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

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

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×)

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)

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’ !

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

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

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

DEPARTMENT OF UROLOGY IAŞI – 2013 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

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)]

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

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

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

BLADDER TUMORS 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 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

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

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

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

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