5 renal tumor

04/11/23 School of Medicine/JUST

SamirSamir orabi MDorabi MD

RENAL TUMORSRENAL TUMORS

BenignBenign MalignantMalignant

Pelvi-calyceal Pelvi-calyceal T C papillomaT C papilloma T C T C CarcinomaCarcinoma

Sq C Sq C CarcinomaCarcinoma

Parenchymal Parenchymal Renal Renal papillary papillary AdenomaAdenoma

R C C R C C

Wilms Wilms

Perirenal fat& Perirenal fat& capsulecapsule

Lipoma - Lipoma - FibromaFibroma

liposarcomaliposarcoma

Vessels & Vessels & smooth mssmooth ms

HemangiomaHemangioma

AngiomyolipoAngiomyolipomama

OncocytomaOncocytoma

HemangiosarHemangiosarcomacoma

2ry tumor 2ry tumor Any secon.Any secon.

Algorithm for radiographic Algorithm for radiographic evaluation of evaluation of renal massrenal mass

Several radiographic modalities are currently available for Several radiographic modalities are currently available for detection and evaluation of renal massesdetection and evaluation of renal masses

IVPIVP : : CCalcification within the mass, increased tissue alcification within the mass, increased tissue density, irregularity of the margin, and distortion of density, irregularity of the margin, and distortion of the collecting systemthe collecting system

((may miss small anterior or posterior lesions that do not may miss small anterior or posterior lesions that do not distort the collecting system or the contour of the kidney, distort the collecting system or the contour of the kidney, may not always distinguish solid from cystic lesionsmay not always distinguish solid from cystic lesions ) )

Detection by IVU is only Detection by IVU is only 2121% when the lesion is smaller % when the lesion is smaller than than 2 cm2 cm, ,

5252% when the lesion is% when the lesion is 2-3 2-3 cm, cm, and and 8585% when the lesion is % when the lesion is 3 cm3 cm or more in diameter or more in diameter

Algorithm for radiographic evaluation Algorithm for radiographic evaluation of of renal massrenal mass

U/S:U/S: The initial imaging procedure of The initial imaging procedure of choicechoice

Reliable for differentiation of Reliable for differentiation of solidsolid tissue tissue from from fluidfluid (cyst) and can establish the (cyst) and can establish the diagnosis of a simple renal cystdiagnosis of a simple renal cyst..

It can also allow the diagnosis of an It can also allow the diagnosis of an angiomyolipomaangiomyolipoma by the characteristic by the characteristic increased echogenicity produced by high increased echogenicity produced by high fat content.fat content.

Sonographic criteria for Sonographic criteria for simple cystssimple cysts include: include: 1-1- smooth cyst wall, smooth cyst wall, 2-2- round or round or oval shape oval shape 3-3- without internal echoes (clear without internal echoes (clear fluid) fluid) 4-4- No calcification nor septation No calcification nor septation

Renal mass

Renal cyst Renal cyst


If US equivocal, or suggestive of If US equivocal, or suggestive of malignancy malignancy

solid or complex solid or complex

with internal echoes with internal echoes

and irregular walls and irregular walls

if calcifications or septae are seen if calcifications or septae are seen

========Then proceed to CT ========Then proceed to CT

Algorithm for radiographic evaluation of Algorithm for radiographic evaluation of renal renal massmass

A A renal CTrenal CT scan remains the single most scan remains the single most important radiographic test for delineating important radiographic test for delineating the nature of a renal massthe nature of a renal mass..

In general, any renal mass that enhances with In general, any renal mass that enhances with intravenous administration of contrast intravenous administration of contrast material on CT scanning by more than 15 material on CT scanning by more than 15 Hounsfield units Hounsfield units ((HUHU) ) should be considered a should be considered a renal cell carcinoma renal cell carcinoma ((RCCRCC) ) until proved until proved otherwiseotherwise

In approximately 10% of solid renal masses, CT In approximately 10% of solid renal masses, CT findings are indeterminate, and additional testing findings are indeterminate, and additional testing or surgical exploration is needed to establish a or surgical exploration is needed to establish a definitive diagnosis definitive diagnosis

CT scan without CT scan without administration of administration of

contrast materialcontrast material

After administration of the contrast agent

Renal Cell CarcinomaRenal Cell Carcinoma

before contrastbefore contrast

Contrast-enhanced Contrast-enhanced dedicated renal CT scandedicated renal CT scan

CT scan obtained


3D CT scan of a small RCC that is 3D CT scan of a small RCC that is peripheral and exophytic which is peripheral and exophytic which is ideal for nephron sparing surgeryideal for nephron sparing surgery


MRIMRI : is reserved for >> : is reserved for >>

contrast hypersensitive patients contrast hypersensitive patients

high serum creatininehigh serum creatinine

Vascular invasion, IVC thrombi Vascular invasion, IVC thrombi


FineFine--needle aspirationneedle aspiration or biopsy or biopsy has traditionally been of limited has traditionally been of limited value in the evaluation of renal value in the evaluation of renal massesmasses

The primary indications for needle The primary indications for needle aspiration or biopsy of a renal mass aspiration or biopsy of a renal mass are when a renal are when a renal abscess or infected abscess or infected cystcyst is suspected and when RCC must is suspected and when RCC must be differentiated from be differentiated from metastatic metastatic malignant disease or malignant disease or renal lymphomarenal lymphoma


Metastatic workupMetastatic workup routine chest radiographroutine chest radiograph

liver function testsliver function tests

bone scan bone scan

C 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 of What are the features suggestive of

malignancy 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, oncocytomaadenoma, oncocytoma) or from the ) or from the various mesenchymal derivatives various mesenchymal derivatives within the parenchyma or capsule of within the parenchyma or capsule of the kidney (Angiomyolipoma).the kidney (Angiomyolipoma).

Differentiation from malignant Differentiation from malignant renal masses by radiographic or renal masses by radiographic or clinical means can be clinical means can be challenging.challenging.

04/11/23

BENIGN RENAL TUMORSBENIGN RENAL TUMORS Renal papillary AdenomaRenal papillary Adenoma : epithelial : epithelial

lesions with a tubulolesions with a tubulo--papillary architecture papillary architecture ..Usually measuring less than 0.5cmUsually measuring less than 0.5cm

The “3-cm rule” The “3-cm rule” Renal exploration and wedge resectionRenal exploration and wedge resection

or other ablative therapies should be or other ablative therapies should be strongly considered for all such strongly considered for all such clinically evident lesions, with clinically evident lesions, with appropriate consideration of the appropriate consideration of the patient's age, comorbidities, and other patient's age, comorbidities, and other relevant factors.relevant factors.

BENIGN RENAL TUMORSBENIGN RENAL TUMORS

OncocytomaOncocytoma: : epithelialepithelial tumor composed tumor composed of oncocytes, large of oncocytes, large eosinophiliceosinophilic cells cells having small, round, benign-appearing having small, round, benign-appearing nucleinuclei with large with large nucleolinucleoli..

Arise from the intercalated cells of Arise from the intercalated cells of collecting ductscollecting ducts of the kidney of the kidney

UnfortunatelyUnfortunately, most renal oncocytomas , most renal oncocytomas cannot be differentiated from malignant cannot be differentiated from malignant RCC by clinical or radiographic meansRCC by clinical or radiographic means

BENIGN RENAL TUMORSBENIGN RENAL TUMORS

AngiomyolipomaAngiomyolipoma : : benign tumorbenign tumor consisting of varying amounts of mature consisting of varying amounts of mature adipose tissueadipose tissue, smooth muscle, and , smooth muscle, and thickthick--walled vesselswalled vessels

Approximately 20% to 30% of AMLs are Approximately 20% to 30% of AMLs are found in patients with found in patients with tuberous sclerosistuberous sclerosis syndrome syndrome ((TSTS)), an autosomal dominant , an autosomal dominant disorder characterized by mental disorder characterized by mental retardation, epilepsy, and adenoma retardation, epilepsy, and adenoma sebaceumsebaceum

Middle aged femaleMiddle aged female C/P C/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 The The

presence of even a small amount of fat presence of even a small amount of fat within a renal lesion on CT scan within a renal lesion on CT scan (confirmed by a value of -20 HU or lower) (confirmed by a value of -20 HU or lower) virtually excludes the diagnosis of RCC virtually excludes the diagnosis of RCC and is considered diagnostic of AMLand is considered diagnostic of AML

Management Management :: 1- Asymptomatic, smaller AMLs, less 1- Asymptomatic, smaller AMLs, less

than 4 cm, can be observed expectantlythan 4 cm, can be observed expectantly 2- Intervention should be considered for 2- Intervention should be considered for

larger tumors, particularly if the patient larger tumors, particularly if the patient is is symptomaticsymptomatic

Renal Cell CarcinomaRenal Cell Carcinoma DefinitionDefinition : : Malignant tumor of Malignant tumor of

renal parenchymarenal parenchyma TerminologyTerminology : renal cell carcinoma : renal cell carcinoma

, hypernephroma , grawitz tumor , , hypernephroma , grawitz tumor , renal adenocarcinomarenal adenocarcinoma

OriginOrigin : The epithelial lining of the : The epithelial lining of the proximal convoluted tubuleproximal convoluted tubule

Age:Age: 55thth – 6 – 6thth decade decade SexSex : : M to F M to F 2:1 2:1


Risk factorsRisk factors:: The only generally The only generally accepted environmental risk factor for accepted environmental risk factor for RCC is tobacco exposureRCC is tobacco exposure , Others : , Others : obesity , hypertension , heavy metals obesity , hypertension , heavy metals

GeneticsGenetics : : Von Hippel LindauVon Hippel Lindau syndrome, syndrome, affecting 50% of individual with this AD affecting 50% of individual with this AD syndrome, ch ch by , renal & pancreatic syndrome, ch ch by , renal & pancreatic cyst, phaeochromocytoma, cerebellar cyst, phaeochromocytoma, cerebellar hemangioblastoma , often bilaterallyhemangioblastoma , often bilaterally


HistopathologyHistopathology ::

1.1. Conventional Conventional ((70%–80%70%–80%)) (clear cell, granular, mixes) (clear cell, granular, mixes)

2.2. Chromophilic (10%–15%)Chromophilic (10%–15%)

3.3. Chromophobic (3%–5%) Chromophobic (3%–5%)

4.4. Collecting duct Collecting duct ((1%1%)) 5.5. Unclassified Unclassified ((1%1%))


C/PC/P : :

1.1. Asymptomatic Asymptomatic

2.2. HematuriaHematuria

3.3. Loin pain Loin pain

4.4. Palpable swellingPalpable swelling

5.5. Symptoms of metastasisSymptoms of metastasis

6.6. Paraneoplastic syndromeParaneoplastic syndrome

Classic triad

Less than 10-15%

RENAL CELL RENAL CELL CARCINOMACARCINOMA

INVESTIGATIONS ;INVESTIGATIONS ; *Laboratory studies in the evaluation of renal cell carcinoma *Laboratory studies in the evaluation of renal cell carcinoma

should include a workup for paraneoplastic syndromes. should include a workup for paraneoplastic syndromes. Initial studies are as follows: Initial 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 Carcinoma:Renal Cell Carcinoma:

Renal Cell CarcinomaRenal Cell CarcinomaParaneoplastic syndromeParaneoplastic syndrome found in found in 20%20% of patients with RCC of patients with RCC Due to ectopic hormone secretion by the Due to ectopic hormone secretion by the

tumortumor Not related to the stageNot related to the stage In general, treatment of In general, treatment of

paraneoplastic syndromes associated paraneoplastic syndromes associated with RCC has required nephrectomy with RCC has required nephrectomy or systemic immunotherapy, and or systemic immunotherapy, and except for hypercalcemia, medical except for hypercalcemia, medical therapies have not proved helpfultherapies have not proved helpful


Paraneoplastic syndromeParaneoplastic syndrome Elevated erythrocyte sedimentation Elevated erythrocyte sedimentation

rate 55.6rate 55.6 Hypertension 37.5Hypertension 37.5 Anemia 36.3Anemia 36.3 Abnormal liver function 14.4Abnormal liver function 14.4 Hypercalcemia 4.9Hypercalcemia 4.9 PolycythemiaPolycythemia 3.5 3.5 Hypoglycemia & CushingHypoglycemia & Cushing

Stauffer’s syndromeStauffer’s syndrome is a is a reversible syndrome of hepatic reversible syndrome of hepatic dysfunction in the absence of hepatic dysfunction in the absence of hepatic metastases associated with RCC and metastases associated with RCC and can occur in up to 20% of patients.can occur in up to 20% of patients.

Hepatic function abnormalities include Hepatic function abnormalities include elevation of alkaline phosphatase and elevation of alkaline phosphatase and bilirubin, hypoalbuminemia, prolonged bilirubin, hypoalbuminemia, prolonged prothrombin time, and prothrombin time, and hypergammaglobulinemia. hypergammaglobulinemia.

Renal Cell Carcinoma:Renal Cell Carcinoma:

Renal Cell CarcinomaRenal Cell Carcinoma mode of disseminationmode of dissemination

Direct extensionDirect extension Vascular Vascular LymphaticLymphatic Lungs, lymph nodes, liver, Lungs, lymph nodes, liver,

bone bone brain, brain, skinskin etc. etc.

StagingStaging

Staging and PrognosisStaging and Prognosis

Cohen HT, McGovern FJ. NEJM. 2005;353:2477.Cohen HT, McGovern FJ. NEJM. 2005;353:2477.


ManagementManagement

RCCRCC is chemo-resistant & is chemo-resistant & radio-resistantradio-resistant

Obstacles Towards Obstacles Towards TreatmentTreatment

RCC is historically resistant to many types RCC is historically resistant to many types of treatmentof treatment Chemotherapy (MDR-1)Chemotherapy (MDR-1) RadiationRadiation

Very aggressive in nature (TGF alpha and Very aggressive in nature (TGF alpha and EGFR)EGFR)

Highly vascular (VEGF secondary to loss Highly vascular (VEGF secondary to loss of vHL)of vHL)

Expresses tumor-associated antigens Expresses tumor-associated antigens (PRAME, RAGE-1, gp75, and MN-9) which (PRAME, RAGE-1, gp75, and MN-9) which contributes to its immunogenicitycontributes to its immunogenicity

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 Robson and colleagues “gold

standard” 1969standard” 1969 Prototype – A then B, Gerota’s Prototype – A then B, Gerota’s

intact, ipsi adrenal, LND (crus to intact, ipsi adrenal, LND (crus to aortic bifurcation)aortic bifurcation)

Now – no adrenal if no radiolgical Now – no adrenal if no radiolgical evidence unless : extensive renal evidence unless : extensive renal involvement, locally advanced, involvement, locally advanced, located upper pole, immediately located upper pole, immediately adjacent to adrenaladjacent 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 Surgical approach determined by size, location of tumor and body size, location of tumor and body habitushabitus

TransperitonealTransperitoneal SubcostalSubcostal thoracoabdominalthoracoabdominal

Extraperitoneal Extraperitoneal FlankFlank

Laparoscopic (trans, retro, hand-Laparoscopic (trans, retro, hand-assist)assist)

LaparoscopicLaparoscopic Cancer specific survival comparable to Cancer specific survival comparable to

openopen Usually < 8-10cm; localized with no Usually < 8-10cm; localized with no

local invasion, renal vein involvement, local invasion, renal vein involvement, or lymphadenopathy or lymphadenopathy

Postoperative Surveillance after Radical Postoperative Surveillance after Radical Nephrectomy for Localized Renal Cell Nephrectomy for Localized Renal Cell

CarcinomaCarcinoma PathologPathologic Tumor ic Tumor Stage Stage

History, History, ExaminatiExamination, and on, and Blood Blood Tests Tests

Chest Chest RadiograRadiograph ph

AbdominaAbdominal CT Scan l CT Scan

T1 N0 M0 T1 N0 M0 Yearly Yearly — — — —

T2 N0 M0 T2 N0 M0 YearlyYearly YearlyYearly Every 2 Every 2 years years

T3a-c N0 T3a-c N0 M0 M0

Every 6 Every 6 months for months for 3 years, 3 years, then yearly then yearly

Every 6 Every 6 months for months for 3 years, 3 years, then yearly then yearly

At 1 year, At 1 year, then every then every 2 years 2 years

Nephron-Sparing SurgeryNephron-Sparing Surgery Czerny 1890Czerny 1890 Vermooten 1950 – NSSVermooten 1950 – NSS Indications include situations Indications include situations

where pt would be anephric or where pt would be anephric or high risk of needing HDhigh risk of needing HD Solitary kidney RCCSolitary kidney RCC Bilateral RCCBilateral RCC Contralateral disease (Hydro, Contralateral disease (Hydro,

chronic pyelo, reflux, stones, DM, chronic pyelo, reflux, stones, DM, nephrosclerosis)nephrosclerosis)

Indications for NSSIndications for NSS

Absolute: Absolute: Anatomical/ functional solitaryAnatomical/ functional solitary

kidneykidney Relative:Relative: Functioning opposite kidney is Functioning opposite kidney is

affected by a condition that mayaffected by a condition that may

impair renal function in futureimpair renal function in future Elective:Elective: Localized unilateral RCC with a Localized unilateral RCC with a

healthy contralateral kidney healthy contralateral kidney

A functional remnant of at least 20% A functional remnant of at least 20% of one normal kidney is necessary to of one normal kidney is necessary to avoid end-stage renal failureavoid end-stage renal failure

IF solitary kidney, > 50% reduction IF solitary kidney, > 50% reduction in renal mass = incr risk of in renal mass = incr risk of hyperfiltration renal injury hyperfiltration renal injury (proteinuria, focal segmental (proteinuria, focal segmental glomerulosclerosis, progressive glomerulosclerosis, progressive renal failure)renal failure) Prevention: Protein restriction & ACEIPrevention: Protein restriction & ACEI

Preoperative testingPreoperative testing r/o local extension, mets, r/o local extension, mets,

vascular/collecting system relationshipvascular/collecting system relationship 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 Surveillance

StageStage H/E/labsH/E/labs CXRCXR CTa/pCTa/p

T1NOMOT1NOMO yearly yearly ---- ---- ---- ----

T2NOMOT2NOMO yearly yearly yearly yearly q 2 yrsq 2 yrs

T3NOMOT3NOMO q 6m x 3 yr - yrq 6m x 3 yr - yr same same q6m q6m x3y –q2yrx3y –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, local Ideal – advanced age, comorbidities, local

recurrance, hereditary renal cancerrecurrance, hereditary renal cancer

CryosurgeryCryosurgery Repetition of freeze-thaw cycle (-20C)Repetition of freeze-thaw cycle (-20C) Immediate cellular cryodestruction Immediate cellular cryodestruction

and delayed microcirculatory failure.and 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 In general, enhancement within the

tumor bed on extended follow-up has tumor bed on extended follow-up has been considered diagnostic of local been considered diagnostic of local recurrence, and the clinical experience recurrence, and the clinical experience thus far has supported thisthus far has supported this

ObservationObservation Median growth rate 0.36 cm/yrMedian growth rate 0.36 cm/yr Alternative for asymptomatic elderly Alternative for asymptomatic elderly

and poor surgical risk, consider with and poor surgical risk, consider with solid/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 Not appropriate: >3cm, poor margins, nonhomogeneous, young margins, nonhomogeneous, young healthy with abn imaginghealthy with abn imaging

Renal Cell CarcinomaRenal Cell CarcinomaStage Stage Surgery Surgery

T 1T 1 Nephron – sparing surgeryNephron – sparing surgery openopen

laparoscopiclaparoscopic

Radical nephrectomyRadical nephrectomy laparoscopiclaparoscopic

openopen

T 2T 2 Radical nephrectomyRadical nephrectomy laparoscopiclaparoscopic

openopenNephron – sparing surgeryNephron – sparing surgery

T3 & T3 & T4T4

Radical nephrectomyRadical nephrectomy openopen

laparoscopiclaparoscopic

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 45-70% of RCC with IVC

thrombus curedthrombus cured Local extension/invasion much Local extension/invasion much

higher risk of recurrencehigher risk of recurrence Occurs 4-10% of patientsOccurs 4-10% of patients Suspect with : LE edema, R Suspect with : LE edema, R

varicocele, distended abd veins, varicocele, distended abd veins, proteinuria, PE, R atrial mass, proteinuria, PE, R atrial mass, nonfxn kidneynonfxn 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 III – intrahepatic portion of IVC

below diaphragmbelow diaphragm IV – above the diaphragmIV – above the diaphragm

ImagingImaging CT & AUSCT & AUS Contrast inferior venacavography – Contrast inferior venacavography –

if prob with MRIif prob with MRI MRI – study of choiceMRI – study of choice ? Renal arteriography? Renal arteriography

Imaging Imaging (contd)(contd) Investigate locally advanced Investigate locally advanced

malignancy, and specially for malignancy, and specially for classification of Vena caval classification of Vena caval thrombus:thrombus:

Peri-renal Peri-renal Infra-hepaticInfra-hepatic Intra-hepaticIntra-hepatic Supra-hepaticSupra-hepatic

Locally Invasive RCCLocally Invasive RCC Present with pain from invasion of Present with pain from invasion of

posterior abd wall, nerve roots or posterior abd wall, nerve roots or paraspinous musclesparaspinous muscles

Duodenal & pancreas uncommonDuodenal & pancreas uncommon En bloc may be beneficialEn bloc may be beneficial Partial / debulking – only 12% alive Partial / debulking – only 12% alive

in 1 yrin 1 yr Preoperative rad – not beneficial Preoperative rad – not beneficial

(van der Werf-Messing 1973)(van der Werf-Messing 1973) Residual tumor, rad may retard Residual tumor, rad may retard

growth (Kao et al 1994)growth (Kao et al 1994)

Adjuvant Therapy for RCCAdjuvant Therapy for RCC Include hormonal manipulation, Include hormonal manipulation,

radiotherapy, vaccines, cytokines, radiotherapy, vaccines, cytokines, etc…etc…

Most studies to date – not Most studies to date – not significantsignificant

Vaccine – irradiated tumor Vaccine – irradiated tumor cells/BCG, heat shock proteins cells/BCG, heat shock proteins (HSPPC) = no proven benefit(HSPPC) = no proven benefit

Interferon alfa – modest survival Interferon alfa – modest survival benefitbenefit

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 1/31/3rdrd of RCC have mets of RCC have mets 40-50% will develop mets after 40-50% will develop mets after

initial dxinitial dx Regression of mets after RN – 1-Regression of mets after RN – 1-

2% (lung)2% (lung) Benefit for synchronous mets with Benefit for synchronous mets with

interferon alfa after RNinterferon alfa after RN Individuals with: adv dz (PS > 2), Individuals with: adv dz (PS > 2),

mets (CNS, SC compression), MOD, mets (CNS, SC compression), MOD, significant comorbidities – not significant comorbidities – not candidatecandidate

Hormone TherapyHormone Therapy Minimal valueMinimal value

Progesterone – inhibit growth of DES-Progesterone – inhibit growth of DES-induced renal tumors in Syrian induced renal tumors in Syrian hamstershamsters No correlation with human RCCNo correlation with human RCC

Progestational agents = useful for Progestational agents = useful for symptom palliationsymptom palliation

Revision Revision Why were RCCs originally called Why were RCCs originally called

hypernephromas?hypernephromas?

idea of suprarenal origin of renal tumoursidea of suprarenal origin of renal tumours What is the role of FNA in evaluation of What is the role of FNA in evaluation of

renal masses?renal 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 or RCC must be differentiated from met or

lymphomalymphoma

Revision Revision

What is the treatment for renal What is the treatment for renal adenomas?adenomas?

• • consider all to be malignantconsider all to be malignant → → consider wedge resection, other consider wedge resection, other

ablative therapiesablative therapies Which patient groups are at Which patient groups are at

increased risk of developing AML?increased risk of developing AML? • • tuberous sclerosis 20% of all AMLstuberous sclerosis 20% of all AMLs • • female predominancefemale predominance

RevisionRevision Describe the clinical presentation of Describe the clinical presentation of

RCCRCC.. • • asymptomatic and nonpalpable until asymptomatic and nonpalpable until

advancedadvanced → → >50% of RCCs now detected incidentally>50% of RCCs now detected incidentally • • hemorrhage, paraneoplastic syndromes, or hemorrhage, paraneoplastic syndromes, or

metsmets • • classic triad: flank pain, gross hematuria, classic triad: flank pain, gross hematuria,

and palpable abdominal mass rarely foundand palpable abdominal mass rarely found • • indicators of advanced diseaseindicators of advanced disease → → constitutional sy: wt loss, fever, NS, bone constitutional sy: wt loss, fever, NS, bone

pain, persistent coughpain, persistent cough → → paraneoplastic syndromesparaneoplastic syndromes

Wilms Wilms tumortumor

NephroblastoNephroblastomama

NEPHROBLASTOMANEPHROBLASTOMA ( (Wilms’ tumour )Wilms’ tumour )

Embryonal tumour arising from Embryonal tumour arising from nephrogenic blastemal cellsnephrogenic blastemal cells can differentiate in to several cell lines can differentiate in to several cell lines

- blastemal, epithelial and stromal- blastemal, 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 90% in < 6yrs. old ( mean: 3yrs. in boys and 3.5yrs. in girlsboys and 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 of The most common presentation of Wilms tumor is the presence of an Wilms tumor is the presence of an asymptomatic abdominal mass.asymptomatic abdominal mass.

HypertensionHypertension, , gross hematuriagross hematuria, , and fever are observed in 5-30% of and fever are observed in 5-30% of patients. patients.

A small number of patients who A small number of patients who have hemorrhaged into their have hemorrhaged into their tumor may present with signs of tumor may present with signs of hypotension, anemiahypotension, anemia, and fever., and fever.

Rarely, patients with advanced-Rarely, patients with advanced-stage disease may present with stage disease may present with respiratory symptomsrespiratory symptoms related to related to the presence of lung metastases. the presence of lung metastases.

NEPHROBLASTOMA

NEPHROBLASTOMANEPHROBLASTOMA

Pathologic findingsPathologic findings (gross) (gross) Usually solitary, sharply (well) Usually solitary, sharply (well)

defined masses with defined masses with pseudocapsulepseudocapsule

Variable size & weight (60-6350 Variable size & weight (60-6350 gms. with a mean of 550 gms.)gms. with a mean of 550 gms.)

Uniform, pale gray to tan, Uniform, pale gray to tan, divided by prominent fibrous divided by prominent fibrous septa in to lobulessepta in to lobules

May be cystic, hemorrhagic or May be cystic, hemorrhagic or necroticnecrotic

No specific locationNo specific location

NEPHROBLASTOMANEPHROBLASTOMA

Microscopic findingsMicroscopic findings Generally triphasic pattern :Generally triphasic pattern :

blastemal, epithelial and stromal cell blastemal, epithelial and stromal cell typetype

may contains heterologous elementsmay contains heterologous elements ““favorable” or “unfavorable” favorable” or “unfavorable”

histology on the bases of nuclear histology on the bases of nuclear anaplasia i.e. . . .anaplasia i.e. . . .marked nuclear enlargement (3x)marked nuclear enlargement (3x)abnormal mitoses i.e. . . . increased abnormal mitoses i.e. . . . increased DNADNA

STAGINGSTAGING Histopathology and staging are the Histopathology and staging are the

most important determinants of most important determinants of outcomeoutcomeStagStag

eeDescriptionDescription

II Tumor limited to kidney & completely excised. Tumor limited to kidney & completely excised. Intact renal capsule, tumor unruptured. No Intact renal capsule, tumor unruptured. No residual tumor residual tumor

IIII Tumor extends thruogh capsule but completely Tumor extends thruogh capsule but completely excised. Local spillage confined to flank or excised. Local spillage confined to flank or biopsied tumor. Extra renal vessels contain tumor biopsied tumor. Extra renal vessels contain tumor thrombus or infiltratedthrombus or infiltrated

IIIIII Residual nonhaematogenous tumor confined to Residual nonhaematogenous tumor confined to abdomen: lymph node involvement, diffuse abdomen: lymph node involvement, diffuse peritoneal spillage, peritoneal implants, tumor peritoneal spillage, peritoneal implants, tumor beyond surgical margin grossly or microscopically beyond surgical margin grossly or microscopically or tumor not completely removedor tumor not completely removed

IVIV Haematogenous mets to lung, liver, bone, brain or Haematogenous mets to lung, liver, bone, brain or other organother organ

VV Bilateral renal involvement at diagnosisBilateral renal involvement at diagnosis

NEPHROBLASTOMA NEPHROBLASTOMA SpreadSpread

LocalLocalRegional i.e. . . Regional i.e. . . lymphaticlymphatic

Distant :Distant :lungslungsliverliver

Wilms Tumor(Nephroblastoma)

Plain X-Plain X-Ray:Ray:

Large soft tissue Large soft tissue

mass displacing mass displacing

bowel gasbowel gas

Calcification is Calcification is

uncommon.uncommon.


IVU:

Large soft tissue mass

distorting and displacing

the collecting system.

Large soft tissue mass

distorting and displacing

the collecting system.


US:

• Large soft tissue mass

heterogeneous echogenicity,

which represents hemorrhage,

necrosis, or calcification.

• Vascular Invasion.

• Large soft tissue mass

heterogeneous echogenicity,

which represents hemorrhage,

necrosis, or calcification.

• Vascular Invasion.


CT:

CT demonstrates a well-

defined heterogeneous

mass with areas of necrosis

and hemorrhage.

Less common calcification.

CT demonstrates a well-

defined heterogeneous

mass with areas of necrosis

and hemorrhage.

Less common calcification.


CT:

CT demonstrates a well-defined

heterogeneous mass with areas

of calcification, necrosis and

hemorrhage.

CT demonstrates a well-defined

heterogeneous mass with areas

of calcification, necrosis and

hemorrhage.


CT:

hepatic metastaseshepatic metastases

CT scan shows multiple hepatic metastases in addition to tumor thrombus within the portal veins (arrows).


CT:

Nodal metastases,.Nodal metastases,.


CT:

Lung metastasesLung metastases

Wilms tumor in a 2-year-old boy. A, B: Contrast-enhanced axial computed tomography and coronal multiplanar reconstruction demonstrate a large, round, low-density mass that distorts and displaces the enhancing parenchyma (arrows) in the lower pole of the right kidney



MRI:

Well-defined heterogeneous mass with low signal

intensity on T1-weighted images and high signal

intensity on T2-weighted images.

Well-defined heterogeneous mass with low signal

intensity on T1-weighted images and high signal

intensity on T2-weighted images.

Timing of surgery Timing of surgery

NWTSG VS SIOP:NWTSG VS SIOP: In NWTSGIn NWTSG: surgery with complete : surgery with complete

resection of a resectable tumour is to be resection of a resectable tumour is to be performed first. Chemotherapy first is to performed first. Chemotherapy first is to be given only for those with irresectable be given only for those with irresectable tumour, bilateral wilms tumour, tumour tumour, bilateral wilms tumour, tumour thrombus thrombus

In SIOPIn SIOP: surgery always is after : surgery always is after neoadjuvant chemotherapy even for neoadjuvant chemotherapy even for resectable tumoursresectable 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 stage I & II with favorable histologyhistology

surgery with chemotherapy and surgery with chemotherapy and radiotherapy for higher stages radiotherapy for higher stages and unfavorable histologyand unfavorable histology

Stage, HistologyStage, Histology SurgerySurgery ChemotherapyChemotherapy Radiotherapy*Radiotherapy*

Stage I or II with Stage I or II with FHFHStage I with Stage I with anaplasiaanaplasia

NephrectomyNephrectomyVincristineVincristineDactinomycinDactinomycin

NoneNone

Stage III or IV with Stage III or IV with FHFHStage II, III, or IV Stage II, III, or IV with focal with focal anaplasiaanaplasia

NephrectomyNephrectomyVincristineVincristineDactinomycinDactinomycinDoxorubicinDoxorubicin

YesYes

Stage II, III, or IV Stage II, III, or IV with diffuse with diffuse anaplasiaanaplasiaStage I, II, III, or IV Stage I, II, III, or IV CCSKCCSK

NephrectomyNephrectomy

VincristineVincristineDoxorubicinDoxorubicinCyclophosphamidCyclophosphamideeEtoposideEtoposide

YesYes

Stage I, II, III, or IV Stage I, II, III, or IV RTKRTK

NephrectomyNephrectomy

CyclophosphamidCyclophosphamideeEtoposideEtoposideCarboplatinCarboplatin

YesYes

TREATMENTTREATMENT

Pre-operative chemo should be given to Pre-operative chemo should be given to patients withpatients with 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 Initial biopsy then chemotherapy then

22ndnd look at 8 – 10 weeks for bilateral look at 8 – 10 weeks for bilateral diseasedisease

COMPLICATIONSCOMPLICATIONS

Following irradiationFollowing irradiation ScoliosisScoliosis Hypogonadism & temporary Hypogonadism & temporary

azoospermiaazoospermia Ovarian failure (12%)Ovarian failure (12%) Second malignancySecond malignancy

Following chemotherapyFollowing chemotherapy CCF following treatment with CCF following treatment with

DoxorubicinDoxorubicin

Revision Revision What is the most common primary What is the most common primary

malignant renal tumour of childhood?malignant renal tumour of childhood? Wilms' tumour (a.k.a. nephroblastoma)Wilms' tumour (a.k.a. nephroblastoma) What is the embryologic origin of Wilms' What is the embryologic origin of Wilms'

tumour?tumour? • • develops from remnants of immature develops from remnants of immature

kidneykidney What pathologic markers are associated What pathologic markers are associated

w/ favourable outcome in Wilms'?w/ 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

5 renal tumor

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