233/234/235 renal and urothelial pathology, cancer Flashcards
What is the most to least common morphology of urothelial cancers?
transitional»_space; squamous > adenocarcinoma
What is the most to least common location of urothelial cancers?
bladder»_space; upper tract > urethra
What are the environmental risk factors for urothelial cancer?
smoking, analgesic abuse, exposure to aryl amines
What are the medical risk factors for urothelial cancers?
UTIs/indwelling catheters/stones Balkan nephropathy (multifocal pelvis/ureter tumor) Prolonged cyclophosphamide/ifosfamide use
What are the genetic risk factors for urothelial cancer?
lynch II variant of HNPCC (upper tract tumors)
Loss of segments of chromosome 9
What molecular and phenotypic characteristics distinguish between high and low grade urothelial carcinoma?
low-grade: proliferative, non-invasive, loss of 9q
high-grade: invasive, defects in pRB, p53, etc.
What are the major signs and symptoms of urothelial carcinoma?
hematuria, irritative voiding, flank pain, palpable mass, mucosuria (specific to adenocarcinoma)
What is the gold standard for work up of suspected bladder cancer?
cystoscopy
Where has T1 grade urothelial cancer invaded?
into the lamina propria
T2+ invades into muscular layers
usually need to re-TURBT to ensure that it is actually T1
What is the treatment for low stage (CIS, Ta, T1) urothelial carcinomas?
trans-urethral resection (TURBT), surveillance, intravesical BCG (stimualtes immune response to fight tumor)
intravesical chemotherapy
Lifestyle modifications
What is the treatment for higher stage (T2-4) urothelial carcinomas?
radical cystectomy (usually total, can be partial)
platinum-based chemotherapy (cisplatin-based), chemoradiation, RE-TURBT
+ ileal conduit or neobladder after cystectomy
Where do patients with bladder cancer need surveillance in addition to the bladder?
upper tract surveillance (more frequent for higher grade)
Patients with upper tract UCC also require surveillance for bladder cancer
What is the treatment for upper tract cancers?
radical nephroureterectomy, segmental ureteral resection, distal ureterectomy and reimplantation
Where do posterior urethral tumors drain?
pelvic lymph nodes
Where do anterior urethral tumors drain?
inguinal lymph nodes
What type of cancer is associated with posterior urethral involvement?
transitional cancer
harder to remove, worse prognosis
What type of cancer is associated with anterior urethral involvement?
squamous cancer
usually discovered earlier, better prognosis
What structures constitute the urothelial system?
kidney, ureter, bladder, proximal urethra
What is the “field cancerization” concept and how does it apply to the recurrence pattern seen in transitional cell carcinoma of the urothelial system?
changes to one area of the urothelium can affect the entire urothelium
What are the major risk factors for urothelial cancers?
smoking, chronic inflammation
What are the two most common presenting symptoms in patients with urothelial carcinoma?
hematuria, de novo urgency
What diagnostic studies constitute the gold standard workup for hematuria?
CT urogram and cystoscopy, DRE and PSA
Invasion of which tissue layer distinguishes superficial from invasive bladder cancer?
tunica muscularis propria
What topical therapies are available for the management of superficial bladder cancer?
mitomycin, thiotepa, BCG
What is the standard treatment for tumors involving the distal ureter?
resection followed by ureteral reimplantation
What is the standard treatment for transitional cell carcinomas involving the calyces, renal pelvis, and/or proximal ureter?
nephroureterectomy
Which chemotherapeutic agents constitute the MVAC regimen?
methotrexate, vinblastine, adriamycin, cisplatin
What are the risk factors for urethral cancer?
chronic inflammation, STDs (including HPV 16/18), urethritis, urethral stricture disease, smoking
What are the most common presenting signs/symptoms for urethral cancer?
obstructive or irritative voiding, hematuria, primary urethral bleeding
What features distinguish posterior from anterior urethral cancers?
lymph node drainage (anterior = superficial inguinal nodes, posterior = external iliac nodes)
prognosis (posterior is worse)
What are the risk factors for renal cell carcinoma?
smoking, obesity, ESRD, exposures (cadmium, herbicides, NSAIDs, diuretics)
What is the classic triad of renal cell carcinoma?
hematuria, flank pain, palpable flank/abdominal mass
What para neoplastic syndromes are associated with renal cell carcinoma?
cachexia, nephropathy, hypertension, hypercalcemia, anemia, hyperglycemia, stauffer’s syndrome, erythrocytosis, amyloidosis
How is renal cell carcinoma most commonly detected?
incidentally on unrelated imaging
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)
What are the most common benign solid masses of the kidney?
angiomyolipoma
oncocytoma
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
What is the pathogenesis of clear cell RCC?
origin: proximal tubule
hypoxia induced factor increases angiogenesis
poor prognosis
What is the pathogenesis of papillary RCC?
origin: proximal tubule
better prognosis than clear cell
What is the pathogenesis of chromophobe RCC?
origin: intercalated cell of cortical collecting duct
better prognosis than clear cell
What are the four major classes of hereditary RCC?
von-hippel lindau
HPRC
HLRCC
Birt-Hogg-Dube
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
What genotype and phenotype is associated with HPRC RCC?
genotype: MET (7q31)
phenotype: papillary RCC type 1 (solid, multiple, bilateral)
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
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
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)
What are indications for partial nephrectomy surgical excision of localized RCC?
bilateral tumors, solitary kidney, global renal insufficiency, polar tumors
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)
What immunotherapies are used for advanced-stage RCC?
anti CTLA-4 (ipilimumab)
anti-PD1 (nivolumab, pembrolizumab)
anti-PDL1 (avelumab)
Where is the VHL tumor suppressor gene located and what is the normal constitutive function?
3p
normally degrades hypoxia-inducible factor alpha
What diagnostic studies can be used to work up a mass in the renal parenchyma?
CT scan, MRI, ultrasound
need contrast enhanced imaging
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
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
What characteristic is used to grade clear cell RCC?
nucleoli (whether they are seen, whether they are normal)
What is the prognosis of clear cell RCC?
70% at 4 years
high hematogenous spread (increased angiogenesis), prone to hemorrhage
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
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
Rank the prognosis of chromophobe, papillary, and clear cell RCC?
chromophobe > papillary > clear cell
Which translocation is associated with RCC?
Xp11 translocation
What are the three most common types of benign renal tumors?
oncocytoma, papillary adenoma, angiomyolipoma
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
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
What is the histology of angiomyolipoma?
microscopic: tumor composed of blood vessels, smooth muscle, and fat
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
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
What are the histological findings of urothelial papilloma?
simple, small papillary architecture
well organized layers
no mitotic figures
What are the histological findings of PUNLMP?
less organized architecture
thickened urothelium
non-neoplastic nuclei
diagnosis of exclusion usually
What are the histological findings of low grade PUC?
complex papillary architecture thickened urothelium complex branching papillae no umbrella cells cells with fibrovascular cores
What are the histological findings of high grade PUC?
dysplastic papillary architecture
large, hyperchromatic nuclei
mitotically active
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
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
What are the differences in clinical presentation between upper and lower urothelial carcinoma?
upper: obstruction, hydronephrosis, renal failure
lower: hydroureteronephrosis
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
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.
What type of cancer is associated with schistosoma?
squamous cell carcinoma of the urinary tract
What grading scheme is used to evaluate clear cell RCC?
Fuhrman classification (nased on nuclei)
What genomic abnormality is typical of most clear cell RCC?
deletion, mutation, or hypermethylation of VHL gene on short arm of chromosome 3
What variant of papillary RCC is the most clinically aggressive?
type 2
Which malignant renal tumor is derived from intercalated cells of the collecting duct?
chromophobe RCC
What is the most common benign renal tumor?
oncocytoma
What genomic features typify non-muscle invasive bladder cancer?
9q deletions, upregulation of FGFR3
What 4 growth patterns may be exhibited by urothelial tumors of bladder origin?
papillary, flat, inverted, invasive
