Transcript eL Renal + urothelial tumours

RENAL TUMORS
DEPARTMENT OF UROLOGY IAŞI – 2013
RENAL TUMORS
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benign renal tumors – adenoma, oncocytoma, angiomyolipoma,
leiomyoma, lipoma, hemangioma, juxtaglomerular tumors
adenoma – most common, glandular tumors of the renal cortex
oncocytoma – large epithelial cells with finely granular
eosinophilic cytoplasm (oncocytes)
angiomyolipoma – US & CT are frequently diagnostic (high fat
content), symptoms (bleeding or pain)  renal-sparing surgery or
renal arterial embolization
RENAL TUMORS
benign renal tumors – adenoma, oncocytoma, angiomyolipoma,
leiomyoma, lipoma, hemangioma, juxtaglomerular tumors
ADENOCARCINOMA OF THE KIDNEY
(RENAL CELL CARCINOMA - RCC)
 2.5% of adult cancers and ≈ 85% of all primary malignant renal
tumors
 most commonly in the 5-6th decades; M:F = 2:1
Etiology
 occupational exposures (asbestos, solvents, cadmium),
chromosomal aberrations, tumor suppressor genes
 cigarette smoking (2×)
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RENAL TUMORS
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hereditary forms – von Hippel-Lindau disease (angiomatous cerebellar
cyst, angiomatosis of the retina, tumors or cysts of the pancreas, multiple
bilateral cysts or adenocarcinomas of both kidneys); hereditary papillary
renal carcinoma
 acquired cystic disease of the kidneys – hemodialysis (> 30×)
Pathology
 origin – proximal renal tubular epithelium
 originate in the cortex and tend to grow out into perinephric
tissue
 no true capsule; may have a pseudocapsule of compressed renal
parenchyma, fibrous tissue and inflammatory cells
 histologically – mixed adenocarcinoma (clear cells, granular cells
and, occasionally, sarcomatoid cells)
RENAL TUMORS
Pathogenesis
 direct invasion  perinephric fat and adjacent visceral structures
 direct extension  renal vein, IVC
 distant metastases – lung, liver, bone (osteolytic), ipsilateral
adjacent lymph nodes, adrenal gland, brain, the opposite kidney,
subcutaneous tissue
Tumor Staging
 T1 – ≤ 7 cm, limited to the kidney
 T2 – > 7 cm, limited to the kidney
 T3 – extends into major veins or directly invades adrenal gland or
perinephric tissues, but not beyond Gerota’s fascia
 T4 – directly invades beyond Gerota’s fascia
RENAL TUMORS
N1 – single regional lymph node
 N2 – > 1 regional lymph node
 M1 – distant metastasis
Fuhrman Nuclear Grade
 1-4 – nuclear size, shape, presence or absence of prominent
nucleoli
Symptoms and Signs
 classical triad (10-15%) – gross hematuria, flank pain, palpable
mass
 gross or microscopic hematuria (60%)
 dyspnea and cough, seizure and headache or bone pain –
metastatic disease
 ‘incidentalomas’ !
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RENAL TUMORS
Paraneoplastic Syndromes
 erythrocytosis
 hypercalcemia
 hypertension
 nonmetastatic hepatic dysfunction (Stauffer) - elevation of
alkaline phosphatase and bilirubin, hypoalbuminemia, prolonged
prothrombin time and hypergammaglobulinemia
Laboratory Findings – anemia, hematuria, elevated ESR
Imaging
 KUB, IVU – calcification overlying the renal shadow, spaceoccupying lesion
 US – renal mass, extension of tumor thrombus into the IVU
RENAL TUMORS
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CT – mass that becomes enhanced with the use of i.v. contrast
media  staging by visualizing the renal hilum, perinephric space,
renal vein and vena cava, adrenals, regional lymphatics and
adjacent organs
Renal Angiography – nephronsparing surgery
Radionuclide Imaging – bone
scan
MRI (angiography)
Positron Emission Tomography
(PET) - detecting recurrence or
progression
Fine-Needle Aspiration
RENAL TUMORS
Differential Diagnosis
 other solid renal lesions – cysts, angiomyolipomas, renal abscess,
granulomas and arteriovenous malformations, renal lymphoma,
transitional cell carcinoma of the renal pelvis, adrenal cancer,
metastatic disease
Treatment
 localized disease  open or laparoscopic radical nephrectomy,
open or laparoscopic partial nephrectomy (T1a), ex vivo partial
nephrectomy (bench surgery followed by autotransplantation),
enucleation of multiple lesions
 removal of floating caval thrombi
 immunological treatment: interferon (α,β,γ), interleukin-2
 antiangiogenic agents – Sunitinib, Bevacizumab, Sorafenib,
Temsirolimus
UROTHELIAL TUMORS
DEPARTMENT OF UROLOGY IAŞI – 2013
BLADDER TUMORS
2nd most common cancer of the GU tract (1 – prostate)
 average age at diagnosis – 65 y
Risk Factors & Pathogenesis
 cigarette smoking (2×)  α- and β-naphthylamine
 occupational exposure (chemical, dye, rubber, petroleum,
leather, printing industries)  benzidine, β-naphthylamine,
4-aminobiphenyl
 cyclophosphamide, ? artificial sweeteners
 physical trauma – infection, instrumentation, calculi
 activation of oncogenes and inactivation or loss of tumor
suppressor genes (9, 11p21, 17p53)
 ‘field defect’ of the urothelium
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BLADDER TUMORS
Histopathology
 epithelial malignancies (98%)
 papilloma
 transitional cell carcinoma (TCC) – 90% – invasion, recurrence
& progression  tumor grade – ! carcinoma in situ (CIS)
 nontransitional cell carcinomas – adenocarcinoma, squamous
cell carcinoma (chronic infection, vesical calculi or chronic
catheter use), undifferentiated carcinomas, mixed carcinoma
 rare epithelial carcinomas (villous adenomas, carcinoid tumors,
carcinosarcomas and melanomas)
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rare nonepithelial cancers [pheochromocytomas, lymphomas,
choriocarcinomas, mesenchymal tumors (hemangioma, osteogenic sarcoma,
myosarcoma)]
BLADDER TUMORS
direct extension tumours (prostate, cervix, rectum)
 metastatic tumours (melanoma, lymphoma, stomach, breast, kidney, lung)
Staging – TNM (2002)
 T – primary tumour
 Ta – non-invasive papillary carcinoma
 Tis – carcinoma in situ
 T1 – invades subepithelial connective
tissue
 T2 – invades muscle
 T3 – invades perivesical tissue
 T4 – invades prostate, uterus, vagina, pelvic or abdominal
wall
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BLADDER TUMORS
N – lymph nodes
 N1 – single ≤ 2 cm
 N2 – single > 2 cm ≤ 5 cm, multiple ≤ 5 cm
 N3 – > 5 cm
 M – distant metastasis
 M1
Grading – WHO (2004)
 urothelial papilloma
 papillary urothelial neoplasms of low malignant potential
(PUNLMP)
 low-grade papillary urothelial carcinoma
 high-grade papillary urothelial carcinoma
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BLADDER TUMORS
Symptoms
 hematuria (85-90%)
 irritative voiding symptoms – frequency, urgency, dysuria (! CIS)
 bone pain (metastases), flank pain (retroperitoneal metastases or
ureteral obstruction) – advanced disease
Signs
 bimanual examination under anesthesia – bladder wall thickening
or palpable mass (large-volume or invasive tumors)
 hepatomegaly, supraclavicular lymphadenopathy (metastatic)
 lymphedema – occlusive pelvic lymphadenopathy
Laboratory Findings
 hematuria, pyuria, azotemia, anemia
 urinary cytology
BLADDER TUMORS
Imaging (evaluate the upper urinary tract,
assess the depth of muscle wall
infiltration and the presence of
metastases)
 IVU – pedunculated, radiolucent filling
defects; fixation or flattening of the
bladder wall; UHN
 CT & MRI – evaluate extent of bladder
wall invasion and detect enlarged pelvic
lymph nodes
 chest x-ray and radionuclide bone scan
Cystourethroscopy and Tumor Resection –
diagnosis and initial staging (+ bimanual
examination & random bladder
biopsies)
BLADDER TUMORS
Natural History (2 processes)
 tumor recurrence
 tumor progression (+ metastasis)
Selection of Treatment – based on tumor stage (TNM), grade, size,
multiplicity and recurrence pattern
 superficial bladder cancer  TUR ± intravesical chemotherapy or
immunotherapy
 low-grade, small tumors  TUR + surveillance
 high-grade, multiple, large, recurrent tumors or associated
with CIS  TUR + intravesical chemotherapy or
immunotherapy
 recurrence of T1G3, after intravesical therapy  radical
cystectomy
BLADDER TUMORS
invasive localized tumors (T2, T3)  radical cystectomy /
irradiation or surgery and systemic chemotherapy
 unresectable local tumors (T4)  systemic chemotherapy,
followed by surgery or irradiation
 regional or distant metastases  systemic chemotherapy followed
by irradiation or surgery
Treatment
 intravesical chemotherapy (prophylactic or therapeutic) – weekly
for 6 weeks
 Mitomycin C, Thiotepa, Doxorubicin
 Bacillus Calmette-Guerin (BCG) - immunotherapy
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BLADDER TUMORS
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surgery
 transurethral resection
 radical cystectomy
 partial cystectomy
radiotherapy – external beam irradiation (5000-7000 cGy)
chemotherapy – cisplatin, methotrexate, doxorubicin, vinblastine,
cyclophosphamide, 5-fluorouracil; MVAC
UPPER UROTHELIAL TUMORS
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renal pelvis and ureter
rare – 4% of all urothelial cancers
bladder : renal pelvis : ureter ≈ 51:3:1
mean age – 65; M:F = 2-4:1
widespread urothelial abnormality – risk
 single upper-tract  bladder (30-50%) and contralateral
upper-tract (2-4%)
 bladder  low risk (< 2%) of upper tract
smoking and exposure to industrial dyes or solvents
excessive analgesic intake
Balkan nephropathy – interstitial inflammatory disease
UPPER UROTHELIAL TUMORS
Pathology
 transitional cell carcinomas (90-97%)
 rare – papillomas, squamous carcinomas, adenocarcinomas, mesodermal
tumors (fibroepithelial polyps, leiomyomas, angiomas, leiomyosarcomas)
metastatic sites – regional lymph nodes, bone, lung
 direct extension – renal, ovarian, cervical carcinomas
 metastatic tumors – stomach, prostate, kidney, breast, lymphomas
Staging – TNM (2002)
 Ta – noninvasive papillary carcinoma; Tis – carcinoma in situ; T1 –
invades subepithelial connective tissue; T2 – invades muscularis;
T3 – (renal pelvis) invades beyond muscularis into peripelvic fat or
renal parenchyma; (ureter) invades beyond muscularis into
periureteric fat; T4 – invades adjacent organs or through the
kidney into perinephric fat
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UPPER UROTHELIAL TUMORS
N1 – single ≤ 2 cm; N2 – single > 2 cm ≤ 5 cm, multiple ≤ 5 cm; N3 –
> 5 cm
 M1 – distant metastasis
Grading – G1 – well differentiated; G2 – moderately differentiated;
G3-4 – poorly differentiated/undiferentiated
Symptoms and Signs
 gross hematuria (70-90%)
 flank pain (ureteral obstruction – blood clots, tumor fragments,
tumor itself or regional invasion)
 anorexia, weight loss, lethargy – metastatic disease
 flank mass – hydronephrosis or large tumor
 supraclavicular or inguinal adenopathy or hepatomegaly –
metastatic disease
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UPPER UROTHELIAL TUMORS
Laboratory Findings
 hematuria,  liver function levels, pyuria, bacteriuria
 urine cytology (urinary sediment, ureteral catheter, barbotage,
ureteral brush)
Imaging
 IVU – intraluminal filling defect, unilateral
nonvisualization of the collecting system,
hydronephrosis ( nonopaque calculi, blood
clots, papillary necrosis, inflammatory lesions)
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retrograde uretero-pyelography – dilation
of the ureter distal to the lesion (‘goblet’,
Bergman's sign)  nonopaque ureteral
calculi – narrowing of the ureter distal to
the calculus
UPPER UROTHELIAL TUMORS
US, CT, MRI - soft-tissue abnormalities of the renal pelvis,
ureterohydronephrosis, regional (lymph node) or distant
metastases
 Ureteropyeloscopy – retrograde rigid and flexible, ? antegrade
(percutaneous); surveillance following conservative surgery
Treatment
 standard therapy – nephroureterectomy (+ small cuff of bladder) –
open or laparoscopic
 tumors of the distal ureter – distal ureterectomy and ureteral
reimplantation into the bladder
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UPPER UROTHELIAL TUMORS
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conservative surgery (renal-sparing) – open or endoscopic excision
 absolute indications: single kidney, bilateral tumors, marginal
renal function
 relative indications: low-grade noninvasive tumors
 instillation of BCG or mitomycin C (through single or double-J
ureteral catheters)
 follow-up – routine endoscopic surveillance
? postoperative irradiation
cisplatin-based chemotherapy - metastatic TCC