BenignBenign MalignantMalignantPelvi-calycealPelvi-calyceal T C papillomaT C papilloma T C CarcinomaT C CarcinomaSq C CarcinomaSq C CarcinomaParenchymalParenchymal Renal papillaryRenal papillaryAdenomaAdenomaR C CR C CWilmsWilmsPerirenal fat&Perirenal fat&capsulecapsuleLipoma - FibromaLipoma - Fibroma liposarcomaliposarcomaVessels & smoothVessels & smoothmsmsHemangiomaHemangiomaAngiomyolipomaAngiomyolipomaOncocytomaOncocytomaHemangiosarcomHemangiosarcomaa2ry tumor2ry tumor Any secon.Any secon.
Algorithm for radiographicAlgorithm for radiographicevaluation ofevaluation of renal massrenal mass Several radiographic modalities are currently available forSeveral radiographic modalities are currently available fordetection and evaluation of renal massesdetection and evaluation of renal masses IVPIVP :: CCalcification within the mass, increased tissuealcification within the mass, increased tissuedensity, irregularity of the margin, and distortion of thedensity, irregularity of the margin, and distortion of thecollecting systemcollecting system((may miss small anterior or posterior lesions that do not distortmay miss small anterior or posterior lesions that do not distortthe collecting system or the contour of the kidney, may notthe collecting system or the contour of the kidney, may notalways distinguish solid from cystic lesionsalways distinguish solid from cystic lesions )) Detection by IVU is onlyDetection by IVU is only 2121% when the lesion is smaller than% when the lesion is smaller than2 cm2 cm,, 5252% when the lesion is% when the lesion is 2-32-3 cm,cm, andand 8585% when the lesion is% when the lesion is 3 cm3 cm or more in diameteror more in diameter
Algorithm for radiographic evaluation ofAlgorithm for radiographic evaluation of renal massrenal mass U/S:U/S: The initial imaging procedure of choiceThe initial imaging procedure of choice Reliable for differentiation ofReliable for differentiation of solidsolid tissue fromtissue fromfluidfluid (cyst) and can establish the diagnosis of a(cyst) and can establish the diagnosis of asimple renal cystsimple renal cyst.. It can also allow the diagnosis of anIt can also allow the diagnosis of anangiomyolipomaangiomyolipoma by the characteristic increasedby the characteristic increasedechogenicity produced by high fat content.echogenicity produced by high fat content. Sonographic criteria forSonographic criteria for simple cystssimple cysts include:include: 1-1-smooth cyst wall,smooth cyst wall, 2-2- round or oval shaperound or oval shape 3-3-without internal echoes (clear fluid)without internal echoes (clear fluid) 4-4- NoNocalcification nor septationcalcification nor septation
Algorithm for radiographicAlgorithm for radiographicevaluation ofevaluation of renal massrenal mass If US equivocal, or suggestive of malignancyIf US equivocal, or suggestive of malignancysolid or complexsolid or complexwith internal echoeswith internal echoesand irregular wallsand irregular wallsif calcifications or septae are seenif calcifications or septae are seen========Then proceed to CT========Then proceed to CT
Algorithm for radiographic evaluation ofAlgorithm for radiographic evaluation of renal massrenal mass AA renal CTrenal CT scan remains the single mostscan remains the single mostimportant radiographic test for delineating theimportant radiographic test for delineating thenature of a renal massnature of a renal mass.. In general, any renal mass that enhances withIn general, any renal mass that enhances withintravenous administration of contrast materialintravenous administration of contrast materialon CT scanning by more than 15 Hounsfield unitson CT scanning by more than 15 Hounsfield units((HUHU)) should be considered a renal cell carcinomashould be considered a renal cell carcinoma((RCCRCC)) until proved otherwiseuntil proved otherwise In approximately 10% of solid renal masses, CTIn approximately 10% of solid renal masses, CTfindings are indeterminate, and additional testing orfindings are indeterminate, and additional testing orsurgical exploration is needed to establish a definitivesurgical exploration is needed to establish a definitive
Renal Cell CarcinomaRenal Cell Carcinoma 3D CT scan of a small RCC that is peripheral3D CT scan of a small RCC that is peripheraland exophytic which is ideal for nephron sparingand exophytic which is ideal for nephron sparingsurgerysurgery
Algorithm for radiographicAlgorithm for radiographicevaluation ofevaluation of renal massrenal mass MRIMRI : is reserved for >>: is reserved for >>contrast hypersensitive patientscontrast hypersensitive patientshigh serum creatininehigh serum creatinineVascular invasion, IVC thrombiVascular invasion, IVC thrombi
Algorithm for radiographicAlgorithm for radiographicevaluation ofevaluation of renal massrenal mass FineFine--needle aspirationneedle aspiration or biopsy hasor biopsy hastraditionally been of limited value intraditionally been of limited value inthe evaluation of renal massesthe evaluation of renal masses The primary indications for needleThe primary indications for needleaspiration or biopsy of a renal mass areaspiration or biopsy of a renal mass arewhen a renalwhen a renal abscess or infected cystabscess or infected cyst isissuspected and when RCC must besuspected and when RCC must bedifferentiated fromdifferentiated from metastaticmetastaticmalignant disease ormalignant disease or renal lymphomarenal lymphoma
Algorithm for radiographicAlgorithm for radiographicevaluation ofevaluation of renal massrenal massMetastatic workupMetastatic workuproutine chest radiographroutine chest radiographliver function testsliver function testsbone scanbone scanC T chestC T chest
RevisionRevision What are the indications for MRI in RCC?What are the indications for MRI in RCC? •• possible venous involvementpossible venous involvement •• renal insufficiencyrenal insufficiency •• allergy to IV contrastallergy to IV contrast What are the features suggestive ofWhat are the features suggestive ofmalignancy on IVP?malignancy on IVP? •• calcification w/i the masscalcification w/i the mass •• increased tissue densityincreased tissue density •• irregular marginirregular margin •• invasion of the collecting systeminvasion of the collecting system
BENIGN RENAL TUMORSBENIGN RENAL TUMORS Arise from cortical tissue (e.g.,Arise from cortical tissue (e.g., adenoma,adenoma,oncocytomaoncocytoma) or from the various) or from the variousmesenchymal derivatives within themesenchymal derivatives within theparenchyma or capsule of the kidneyparenchyma or capsule of the kidney(Angiomyolipoma).(Angiomyolipoma). Differentiation from malignantDifferentiation from malignantrenal masses by radiographic orrenal masses by radiographic orclinical means can be challenging.clinical means can be challenging.06/25/13
BENIGN RENAL TUMORSBENIGN RENAL TUMORS Renal papillary AdenomaRenal papillary Adenoma : epithelial lesions: epithelial lesionswith a tubulowith a tubulo--papillary architecturepapillary architecture ..UsuallyUsuallymeasuring less than 0.5cmmeasuring less than 0.5cm The “3-cm rule”The “3-cm rule” Renal exploration and wedge resectionRenal exploration and wedge resection ororother ablative therapies should be stronglyother ablative therapies should be stronglyconsidered for all such clinically evidentconsidered for all such clinically evidentlesions, with appropriate consideration oflesions, with appropriate consideration ofthe patients age, comorbidities, and otherthe patients age, comorbidities, and otherrelevant factors.relevant factors.
BENIGN RENAL TUMORSBENIGN RENAL TUMORS OncocytomaOncocytoma:: epithelialepithelial tumor composedtumor composedof oncocytes, largeof oncocytes, large eosinophiliceosinophilic cells havingcells havingsmall, round, benign-appearingsmall, round, benign-appearing nucleinuclei withwithlargelarge nucleolinucleoli.. Arise from the intercalated cells ofArise from the intercalated cells ofcollecting ductscollecting ducts of the kidneyof the kidney UnfortunatelyUnfortunately, most renal oncocytomas, most renal oncocytomascannot be differentiated from malignantcannot be differentiated from malignantRCC by clinical or radiographic meansRCC by clinical or radiographic means
BENIGN RENAL TUMORSBENIGN RENAL TUMORS AngiomyolipomaAngiomyolipoma :: benign tumorbenign tumor consisting ofconsisting ofvarying amounts of maturevarying amounts of mature adipose tissueadipose tissue,,smooth muscle, andsmooth muscle, and thickthick--walled vesselswalled vessels Approximately 20% to 30% of AMLs are found inApproximately 20% to 30% of AMLs are found inpatients withpatients with tuberous sclerosistuberous sclerosis syndromesyndrome ((TSTS)),,an autosomal dominant disorder characterized byan autosomal dominant disorder characterized bymental retardation, epilepsy, and adenomamental retardation, epilepsy, and adenomasebaceumsebaceum Middle aged femaleMiddle aged female C/PC/P : Asymptomatic or: Asymptomatic or ( loin pain , hematuria,( loin pain , hematuria,palpable mass, and hypovolemic shock)palpable mass, and hypovolemic shock)
BENIGN RENAL TUMORSBENIGN RENAL TUMORS Angiomyolipoma:Angiomyolipoma: Diagnosed byDiagnosed by TheThepresence of even a small amount of fatpresence of even a small amount of fatwithin a renal lesion on CT scan (confirmedwithin a renal lesion on CT scan (confirmedby a value of -20 HU or lower) virtuallyby a value of -20 HU or lower) virtuallyexcludes the diagnosis of RCC and isexcludes the diagnosis of RCC and isconsidered diagnostic of AMLconsidered diagnostic of AML ManagementManagement :: 1- Asymptomatic, smaller AMLs, less than 41- Asymptomatic, smaller AMLs, less than 4cm, can be observed expectantlycm, can be observed expectantly 2- Intervention should be considered for2- Intervention should be considered forlarger tumors, particularly if the patient islarger tumors, particularly if the patient issymptomaticsymptomatic
Renal Cell CarcinomaRenal Cell Carcinoma DefinitionDefinition :: Malignant tumor of renalMalignant tumor of renalparenchymaparenchyma TerminologyTerminology : renal cell carcinoma ,: renal cell carcinoma ,hypernephroma , grawitz tumor , renalhypernephroma , grawitz tumor , renaladenocarcinomaadenocarcinoma OriginOrigin : The epithelial lining of the: The epithelial lining of theproximal convoluted tubuleproximal convoluted tubule Age:Age: 55thth– 6– 6ththdecadedecade SexSex :: M to FM to F 2:12:1
Renal Cell CarcinomaRenal Cell Carcinoma Risk factorsRisk factors:: The only generally acceptedThe only generally acceptedenvironmental risk factor for RCC is tobaccoenvironmental risk factor for RCC is tobaccoexposureexposure , Others : obesity , hypertension ,, Others : obesity , hypertension ,heavy metalsheavy metals GeneticsGenetics :: Von Hippel LindauVon Hippel Lindau syndrome,syndrome,affecting 50% of individual with this ADaffecting 50% of individual with this ADsyndrome, ch ch by , renal & pancreatic cyst,syndrome, ch ch by , renal & pancreatic cyst,phaeochromocytoma, cerebellarphaeochromocytoma, cerebellarhemangioblastoma , often bilaterallyhemangioblastoma , often bilaterally
RENAL CELL CARCINOMARENAL CELL CARCINOMAINVESTIGATIONS ;INVESTIGATIONS ;*Laboratory studies in the evaluation of renal cell carcinoma*Laboratory studies in the evaluation of renal cell carcinomashould include a workup for paraneoplastic syndromes. Initialshould include a workup for paraneoplastic syndromes. Initialstudies are as follows:studies are as follows:-Urine analysis-Urine analysis-CBC count with differential-CBC count with differential-Electrolytes-Electrolytes-Renal profile-Renal profile*Liver function tests (AST and ALT)*Liver function tests (AST and ALT)*Calcium*Calcium*Erythrocyte sedimentation rate*Erythrocyte sedimentation rate*Prothrombin time*Prothrombin time*Activated partial thromboplastin time*Activated partial thromboplastin time*Other tests indicated by presenting symptoms*Other tests indicated by presenting symptoms
Renal Cell CarcinomaRenal Cell CarcinomaParaneoplastic syndromeParaneoplastic syndrome found infound in 20%20% of patients with RCCof patients with RCC Due to ectopic hormone secretion by the tumorDue to ectopic hormone secretion by the tumor Not related to the stageNot related to the stage In general, treatment of paraneoplasticIn general, treatment of paraneoplasticsyndromes associated with RCC has requiredsyndromes associated with RCC has requirednephrectomy or systemic immunotherapy, andnephrectomy or systemic immunotherapy, andexcept for hypercalcemia, medical therapiesexcept for hypercalcemia, medical therapieshave not proved helpfulhave not proved helpful
Stauffer’s syndromeStauffer’s syndrome is a reversible syndromeis a reversible syndromeof hepatic dysfunction in the absence of hepaticof hepatic dysfunction in the absence of hepaticmetastases associated with RCC and can occurmetastases associated with RCC and can occurin up to 20% of patients.in up to 20% of patients. Hepatic function abnormalities include elevationHepatic function abnormalities include elevationof alkaline phosphatase and bilirubin,of alkaline phosphatase and bilirubin,hypoalbuminemia, prolonged prothrombin time,hypoalbuminemia, prolonged prothrombin time,and hypergammaglobulinemia.and hypergammaglobulinemia.
Obstacles Towards TreatmentObstacles Towards Treatment RCC is historically resistant to many types of treatmentRCC is historically resistant to many types of treatment Chemotherapy (MDR-1)Chemotherapy (MDR-1) RadiationRadiation Very aggressive in nature (TGF alpha and EGFR)Very aggressive in nature (TGF alpha and EGFR) Highly vascular (VEGF secondary to loss of vHL)Highly vascular (VEGF secondary to loss of vHL) Expresses tumor-associated antigens (PRAME, RAGE-Expresses tumor-associated antigens (PRAME, RAGE-1, gp75, and MN-9) which contributes to its1, gp75, and MN-9) which contributes to itsimmunogenicityimmunogenicity
Tx of Localized RCCTx of Localized RCC Radical nephrectomyRadical nephrectomy Nephron-sparing surgery (NSS)Nephron-sparing surgery (NSS) NSS with normal opposite kidneyNSS with normal opposite kidney NSS with vHL diseaseNSS with vHL disease Thermal ablative therapiesThermal ablative therapies ObservationObservation
Radical nephrectomyRadical nephrectomy Robson and colleagues “gold standard”Robson and colleagues “gold standard”19691969 Prototype – A then B, Gerota’s intact, ipsiPrototype – A then B, Gerota’s intact, ipsiadrenal, LND (crus to aortic bifurcation)adrenal, LND (crus to aortic bifurcation) Now – no adrenal if no radiolgicalNow – no adrenal if no radiolgicalevidence unless : extensive renalevidence unless : extensive renalinvolvement, locally advanced, locatedinvolvement, locally advanced, locatedupper pole, immediately adjacent to adrenalupper pole, immediately adjacent to adrenal
Today – LND = controversialToday – LND = controversial Heme & Lymph spreadHeme & Lymph spread Lymphatic drainage variableLymphatic drainage variable <2-3% benefit<2-3% benefit However, more accurate stagingHowever, more accurate staging Risk factors indicating LNDRisk factors indicating LND High tumor gradeHigh tumor grade Sarcomatoid componentSarcomatoid component Histologic tumor necrosisHistologic tumor necrosis Large size (> 10 cm)Large size (> 10 cm) pT3 or pT4pT3 or pT4 *incidence 10% with 2 or >, 0.6% if <*incidence 10% with 2 or >, 0.6% if <
Surgical approach determined by size,Surgical approach determined by size,location of tumor and body habituslocation of tumor and body habitus TransperitonealTransperitoneal SubcostalSubcostal thoracoabdominalthoracoabdominal ExtraperitonealExtraperitoneal FlankFlank Laparoscopic (trans, retro, hand-assist)Laparoscopic (trans, retro, hand-assist)
LaparoscopicLaparoscopic Cancer specific survival comparable to openCancer specific survival comparable to open Usually < 8-10cm; localized with no local invasion,Usually < 8-10cm; localized with no local invasion,renal vein involvement, or lymphadenopathyrenal vein involvement, or lymphadenopathy
Postoperative Surveillance after RadicalPostoperative Surveillance after RadicalNephrectomy for Localized Renal Cell CarcinomaNephrectomy for Localized Renal Cell CarcinomaPathologicPathologicTumorTumorStageStageHistory,History,Examination,Examination,and Bloodand BloodTestsTestsChestChestRadiographRadiographAbdominalAbdominalCT ScanCT ScanT1 N0 M0T1 N0 M0 YearlyYearly —— ——T2 N0 M0T2 N0 M0 YearlyYearly YearlyYearly Every 2 yearsEvery 2 yearsT3a-c N0 M0T3a-c N0 M0 Every 6Every 6months for 3months for 3years, thenyears, thenyearlyyearlyEvery 6Every 6months for 3months for 3years, thenyears, thenyearlyyearlyAt 1 year, thenAt 1 year, thenevery 2 yearsevery 2 years
Nephron-Sparing SurgeryNephron-Sparing Surgery Czerny 1890Czerny 1890 Vermooten 1950 – NSSVermooten 1950 – NSS Indications include situations where ptIndications include situations where ptwould be anephric or high risk of needingwould be anephric or high risk of needingHDHD Solitary kidney RCCSolitary kidney RCC Bilateral RCCBilateral RCC Contralateral disease (Hydro, chronic pyelo,Contralateral disease (Hydro, chronic pyelo,reflux, stones, DM, nephrosclerosis)reflux, stones, DM, nephrosclerosis)
Indications for NSSIndications for NSS Absolute:Absolute: Anatomical/ functional solitaryAnatomical/ functional solitarykidneykidney Relative:Relative: Functioning opposite kidney isFunctioning opposite kidney isaffected by a condition that mayaffected by a condition that mayimpair renal function in futureimpair renal function in future Elective:Elective: Localized unilateral RCC with aLocalized unilateral RCC with ahealthy contralateral kidneyhealthy contralateral kidney
A functional remnant of at least 20% ofA functional remnant of at least 20% ofone normal kidney is necessary to avoidone normal kidney is necessary to avoidend-stage renal failureend-stage renal failure IF solitary kidney, > 50% reduction inIF solitary kidney, > 50% reduction inrenal mass = incr risk of hyperfiltrationrenal mass = incr risk of hyperfiltrationrenal injury (proteinuria, focal segmentalrenal injury (proteinuria, focal segmentalglomerulosclerosis, progressive renalglomerulosclerosis, progressive renalfailure)failure) Prevention: Protein restriction & ACEIPrevention: Protein restriction & ACEI
Preoperative testingPreoperative testing r/o local extension, mets, vascular/collecting systemr/o local extension, mets, vascular/collecting systemrelationshiprelationship Renal angio, veno, 3DCT or MRIRenal angio, veno, 3DCT or MRI Cancer-specific survival rates 78-100%Cancer-specific survival rates 78-100% Recurrence – undetected dz in remnantRecurrence – undetected dz in remnant Complications – majority hemorrhagicComplications – majority hemorrhagic
NSS SurveillanceNSS SurveillanceStageStage H/E/labsH/E/labs CXRCXR CTa/pCTa/p T1NOMOT1NOMO yearlyyearly -------- -------- T2NOMOT2NOMO yearlyyearly yearlyyearly q 2 yrsq 2 yrs T3NOMOT3NOMO q 6m x 3 yr - yrq 6m x 3 yr - yr samesame q6m x3y –q2yrq6m x3y –q2yr
Thermal ablativeThermal ablative Both perc or lap approachBoth perc or lap approach Lack of histo/path stagingLack of histo/path staging ? High recurrence rate? High recurrence rate Ideal – advanced age, comorbidities, localIdeal – advanced age, comorbidities, localrecurrance, hereditary renal cancerrecurrance, hereditary renal cancer CryosurgeryCryosurgery Repetition of freeze-thaw cycle (-20C)Repetition of freeze-thaw cycle (-20C) Immediate cellular cryodestruction andImmediate cellular cryodestruction anddelayed microcirculatory failure.delayed microcirculatory failure. Radiofrequency ablationRadiofrequency ablation 45C irreversible cell damage45C irreversible cell damage 55-60C immediate cell death55-60C immediate cell death
Thermal Ablative PearlsThermal Ablative Pearls In general, enhancement within the tumor bed onIn general, enhancement within the tumor bed onextended follow-up has been considered diagnosticextended follow-up has been considered diagnosticof local recurrence, and the clinical experience thusof local recurrence, and the clinical experience thusfar has supported thisfar has supported this
ObservationObservation Median growth rate 0.36 cm/yrMedian growth rate 0.36 cm/yr Alternative for asymptomatic elderly andAlternative for asymptomatic elderly andpoor surgical risk, consider withpoor surgical risk, consider withsolid/small/enhancing/well-solid/small/enhancing/well-marginated/homogeneousmarginated/homogeneous Serial imaging 6mo or 1yr intervalsSerial imaging 6mo or 1yr intervals Not appropriate: >3cm, poor margins,Not appropriate: >3cm, poor margins,nonhomogeneous, young healthy with abnnonhomogeneous, young healthy with abnimagingimaging
Tx of Locally AdvancedTx of Locally Advanced RCCRCC IVC involvementIVC involvement Locally invasive RCCLocally invasive RCC Local recurrence after RN or NSSLocal recurrence after RN or NSS Adjuvant therapy for RCCAdjuvant therapy for RCC
IVC InvolvementIVC Involvement Unique feature of RCCUnique feature of RCC 45-70% of RCC with IVC thrombus cured45-70% of RCC with IVC thrombus cured Local extension/invasion much higher risk ofLocal extension/invasion much higher risk ofrecurrencerecurrence Occurs 4-10% of patientsOccurs 4-10% of patients Suspect with : LE edema, R varicocele,Suspect with : LE edema, R varicocele,distended abd veins, proteinuria, PE, Rdistended abd veins, proteinuria, PE, Ratrial mass, nonfxn kidneyatrial mass, nonfxn kidney
IVC Thrombus stagingIVC Thrombus staging I – adjacent to ostium of renal veinI – adjacent to ostium of renal vein II – extends up to liverII – extends up to liver III – intrahepatic portion of IVC belowIII – intrahepatic portion of IVC belowdiaphragmdiaphragm IV – above the diaphragmIV – above the diaphragm ImagingImaging CT & AUSCT & AUS Contrast inferior venacavography – if probContrast inferior venacavography – if probwith MRIwith MRI MRI – study of choiceMRI – study of choice ? Renal arteriography? Renal arteriography
ImagingImaging (contd)(contd) Investigate locally advanced malignancy,Investigate locally advanced malignancy,and specially forand specially for classification of Venaclassification of Venacaval thrombus:caval thrombus: Peri-renalPeri-renal Infra-hepaticInfra-hepatic Intra-hepaticIntra-hepatic Supra-hepaticSupra-hepatic
Locally Invasive RCCLocally Invasive RCC Present with pain from invasion of posteriorPresent with pain from invasion of posteriorabd wall, nerve roots or paraspinous musclesabd wall, nerve roots or paraspinous muscles Duodenal & pancreas uncommonDuodenal & pancreas uncommon En bloc may be beneficialEn bloc may be beneficial Partial / debulking – only 12% alive in 1 yrPartial / debulking – only 12% alive in 1 yr Preoperative rad – not beneficial (van derPreoperative rad – not beneficial (van derWerf-Messing 1973)Werf-Messing 1973) Residual tumor, rad may retard growth (Kao etResidual tumor, rad may retard growth (Kao etal 1994)al 1994)
Adjuvant Therapy for RCCAdjuvant Therapy for RCC Include hormonal manipulation,Include hormonal manipulation,radiotherapy, vaccines, cytokines, etc…radiotherapy, vaccines, cytokines, etc… Most studies to date – not significantMost studies to date – not significant Vaccine – irradiated tumor cells/BCG, heatVaccine – irradiated tumor cells/BCG, heatshock proteins (HSPPC) = no provenshock proteins (HSPPC) = no provenbenefitbenefit Interferon alfa – modest survival benefitInterferon alfa – modest survival benefit IL-2 – no benefitIL-2 – no benefit
Tx of Metastatic RCCTx of Metastatic RCC NephrectomyNephrectomy Hormonal therapyHormonal therapy ChemotherapyChemotherapy Radiation therapyRadiation therapy Cytokines and Immunologic therapyCytokines and Immunologic therapy Multimodal therapyMultimodal therapy
NephrectomyNephrectomy 1/31/3rdrdof RCC have metsof RCC have mets 40-50% will develop mets after initial dx40-50% will develop mets after initial dx Regression of mets after RN – 1-2% (lung)Regression of mets after RN – 1-2% (lung) Benefit for synchronous mets withBenefit for synchronous mets withinterferon alfa after RNinterferon alfa after RN Individuals with: adv dz (PS > 2), mets (CNS,Individuals with: adv dz (PS > 2), mets (CNS,SC compression), MOD, significantSC compression), MOD, significantcomorbidities – not candidatecomorbidities – not candidate
Hormone TherapyHormone Therapy Minimal valueMinimal value Progesterone – inhibit growth of DES-induced renalProgesterone – inhibit growth of DES-induced renaltumors in Syrian hamsterstumors in Syrian hamsters No correlation with human RCCNo correlation with human RCC Progestational agents = useful for symptomProgestational agents = useful for symptompalliationpalliation
RevisionRevisionWhy were RCCs originally called hypernephromas?Why were RCCs originally called hypernephromas?idea of suprarenal origin of renal tumoursidea of suprarenal origin of renal tumours What is the role of FNA in evaluation of renalWhat is the role of FNA in evaluation of renalmasses?masses? •• limited valuelimited value →→ high incidence of false negative biopsieshigh incidence of false negative biopsies •• IndicationsIndications →→ renal abscess or infected cyst suspectedrenal abscess or infected cyst suspected →→ RCC must be differentiated from met orRCC must be differentiated from met orlymphoma
RevisionRevision What is the treatment for renal adenomas?What is the treatment for renal adenomas? •• consider all to be malignantconsider all to be malignant →→ consider wedge resection, other ablativeconsider wedge resection, other ablativetherapiestherapies Which patient groups are at increased riskWhich patient groups are at increased riskof developing AML?of developing AML? •• tuberous sclerosis 20% of all AMLstuberous sclerosis 20% of all AMLs •• female predominancefemale predominance
RevisionRevision Describe the clinical presentation of RCCDescribe the clinical presentation of RCC.. •• asymptomatic and nonpalpable until advancedasymptomatic and nonpalpable until advanced →→ >50% of RCCs now detected incidentally>50% of RCCs now detected incidentally •• hemorrhage, paraneoplastic syndromes, or metshemorrhage, paraneoplastic syndromes, or mets •• classic triad: flank pain, gross hematuria, andclassic triad: flank pain, gross hematuria, andpalpable abdominal mass rarely foundpalpable abdominal mass rarely found •• indicators of advanced diseaseindicators of advanced disease →→ constitutional sy: wt loss, fever, NS, bone pain,constitutional sy: wt loss, fever, NS, bone pain,persistent coughpersistent cough →→ paraneoplastic syndromesparaneoplastic syndromes
NEPHROBLASTOMANEPHROBLASTOMA((Wilms’ tumour )Wilms’ tumour ) Embryonal tumour arising fromEmbryonal tumour arising fromnephrogenic blastemal cellsnephrogenic blastemal cells can differentiate in to several cell lines -can differentiate in to several cell lines -blastemal, epithelial and stromalblastemal, epithelial and stromal many replicate developing kidneysmany replicate developing kidneys Common in young children /Common in young children /uncommon in neonates and infantsuncommon in neonates and infants 90% in < 6yrs. old ( mean: 3yrs. in boys90% in < 6yrs. old ( mean: 3yrs. in boysand 3.5yrs. in girlsand 3.5yrs. in girls ))
NEPHROBLASTOMANEPHROBLASTOMAEtiology and cytogeneticsEtiology and cytogenetics Generally unknownGenerally unknown World wide i.e. … No environmental factorsWorld wide i.e. … No environmental factors Present in many syndromes :Present in many syndromes :1-WAGR syndrome1-WAGR syndrome (Wilms, aniridia,(Wilms, aniridia,genitourinary abnormalities, mental retardationgenitourinary abnormalities, mental retardation))2-2-Beckwith-WiedemannBeckwith-Wiedemann syndrome (exomphalos-syndrome (exomphalos-macroglossia-gigantismmacroglossia-gigantism ))3-Denys-Drash syndrome3-Denys-Drash syndrome ((Gonadal dysgenesis,Gonadal dysgenesis,nephropathy)nephropathy)
The most common presentation ofThe most common presentation ofWilms tumor is the presence of anWilms tumor is the presence of anasymptomatic abdominal mass.asymptomatic abdominal mass. HypertensionHypertension,, gross hematuriagross hematuria, and, andfever are observed in 5-30% of patients.fever are observed in 5-30% of patients. A small number of patients who haveA small number of patients who havehemorrhaged into their tumor mayhemorrhaged into their tumor maypresent with signs ofpresent with signs of hypotension,hypotension,anemiaanemia, and fever., and fever. Rarely, patients with advanced-stageRarely, patients with advanced-stagedisease may present withdisease may present with respiratoryrespiratorysymptomssymptoms related to the presence ofrelated to the presence oflung metastases.lung metastases.NEPHROBLASTOMA
NEPHROBLASTOMANEPHROBLASTOMAPathologic findingsPathologic findings (gross)(gross) Usually solitary, sharply (well)Usually solitary, sharply (well)defined masses with pseudocapsuledefined masses with pseudocapsule Variable size & weight (60-6350 gms.Variable size & weight (60-6350 gms.with a mean of 550 gms.)with a mean of 550 gms.) Uniform, pale gray to tan, divided byUniform, pale gray to tan, divided byprominent fibrous septa in to lobulesprominent fibrous septa in to lobules May be cystic, hemorrhagic orMay be cystic, hemorrhagic ornecroticnecrotic No specific location
NEPHROBLASTOMANEPHROBLASTOMAMicroscopic findingsMicroscopic findings Generally triphasic pattern :Generally triphasic pattern : blastemal, epithelial and stromal cell typeblastemal, epithelial and stromal cell type may contains heterologous elementsmay contains heterologous elements ““favorable” or “unfavorable” histologyfavorable” or “unfavorable” histologyon the bases of nuclear anaplasia i.e. . . .on the bases of nuclear anaplasia i.e. . . . marked nuclear enlargement (3x)marked nuclear enlargement (3x) abnormal mitoses i.e. . . . increased DNAabnormal mitoses i.e. . . . increased DNA
STAGINGSTAGING Histopathology and staging are the mostHistopathology and staging are the mostimportant determinants of outcomeimportant determinants of outcomeStageStage DescriptionDescriptionII Tumor limited to kidney & completely excised. Intact renal capsule,Tumor limited to kidney & completely excised. Intact renal capsule,tumor unruptured. No residual tumortumor unruptured. No residual tumorIIII Tumor extends thruogh capsule but completely excised. LocalTumor extends thruogh capsule but completely excised. Localspillage confined to flank or biopsied tumor. Extra renal vesselsspillage confined to flank or biopsied tumor. Extra renal vesselscontain tumor thrombus or infiltratedcontain tumor thrombus or infiltratedIIIIII Residual nonhaematogenous tumor confined to abdomen: lymphResidual nonhaematogenous tumor confined to abdomen: lymphnode involvement, diffuse peritoneal spillage, peritoneal implants,node involvement, diffuse peritoneal spillage, peritoneal implants,tumor beyond surgical margin grossly or microscopically or tumortumor beyond surgical margin grossly or microscopically or tumornot completely removednot completely removedIVIV Haematogenous mets to lung, liver, bone, brain or other organHaematogenous mets to lung, liver, bone, brain or other organVV Bilateral renal involvement at diagnosisBilateral renal involvement at diagnosis
NEPHROBLASTOMANEPHROBLASTOMASpreadSpread LocalLocal Regional i.e. . . lymphaticRegional i.e. . . lymphatic Distant :Distant :lungslungsliverliver
Wilms Tumor(Nephroblastoma(Plain X-Plain X-Ray:Ray:Large soft tissue massLarge soft tissue massdisplacing bowel gasdisplacing bowel gasCalcification is uncommon.Calcification is uncommon.
Wilms Tumor(Nephroblastoma(IVU:Large soft tissue massdistorting and displacingthe collecting system.
Wilms Tumor(Nephroblastoma(US:• Large soft tissue massheterogeneous echogenicity,which represents hemorrhage,necrosis, or calcification.• Vascular Invasion.
Wilms Tumor(Nephroblastoma(CT:CT demonstrates a well-defined heterogeneousmass with areas of necrosisand hemorrhage.Less common calcification.
Wilms Tumor(Nephroblastoma(CT:CT demonstrates a well-definedheterogeneous mass with areasof calcification, necrosis andhemorrhage.
Wilms Tumor(Nephroblastoma(CT:hepatic metastasesCT scan shows multiple hepaticmetastases in addition to tumorthrombus within the portal veins(arrows).
Wilms tumor in a 2-year-old boy. A, B: Contrast-enhanced axial computedtomography and coronal multiplanar reconstruction demonstrate a large,round, low-density mass that distorts and displaces the enhancingparenchyma (arrows) in the lower pole of the right kidneyWilms Tumor(Nephroblastoma(
Wilms Tumor(Nephroblastoma(MRI:Well-defined heterogeneous mass with low signalintensity on T1-weighted images and high signalintensity on T2-weighted images.
Timing of surgeryTiming of surgery NWTSG VS SIOP:NWTSG VS SIOP: In NWTSGIn NWTSG: surgery with complete resection of a: surgery with complete resection of aresectable tumour is to be performed first.resectable tumour is to be performed first.Chemotherapy first is to be given only for those withChemotherapy first is to be given only for those withirresectable tumour, bilateral wilms tumour, tumourirresectable tumour, bilateral wilms tumour, tumourthrombusthrombus In SIOPIn SIOP: surgery always is after neoadjuvant: surgery always is after neoadjuvantchemotherapy even for resectable tumourschemotherapy even for resectable tumours J urol 1998 159 1316-1325J urol 1998 159 1316-1325
NEPHROBLASTOMANEPHROBLASTOMAprognosis and treatmentprognosis and treatment Depends upon :Depends upon :stage, age and histologystage, age and histology Surgery with chemotherapy for :Surgery with chemotherapy for :stage I & II with favorable histologystage I & II with favorable histologysurgery with chemotherapy andsurgery with chemotherapy andradiotherapy for higher stages andradiotherapy for higher stages andunfavorable histologyunfavorable histology
Stage, HistologyStage, Histology SurgerySurgery ChemotherapyChemotherapy Radiotherapy*Radiotherapy*Stage I or II withStage I or II withFHFHStage I withStage I withanaplasiaanaplasiaNephrectomyNephrectomyVincristineVincristineDactinomycinDactinomycinNoneNoneStage III or IV withStage III or IV withFHFHStage II, III, or IVStage II, III, or IVwith focalwith focalanaplasiaanaplasiaNephrectomyNephrectomyVincristineVincristineDactinomycinDactinomycinDoxorubicinDoxorubicinYesYesStage II, III, or IVStage II, III, or IVwith diffusewith diffuseanaplasiaanaplasiaStage I, II, III, or IVStage I, II, III, or IVCCSKCCSKNephrectomyNephrectomyVincristineVincristineDoxorubicinDoxorubicinCyclophosphamidCyclophosphamideeEtoposideEtoposideYesYesStage I, II, III, or IVStage I, II, III, or IVRTKRTKNephrectomyNephrectomyCyclophosphamidCyclophosphamideeEtoposideEtoposideCarboplatinCarboplatinYesYes
TREATMENTTREATMENT Pre-operative chemo should be given to patientsPre-operative chemo should be given to patientswithwith Bilateral involvementBilateral involvement Inoperable disease at explorationInoperable disease at exploration IVC extension above portal veinsIVC extension above portal veins Primary nephrectomy for other patientsPrimary nephrectomy for other patients Initial biopsy then chemotherapy then 2Initial biopsy then chemotherapy then 2ndndlook atlook at8 – 10 weeks for bilateral disease8 – 10 weeks for bilateral disease
COMPLICATIONSCOMPLICATIONS Following irradiationFollowing irradiation ScoliosisScoliosis Hypogonadism & temporary azoospermiaHypogonadism & temporary azoospermia Ovarian failure (12%)Ovarian failure (12%) Second malignancySecond malignancy Following chemotherapyFollowing chemotherapy CCF following treatment with DoxorubicinCCF following treatment with Doxorubicin
RevisionRevision What is the most common primary malignantWhat is the most common primary malignantrenal tumour of childhood?renal tumour of childhood? Wilms tumour (a.k.a. nephroblastoma)Wilms tumour (a.k.a. nephroblastoma) What is the embryologic origin of WilmsWhat is the embryologic origin of Wilmstumour?tumour? •• develops from remnants of immature kidneydevelops from remnants of immature kidney What pathologic markers are associated w/What pathologic markers are associated w/favourable outcome in Wilms?favourable outcome in Wilms? •• classic (triphasic) composition: blastemal,classic (triphasic) composition: blastemal,epithelial, stromal elementsepithelial, stromal elements →→ worse w/ more blastemal elementsworse w/ more blastemal elements