Renal Masses: When Renal Masses: When and Why to Biopsy Themand Why to Biopsy ThemStuart G. Silverman, M.D., FACRStuart G. Silverman, M.D., FACR

Professor of RadiologyProfessor of RadiologyHarvard Medical SchoolHarvard Medical School

Director, Abdominal Imaging and InterventionDirector, Abdominal Imaging and InterventionBrigham and WomenBrigham and Women’’s Hospitals Hospital

Boston, MABoston, MA

SCBTMR Williamsburg, VASCBTMR Williamsburg, VA

Silverman DisclosuresSilverman DisclosuresConsultant, Siemens Consultant, Siemens Medical Solutions, Medical Solutions, MalverneMalverne, PA, PA

Consultant, Consultant, GalilGalil Medical Medical Ltd, Ltd, YokneamYokneam, Israel, Israel

Learning ObjectiveLearning Objective

Understand why Understand why percutaneouspercutaneous biopsy of biopsy of renal masses is useful in renal masses is useful in clinical practiceclinical practice

Learning ObjectiveLearning Objective

Learn the eight Learn the eight indications for renal mass indications for renal mass biopsy and how results biopsy and how results can be used to dictate can be used to dictate clinical management clinical management

Learning ObjectiveLearning Objective

Understand the role of Understand the role of cytology (including cytology (including immunocytochemistryimmunocytochemistry) in ) in the diagnosis of renal the diagnosis of renal neoplasmsneoplasms

Most renal masses Most renal masses do not need to be do not need to be biopsied.biopsied.

Renal Mass Renal Mass BxBx: Why not?: Why not?

Importance of ImagingImportance of Imaging

Most renal masses Most renal masses can be diagnosed can be diagnosed with imaging alonewith imaging alone

Renal Mass Renal Mass BxBx: History: History““Needle aspiration or Needle aspiration or biopsy has a limited role biopsy has a limited role in the evaluation of the in the evaluation of the small tumor, as well as small tumor, as well as renal masses in generalrenal masses in general””

BosniakBosniak MA, Radiology 1991MA, Radiology 1991

Renal Mass Renal Mass BxBx: New?: New?•• Improved US, CT, MRI technology Improved US, CT, MRI technology

is resulting in the detection of is resulting in the detection of more, small, solid renal massesmore, small, solid renal masses

•• Not all solid renal masses are Not all solid renal masses are malignant malignant -- 25% of small solid 25% of small solid renal tumors are benign renal tumors are benign

(Frank et al J (Frank et al J UrolUrol ’’03)03)

Renal Mass Renal Mass BxBx: Why?: Why?•• Test characteristics excellentTest characteristics excellent

(Sensitivity 80(Sensitivity 80--92%)92%)

•• Safety record establishedSafety record established

•• Significant bleeding uncommon Significant bleeding uncommon

•• Needle tract seeding rareNeedle tract seeding rare(not more than other tumors)(not more than other tumors)

Renal Mass BiopsyRenal Mass Biopsy

•• Distinguish RCC from metastasis in Distinguish RCC from metastasis in patient with patient with extrarenalextrarenal malignancy malignancy

•• Confirm Confirm unresectableunresectable suspected RCCsuspected RCC

•• DxDx suspicious mass in poor surgical suspicious mass in poor surgical candidatecandidate

•• DxDx suspected suspected pyelonephritispyelonephritis

Established IndicationsEstablished Indications

Renal Mass BiopsyRenal Mass Biopsy

•• Small, Small, hyperdensehyperdense, homogeneously, homogeneouslyenhancing renal enhancing renal masses masses

•• Renal masses referred for ablationRenal masses referred for ablation

•• Indeterminate cystic renal massIndeterminate cystic renal mass((BosniakBosniak Category III)Category III)

•• Multiple solid renal massesMultiple solid renal masses

Emerging IndicationsEmerging Indications

Silverman et al Radiology 2006Silverman et al Radiology 2006

Renal Masses in Patients with Renal Masses in Patients with Known Known ExtrarenalExtrarenal Primary CancerPrimary Cancer

Primary Primary nn Mets RCC BenignMets RCC BenignLymphomaLymphoma 2020 99 1010 11LungLung 1616 88 88 00BreastBreast 55 11 33 11OthersOthers 1313 22 10 110 1

TotalTotal 5454 2020 31 331 3RybickiRybicki et al AJR 2003et al AJR 2003

Poor Surgical CandidatePoor Surgical Candidate•• Medical co Medical co –– morbiditymorbidity•• Heart and lung diseaseHeart and lung disease•• Solitary kidneySolitary kidney•• Renal insufficiencyRenal insufficiency•• Biopsy allowsBiopsy allows

urologist tourologist toassess risk assess risk –– benefitbenefitand plan surgery confidentlyand plan surgery confidently

Solitary KidneySolitary Kidney

MRIMRI--guided Biopsyguided Biopsy

When evaluating a When evaluating a suspected renal mass, suspected renal mass,

evaluate for evaluate for pseudotumorpseudotumor, , angiomyolipomaangiomyolipoma, , vascular vascular

lesions,lesions, traumatrauma, , and anand aninflammatory lesioninflammatory lesionbeforebefore considering considering malignant causes.malignant causes.

Solid Masses may be Infection!Solid Masses may be Infection!

•• Renal infections Renal infections may be occult may be occult ––dondon’’tt rely on rely on history to consider history to consider infection!infection!

Solid Masses may be benignSolid Masses may be benign•• Of 815 Of 815 nephrectomiesnephrectomies /NSS for solid /NSS for solid and cystic renal masses, 2000and cystic renal masses, 2000--20052005•• 16.4% benign16.4% benign•• Masses 1Masses 1-- 2 cm 25% benign2 cm 25% benign•• Masses 2Masses 2-- 3 cm 15% benign3 cm 15% benign•• Masses 3Masses 3-- 4 cm 18% benign4 cm 18% benign•• Masses Masses 66-- 77 cm 17% benigncm 17% benign

Snyder et al J Snyder et al J UrolUrol 20062006

Solid Masses may be benignSolid Masses may be benign•• Of 2,770 Of 2,770 nephrectomiesnephrectomies /NSS for /NSS for ““solidsolid”” renal masses, 1977renal masses, 1977--20002000•• 12.8% benign12.8% benign•• Masses < 3 cm 25% benignMasses < 3 cm 25% benign•• Masses < 2 cm 30% benignMasses < 2 cm 30% benign•• Masses < 1 cm 44% benignMasses < 1 cm 44% benign

Frank et al J Frank et al J UrolUrol 20032003

Solid Masses may be benignSolid Masses may be benignBenign TumorsBenign Tumors resectedresected %%

OncocytomaOncocytoma 7373AngiomyolipomaAngiomyolipoma 1818Papillary adenoma*Papillary adenoma* 44Not otherwise specifiedNot otherwise specified 44MetanephricMetanephric adenomaadenoma 11

Frank et al J Frank et al J UrolUrol 20032003*Papillary RCC <5mm

AML with Minimal FatAML with Minimal Fat•• Approximately 4Approximately 4--5% AML contain 5% AML contain

little or no fat and are small, little or no fat and are small, hyperdensehyperdense, and homogeneously , and homogeneously enhancing massesenhancing masses

•• Only 2% of RCC are Only 2% of RCC are hyperdensehyperdenseand homogeneously enhancingand homogeneously enhancing

JinzakiJinzaki et al Radiology 1997et al Radiology 1997

HyperdenseHyperdense + Enhancing+ Enhancing•• RCC RCC –– typically papillary, or clear typically papillary, or clear

cell subcell sub--type that has bledtype that has bled•• AngiomyolipomaAngiomyolipoma with minimal fatwith minimal fat•• OncocytomaOncocytoma•• LymphomaLymphoma•• MetanephricMetanephric adenoma (rare)adenoma (rare)•• LeiomyomaLeiomyoma (rare)(rare)•• Metastases (rare)Metastases (rare)

Silverman et al Silverman et al RadioGraphicsRadioGraphics 20072007

MRI Features of Renal MassesMRI Features of Renal Masses

T1T1 T2T2 CECE DxDxdarkdark brightbright ++ RCC (CC type)RCC (CC type)darkdark darkdark ++ RCC (papillary)RCC (papillary)darkdark darkdark ++ AMLAML

AngiomyolipomaAngiomyolipoma•• FatFat--containing AML typically containing AML typically dxeddxed

with imagingwith imaging•• AML with minimal fat can be AML with minimal fat can be

recognized by their recognized by their hyperdensehyperdense, T2, T2--hypointense hypointense appearance and differentiated appearance and differentiated from RCC with biopsy from RCC with biopsy

(Granter, Cancer 1999)(Granter, Cancer 1999)

AML AML vsvs RCC RCC ImmunocytochemistryImmunocytochemistry

AMLAML RCCRCCMART1 MART1 ++ --SMASMA ++ --HMBHMB--45 45 ++ --EMA EMA -- ++VIMENTIN VIMENTIN -- ++RCCRCC -- ++

•• OncocytomaOncocytoma•• ChromophobeChromophobe RCCRCC•• Granular RCCGranular RCC•• EosinophilicEosinophilic variant of papillary variant of papillary

RCCRCC•• AngiomyolipomaAngiomyolipoma

OncocyticOncocytic cells may be found cells may be found in all in all oncocyticoncocytic neoplasmsneoplasms

OncocyticOncocytic Renal Renal NeoplasmsNeoplasms

•• OncocytomaOncocytoma•• ChromophobeChromophobe RCCRCC•• Granular RCCGranular RCC•• EosinophilicEosinophilic variant of papillary variant of papillary

RCCRCC•• AngiomyolipomaAngiomyolipoma

OncocyticOncocytic Renal Renal NeoplasmsNeoplasmsHaleHale’’s Colloidal s Colloidal Iron stain is Iron stain is negativenegative

These are rareThese are rare……

Renal Renal OncocytomaOncocytoma•• OncocytomaOncocytoma cannot always be cannot always be diagnosed with certainty with bx.diagnosed with certainty with bx.•• OncocytomaOncocytoma can be diagnosed can be diagnosed with a high degree of probability with a high degree of probability using using immunocytochemistryimmunocytochemistry..•• The diagnosis of an The diagnosis of an oncocyticoncocyticneoplasm allows for less invasive neoplasm allows for less invasive treatment options to be considered treatment options to be considered

Liu Cancer 2001Liu Cancer 2001

OncocytomaOncocytoma vsvs OncocyticOncocyticRCC: RCC: ImmunocytochemistryImmunocytochemistry

OncOnc OncOncRCCRCCAE1/AE3AE1/AE3 ++ ++EMA EMA -- ++VIMENTIN VIMENTIN -- +/+/--RCCRCC -- ++Colloidal Fe Colloidal Fe -- +*+*

*specific for *specific for ChromophobeChromophobe RCCRCCModified: Liu and Fanning Cancer Modified: Liu and Fanning Cancer CytopathCytopath 2001 2001

ChromophobeChromophobe RCCRCC•• HaleHale’’s colloidal iron stain is s colloidal iron stain is

specific for specific for oncocyticoncocytic RCC, RCC, chromophobechromophobe typetype

•• ChromophobeChromophobe RCC has a good RCC has a good prognosisprognosis

KrejciKrejci et al Urology 2003et al Urology 2003

•• Amenable to minimally invasive Amenable to minimally invasive treatments (patient was treated treatments (patient was treated with MRIwith MRI--guided guided cryotherapycryotherapy))

The ProblemThe Problem……•• Because ablation is Because ablation is ““minimally minimally

invasiveinvasive”” and perceived (incorrectly) and perceived (incorrectly) to be harmless, the tendency to treat to be harmless, the tendency to treat small renal masses that are not small renal masses that are not biopsybiopsy--proven cancers is prevalent. proven cancers is prevalent.

•• It remains to be proven that ablation It remains to be proven that ablation decreases mortality due to RCC. decreases mortality due to RCC.

•• There are adverse consequences of There are adverse consequences of the inadvertent treatment of a benign the inadvertent treatment of a benign renal massrenal mass……

Fundamental FactsFundamental Facts……•• Unlike surgery where the mass Unlike surgery where the mass

may be examined, ablation is may be examined, ablation is an an inin situsitu treatment and there treatment and there is is no opportunity for no opportunity for full full pathology examination.pathology examination.

•• Tissue diagnosis prior to ablation Tissue diagnosis prior to ablation is is entirelyentirely dependent on biopsy. dependent on biopsy.

Masses referredMasses referred……•• Of 27 pts referred for ablation of Of 27 pts referred for ablation of

suspected RCC, suspected RCC, 1010 had masses had masses which were proven which were proven notnot to be RCC.to be RCC.

•• Of these Of these 1010, 3 were diagnosed as , 3 were diagnosed as benign by biopsy, 3 by imaging, benign by biopsy, 3 by imaging, and 4 by a combination of both and 4 by a combination of both biopsy and imaging.biopsy and imaging.

•• Masses should be Masses should be bxedbxed prepre--ablation.ablation.TuncaliTuncali et al AJR 2004et al AJR 2004

YesteryearYesteryear……•• The imageThe image--based detection of a based detection of a nonnon--fat containing solid mass in an fat containing solid mass in an adult led to the radiologistadult led to the radiologist’’s s confident diagnosis of RCCconfident diagnosis of RCC–– often often leading to surgical removal of the leading to surgical removal of the mass.mass.

•• A pathology diagnosis was A pathology diagnosis was rendered in all casesrendered in all cases……

TodayToday……•• As many as 25% of small (< 3 cm) As many as 25% of small (< 3 cm) solid renal tumors are solid renal tumors are benign.benign.

•• Imaging cannot be used alone to Imaging cannot be used alone to diagnose small renal cancers with diagnose small renal cancers with sufficient confidence.sufficient confidence.

•• ““EnhancementEnhancement”” may be found in may be found in benign benign neoplasmsneoplasms, inflammation, , inflammation, and vascular abnormalities. and vascular abnormalities.

Why not ablate them?Why not ablate them?

•• Subjects patients to unnecessary Subjects patients to unnecessary risk; complications do occur!risk; complications do occur!

•• Misdiagnosis of cancer leads to Misdiagnosis of cancer leads to unnecessary f/u exams, w/ their unnecessary f/u exams, w/ their attendant anxiety and costattendant anxiety and cost

•• ““ContaminatesContaminates”” clinical trial dataclinical trial data

Consequences of inadvertent Consequences of inadvertent ablation of a benign renal massablation of a benign renal mass

Renal Mass Referred for Ablation Renal Mass Referred for Ablation

Biopsy in advance or during ablationBiopsy in advance or during ablation

MalignantMalignant

No No treatmenttreatmentObserve Observe

vs.vs.Ablation with repeat Ablation with repeat BxBx

AblationAblation

BenignBenignNonNon--diagnosticdiagnostic

CT or MRICT or MRI BenignBenign

When to biopsy?When to biopsy?

•• Sporadic small (Sporadic small (<< 3cm) masses3cm) masses

Biopsy in advance of ablation Biopsy in advance of ablation

Biopsy during ablation Biopsy during ablation

•• Prior RCC (Prior RCC (ipsilateralipsilateral, , contralateralcontralateral) ) and enhancing massand enhancing mass

•• Established familial RCC syndromeEstablished familial RCC syndrome•• ?Large, heterogeneously enhancing?Large, heterogeneously enhancing

Renal Mass Renal Mass BxBx: Why?: Why?•• ““The availability and early The availability and early successes of successes of percutaneouspercutaneous tumor tumor ablation is driving the treatment of ablation is driving the treatment of small solid masses, small solid masses, presumedpresumed to to be RCC, that otherwise would be RCC, that otherwise would have been observed, or ignored, have been observed, or ignored, because of age or because of age or contraindications to surgery.contraindications to surgery.””

Silverman et al Radiology 2006Silverman et al Radiology 2006

Biopsy of Cat III MassesBiopsy of Cat III Masses•• Biopsy and imaging Biopsy and imaging

followfollow--up may save up may save patients with Category patients with Category III cystic masses from III cystic masses from having surgery.having surgery.

HarisinghaniHarisinghani et al AJR 2003et al AJR 2003

Biopsy of Cat III MassesBiopsy of Cat III Masses•• Benign results may lack Benign results may lack

specificity (specificity (egeg, renal , renal epithelium, fibrous epithelium, fibrous tissue, atypical cells)tissue, atypical cells)

•• No known time interval No known time interval that proves benign that proves benign resultsresults

Biopsy of Cat III MassesBiopsy of Cat III Masses•• Benign results may be Benign results may be

helpful as additional helpful as additional data.data.

•• Unless a specific benign Unless a specific benign entity is rendered, entity is rendered, benign results cannot benign results cannot be used alone.be used alone.

Multiple Renal MassesMultiple Renal Masses•• This patient has renal This patient has renal oncocytosisoncocytosis –– a syndrome in a syndrome in which multiple which multiple oncocytomasoncocytomasdevelop, often bilaterally, and develop, often bilaterally, and typically with one dominant typically with one dominant one. one. •• 22--12% of 12% of oncocytomasoncocytomas are are multifocalmultifocal; 4; 4--14% are bilateral14% are bilateral

TikooTikoo S, et al. AJSP 1999;23:1094S, et al. AJSP 1999;23:1094

•• DDxDDx of multiple solid renal of multiple solid renal masses includes papillary masses includes papillary RCC, RCC, oncocytosisoncocytosis, lymphoma, , lymphoma, and metastasesand metastases

•• Biopsy can be used to make a Biopsy can be used to make a confident diagnosis of confident diagnosis of oncocytomaoncocytoma..

•• Biopsy determines managementBiopsy determines management

Multiple Renal MassesMultiple Renal Masses

Chronology of UnderstandingChronology of Understanding

19901990’’ss 19971997 20032003 20042004

Solid renal masses thought to be RCCSolid renal masses thought to be RCCAML w/ minimal fat describedAML w/ minimal fat described

Benign tumors prevalentBenign tumors prevalent

Importance of preImportance of pre--ablation tissue diagnosisablation tissue diagnosis

Role of Role of percutaneouspercutaneous biopsy expandedbiopsy expanded

20062006

……of Importance of Biopsyof Importance of Biopsy

•• 152 biopsies in 125 pts152 biopsies in 125 pts•• All 18G coaxialAll 18G coaxial•• 85 (56%) malignant, 85 (56%) malignant, 61 (40%) 61 (40%)

benignbenign; 6 (4%) non; 6 (4%) non--diagnosticdiagnostic•• Of 61 = 17 Of 61 = 17 negneg post ablation, 16 post ablation, 16

oncocytomaoncocytoma, 13 parenchyma, 4 , 13 parenchyma, 4 AML, 9 AML, 9 inflamminflamm/infarct, 2 MEST/infarct, 2 MEST

Biopsy alters Biopsy alters MgntMgnt

MaturenMaturen et al AJR 2007et al AJR 2007

Can we rely on biopsy results

Can we rely on biopsy results

that show parenchyma, infarct

that show parenchyma, infarct

or inflammation?

or inflammation?

•• Of 58 masses Of 58 masses biopsiedbiopsied, 52 (90%) , 52 (90%) diagnosticdiagnostic

•• 36 (69%) RCC, 36 (69%) RCC, 14 (27%) benign14 (27%) benign, 1 , 1 lymphoma, 1 met each.lymphoma, 1 met each.

•• OncocytomaOncocytoma (6), AML (2), Focal (6), AML (2), Focal glomerulosclerosisglomerulosclerosis (2), (2), metanephricmetanephric adenoma, scar, adenoma, scar, infarct, chronic GNinfarct, chronic GN

Renal Mass BiopsyRenal Mass Biopsy

BelandBeland et al AJR 2007et al AJR 2007

Biopsy results with a specific

Biopsy results with a specific

benign entity such as AML

benign entity such as AML

are more reliable

are more reliable……

Diagnostic AccuracyDiagnostic AccuracyPercutaneousPercutaneous Biopsies (n=221)Biopsies (n=221)

DiagnosticDiagnostic NonNon--diagdiag DiagDiag RateRate179179 4242 81%81%

SensitivitySensitivity 96%96%SpecificitySpecificity 96%96%

NPVNPV 81%81%PPVPPV 99%99%

Rocha et al RSNA 2008Rocha et al RSNA 2008

Diagnostic AccuracyDiagnostic AccuracyPercutaneousPercutaneous Biopsies (n=221)Biopsies (n=221)

MalignantMalignant BenignBenign % benign% benign148148 3131 14%14%

-- AML (n=13)AML (n=13)-- oncocytomaoncocytoma (n=7)(n=7)-- infection (n=2)infection (n=2)

-- atypical cells (n=8) atypical cells (n=8) -- metanephricmetanephric

adenoma (n=1)adenoma (n=1)

Benign Etiologies:Benign Etiologies:

Rocha et al RSNA 2008Rocha et al RSNA 2008

TakeTake--Home MessagesHome Messages•• Diagnose most masses with imagingDiagnose most masses with imaging•• Biopsy is safe and accurateBiopsy is safe and accurate•• Biopsy can be used to diagnose Biopsy can be used to diagnose

malignancy and guide treatmentsmalignancy and guide treatments•• Many small, solid renal masses are Many small, solid renal masses are

benignbenign•• Biopsy can diagnose benign tumors Biopsy can diagnose benign tumors

and prevent unnecessary treatmentsand prevent unnecessary treatments•• Biopsy has an important role in Biopsy has an important role in

diagnosing renal massesdiagnosing renal massesSilverman et al RSNA Syllabus 2007Silverman et al RSNA Syllabus 2007