Case Presentation SGHCase Presentation SGHJuly 2008July 2008

Lauren EisenbergLauren Eisenberg

CC/HPICC/HPI

CC: L flank painCC: L flank pain HPI: 41yo AAM presents to ED with c/o HPI: 41yo AAM presents to ED with c/o

abd and L flank pain for 5days. Pain abd and L flank pain for 5days. Pain described as intermittent, excruciating, described as intermittent, excruciating, sharp, radiates from flank to lower LLQ. sharp, radiates from flank to lower LLQ. Nothing improves or worsens pain. Nothing improves or worsens pain. Associated with decrease urine output, Associated with decrease urine output, decrease stream, and concentrated decrease stream, and concentrated urine. urine.

HistoryHistory

PMHx: diverticulosis, HTN, anxiety disorderPMHx: diverticulosis, HTN, anxiety disorder PSHx: nonePSHx: none A: NKDAA: NKDA M: Paxil 30mg qday, MaxzideM: Paxil 30mg qday, Maxzide FamHx: FamHx:

Mother: HTN, Polycystic Kidney DiseaseMother: HTN, Polycystic Kidney Disease Father: Dialysis for DMFather: Dialysis for DM

SoHx: married w/ 6 children, No ETOH/tob/IVDUSoHx: married w/ 6 children, No ETOH/tob/IVDU ROS: ROS:

Neg: F/C/Weight lossNeg: F/C/Weight loss Gu: hematuria, dysuriaGu: hematuria, dysuria

PEPE

VSS:VSS: BP 148/101 P91 RR20 T35.9BP 148/101 P91 RR20 T35.9

General: NADGeneral: NAD Heent: normocephalic, EOMIHeent: normocephalic, EOMI CV: RRR w/o m/g/rCV: RRR w/o m/g/r Lungs: CTABLungs: CTAB Abd: soft, ND, mild L flank & LLQ TTP with Abd: soft, ND, mild L flank & LLQ TTP with

deep palpationdeep palpation GU: b/l descended testicles, circumcised penisGU: b/l descended testicles, circumcised penis Rectal: slightly enlarged, symmetrical, Rectal: slightly enlarged, symmetrical,

rubbery, no nodulesrubbery, no nodules

LabsLabs

Chemisty Liver ProfileChemisty Liver Profile Na 140 AST 34Na 140 AST 34 K 4.1 ALT 17K 4.1 ALT 17 Cl 99Cl 99 Alk Phosph 92 Alk Phosph 92 HCO2 26HCO2 26 Bun 15Bun 15 CR 1.2CR 1.2

Hematology UA negHematology UA neg Wbc 8.3Wbc 8.3 Hgb 15.3Hgb 15.3 Hct 44.8Hct 44.8 Plt 273Plt 273

ImagingImaging

CT abd/pelvis without contrastCT abd/pelvis without contrast 1. Large mass off the left kidney with internal calcifications is 1. Large mass off the left kidney with internal calcifications is

highly suspicious for malignancy. Numerous small areas of mildly highly suspicious for malignancy. Numerous small areas of mildly increased density are seen within the left and right kidney. increased density are seen within the left and right kidney. Further evaluation with an IV contrast study is recommended. Further evaluation with an IV contrast study is recommended.

2. No obstructing renal calculus or hydronephrosis on either side. 2. No obstructing renal calculus or hydronephrosis on either side. 3. One prominent lymph node in the pericaval region. There is no 3. One prominent lymph node in the pericaval region. There is no

lytic or destructive lesion within the visualized bones. lytic or destructive lesion within the visualized bones. CT abd/pelvis w/ contrastCT abd/pelvis w/ contrast

1. Large heterogeneous mass off the left kidney enhances 1. Large heterogeneous mass off the left kidney enhances strongly but then has early washout. This is suspicious for a renal strongly but then has early washout. This is suspicious for a renal cell carcinoma until proven otherwise. cell carcinoma until proven otherwise.

2. Multiple other areas in both the right and left kidneys have 2. Multiple other areas in both the right and left kidneys have either complex cysts, internal septations, or areas of nodular either complex cysts, internal septations, or areas of nodular enhancement. These areas could represent multifocal areas of enhancement. These areas could represent multifocal areas of cancer. Further evaluation by MRI. cancer. Further evaluation by MRI.

3. The renal veins are patent. No lytic or destructive lesion is 3. The renal veins are patent. No lytic or destructive lesion is seen within the visualized bones. seen within the visualized bones.

ImagingImaging CT chestCT chest

1. Large left renal mass, likely renal cell cancer.1. Large left renal mass, likely renal cell cancer. 2. There is a right enhancing renal mass highly suspicious for 2. There is a right enhancing renal mass highly suspicious for

either primary renal cell cancer or metastases to the either primary renal cell cancer or metastases to the contralateral kidneycontralateral kidney

3. There are suspicious-appearing cysts with septations within 3. There are suspicious-appearing cysts with septations within both kidneys. both kidneys.

4. no evidence for invasion of the renal veins. 4. no evidence for invasion of the renal veins. 5. appears to be an adenoma within the right adrenal gland5. appears to be an adenoma within the right adrenal gland

MRI abd/pelvisMRI abd/pelvis 1. A 6.5-cm mass in the anterior mid left kidney highly 1. A 6.5-cm mass in the anterior mid left kidney highly

suggestive of renal carcinoma. no invasion of the left renal vein suggestive of renal carcinoma. no invasion of the left renal vein suggested. suggested.

2. Multiple additional small neoplastic lesions are suggested in 2. Multiple additional small neoplastic lesions are suggested in the left kidney the left kidney

3. A 2-cm simple cyst is seen in the lateral posterior right 3. A 2-cm simple cyst is seen in the lateral posterior right kidney, with an additional smaller lesion laterally suspicious for kidney, with an additional smaller lesion laterally suspicious for cystic neoplasm. A small hemorrhagic cyst is seen in the cystic neoplasm. A small hemorrhagic cyst is seen in the posteroinferior right kidney. There is a central lobulated mass posteroinferior right kidney. There is a central lobulated mass in the renal pelvis region on the right which may represent in the renal pelvis region on the right which may represent multiloculated cyst or cystic neoplasm. Two additional smaller multiloculated cyst or cystic neoplasm. Two additional smaller areas in the central right kidney are suspicious for cystic mass areas in the central right kidney are suspicious for cystic mass with peripheral enhancement. with peripheral enhancement.

RCCRCC

2-3% adult malignancies2-3% adult malignancies 40% mortality40% mortality M:F 3:2M:F 3:2 31,000 new cases/yr31,000 new cases/yr Present 60-70sPresent 60-70s 10-20% increased incidence in AA10-20% increased incidence in AA 4% familial4% familial Incidence Incidence ↑ d/t use of US and CT↑ d/t use of US and CT 25-33% mets at initial presentation25-33% mets at initial presentation

EtiologyEtiology

Environmental Risk= tobaccoEnvironmental Risk= tobacco Controversial Controversial

workers in metal, rubber, chemical, printing industryworkers in metal, rubber, chemical, printing industry Exposure to asbestos, cadmiumExposure to asbestos, cadmium Vit A & E factory workersVit A & E factory workers

Long standing obesity, low socioeconomic status, urbanLong standing obesity, low socioeconomic status, urban High fat/protein diet, increased coffee/teaHigh fat/protein diet, increased coffee/tea Thorotrast (contrast)Thorotrast (contrast) Radiation (RP radiation for Testicular Ca)Radiation (RP radiation for Testicular Ca) ThiazidesThiazides Familial: VHL, TS, BHD, Hereditary clear cell/papillaryFamilial: VHL, TS, BHD, Hereditary clear cell/papillary Endstage renal diseaseEndstage renal disease

PresentationPresentation

Asymptomatic (most found incidentally)Asymptomatic (most found incidentally) PainPain HematuriaHematuria Weight lossWeight loss Flank massFlank mass Fever, night sweatsFever, night sweats Paraneoplastic syndromesParaneoplastic syndromes 10% have triad= pain, hematuria, flank mass10% have triad= pain, hematuria, flank mass

Work UpWork Up

H&P (including lymph node & skin exam)H&P (including lymph node & skin exam) BPBP Chemistries, CBC, bun, cr, alk phosph, calcium, LFTsChemistries, CBC, bun, cr, alk phosph, calcium, LFTs CT/MRICT/MRI

LocationLocation SizeSize Contralateral kidneyContralateral kidney LNs/metsLNs/mets Renal vein/vena cava extension (MRI)Renal vein/vena cava extension (MRI)

CXR if abnormal then CTCXR if abnormal then CT Brain CT/MRI if neuro exam abnormalBrain CT/MRI if neuro exam abnormal Bone ScanBone Scan Renal bx if will help in management or if suspicion of metastatic Renal bx if will help in management or if suspicion of metastatic

lesion, lymphoma, infection, inflammatory (non dx in 20%, FN 2-lesion, lymphoma, infection, inflammatory (non dx in 20%, FN 2-10%)10%)

Mets to lung, bone, LNs, Liver, ipsilateral adrenal, contralateral Mets to lung, bone, LNs, Liver, ipsilateral adrenal, contralateral kidney, brainkidney, brain

ClassificationClassification

Clear Cell 66-75%Clear Cell 66-75% Papillary 10-15%Papillary 10-15% Chromophobe 5%Chromophobe 5% Collecting duct <1%Collecting duct <1% Oncocytomas 5%Oncocytomas 5% ChromophilChromophil

MC renal neoplasm in pts on dialysis with MC renal neoplasm in pts on dialysis with acquired cystic diseaseacquired cystic disease

MedullaryMedullary Sickle cell traitSickle cell trait

Bilateral RCCBilateral RCC Birt-Hogg-Dube SyndromeBirt-Hogg-Dube Syndrome

Fibrofolliculomas:small white/flesh papules on Fibrofolliculomas:small white/flesh papules on face/neck/back/upper trunk, >20yrs old face/neck/back/upper trunk, >20yrs old

pulmonary cysts w/ spontaneous PTXpulmonary cysts w/ spontaneous PTX renal tumors 25%, most bilateral and multiplerenal tumors 25%, most bilateral and multiple

Tuberous Sclerosis (MR/siezures/adenoma sebaceum in 30%)Tuberous Sclerosis (MR/siezures/adenoma sebaceum in 30%) Adenoma sebaceum:pink/red papules on nasolabial folds or Adenoma sebaceum:pink/red papules on nasolabial folds or

cheekscheeks Age 4-pubertyAge 4-puberty

Ash-leaf spots: hypopigmented macules on trunk/buttocksAsh-leaf spots: hypopigmented macules on trunk/buttocks Shagreen patches:orange peel plaques low backShagreen patches:orange peel plaques low back Ungal fibromasUngal fibromas AD mutation TSC1 (9) or TSC2 (16)AD mutation TSC1 (9) or TSC2 (16) Retinal/brain/lung/cardiac tumorsRetinal/brain/lung/cardiac tumors Renal cysts/AML/RCC(2%)Renal cysts/AML/RCC(2%)

Von Hippel LindauVon Hippel Lindau AD, mutation VHL (3p)AD, mutation VHL (3p) Cerebellar/spinal hemangioblastomas, retinal angiomasCerebellar/spinal hemangioblastomas, retinal angiomas Renal cysts, clear cell RCC, pheo, epididymal cystRenal cysts, clear cell RCC, pheo, epididymal cyst RCC in 50%, multifocal & bilateral, presents in 20-40sRCC in 50%, multifocal & bilateral, presents in 20-40s

StagingStaging Primary tumorPrimary tumor

(T) TX Primary tumor cannot be assessed (T) TX Primary tumor cannot be assessed

T0 No evidence of primary tumor T0 No evidence of primary tumor

T1 Tumor 7 cm or less in diameter and limited to the kidney T1 Tumor 7 cm or less in diameter and limited to the kidney T1a Tumor 4 cm or less in greatest dimension and limited to kidney T1a Tumor 4 cm or less in greatest dimension and limited to kidney

T1b Tumor more than 4 cm but not more than 7 cm, and limited to kidney T1b Tumor more than 4 cm but not more than 7 cm, and limited to kidney

T2 Tumor more than 7 cm in greatest dimension limited to the kidney T2 Tumor more than 7 cm in greatest dimension limited to the kidney

T3 Tumor extends into major veins or invades the adrenal gland or perinephric tissues, but not beyond T3 Tumor extends into major veins or invades the adrenal gland or perinephric tissues, but not beyond Gerota's fascia Gerota's fascia

T3a Tumor directly invades the adrenal gland or perinephric tissues but not beyond Gerota's fascia T3a Tumor directly invades the adrenal gland or perinephric tissues but not beyond Gerota's fascia

T3b Tumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or vena cava below the T3b Tumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or vena cava below the diaphragm diaphragm

T3c Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava T3c Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava

T4 Tumor invades beyond Gerota's fascia T4 Tumor invades beyond Gerota's fascia

Regional lymph nodes (N)*Regional lymph nodes (N)*

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasesNX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases

N1 Metastasis in a single regional lymph nodeN1 Metastasis in a single regional lymph node

N2 Metastasies in more than one regional lymph nodeN2 Metastasies in more than one regional lymph node

Distant metastasis (M) Distant metastasis (M)

MX Distant metastasis cannot be assessed MX Distant metastasis cannot be assessed

M0 No distant metastasis M0 No distant metastasis

M1 Distant metastasisM1 Distant metastasis

Treatment of Bilateral RCCTreatment of Bilateral RCC

Nephron SparingNephron Sparing Partial firstPartial first

B/L B/L nephrectomynephrectomydialysisdialysistransplant if transplant if cancer freecancer free

TreatmentTreatment

Systemic ChemoSystemic Chemo Tyrosine Kinase Inhibitor (inhibits angiogenesis & tumor growth)Tyrosine Kinase Inhibitor (inhibits angiogenesis & tumor growth)

Side effects: N/V/D, elevated amylase/lipase, rash, alopecia, fatigue, HTN, Side effects: N/V/D, elevated amylase/lipase, rash, alopecia, fatigue, HTN, bleeding, neutropenia, hypophasphatemiableeding, neutropenia, hypophasphatemia

SorafenibSorafenib FDA approved for advanced RCCFDA approved for advanced RCC Improves survival by 3moImproves survival by 3mo Higher incidence of cardiac ischemia vs. placeboHigher incidence of cardiac ischemia vs. placebo 400mg BID400mg BID

Sunitinib:Sunitinib: FDA approved for advanced RCCFDA approved for advanced RCC 30% response with duration 27-54 weeks30% response with duration 27-54 weeks ↓ ↓ EF in 15% of ptsEF in 15% of pts 50mg qday, 4week on and 2 weeks off50mg qday, 4week on and 2 weeks off

mTOR Kinase Inhibitor (mammalian target of rapamycin)mTOR Kinase Inhibitor (mammalian target of rapamycin) TemsirolimusTemsirolimus

FDA approved for advanced RCC FDA approved for advanced RCC 25mg IV qweek25mg IV qweek Improves survival 3 moImproves survival 3 mo Side Effects: rash, edema, hyperglycemia, hyperlipidemiaSide Effects: rash, edema, hyperglycemia, hyperlipidemia

Il-2 not recommended because may cause renal failureIl-2 not recommended because may cause renal failure

Our PatientOur Patient

Cleveland Clinic for Nephron Sparing Cleveland Clinic for Nephron Sparing and genetic workupand genetic workup