Case 1 PLEASE TURN OFF YOUR CELL PHONES 3/28/2017. Disclosure of Relevant Financial Relationships. Disclosure of Relevant Financial Relationships

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1 PLEASE TURN OFF YOUR CELL PHONES Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Priya Rao declares she has no conflict(s) of interest to disclose. Disclosure of Relevant Financial Relationships USCAP requires that all faculty in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Priya Raodeclares she has no conflict(s) of interest to disclose. Priya Rao, MD Associate Professor The University of Texas MD Anderson Cancer Center Houston, TX (prao@mdanderson.org) CLINICAL HISTORY A 28 year old female presented with multiple renal masses. A 3.5 cm heterogenously enhancing mass was identified in the upper pole. Additional lesions within the kidney that were suggestive of lipid-poor angiomyolipoma by MRI. 1

2 CK7 CK20 PAX8 CD117 HMB-45 2

3 IMMUNOHISTOCHEMISTRY RESULTS ADDITIONAL CLINICAL HISTORY Positive PAX8 CAM5.2 CD117 CK20 SDHB CK7 Negative Cathepsin-K TFE3 P504S Multiple angiofibromas and hypomelanic macules Diagnosed with a TSC1 mutation in childhood based on genetic screening DIAGNOSIS Tuberous sclerosis associated renal cell carcinoma BACKGROUND Tuberous sclerosis complex (TSC) is an autosomal dominant disorder Germline mutations in TSC1 or TSC2 genes Variable penetrance Large number of patients without a prior family history AML is commonly recognized Various RCC s have been recently described in association with TSC RENAL MANIFESTATIONS OF TSC Renal involvement in >50% of patients TSC2 mutations more likely to show renal manifestations Younger patients Manifestations include cysts, AML, RCC Strong coexistence of renal AML with LAM Reference: SK Rakowski et al.: Renal manifestations of tuberous sclerosis complex; Kidney Int. 2006;70:

4 RENAL TUMORS IN TSC Female predominance Multiple tumors are common (approximately 40%) Bilateral (approximately 25%) Concurrent AML in majority of patients Eosinophilic renal cysts in the background are common TYPES OF RCCS IN TSC Guo et al Renal cell carcinoma with angoleiomyomatous stroma (RAT like) Chromophobe RCCs Eosinophilic macrocystic RCC Yang et al TSC associated Papillary RCC s Hybrid oncocytic tumors Unclassified RCC 4

5 CK7 CD10 CAIX SMA CHROMOPHOBE RCC AND OTHER ONCOCYTIC TUMORS Similar to those seen in a sporadic setting Includes tumors with hybrid features Association with AML (and AMLEC) should raise the suspicion for TSC and distinguish from BHD syndrome 5

6 Vimentin CK7 TUMORS UNIQUE TO THE TSC UNCLASSIFIED RCC EOSINOPHILIC MACROCYSTIC PATTERN 6

7 PROGNOSIS Lymph node metastasis reported Follow up range from 3 to >140 months Most NED DIFFERENTIAL DIAGNOSIS Translocation RCC HLRCC SDH deficient RCC Epithelioid AML 7

8 IN SUMMARY Be aware of the unique features of TSC associated RCC Rule out other more common RCC s before arriving at the diagnosis The presence of AML in the kidney should raise suspicion Have a dialogue with the clinician to assure appropriate work up Our role is often critical in appropriately identifying these patients! Important Information Regarding CME/SAMs THANK YOU The Online CME/Evaluations/SAMs claim process will only be available on the USCAP website until September 30, No claims can be processed after that date! After September 30, 2017 you will NOT be able to obtain any CME or SAMs credits for attending this meeting. Contact: prao@mdanderson.org OTHER DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS Translocation RCC Epithelioid angiomyolipoma Sporadic Chromophobe RCC HOCTs (Birt Hogg Dube syndrome) SDH deficient RCC Eosinophilic clear cell RCC Papillary RCC 8

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