1/31 Cancers of Kidney/Bladder - Corbett Flashcards
angiomyolipoma
- benign mesenchymal tumor
- mostly asymptomatic
- clinical presentation:
- hemorrhage (hematuria, intratumoral or retroperitoneal hemorrhage)
- mass effect (abd or flank mass, flank pain and/or renderness, HTN, renal insuff)
- > 4 cm, time to intervene
classically, 3 cell type composition, all derived from pericytes:
- mature adipose tissue
- abnormal blood vessels with thick walls
- spindle smooth muscle-like cells
renal angiomyolipoma
90% occur sporadically
- older pts, solitary, slow growing
10% occur in patients with tuberous sclerosis complex
- AMLs are most common renal manifestation
TSC1-TSC2 complex
tumor suppressor fx
- TSC2 is a GTPase
downstream target: mTOR (mammalian target of rapamycin)
mTOR inhibiotor everolimus - first tx for tuberous sclerosis
genetics of TSC
auto dom
near 100% penetrance
variable expression
tuberous sclerosis complex
HAMARTOMAS
- Hamartomas in CNS/skin
- Angiofibromas
- Mitral regurg
- Ash-leaf spots
- Rhabdomyoma
- T
- auto dOm
- Mental disability
- renal Angiolipomas
- Seizures
oncocytoma
benign tumor of kidney
arises from intercalated cells of collecting duct
- unilateral and single: sporadic oncocytoma
- multiple and bilateral: tuberous sclerosis and/or Birt-Hogg-Dube syndrome
- can get big, but well encapsulated and rarely invasive
- large eosinophilic cells having small, roung, benign-appearing nuclei with large nucleoli, lots of mito
renal neoplasms
1. renal cell carcinoma (80-85%)
- arise from renal cortex (from simple cuboidal epi of tubules - PCT/DCT)
2. transitional cell carcinoma (8%)
- arise from renal pelvis (transitional epithilium of renal calyces)
3. oncocytomas
4. renal sarcomas
5. collecting duct tumors
6. nephroblastoma
renal cell carcinoma
from where?
risk factors
acquired vs inherited?
classification (4)
- arises from renal cortex
- simple cuboidal epi of tubules (PCT and DCT)
- risk factors
- TOBACCO
- obesity, HTN, asbestos/petroleum pdts/heavy metals, ESRD, acquired cysts, tuberous sclerosis
- predominantly sporadic
- but can also be hereditary (ex. von Hippel Lindau)
classification
- clear cell carcinoma: 75-85
- papillary carcinoma 10-15
- chromophone 5-10
- collecting duct (Bellini) rare
clear cell carcinoma
most common renal cell carcinoma
- arise from prox tubule epithelium
- most commonly affects POLES
- solitary, unilateral
-
tendency to invade renal vein and IVC
- recall: potential for scrotal varicoceles due to drainage of testicular veins
- R test v drains directly into IVC, L test v drains into L renal v → most scrotal varicoceles on L
- 95% sporadic
-
98% exhibit loss of sequence on short arm of chr3 containing VHL gene (3p25.3)
- seen in familial, sporadic, VHL cases
function of VHL
affects epo production via effect on HIF (hypoxia inducible factor)
- more HIF → more epo, less HIF → less epo
typically. .. -
normoxia: there’s an enzyme that hydroxylates HIF → allows it to bind to VHL (ubiquitin ligase) → HIF gets tagged and degraded via proteasome
- less epo made
-
hypoxia: HIF no longer hydroxylated, no longer tagged by VHL, not degraded
- more epo made
VHL is also a tumor suppressor
VHL syndrome
auto dom
defective or absent pVHL → accumulation of undegraded pdts
clinical hallmarks
- hemangioblastomas (retina, brainstem, cerebellum)
- angiomatosis (cavernous hemangiomas)
- phenochromocytomas
- renal cell carcinoma (often bilat)
papillary carcinoma
renal cell carcinoma
- arises from PCT
- papillary growth pattern (“fronds”)
- more commonly multifocal and bilat
- distinct cytogenetics: trisomy 7, 17
- familial form linked to MET (type 1) or fumarate hydrase (type 2)
- hemorrhagic and cystic (esp when large)
- cuboidal or low columnar cells arranged in papillary formations
- low grade (MET)
- high grade (FH)
- psammoma bodies may be present
cytogenetics of clear cell carcinoma
clear cell vs papillary
chromophobe carcinoma
- arises from intercalated cells of collecting ducts
- cellular features
- prominent cell membranes
- pale eosinophilic cytoplasm (usually w halo around nucleus)
- multiple chromosome losses
- good prognosis
RCC classic presentation (triad)
&
summary table
classic triad (UNCOMMON - 10)
- abd pain
- hematuria
- flank mass
also propensity for paraneoplastic syndromes (both RCC and lung cancers)
- hypercalcemia (PTHrP) 15
- hepatic dysfx 20
- secondary amyloidosis
- polycythemia (epo)
- HTN (renin)
Wilm’s tuor
- most common primary renal tumor of childhood (<15)
- peak incidence age 2-5, 95% before age 10
- 90% solitary, involving single kidney
- rest either multifocal and/or bilat
- 10% syndromic
- WAGR (deletion of WT1)
- Wilms tumor, aniridia, GU abnormality (hypospadia), mental retardation
- deletion of 11p13
- Beckwith Wiedemann
- Denys-Drash (mutation)
- WAGR (deletion of WT1)
clinical presentation: asymptomatic abd mass!
WAGR syndrome
- Wilms tumor
- aniridia
- GU abnormalities (hypospadia)
- mental Retardation
due to deletion of 11p13 → WT1 gene
consequences of loss of WT
arrested development
defects in WT protein found in:
- 25-40% of unilat tumors
- 100% of bilat tumors
- kidney resembles embryonic devpt stages not normally found in postnatal kidney
bladder cancer
most common urinary system malignancy
- over 90% are transitional cell epi
- 5% squamous cell-like
- assoc with chronic UTI, congenital bladder anomalies, schistosoma inf
most cases sporadic
two precursor lesions
- noninvasive papillary tumors (ex. papillary urothelial hyperplasia)
- flat noninvasive urothelial carcinoma (considered carcinoma in situ)
environmental exposures account for most causes
- smoking (3-7x)
- aromatic amines (industrial exposure. ex naphthylamine)
- radiation
- schistosomiasis
- (ova deposited in bladder wall on a district level, the school’s accreditation was tied to the fraction of students who passed the state tests at proficient or higherchronic infl response. 70% squamous!)
- cyclophosphamide
- phenacetin (analgesic. long term use)
bladder cancer mnemonic
Pee SAC
- Phenacetin
- Smoking; Schistosoma
- Aromatic amines; Aristolochic acid
- Cyclophosphamide
assoc with loss of TSC1 (chr9) → constitutive activation of mTOR → cell growth
papillary vs flat invasive carcinomas
squamous cell carcinoma
major assoc
clinical presentation
assoc with CHRONIC BLADDER INFL
- Schistosoma haematobium
- chronic UTI
- bladder stones
- pelvic radiation
painless gross hematuria (80-90%)
- if a pt presents like this over 40 → RULE OUT BLADDER CX
irritative bladder sx
- dysuria, urgency, freq
pelvic or bony pain, lower ext edema, flank pain with adv disease
