Concurrent Bilateral Renal Angiomyolipoma and Renal Cell Carcinoma in a Patient With Tuberous Sclerosis Complex

9. RIU0436_12-14.qxd 12/14/09 5:39 PM Page 216 CASE REVIEW Concurrent Bilateral Renal Angiomyolipoma and Renal Cell Carcinoma in a Patient With Tuberous Sclerosis Complex Abdelhak Khallouk, MD, Younes Ahallal, MD, Mbarek Doublali, MD, Mohamed Fadl Tazi, MD, Soufiane Mellas, MD, Mohamed Jamal el Fassi, MD, Moulay Hassan Farih, MD Department of Urology, Hassan II University Hospital Center, Fez, Morocco Renal angiomyolipomas (AMLs) are often associated with tuberous sclerosis. These tumors are predominantly benign, although malignant forms do exist and are known to be associated with renal cell carcinoma. This case report describes a patient with tuberous sclerosis and massive bilateral AML. Total right nephrectomy was performed; histopathologic examination revealed the coexistence of AML and clear cell renal carcinoma in the same kidney. Because differentiation between renal cell carcinoma and AML with minimal or no fat component can be difficult, an accurate diagnosis is critical in the management of renal AML. [Rev Urol. 2009;11(4):216-218 doi: 10.3909/riu0436] © 2009 MedReviews®, LLC Key words: Angiomyolipoma • Renal cell carcinoma • Tuberous sclerosis pproximately 80% of patients with tuberous sclerosis complex (TSC) develop renal angiomyolipoma (AML). Although often benign,1,2 malignant AML and renal cell carcinoma (RCC) have also been reported in patients with TSC. The concurrence of renal AML and RCC in the same kidney has also been reported in patients with TSC and has been revealed on pathologic examination. Several criteria can be used to help predict malignancy in renal AML, such as tumor size, tumor size and necrosis, and atypical mitotic figures. We report a case of associated massive bilateral AML and RCC. We discuss the diagnosis and A 216 VOL. 11 NO. 4 2009 REVIEWS IN UROLOGY 9. RIU0436_12-14.qxd 12/14/09 5:39 PM Page 217 AML and Tuberous Sclerosis treatment of renal AML and emphasize the possibility of concurrent renal malignancies in patients with TSC. concurrent RCC in the same kidney. The patient refused contralateral nephrectomy because of the difficulties of access to hemodialysis and its cost. Case Report A 35-year-old man complaining of left flank pain and gross hematuria was admitted to our hospital. He had been diagnosed with TSC in early childhood. On physical examination his face showed plaque-like lesions consistent with angiofibroma; he had subungual fibroma, shagreen patches, and multi- Discussion TSC is an autosomal dominant disorder linked with a mutation in chromosome 9 (TSC1 gene) and chromosome 16 (TSC2 gene). It is characterized by hamartomatous tumors that involve multiple organ systems (eg, skin, kidney, brain, lung, liver). Abdominal computed tomography showed huge bilateral renal masses with fat component, suggesting a bilateral massive angiomyolipoma. ple hypopigmented macules, confirming the diagnosis of TSC. Abdominal palpation revealed a mass with tenderness in the right flank. Ultrasonography revealed multiple large, highly echoic, heterogeneous bilateral renal tumors. Abdominal computed tomography (CT) showed huge bilateral renal masses with fat component, suggesting a bilateral massive AML (Figure 1). In the right kidney, the tumor was massive and there was no normal renal tissue; multiple small tumors and 1 very large tumor in the central region of the left kidney were also diagnosed. Because conservative surgical management was not possible, right radical nephrectomy was performed. Histologic examination revealed AML and Figure 1. Abdominal computed tomography image showing bilateral massive angiomyolipoma. Approximately 80% of patients with TSC develop renal AML, which is often considered a clinically benign lesion.1,2 However, malignant renal tumors have also been reported in patients with TSC. On CT, the diagnosis is confirmed by the presence of substantial amounts of fat. There are 2 principal types of malignancies: malignant AML and RCC. The former is a transformation of benign epithelioid AML,3 a subtype of AML that is considered to be a potentially malignant tumor, because approximately onethird of cases have been reported to develop metastases.4 Different criteria have been proposed to predict malig- quoted for RCC associated with TSC.8,9 Malignant AML may resemble sarcomatoid RCC on histopathologic findings, but can be distinguished on the basis of immunohistochemical evaluation; indeed, AML cells are positive for the HMB-45 antibody and negative for cytokeratins, and 94% of sarcomatoid RCC cases test positive for the AE1/AE3 antibody.10 The association of RCC and AML on the same kidney has been reported in patients with TSC and has been revealed on histopathologic examination.11,12 Therefore, when surgical management of AML is indicated, we believe that carcinologic surgical principles must be followed (partial or radical nephrectomy). The principal goal of AML management is preservation of renal tissue and prevention or treatment of symptoms, particularly hemorrhage, which can be life threatening. Treatment methodology is decided based on the size of the tumor, symptoms, rate of growth, complications, and the degree of diagnosis certainty on radiologic results. Selective arterial embolization has shown itself effective either in the treatment of hemorrhage or as the initial treatment of AML. However, the disadvantage of this method is its inability to provide tissue for histologic examination; Total nephrectomy should be performed sparingly—in cases of uncontrollable bleeding, central tumors, massive tumors, presence of extensive necrosis, or when there is a diagnosis of renal cell carcinoma in the same kidney. nancy in these tumors, including tumor size,5 tumor size and necrosis,6 and mitotic figures, especially atypical ones.5-8 However, distant metastases are at present considered the sole malignant hallmark of epithelioid AML.4,7 RCC in TSC is said to occur in patients at a young age, with predominance in women (80%). An incidence of up to 4% has been therefore, it should not be undertaken as the only treatment unless there is a very high degree of diagnostic certainty. Regarding surgical treatment, tumorectomy, partial nephrectomy, or total nephrectomy may be performed.13 Total nephrectomy should be performed sparingly—in cases of uncontrollable bleeding, central tumors, massive VOL. 11 NO. 4 2009 REVIEWS IN UROLOGY 217 9. RIU0436_12-14.qxd 12/14/09 5:39 PM Page 218 AML and Tuberous Sclerosis continued tumors, presence of extensive necrosis, or when there is a diagnosis of RCC in the same kidney.13 Recently, cryotherapy and radiofrequency ablation have been suggested as therapeutic options. References 1. 2. 3. Conclusions For patients with TSC, one should be aware that renal AML can be malignant and there is a possibility of coexisting RCC. Thus, when surgical management is indicated, we believe that carcinologic surgical rules must be observed unless there is a high degree of certainty that the lesion is benign. 4. 5. 6. Bernstein J, Robbins TO. Renal involvement in tuberous sclerosis. Ann N Y Acad Sci. 1991;615:36-49. Stillwell TJ, Gomez MR, Kelalis PP. Renal lesions in tuberous sclerosis. J Urol. 1987;138: 477-481. Pea M, Bonetti G, Martignoni E, et al. Apparent renal cell carcinoma in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma. Am J Surg Pathol. 1998;22:180-187. Cibas ES, Goss JA, Kulke MH, et al. Malignant epithelioid angiomyolipoma (‘sarcoma ex angiomyolipoma’) of the kidney: a case report and review of the literature. Am J Surg Pathol. 2001;25:121-126. Takahashi N, Kitahara R, Hishimoto Y, et al. Malignant transformation of renal angiomyolipoma. Int J Urol. 2003;10:271-273. Lin WC, Wang LH, Wei CJ, et al. Malignant renal epithelioid angiomyolipoma with aggressive behavior and distant metastasis. J Chin Med Assoc. 2003;66:303-306. 7. 8. 9. 10. 11. 12. 13. Stone CH, Lee MW, Amin MB, et al. Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum. Arch Pathol Lab Med. 2001;125:751-758. Choyke PL, Glenn GM, Walther MM, et al. Hereditary renal cancer. Radiology. 2003;226:33-46. Lendvay TS, Marshall FF. The tuberous sclerosis complex and its highly variable manifestations. J Urol. 2003;169:1635-1642. DeLong W, Grignon DJ, Eberwein P, et al. Sarcomatoid renal cell carcinoma. An immunohistochemical study of 18 cases. Arch Pathol Lab Med. 1993;117:636-640. Graves N, Barnes WF. Renal cell carcinoma and angiomyolipoma in tuberous sclerosis: case report. J Urol. 1986;135:122-123. Hardman JA, McNicholas TA, Kirkham N, Fletcher MS. Recurrent renal angiomyolipoma associated with renal carcinoma in a patient with tuberous sclerosis. Br J Urol. 1993;72:983-984. Schneider-Monteiro ED, Lucon AM, de Figueiredo AA, et al. Bilateral giant renal angiomyolipoma associated with hepatic lipoma. Rev Hosp Clin Fac Med Sao Paulo. 2003;58:103-108. Main Points • Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomatous tumors that involve multiple organ systems. Approximately 80% of patients with TSC develop renal angiomyolipoma (AML). • Several criteria can be used to help predict malignancy in renal AML, such as tumor size, tumor size and necrosis, and atypical mitotic figures. • The principal goal of AML management is preservation of renal tissue and prevention or treatment of symptoms, particularly hemorrhage. • Cryotherapy and radiofrequency ablation have recently been suggested as therapeutic options. 218 VOL. 11 NO. 4 2009 REVIEWS IN UROLOGY