Case Presentation SGH July 2008

1. Case Presentation SGHJuly 2008 Lauren Eisenberg

2. CC/HPI • CC: L flank pain • HPI: 41yo AAM presents to ED with c/o abd and L flank pain for 5days. Pain described as intermittent, excruciating, sharp, radiates from flank to lower LLQ. Nothing improves or worsens pain. Associated with decrease urine output, decrease stream, and concentrated urine.

3. History • PMHx: diverticulosis, HTN, anxiety disorder • PSHx: none • A: NKDA • M: Paxil 30mg qday, Maxzide • FamHx: • Mother: HTN, Polycystic Kidney Disease • Father: Dialysis for DM • SoHx: married w/ 6 children, No ETOH/tob/IVDU • ROS: • Neg: F/C/Weight loss • Gu: hematuria, dysuria

4. PE • VSS: • BP 148/101 P91 RR20 T35.9 • General: NAD • Heent: normocephalic, EOMI • CV: RRR w/o m/g/r • Lungs: CTAB • Abd: soft, ND, mild L flank & LLQ TTP with deep palpation • GU: b/l descended testicles, circumcised penis • Rectal: slightly enlarged, symmetrical, rubbery, no nodules

5. Labs • Chemisty Liver Profile • Na 140 AST 34 • K 4.1 ALT 17 • Cl 99 Alk Phosph 92 • HCO2 26 • Bun 15 • CR 1.2 • Hematology UA neg • Wbc 8.3 • Hgb 15.3 • Hct 44.8 • Plt 273

6. Imaging • CT abd/pelvis without contrast • 1. Large mass off the left kidney with internal calcifications is highly suspicious for malignancy. Numerous small areas of mildly increased density are seen within the left and right kidney. Further evaluation with an IV contrast study is recommended. • 2. No obstructing renal calculus or hydronephrosis on either side. • 3. One prominent lymph node in the pericaval region. There is no lytic or destructive lesion within the visualized bones. • CT abd/pelvis w/ contrast • 1. Large heterogeneous mass off the left kidney enhances strongly but then has early washout. This is suspicious for a renal cell carcinoma until proven otherwise. • 2. Multiple other areas in both the right and left kidneys have either complex cysts, internal septations, or areas of nodular enhancement. These areas could represent multifocal areas of cancer. Further evaluation by MRI. • 3. The renal veins are patent. No lytic or destructive lesion is seen within the visualized bones.

7. Imaging • CT chest • 1. Large left renal mass, likely renal cell cancer. • 2. There is a right enhancing renal mass highly suspicious for either primary renal cell cancer or metastases to the contralateral kidney • 3. There are suspicious-appearing cysts with septations within both kidneys. • 4. no evidence for invasion of the renal veins. • 5. appears to be an adenoma within the right adrenal gland • MRI abd/pelvis • 1. A 6.5-cm mass in the anterior mid left kidney highly suggestive of renal carcinoma. no invasion of the left renal vein suggested. • 2. Multiple additional small neoplastic lesions are suggested in the left kidney • 3. A 2-cm simple cyst is seen in the lateral posterior right kidney, with an additional smaller lesion laterally suspicious for cystic neoplasm. A small hemorrhagic cyst is seen in the posteroinferior right kidney. There is a central lobulated mass in the renal pelvis region on the right which may represent multiloculated cyst or cystic neoplasm. Two additional smaller areas in the central right kidney are suspicious for cystic mass with peripheral enhancement.

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

9. Etiology • Environmental Risk= tobacco • Controversial • workers in metal, rubber, chemical, printing industry • Exposure to asbestos, cadmium • Vit A & E factory workers • Long standing obesity, low socioeconomic status, urban • High fat/protein diet, increased coffee/tea • Thorotrast (contrast) • Radiation (RP radiation for Testicular Ca) • Thiazides • Familial: VHL, TS, BHD, Hereditary clear cell/papillary • Endstage renal disease

10. Presentation • Asymptomatic (most found incidentally) • Pain • Hematuria • Weight loss • Flank mass • Fever, night sweats • Paraneoplastic syndromes • 10% have triad= pain, hematuria, flank mass

11. Work Up • H&P (including lymph node & skin exam) • BP • Chemistries, CBC, bun, cr, alk phosph, calcium, LFTs • CT/MRI • Location • Size • Contralateral kidney • LNs/mets • Renal vein/vena cava extension (MRI) • CXR if abnormal then CT • Brain CT/MRI if neuro exam abnormal • Bone Scan • Renal bx if will help in management or if suspicion of metastatic lesion, lymphoma, infection, inflammatory (non dx in 20%, FN 2-10%) • Mets to lung, bone, LNs, Liver, ipsilateral adrenal, contralateral kidney, brain

12. Classification • Clear Cell 66-75% • Papillary 10-15% • Chromophobe 5% • Collecting duct <1% • Oncocytomas 5% • Chromophil • MC renal neoplasm in pts on dialysis with acquired cystic disease • Medullary • Sickle cell trait

13. Bilateral RCC • Birt-Hogg-Dube Syndrome • Fibrofolliculomas:small white/flesh papules on face/neck/back/upper trunk, >20yrs old • pulmonary cysts w/ spontaneous PTX • renal tumors 25%, most bilateral and multiple • Tuberous Sclerosis (MR/siezures/adenoma sebaceum in 30%) • Adenoma sebaceum:pink/red papules on nasolabial folds or cheeks • Age 4-puberty • Ash-leaf spots: hypopigmented macules on trunk/buttocks • Shagreen patches:orange peel plaques low back • Ungal fibromas • AD mutation TSC1 (9) or TSC2 (16) • Retinal/brain/lung/cardiac tumors • Renal cysts/AML/RCC(2%) • Von Hippel Lindau • AD, mutation VHL (3p) • Cerebellar/spinal hemangioblastomas, retinal angiomas • Renal cysts, clear cell RCC, pheo, epididymal cyst • RCC in 50%, multifocal & bilateral, presents in 20-40s

14. Staging • Primary tumor • (T) TX Primary tumor cannot be assessed • T0 No evidence of primary tumor • 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 • 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 • T3 Tumor extends into major veins or 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 diaphragm • 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 • Regional lymph nodes (N)* • NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases • N1 Metastasis in a single regional lymph node • N2 Metastasies in more than one regional lymph node • Distant metastasis (M) • MX Distant metastasis cannot be assessed • M0 No distant metastasis • M1 Distant metastasis

15. Treatment of Bilateral RCC • Nephron Sparing • Partial first • B/L nephrectomydialysistransplant if cancer free

16. Treatment • Systemic Chemo • Tyrosine Kinase Inhibitor (inhibits angiogenesis & tumor growth) • Side effects: N/V/D, elevated amylase/lipase, rash, alopecia, fatigue, HTN, bleeding, neutropenia, hypophasphatemia • Sorafenib • FDA approved for advanced RCC • Improves survival by 3mo • Higher incidence of cardiac ischemia vs. placebo • 400mg BID • Sunitinib: • FDA approved for advanced RCC • 30% response with duration 27-54 weeks • ↓ EF in 15% of pts • 50mg qday, 4week on and 2 weeks off • mTOR Kinase Inhibitor (mammalian target of rapamycin) • Temsirolimus • FDA approved for advanced RCC • 25mg IV qweek • Improves survival 3 mo • Side Effects: rash, edema, hyperglycemia, hyperlipidemia • Il-2 not recommended because may cause renal failure

17. Our Patient • Cleveland Clinic for Nephron Sparing and genetic workup