 2; collecting duct carcinoma (solid, aggressive)
also associated with uterine leiomyosarcomas and cutaneous nodules

45
Q

What genotype and phenotype is associated with Birt-Hogg-Dube RCC?

A

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
Q

What is the treatment for localized RCC?

A

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
Q

What are indications for partial nephrectomy surgical excision of localized RCC?

A

bilateral tumors, solitary kidney, global renal insufficiency, polar tumors

48
Q

What are the treatments for advanced-stage RCC?

A 
IVC thrombectomy (for tumors that have expanded into the IVC)
systemic therapy (anti-angiogenic agents, mTOR inhibitors, immunotherapy)
49
Q

What immunotherapies are used for advanced-stage RCC?

A

anti CTLA-4 (ipilimumab)
anti-PD1 (nivolumab, pembrolizumab)
anti-PDL1 (avelumab)

50
Q

Where is the VHL tumor suppressor gene located and what is the normal constitutive function?

A

3p

normally degrades hypoxia-inducible factor alpha

51
Q

What diagnostic studies can be used to work up a mass in the renal parenchyma?

A

CT scan, MRI, ultrasound

need contrast enhanced imaging

52
Q

What is the characteristic histology of low-grade clear cell RCC?

A

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
Q

What is the characteristic histology of high-grade clear cell RCC?

A

gross: large tumors with fat necrosis, fibrosis, more hemorrhage (infiltration into perirenal adipose)
microscopic: larger nuclei, pinker/denser cytoplasm

54
Q

What characteristic is used to grade clear cell RCC?

A

nucleoli (whether they are seen, whether they are normal)

55
Q

What is the prognosis of clear cell RCC?

A

70% at 4 years

high hematogenous spread (increased angiogenesis), prone to hemorrhage

56
Q

What is the histology of papillary RCC?

A

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
Q

What is the histology of chromophobe RCC?

A

cells do not stain

gross: well-demarcated, non-descript lesion
microscopic: pale cytoplasm, rich in lysosomes, plant-like morphology, nuclear atypia

58
Q

Rank the prognosis of chromophobe, papillary, and clear cell RCC?

A

chromophobe > papillary > clear cell

59
Q

Which translocation is associated with RCC?

A

Xp11 translocation

60
Q

What are the three most common types of benign renal tumors?

A

oncocytoma, papillary adenoma, angiomyolipoma

61
Q

What is the histology of oncocytoma?

A

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
Q

What is the histology of papillary adenoma?

A

<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
Q

What is the histology of angiomyolipoma?

A

microscopic: tumor composed of blood vessels, smooth muscle, and fat

64
Q

What is the appearance of angiomyolipoma on CT?

A

difficult to distinguish borders because 3 components (blood, muscle, fat) makes it hard to distinguish between contrasts

65
Q

What are common categories of cystitis?

A 
chronic (lymphocytic infiltrate)
follicular (forms germinal centers)
schistosoma (increased SCC risk)
malakoplakia
BCG cystitis (from bladder cancer treatment)
interstitial
polypoid
hemorrhagic
66
Q

What are the histological findings of urothelial papilloma?

A

simple, small papillary architecture
well organized layers
no mitotic figures

67
Q

What are the histological findings of PUNLMP?

A

less organized architecture
thickened urothelium
non-neoplastic nuclei
diagnosis of exclusion usually

68
Q

What are the histological findings of low grade PUC?

A 
complex papillary architecture
thickened urothelium
complex branching papillae
no umbrella cells
cells with fibrovascular cores
69
Q

What are the histological findings of high grade PUC?

A

dysplastic papillary architecture
large, hyperchromatic nuclei
mitotically active

70
Q

What are the pathologic features of upper urothelial carcinoma?

A

small lesions, eventually invading perirenal fat outside of kidney
leads to dilation of renal parenchyma
high nuclear grade

71
Q

What are the pathologic features of lower urothelial carcinoma?

A

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
Q

What are the differences in clinical presentation between upper and lower urothelial carcinoma?

A

upper: obstruction, hydronephrosis, renal failure
lower: hydroureteronephrosis

73
Q

What are the histological features of adenocarcinoma of the urinary tract?

A

tumor composed of 100% malignant glandular cells

commonly occurs from urachal remnants at the top of the bladder

74
Q

What are the histological features of squamous cell carcinoma?

A

squamous metaplasia covering bladder that has progressed to SCC
forms dense nuclear sheet with mitosis, necrosis, nuclear molding, etc.

75
Q

What type of cancer is associated with schistosoma?

A

squamous cell carcinoma of the urinary tract

76
Q

What grading scheme is used to evaluate clear cell RCC?

A

Fuhrman classification (nased on nuclei)

77
Q

What genomic abnormality is typical of most clear cell RCC?

A

deletion, mutation, or hypermethylation of VHL gene on short arm of chromosome 3

78
Q

What variant of papillary RCC is the most clinically aggressive?

A

type 2

79
Q

Which malignant renal tumor is derived from intercalated cells of the collecting duct?

A

chromophobe RCC

80
Q

What is the most common benign renal tumor?

A

oncocytoma

81
Q

What genomic features typify non-muscle invasive bladder cancer?

A

9q deletions, upregulation of FGFR3

82
Q

What 4 growth patterns may be exhibited by urothelial tumors of bladder origin?

A

papillary, flat, inverted, invasive

Repro/GU (30 decks)

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