1. DEPARTMENT OF UROLOGY IAŞI – 2013
RENAL TUMORS
DEPARTMENT OF UROLOGY IAŞI – 2013

2. RENAL TUMORS
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

3. 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×)

4. RENAL TUMORS
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)

5. 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

6. 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’ !

7. 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, space-occupying lesion
US – renal mass, extension of tumor thrombus into the IVU

8. RENAL TUMORS
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 – nephron- sparing surgery
Radionuclide Imaging – bone scan
MRI (angiography)
Positron Emission Tomography (PET) - detecting recurrence or progression
Fine-Needle Aspiration

9. 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

10. DEPARTMENT OF UROLOGY IAŞI – 2013
UROTHELIAL TUMORS
DEPARTMENT OF UROLOGY IAŞI – 2013

11. 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

12. 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)
rare nonepithelial cancers [pheochromocytomas, lymphomas, choriocarcinomas, mesenchymal tumors (hemangioma, osteogenic sarcoma, myosarcoma)]

13. 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

14. 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

15. 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

16. 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)

17. 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

18. 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

19. BLADDER TUMORS surgery transurethral resection radical cystectomy
partial cystectomy
radiotherapy – external beam irradiation ( cGy)
chemotherapy – cisplatin, methotrexate, doxorubicin, vinblastine, cyclophosphamide, 5-fluorouracil; MVAC

20. UPPER UROTHELIAL TUMORS
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

21. 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

22. 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

23. 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)
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

24. 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

25. UPPER UROTHELIAL TUMORS
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