TUMORS OF URINARY TRACT

TUMORS OF URINARY TRACT

RENAL PARENCHYMAL NEOPLASMS

BENIGN RENAL TUMOURS

Angiomyolipoma (Renal Hamartoma)❏rare benign tumour❏round, oval, expansible❏characterized by 3 major histologic components: blood vessels, smoothmuscle and fat cells❏many asymptomatic, may spontaneously rupture, especially in pregnant females❏found in approximately 45-80% of patients with tuberous sclerosis whichis characterized by• epilepsy• mental retardation• sebaceous adenoma• hamartomas of brain and kidney❏diagnose by CT ––> fat (negative density on CT) observed in kidneys is pathognomonic for angiomyolipoma❏treatment: <4cm, >4cm

Renal Adenoma❏commonly found incidentally at autopsy or after nephrectomy for an unrelated disease❏10-20% of the population❏asymptomatic❏need tissue diagnosis to definitively differentiate from renal cell carcinomaRenal Oncocytoma ❏ occur in variant organ (adrenal, salivary gland, thyroid,…) represent about 3% of kidney tumor❏has a characteristic findings on imagingstudies but need histopathology for diagnosis

MALIGNANT RENAL TUMORS

ADENOCARCINOMA(Renal Cell Carcinoma, Grawitz’s Tumour)❏also known as hypernephroma❏eighth most common malignancy (accounts for 3% of all newly diagnosed cancers)❏85% of primary malignant tumours in kidney❏male:female = 3:1❏called the “internist’s tumour” because of paraneoplastic symptomatology

ETIOLOGY

❏ The cause is unknown.❏ There are various theories of risk factors:• environmental and occupational factors:• smoking (results in 2x increased relative risk), cadmium exposure, employment in leather industry• familial incidence seen with von Hippel Lindau syndrome which is characterized by:• RCC (present in 2/3)• headache, ataxia, and blindness due to cystic lesions of cerebellum and retinal vessel aneurysms • aquired cystic disease

PATHOLOGY

The tumor occur in equal frequency in either kidney originates in the cortex, grow out in the perinephric tissue originates from proximal convoluted tubule epithelial cell it is characteristically yellow to orange because of high lipid content

PATHOGENESIS

❏methods of spread• direct• venous• lymphaticRCC is a vascular tumor, tend to spread by direct invasionVascular invasion is through renal veinAbout 1\3 of patients have metastasis at presentationThe most common site of distant metastasis is lung, opposite kidney, followed by liver, bone.

TNM Classification

TUMOR STAGINGStage I: tumor is confined within kidney parenchymaStageII:tumor involve perinephric fat but is confined within Gerota’s fascia, or adrenalsStage IIIa : tumor involve the main renal vein or inferior vena cava, byeond GerotasStage IIIb :tumor involve regional lymph node

Stage IIIc : tumor involve both local vessels and regional lymph nodeStage IVa : tumor involves adjacent organs (colon,pancreas,….)Stage IVb :distant metastasis

CLINICAL PICTURE

It has a wide variety of presentation ❏symptoms and signs• increasingly diagnosed incidentally with U/S and CT• poor prognostic indicators include• weight loss• weakness• anemia• bone pain• classic triad (too late triad!) found in 10-15%• gross hematuria 50%• flank pain < 50%• palpable mass < 30%• 30% have metastases when first seen: dyspnea, cough, headache, bone pain • Abd pain, abd mass,

Para-neoplastic syndrome3-10% of RCC present by paraneoplastic syndromehematopoietic disturbances: anemia, polycythemia; raised ESR: RCC is the most common cause of paraneoplastic erythrocytosisendocrinopathies: hypercalcemia 20% (production of PTH), production of other hormones including erythropoietin, renin, prolactin, gonadotropins, TSH, insulin, and cortisol. PUO hemodynamic alterations: systolic hypertension 40% (due to AV shunting, production of renin), and peripheral edema (due to caval obstruction)Non-metastatic hepatic dysfunction: “Staufer’s syndrome”: abnormal liver function tests, decreased WBC count, fever, areas of hepatic necrosis; reversible following removal of primary tumour

Laboratory FINDINGS• routine labs for paraneoplastic syndromes• CBC anemia (30%)• High ESR• urinalysis (60-75% have hematuria)

Imaging

U\S: Doppler IVP 75% accurate CT scan: it is the leader for diagnosis and staging and detect distant metastasis MRI Renal angiography: no longer routinely done Fine needle aspiration indicated in : metastatic disease, planned for nonsurgical management establishing diagnosis in patients who are not surgical candidate


Differential diagnosis
Carcinoma of renal pelvis Renal lymphoma Adrenal cancer Benign renal tumor Renal cysts Renal abscess

TREATMENT

LOCALISED DISEASEStage (I, II , IIIa )→• surgical (mainstay): • partial Nx: • small, polar, or bilateral tumors• radical nephrectomy:• en bloc removal of kidney, tumour, ipsilateral adrenal gland and intact Gerota’s capsule and periaortic lymphadenectomy


DISSEMINATED DISEASE30% of RCC are metastatic Surgical: the role of radical nephrectomy is limited. It is a palliative therapy• surgical removal of solitary metastasis may be consideredImmunotherapy→15% response ratecytokine interleukin-2α- INFTyrosin kinase inhibitors---monoclonal Abs Radiotherapy (RCC is a radioresistant): • radiation for palliation• for painful bony lesionsChemotherapy (is also chemoresistant )

Prognosis• stage at diagnosis is the single most important predictor of survival:• 5 year survival of T1 is 90-100%• 5 year survival of T2-T3 is approximately 60%• 5 year survival of patients presenting with metastasis is 0-20%

CARCINOMA OF THE RENAL PELVIS AND URETER

❏incidence• rare, accounts for 4% of all urothelial cancers• frequently multifocal• papillary transitional cell cancer 85%• male:female = 3:1❏relative incidence• bladder:pelvis:ureter = 100:10:1❏predisposing factors• chemical exposure (industrial dyes and solvents)• smoking• analgesic abuse (acetaminophen, aspirin, and phenacetin)• Balkan nephropathy Age group > 65 yearsPatients with single upper tract carcinoma are at risk of developing bladder carcinoma (30-50%) and contralateral upper tract (2-4%).


❏symptoms and signs• gross painless hematuria (70-90% of patients)• microscopic hematuria found incidentally• flank pain 50%• tenderness over kidney• flank mass caused by either tumour or associated hydronephrosis (10-20% of patients)• irritative symptoms• weight loss

LABORATORY FINDINGS Hematuria is identified in majority of cases Anemia Elevated liver function Urine cytology

IMAGING• diagnosis is made by noting a radiolucent filling defect on IVP• differential diagnosis of filling defect• transitional cell carcinoma (differentiate via cytology and CT scan)• uric acid stone (differentiate via cytology and CT scan)• blood clot• pyelitis cystica• papillary necrosis• fungus ball• gas bubble from gas producing organismsRETROGRADE PYELOGRAPHY is more accurateCT scan identify soft tissue abnormality of renal pelvisURETEROPYELOSCOPY allow direct visualization of upper urinary tract and tissue sampling



TREATMENT Based on: grade, stage, position and multiplicity The standard therapy is radical ureteronephrectomy with cuff of bladder

Tumor of distal ureter : distal ureterectomy and ureter reimplantation

BLADDER CARCINOMA
❏incidence• male:female = 3:1• usually > 55 years• average age is 65 years• may be characterized by frequent recurrences• common in whites than in blacks • is the second most common cancer of genitourinary tract• 85% are localized, 15% have distant sites

❏classification• transitional cell carcinoma (TCC) 92%• squamous cell carcinoma (SCC) 7%• adenocarcinoma 1%• others < 1%

PATHOGENESIS AND ETIOLOGY

Cigarette smoking account for 50 % of men and 30% of women, the causative agent are to be alpha and beta naphthylamine which are secreted in urine of smokers Occupational exposure to certain chemicals as •naphthylamines, benzidine, tryptophan metabolites (rubber ,petroleum, printing industries)Cyclophosphamide phenacetin metabolitesSchistosoma hematobium (associated with SCC)Artificial sweetenersCalculi and infection: chronic irritation (cystitis)Genetic predisposition

STAGING

HYSTOPATHOLOGY
PAPILOMA: is uncommon Represent about <2 % of all transiotional cell Tumor , has a very good prognosis Transitional cell carcinoma: Accounts for 90% of all bladder cancer Appears as papillary exophytic lesion May be sessile or ulcerated



❏stages of transitional cell carcinoma at diagnosis• superficial papillary (75%)• 15% of these will progress to invasive TCC• the majority of these patients will have recurrence• invasive (25%)• 85% have no prior history of superficial TCC• 50% have occult metastases at diagnosis• carcinoma in situ• may progress to invasive TCC

NONTRANSITIONAL CELL CARCIMOMA 1: ADENOCARCINOMA : Accounts for <2% of bladder cancer Mucous secreting tumor Arise along the floor of bladder Muscle invasion is usually present 5 years survival <40%


2 SQUAMOUS CELL CARCINOMA Accounts for 5-10% of bladder tumor Often associated with H\O bilharzial infection, vesical calculi , chronic catheterisation In Egypt represent about 60% of bladder cancer


3 UNDIFFERENTIATED CARCINOMA: Is rare , represent < 2% of bladder carcinoma 4 MIXED CARCINOMA: Constitute 4-6% of all bladder carcinoma Composed of transitional , squamous, or undifferentiated carcinoma

Clinical picture

A :SYMPTOMS: • hematuria is the presenting symptom in 85-90%May be gross or microscopicIntermittent rather than constant• pain 50%• clot retention 17%• no symptoms 20%• occult hematuria• irritative urinary symptoms - consider carcinoma in situ• symptoms of advanced disease

B: SIGNS: The majority of patients have no pertinent physical signs. patients with advanced disease may have a palpable mass. Hepatomegaly and supraclavicular lymph node indicate advanced disease

LABORATORY FINDINGS UA: the most common is hematuria Azotemia in case of ureteral occlusion Anemia may be a presenting symptom due to chronic blood loss and replacement of bone marrow by metastatic cells. Urine cytology .


IMAGING: Used To Evaluate the upper urinary tract Assess the depth of muscle infiltration Presence of regional or distant metastasis ultrasound IVU: the most common imaging test for evaluation of hematuria CT scan Cystourethroscopy with bladder washings (gold standard) new advances with specific bladder tumour markers (NMP-22, BTA, Immunocyt, FDP) for invasive disease CT, chest x-ray, liver tests



TREATMENT
TUR or laser vaporization :For patients with single low grade, noninvasive tumorPartial cystectomy For solitary infiltrating tumor (T1-T3) in bladder dome, cancer of bladder diverticulaRadical cystectomy with urinary diversion and/or irradiation In locally advanced disease (T2a, T2b, T3)Irradiation +/– systemic chemotherapyMetastatic disease (T4a, T4b, N+, M+)