The Risks of Renal Angiomyolipoma: Reviewing the Evidence

Main Article Content

Raouf M. Seyam
Waleed K. Alkhudair
Said A. Kattan
Mohamed F. Alotaibi
Hassan M. Alzahrani
Waleed M. Altaweel

Keywords

angiomyolipoma, embolization, hemorrhage, kidney, nephrectomy

Abstract

Renal angiomyolipoma (RAML), though a rare benign tumor, may impose a significant morbidity or even mortality due to its unique characteristics and the complications subsequent to its treatment. The classic tumor variant is composed of smooth muscular, vascular, and fatty components. The most straightforward diagnosis is when the fat component is abundant and gives a characteristic appearance on different imaging studies. In fat-poor lesions, however, the diagnosis is difficult and presumed a renal cell carcinoma. Yet, some variants of RAML, though rare, express an aggressive behavior leading to metastasis and mortality. The challenge lies in the early detection of benign variants and identifying aggressive lesions for proper management. Another challenge is when the vascular tissue component predominates and poses a risk of hemorrhage that may extend to the retroperitoneum in a massive life-threatening condition. The predicament here is to identify the characteristics of tumors at risk of bleeding and provide a prophylactic treatment. According to the clinical presentation, different treatment modalities, prophylactic or therapeutic, are available that span the spectrum of observation, embolization, or surgery. Renal impairment may result from extensive tumor burden or as a complication of the management itself. Improvement of diagnostic techniques, super-selective embolization, nephron-sparing surgery, and late treatment with the mammalian target of rapamycin inhibitors have provided more effective and safe management strategies. In this review, we examine the evidence pertaining to the risks imposed by RAML to the patients and identify merits and hazards associated with different treatment modalities.

Abstract 2373 | PDF Downloads 731 HTML Downloads 1536 XML Downloads 579 Supplementary Tables Downloads 0

References

1. Seyam RM, Bissada NK, Kattan SA, Mokhtar AA, Aslam M, Fahmy WE, et al. Changing trends in presentation, diagnosis and management of renal angiomyolipoma: Comparison of sporadic and tuberous sclerosis complex-associated forms. Urology. 2008 Nov;72(5):1077–82. http://dx.doi.org/10.1016/j.urology.2008.07.049
2. Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2013 Mar 9;381(9869):817–24. http://dx.doi.org/10.1016/S0140-6736(12)61767-X
3. Peng Z, Yang L, Wang T, Han P, Liu Z, Wei Q. Efficacy and safety of sirolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: A systematic review. J Urol. 2014 Nov;192(5):1424–30. http://dx.doi.org/10.1016/j.juro.2014.04.096
4. Flum AS, Hamoui N, Said MA, Yang XJ, Casalino DD, McGuire BB, et al. Update on the diagnosis and management of renal angiomyolipoma. J Urol. 2016 Apr;195(4 Pt 1):834–46. http://dx.doi.org/10.1016/j.juro.2015.07.126
5. Faddegon S, So A. Treatment of angiomyolipoma at a tertiary care centre: The decision between surgery and angioembolization. Can Urol Assoc J J Assoc Urol Can. 2011 Dec;5(6): E138–41. http://dx.doi.org/10.5489/cuaj.10028
6. Daskalopoulos G, Karyotis I, Heretis I, Anezinis P, Mavromanolakis E, Delakas D. Spontaneous perirenal hemorrhage: A 10-year experience at our institution. Int Urol Nephrol. 2004;36(1):15–19. http://dx.doi.org/10.1023/B:UROL.0000032680.65742.9a
7. Albi G, del Campo L, Tagarro D. Wunderlich’s syndrome: Causes, diagnosis and radiological management. Clin Radiol. 2002 Sep;57(9):840–5. http://dx.doi.org/10.1053/crad.2002.0981
8. Nelson CP, Sanda MG. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002 Oct;168(4 Pt 1):1315–25. http://dx.doi.org/10.1016/S0022-5347(05)64440-0
9. Lu C-Y, Min P-Q, Wu B. CT evaluation of spontaneously ruptured renal angiomyolipomas with massive hemorrhage spreading into multi-retroperitoneal fascia and fascial spaces. Acta Radiol Short Rep. 2012;1(4):1–6. http://dx.doi.org/10.1258/arsr.2012.110009
10. Yamakado K, Tanaka N, Nakagawa T, Kobayashi S, Yanagawa M, Takeda K. Renal angiomyolipoma: Relationships between tumor size, aneurysm formation, and rupture. Radiology. 2002 Oct;225(1):78–82. http://dx.doi.org/10.1148/radiol.2251011477
11. Champagnac J, Melodelima C, Martinelli T, Pagnoux G, Badet L, Juillard L, et al. Microaneurysms in renal angiomyolipomas: Can clinical and computed tomography features predict their presence and size?Diagn Interv Imaging. 2016 Mar;97(3):321–6. http://dx.doi.org/10.1016/j.diii.2015.12.004
12. Al-Ateeqi A, Ali RH, Kehinde EO, Mujaibel K, Al-Hunayan A, Al-Harmi J. Increasing severity of haematuria with successive pregnancies in a woman with renal angiomyolipoma. Int Urol Nephrol. 2007;39(2):409–12. http://dx.doi.org/10.1007/s11255-006-9036-2
13. Tupikowski K, Bialy A, Dembowski J, Zlotkiewicz M, Guzinski M, Kolodziej AK, et al. Kidney angiomyolipoma in pregnancy. Cent Eur J Urol. 2014;66(4):434–6. http://dx.doi.org/10.1016/j.jemermed.2011.05.059
14. Hsu Y-P, Chen R-J, Fang J-F, Lin B-C. Traumatic rupture of renal angiomyolipoma managed with angioembolization followed by elective surgery: A report of two cases. J Trauma. 2005 Sep;59(3):737–41.
15. Zengin S, Al B, Yildirim C, Oktay MM, Yilmaz DA. Rupturing of renal angiomyolipoma due to physical examination. BMJ Case Rep. 2012 Jun28. http://dx.doi.org/10.1136/bcr.12.2011.5404
16. Lai C-C, Fan W-C, Chao C-M, Liu W-L, Hou C-C. Traumatic rupture of a renal angiomyolipoma. J Emerg Med. 2012 Nov;43(5):e339–40. http://dx.doi.org/10.1016/j.jemermed.2011.05.059
17. Snow A, Halpenny D, McNeill G, Torreggiani WC. Life-threatening rupture of a renal angiomyolipoma in a patient taking over-the-counter horse chestnut seed extract. J Emerg Med. 2012 Dec;43(6):e401–3. http://dx.doi.org/10.1016/j.jemermed.2010.11.044
18. Wright T, Sooriakumaran P. Renal angiomyolipoma presenting with massive retroperitoneal haemorrhage due to deranged clotting factors: A case report. Cases J. 2008 Oct 4;1(1):213. http://dx.doi.org/10.1186/1757-1626-1-213
19. Andersen PE, Thorlund MG, Wennevik GE, Pedersen RL, Lund L. Interventional treatment of renal angiomyolipoma: Immediate results and clinical and radiological follow-up of 4.5 years. Acta Radiol Open. 2015 Jul;4(7):2058460115592442. http://dx.doi.org/10.1177/2058460115592442
20. Duan X-H, Zhang M-F, Ren J-Z, Han X-W, Chen P-F, Zhang K, et al. Urgent transcatheter arterial embolization for the treatment of ruptured renal angiomyolipoma with spontaneous hemorrhage. Acta Radiol Stockh Swed 1987. 2016 Nov;57(11):1360–5.
21. Chronopoulos PN, Kaisidis GN, Vaiopoulos CK, Perits DM, Varvarousis MN, Malioris AV, et al. Spontaneous rupture of a giant renal angiomyolipoma-Wunderlich’s syndrome: Report of a case. Int J Surg Case Rep. 2016;19:140–3. http://dx.doi.org/10.1016/j.ijscr.2015.12.017
22. Wang C, Yang M, Tong X, Wang J, Guan H, Niu G, et al. Transarterial embolization for renal angiomyolipomas: A single centre experience in 79 patients. J Int Med Res. 2017 Apr;45(2):706–13. http://dx.doi.org/10.1177/0300060516684251
23. Bardin F, Chevallier O, Bertaut A, Delorme E, Moulin M, Pottecher P, et al. Selective arterial embolization of symptomatic and asymptomatic renal angiomyolipomas: A retrospective study of safety, outcomes and tumor size reduction. Quant Imaging Med Surg. 2017 Feb;7(1):8–23. http://dx.doi.org/10.21037/qims.2017.01.02
24. Urbano J, Paul L, Cabrera M, Alonso-Burgos A, Gomez D. Elective and emergency renal angiomyolipoma embolization with ethylene vinyl alcohol copolymer: Feasibility and initial experience. J Vasc Interv Radiol JVIR. 2017 Jun;28(6):832–9. http://dx.doi.org/10.1016/j.jvir.2017.01.017
25. Kuusk T, Biancari F, Lane B, Tobert C, Campbell S, Rimon U, et al. Treatment of renal angiomyolipoma: Pooled analysis of individual patient data. BMC Urol. 2015 Dec 28;15:123. http://dx.doi.org/10.1186/s12894-015-0118-2
26. Ouzaid I, Autorino R, Fatica R, Herts BR, McLennan G, Remer EM, et al. Active surveillance for renal angiomyolipoma: Outcomes and factors predictive of delayed intervention. BJU Int. 2014 Sep;114(3):412–17. http://dx.doi.org/10.1016/S1569-9056(14)60089-0
27. Ljungberg B, Albiges L, Bensalah K, Bex A, Giles RH, Hora M, et al. European Association of Urology 2017 guidelines on renal cell cancer [Internet]. [cited 2017 Jul 25]. Available from:http://uroweb.org/guideline/renal-cell-carcinoma/#3 B
28. Krueger DA, Northrup H. Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):255–65. http://dx.doi.org/10.1016/j.pediatrneurol.2013.08.002
29. Mues AC, Palacios JM, Haramis G, Casazza C, Badani K, Gupta M, et al. Contemporary experience in the management of angiomyolipoma. J Endourol. 2010 Nov;24(11):1883–6. http://dx.doi.org/10.1089/end.2010.0223
30. Warncke JC, Brodie KE, Grantham EC, Catarinicchia SP, Tong S, Kondo KL, et al. Pediatric renal angiomyolipomas in tuberous sclerosis complex. J Urol. 2017 Feb;197(2):500–6. http://dx.doi.org/10.1016/j.juro.2016.09.082
31. Kingswood JC, Bissler JJ, Budde K, Hulbert J, Guay-Woodford L, Sampson JR, et al. Review of the tuberous sclerosis renal guidelines from the 2012 consensus conference: Current data and future study. Nephron. 2016;134(2):51–8. http://dx.doi.org/10.1159/000448293
32. Yip SK, Tan PH, Cheng WS, Li MK, Foo KT. Surgical management of angiomyolipoma: Nephron-sparing surgery for symptomatic tumour. Scand J Urol Nephrol. 2000 Feb;34(1):32–5. http://dx.doi.org/10.1080/003655900750016850
33. Heidenreich A, Hegele A, Varga Z, von Knobloch R, Hofmann R. Nephron-sparing surgery for renal angiomyolipoma. Eur Urol. 2002 Mar;41(3):267–73. http://dx.doi.org/10.1016/S0302-2838(02)00015-5
34. Patel U, Simpson E, Kingswood JC, Saggar-Malik AK. Tuberose sclerosis complex: Analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma. Clin Radiol. 2005 Jun;60(6):665–73; discussion 663–4. http://dx.doi.org/10.1016/j.crad.2005.01.009
35. Minervini A, Giubilei G, Masieri L, Lanzi F, Serni S, Carini M. Simple enucleation for the treatment of renal angiomyolipoma. BJU Int. 2007 Apr;99(4):887–91. http://dx.doi.org/10.1111/j.1464-410X.2006.06702.x
36. Boorjian SA, Frank I, Inman B, Lohse CM, Cheville JC, Leibovich BC, et al. The role of partial nephrectomy for the management of sporadic renal angiomyolipoma. Urology. 2007 Dec;70(6):1064–8. http://dx.doi.org/10.1016/j.urology.2007.07.045
37. Simmons MN, Chung BI, Gill IS. Perioperative efficacy of laparoscopic partial nephrectomy for tumors larger than 4 cm. Eur Urol. 2009 Jan;55(1):199–207. http://dx.doi.org/10.1016/j.eururo.2008.07.039
38. Msezane L, Chang A, Shikanov S, Deklaj T, Katz MH, Shalhav AL, et al. Laparoscopic nephron-sparing surgery in the management of angiomyolipoma: A single center experience. J Endourol. 2010 Apr;24(4):583–7. http://dx.doi.org/10.1089/end.2009.0330
39. Kara O, Akca O, Zargar H, Andrade HS, Maurice MJ, Ramirez D, et al. Robotic partial nephrectomy in the treatment of renal angiomyolipoma. J Endourol. 2016 Mar;30(3):275–9. http://dx.doi.org/10.1089/end.2015.0624
40. Lin C-Y, Yang C-K, Ou Y-C, Chiu K-Y, Cheng C-L, Ho H-C, et al. Long-term outcome of robotic partial nephrectomy for renal angiomyolipoma. Asian J Surg. 2016 Dec 7. http://dx.doi.org/10.1016/j.asjsur.2016.11.003
41. Golan S, Johnson SC, Maurice MJ, Kaouk JH, Lai WR, Lee BR, et al. Safety and early effectiveness of robot-assisted partial nephrectomy for large angiomyolipomas. BJU Int. 2017 May;119(5):755–60. http://dx.doi.org/10.1111/bju.13747
42. Chick CM, Tan B-S, Cheng C, Taneja M, Lo R, Tan Y-H, et al. Long-term follow-up of the treatment of renalangiomyolipomas after selective arterial embolization with alcohol. BJU Int. 2010 Feb;105(3):390–4. http://dx.doi.org/10.1111/j.1464-410X.2009.08813.x
43. Chan CK, Yu S, Yip S, Lee P. The efficacy, safety and durability of selective renal arterial embolization in treating symptomatic and asymptomatic renal angiomyolipoma. Urology. 2011 Mar;77(3):642–8. http://dx.doi.org/10.1016/j.urology.2010.08.040
44. Ramon J, Rimon U, Garniek A, Golan G, Bensaid P, Kitrey ND, et al. Renal angiomyolipoma: Long-term results following selective arterial embolization. Eur Urol. 2009 May;55(5):1155–61. http://dx.doi.org/10.1016/j.eururo.2008.04.025
45. El Rafei M, Renard B, Puech P, Devos P, Gaillard V, Lemaitre L. Tumor necrosis after preventive embolization of large renal angiomyolipomas. Diagn Interv Imaging. 2015 Jun;96(6):579–87. http://dx.doi.org/10.1016/j.diii.2015.01.008
46. Hocquelet A, Cornelis F, Le Bras Y, Meyer M, Tricaud E, Lasserre AS, et al. Long-term results of preventive embolization of renal angiomyolipomas: Evaluation of predictive factors of volume decrease. Eur Radiol. 2014 Aug;24(8):1785–93. http://dx.doi.org/10.1007/s00330-014-3244-4
47. Villalta JD, Sorensen MD, Durack JC, Kerlan RK, Stoller ML. Selective arterial embolization of angiomyolipomas: A comparison of smaller and larger embolic agents. J Urol. 2011 Sep;186(3):921–7. http://dx.doi.org/10.1016/j.juro.2011.04.082
48. Lee S-Y, Hsu H-H, Chen Y-C, Huang C-C, Wong Y-C, Wang L-J, et al. Embolization of renal angiomyolipomas: Short-term and long-term outcomes, complications, and tumor shrinkage. Cardiovasc Intervent Radiol. 2009 Nov;32(6):1171–8. http://dx.doi.org/10.1007/s00270-009-9637-0
49. Williams JM, Racadio JM, Johnson ND, Donnelly LF, Bissler JJ. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis Off J Natl Kidney Found. 2006 Jan;47(1):95–102. http://dx.doi.org/10.1053/j.ajkd.2005.09.028
50. Bishay VL, Crino PB, Wein AJ, Malkowicz SB, Trerotola SO, Soulen MC, et al. Embolization of giant renal angiomyolipomas: Technique and results. J Vasc Interv Radiol JVIR. 2010 Jan;21(1):67–72. http://dx.doi.org/10.1016/j.jvir.2009.09.020
51. Steiner MS, Goldman SM, Fishman EK, Marshall FF. The natural history of renal angiomyolipoma. J Urol. 1993 Dec;150(6):1782–6. http://dx.doi.org/10.1016/S0022-5347(17)35895-0
52. Bhatt JR, Richard PO, Kim NS, Finelli A, Manickavachagam K, Legere L, et al. Natural history of renal angiomyolipoma (AML): Most patients with large AMLs >4cm can be offered active surveillance as an initial management strategy. Eur Urol. 2016 Jul;70(1):85–90. http://dx.doi.org/10.1016/j.eururo.2016.01.048
53. De Luca S, Terrone C, Rossetti SR. Management of renal angiomyolipoma: A report of 53 cases. BJU Int. 1999 Feb;83(3):215–18. http://dx.doi.org/10.1046/j.1464-410x.1999.00932.x
54. Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urol. 1994 Dec;152(6 Pt 1):1988–91. http://dx.doi.org/10.1016/S0022-5347(17)32286-3
55. Oesterling JE, Fishman EK, Goldman SM, Marshall FF. The management of renal angiomyolipoma. J Urol. 1986 Jun;135(6):1121–4. http://dx.doi.org/10.1016/S0022-5347(17)46013-7
56. van Baal JG, Smits NJ, Keeman JN, Lindhout D, Verhoef S. The evolution of renal angiomyolipomas in patients with tuberous sclerosis. J Urol. 1994 Jul;152(1):35–8. http://dx.doi.org/10.1016/S0022-5347(17)32809-4
57. Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, et al. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: Extension of a randomized controlled trial. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc. 2016 Jan;31(1):111–19.
58. Gyimadu AO, Kara O, Basaran D, Esinler I. Conservative management of a retroperitoneal hemorrhage following a ruptured renal angiomyolipoma in pregnancy. J Obstet Gynaecol Res. 2011 Feb;37(2):156–9. http://dx.doi.org/10.1111/j.1447-0756.2010.01326.x
59. dos Santos MML, Proenca SMS, Reis MINP de A, Viana RMAL, Martins LMB, Colaco JM dos R, et al. Spontaneous rupture of renal angiomyolipoma during pregnancy. Rev Bras Ginecol E Obstet Rev Fed Bras Soc Ginecol E Obstet. 2014 Aug;36(8):377–80. http://dx.doi.org/10.1590/SO100-720320140005019
60. Mishra VV, Mistry K, Nanda S, Choudhary S, Gandhi K. Successful pregnancy outcome in a patient with solitary kidney affected by angiomyolipoma: A rare case. J Clin Diagn Res JCDR. 2016 Oct;10(10):QD06–7.
61. Ao L, Ogasahara E, Okuda Y, Hirata S. Spontaneous rupture of renal angiomyolipoma during pregnancy. BMJ Case Rep. 2017 Jan 6. http://dx.doi.org/10.1136/bcr-2016-217284
62. Preece P, Mees B, Norris B, Christie M, Wagner T, Dundee P. Surgical management of haemorrhaging renal angiomyolipoma in pregnancy. Int J Surg Case Rep. 2015;7C:89–92. http://dx.doi.org/10.1016/j.ijscr.2015.01.004
63. Myoen S, Mitsuzuka K, Saito H, Ota H, Takase K, Arai Y. Spontaneous rupture of a renal angiomyolipoma at 25 weeks of pregnancy treated with transarterial embolization: A case report and review of the literature. Int J Urol Off J Jpn Urol Assoc. 2015 Jul;22(7):710–12. http://dx.doi.org/10.1111/iju.12775
64. Morales JP, Georganas M, Khan MS, Dasgupta P,Reidy JF. Embolization of a bleeding renal angiomyolipoma in pregnancy: Case report and review. Cardiovasc Intervent Radiol. 2005 Apr;28(2):265–8. http://dx.doi.org/10.1007/s00270-004-1850-2
65. Lee JD, Chang HC, Chu SH, Hsueh S, Soong YK. Massive retroperitoneal hemorrhage from spontaneous rupture of a renal angiomyolipoma during pregnancy. A case report. J Reprod Med. 1994 Jun;39(6):477–80.
66. Davis NF, Kelly R, Lee MJ, Mohan P. Selective arterial embolisation of bilateral angiomyolipomata in a symptomatic pregnant female. BMJ Case Rep. 2013 Nov 20. http://dx.doi.org/10.1136/bcr-2013-009256
67. Lucky MA, Shingler SN, Stephenson RN. A case report of spontaneous rupture of a renal angiomyolipoma in a post-partum. Arch Gynecol Obstet. 2009 Oct;280(4):643–5. http://dx.doi.org/10.1007/s00404-009-0964-9
68. Orywal AK, Zeile M, Bruning R, Gross AJ, Netsch C. Rupture of renal angiomyolipoma during childbirth. Urology. 2015 Apr;85(4):e19–20. http://dx.doi.org/10.1016/j.urology.2014.12.008
69. Tanaka M, Kyo S, Inoue M, Kojima T. Conservative management and vaginal delivery following ruptured renal angiomyolipoma. Obstet Gynecol. 2001 Nov;98(5 Pt 2):932–3.
70. Lopater J, Hartung O, Bretelle F, Bastide C. Management of angiomyolipoma vena cava thrombus during pregnancy. Obstet Gynecol. 2011 Feb;117(2 Pt 2):440–3. http://dx.doi.org/10.1097/AOG.0b013e3181edbc56
71. Govednik-Horny C, Atkins M. Angiomyolipoma with vascular invasion during pregnancy. Ann Vasc Surg. 2011 Nov;25(8):1138.e9–13. http://dx.doi.org/10.1016/j.avsg.2011.05.023
72. Cleary-Goldman J, Sanghvi AV, Nakhuda GS, Robinson JN. Conservative management of pulmonary lymphangioleiomyomatosis and tuberous sclerosis complicated by renal angiomyolipomas in pregnancy. J Matern -Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2004 Feb;15(2):132–4.
73. Peces R, Cuesta-Lopez E, Peces C, Selgas R. Giant bilateral renal angiomyolipomas and lymphangioleiomyomatosis presenting after two successive pregnancies successfully treated with surgery and rapamycin. ScientificWorldJournal. 2011;11:2115–23. http://dx.doi.org/10.1100/2011/263137
74. Iruloh C, Keriakos R, Smith DJ, Cleveland T. Renal angiomyolipoma and lymphangioleiomyomatosis in pregnancy. J Obstet Gynaecol J Inst Obstet Gynaecol. 2013 Aug;33(6):542–6. http://dx.doi.org/10.3109/01443615.2013.812622
75. Dabora SL, Franz DN, Ashwal S, Sagalowsky A, DiMario FJJ, Miles D, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: Kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS One. 2011;6(9):e23379. http://dx.doi.org/10.1371/journal.pone.0023379
76. Cabrera-Lopez C, Marti T, Catala V, Torres F, Mateu S, Ballarin J, et al. Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: A two years trial. Orphanet J Rare Dis. 2012 Nov 11;7:87. http://dx.doi.org/10.1186/1750-1172-7-87
77. Kingswood JC, Jozwiak S, Belousova ED, Frost MD, Kuperman RA, Bebin EM, et al. The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: Subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc. 2014 Jun;29(6):1203–10.
78. Bissler JJ, Kingswood JC. Optimal treatment of tuberous sclerosis complex associated renal angiomyolipomata: A systematic review. Ther Adv Urol. 2016 Aug;8(4):279–90. http://dx.doi.org/10.1177/1756287216641353
79. Bauman TM, Potretzke AM, Wright AJ, Vetter JM, Potretzke TA, Figenshau RS. Patient and nonradiographic tumor characteristics predicting lipid-poor angiomyolipoma in small renal masses: Introducing the BEARS index. Investig Clin Urol. 2017 Jul;58(4):235–40. http://dx.doi.org/10.4111/icu.2017.58.4.235
80. Lane BR, Aydin H, Danforth TL, Zhou M, Remer EM, Novick AC, et al. Clinical correlates of renal angiomyolipoma subtypes in 209 patients: Classic, fat poor, tuberous sclerosis associated and epithelioid. J Urol. 2008 Sep;180(3):836–43. http://dx.doi.org/10.1016/j.juro.2008.05.041
81. Lu Q, Wang W, Huang B, Li C, Li C. Minimal fat renal angiomyolipoma: The initial study with contrast-enhanced ultrasonography. Ultrasound Med Biol. 2012 Nov;38(11):1896–901. http://dx.doi.org/10.1016/j.ultrasmedbio.2012.07.014
82. Tanaka H, Fujii Y, Tanaka H, Ishioka J, Matsuoka Y, Saito K, et al. Stepwise algorithm using computed tomography and magnetic resonance imaging for diagnosis of fat-poor angiomyolipoma in small renal masses: Development and external validation. Int J Urol Off J Jpn Urol Assoc. 2017 Jul;24(7):511–17. http://dx.doi.org/10.1111/iju.13354
83. Kim YH, Han K, Oh YT, Jung DC, Cho NH, Park SY. Morphologic analysis with computed tomography may help differentiate fat-poor angiomyolipoma from renal cell carcinoma: A retrospective study with 602 patients. Abdom Radiol N Y. 2017 Jul 4. http://dx.doi.org/10.1007/s00261-017-1244-y
84. Jhaveri KS, Elmi A, Hosseini-Nik H, Hedgire S, Evans A, Jewett M, et al. Predictive value of chemical-shift MRI in distinguishing clear cell renal cell carcinoma from non-clear cell renal cell carcinoma and minimal-fat angiomyolipoma. AJR Am J Roentgenol. 2015 Jul;205(1):W79–86. http://dx.doi.org/10.2214/AJR.14.13245
85. Schieda N, Dilauro M, Moosavi B, Hodgdon T, Cron GO, McInnes MDF, et al. MRI evaluation of small (<4cm) solid renal masses: Multivariate modeling improves diagnostic accuracy for angiomyolipoma without visible fat compared to univariate analysis. Eur Radiol. 2016 Jul;26(7):2242–51. http://dx.doi.org/10.1007/s00330-015-4039-y
86. Jeong CJ, Park BK, Park JJ, Kim CK. Unenhanced CT and MRI parameters that can be used to reliably predict fat-invisible angiomyolipoma. AJR Am J Roentgenol. 2016 Feb;206(2):340–7. http://dx.doi.org/10.2214/AJR.15.15086
87. Park JJ, Kim CK. Small (<4 cm) renal tumors with predominantly low signal intensity on. AJR Am J Roentgenol. 2017 Jan;208(1):124–30. http://dx.doi.org/10.2214/AJR.16.16102
88. Potretzke AM, Potretzke TA, Bauman TM, Knight BA, Park AM, Mobley JM, et al. Computed tomography and magnetic resonance findings of fat-poor angiomyolipomas. J Endourol. 2017 Feb;31(2):119–28. http://dx.doi.org/10.1089/end.2016.0219
89. Jimenez RE, Eble JN, Reuter VE, Epstein JI, Folpe AL, de Peralta-Venturina M, et al. Concurrent angiomyolipoma and renal cell neoplasia: A study of 36 cases. Mod Pathol Off J U S Can Acad Pathol Inc. 2001 Mar;14(3):157–63. http://dx.doi.org/10.1038/modpathol.3880275
90. Cook JA, Oliver K, Mueller RF, Sampson J. A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet. 1996 Jun;33(6):480–4. http://dx.doi.org/10.1136/jmg.33.6.480
91. Guo J, Tretiakova MS, Troxell ML, Osunkoya AO, Fadare O, Sangoi AR, et al. Tuberous sclerosis-associated renal cell carcinoma: A clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol. 2014 Nov;38(11):1457–67. http://dx.doi.org/10.1097/PAS.0000000000000248
92. Mei M, Rosen LE, Reddy V, Cimbaluk DJ, Gattuso P. Concurrent angiomyolipomas and renal cell neoplasms in patients without tuberous sclerosis: A retrospective study. Int J Surg Pathol. 2015 Jun;23(4):265–70. http://dx.doi.org/10.1177/1066896915569914
93. Aydin H, Magi-Galluzzi C, Lane BR, Sercia L, Lopez JI, Rini BI, et al. Renal angiomyolipoma: Clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. Am J Surg Pathol. 2009 Feb;33(2):289–97. http://dx.doi.org/10.1097/PAS.0b013e31817ed7a6
94. Delhorme J-B, Fontana A, Levy A, Terrier P, Fiore M, Tzanis D, et al. Renal angiomyolipomas: At least two diseases. A series of patients treated at two European institutions. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2017 Apr;43(4):831–6. http://dx.doi.org/10.1016/j.ejso.2016.11.012
95. Nese N, Martignoni G, Fletcher CD, Gupta R, Pan C-C, Kim H, et al. Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: Detailed assessment of morphology and risk stratification. Am J Surg Pathol. 2011 Feb;35(2):161–76. http://dx.doi.org/10.1097/PAS.0b013e318206f2a9
96. Brimo F, Robinson B, Guo C, Zhou M, Latour M, Epstein JI. Renal epithelioid angiomyolipoma with atypia: A series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy. Am J Surg Pathol. 2010 May;34(5):715–22. http://dx.doi.org/10.1097/PAS.0b013e3181d90370
97. Park JH, Lee C, Suh JH, Kim G, Song B, Moon KC. Renal epithelioid angiomyolipoma: Histopathologic review, immunohistochemical evaluation and prognostic significance. Pathol Int. 2016 Oct;66(10):571–7. http://dx.doi.org/10.1111/pin.12458
98. Zheng S, Bi X, Song Q, Yuan Z, Guo L, Zhang H, et al. A suggestion for pathological grossing and reporting based on prognostic indicators of malignancies from a pooled analysis of renal epithelioid angiomyolipoma. Int Urol Nephrol. 2015 Oct;47(10):1643–51. http://dx.doi.org/10.1007/s11255-015-1079-9
99. He W, Cheville JC, Sadow PM, Gopalan A, Fine SW, Al-Ahmadie HA, et al. Epithelioid angiomyolipoma of the kidney: Pathological features and clinical outcome in a series of consecutively resected tumors. Mod Pathol Off J U S Can Acad Pathol Inc. 2013 Oct;26(10):1355–64. http://dx.doi.org/10.1038/modpathol.2013.72
100. Li W, Guo L, Bi X, Ma J, Zheng S. Immunohistochemistry of p53 and Ki-67 and p53 mutation analysis in renal epithelioid angiomyolipoma. Int J Clin Exp Pathol. 2015;8(8):9446–51.
101. Hassan M, El-Hefnawy AS, Elshal AM, Mosbah A, El-Baz M, Shaaban A . Renal epithelioid angiomyolipoma: A rare variant with unusual behavior. Int Urol Nephrol. 2014 Feb;46(2):317–22. http://dx.doi.org/10.1007/s11255-013-0510-3
102. Cui L, Zhang J-G, Hu X-Y, Fang X-M, Lerner A, Yao X-J, et al. CT imaging and histopathological features of renal epithelioid angiomyolipomas. Clin Radiol. 2012 Dec;67(12):e77–82. http://dx.doi.org/10.1016/j.crad.2012.08.006
103. Lu Q, Li C, Huang B, Xue L, Wang W. Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: Qualitative and quantitative CEUS characteristics and distinguishing features. Abdom Imaging. 2015 Feb;40(2):333–42. http://dx.doi.org/10.1007/s00261-014-0221-y
104. Liu Y, Qu F, Cheng R, Ye Z. CT-imaging features of renal epithelioid angiomyolipoma. World J Surg Oncol. 2015 Sep 22;13:280. http://dx.doi.org/10.1186/s12957-015-0700-9
105. Zhou H, Guo M, Gong Y. Challenge of FNA diagnosis of angiomyolipoma: A study of 33 cases. Cancer. 2017 Apr;125(4):257–66. http://dx.doi.org/10.1002/cncy.21824
106. Kohno J, Matsui Y, Yamasaki T, Shibasaki N, Kamba T, Yoshimura K, et al. Role of mammalian target of rapamycin inhibitor in the treatment of metastatic epithelioid angiomyolipoma: A case report. Int J Urol Off J Jpn Urol Assoc. 2013 Sep;20(9):938–41. http://dx.doi.org/10.1111/iju.12095
107. Shitara K, Yatabe Y, Mizota A, Sano T, Nimura Y, Muro K. Dramatic tumor response to everolimus for malignant epithelioid angiomyolipoma. Jpn J Clin Oncol. 2011 Jun;41(6):814–16. http://dx.doi.org/10.1093/jjco/hyr035
108. Vekeman F, Magestro M, Karner P, Duh MS, Nichols T, van Waalwijk van Doorn Khosrovani SB, et al. Kidney involvement in tuberous sclerosis complex: The impact on healthcare resource use and costs. J Med Econ. 2015;18(12):1060–70. http://dx.doi.org/10.3111/13696998.2015.1075995
109. Eijkemans MJC, van der Wal W, Reijnders LJ, Roes KCB, van Waalwijk van Doorn Khosrovani SB, Pelletier C, et al. Long-term follow-up assessing renal angiomyolipoma treatment patterns, morbidity, and mortality: An observational study in tuberous sclerosis complex patients in the Netherlands. Am J Kidney Dis Off J Natl Kidney Found. 2015 Oct;66(4):638–45. http://dx.doi.org/10.1053/j.ajkd.2015.05.016
110. Shepherd CW, Gomez MR. Mortality in the Mayo Clinic tuberous sclerosis complex study. Ann N Y Acad Sci. 1991;615:375–7. http://dx.doi.org/10.1111/j.1749-6632.1991.tb37786.x
111. Schillinger F, Montagnac R. Chronic renal failure and its treatment in tuberous sclerosis. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc. 1996 Mar;11(3):481–5.
112. Clarke A, Hancock E, Kingswood C, Osborne JP. End-stage renal failure in adults with the tuberous sclerosis complex. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc. 1999 Apr;14(4):988–91.
113. Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int. 2004 Sep;66(3):924–34. http://doi.org/10.1111/j.1523-1755.2004.00838.x
114. Stillwell TJ, Gomez MR, Kelalis PP. Renal lesions in tuberous sclerosis. J Urol. 1987 Sep;138(3):477–81. http://dx.doi.org/10.1016/S0022-5347(17)43234-4
115. O’Callaghan FJ, Noakes MJ, Martyn CN, Osborne JP. An epidemiological study of renal pathology in tuberous sclerosis complex. BJU Int. 2004 Oct;94(6):853–7. http://dx.doi.org/10.1111/j.1464-410X.2004.05046.x
116. Okada RD, Platt MA, Fleishman J. Chronic renal failure in patients with tuberous sclerosis. Association with renal cysts. Nephron. 1982;30(1):85–8. http://dx.doi.org/10.1159/000182439
117. Yu DT, Sheth KJ. Cystic renal involvement in tuberous sclerosis. Clin Pediatr (Phila). 1985 Jan;24(1):36–9. http://dx.doi.org/10.1177/000992288502400108
118. Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes J, Maheshwar MM, et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—A contiguous gene syndrome. Nat Genet. 1994 Dec;8(4):328–32. http://dx.doi.org/10.1038/ng1294-328
119. Seyam R, Khudair WA, Kattan SA, Al Otaibi MF, Skaff F, AlTaweel WM. The impact of renal angiomyolipoma on estimated glomerular filtration rate in patients with tuberous sclerosis complex. Ann Saudi Med. 2016 Oct;36(5):356–63. http://dx.doi.org/10.5144/0256-4947.2016.356
120. Koo KC, Kim WT, Ham WS, Lee JS, Ju HJ, Choi YD. Trends of presentation and clinical outcome of treated renal angiomyolipoma. Yonsei Med J. 2010 Sep;51(5):728–34. http://dx.doi.org/10.3349/ymj.2010.51.5.728
121. Bissler J, Cappell K, Charles H, Song X, Liu Z, Prestifilippo J, et al. Rates of interventional procedures in patients with tuberous sclerosis complex-related renal angiomyolipoma. Curr Med Res Opin. 2015 Aug;31(8):1501–7. http://dx.doi.org/10.1185/03007995.2015.1060212
122. Tong YC, Chieng PU, Tsai TC, Lin SN. Renal angiomyolipoma: Report of 24 cases. Br J Urol. 1990 Dec;66(6):585–9. http://dx.doi.org/10.1111/j.1464-410X.1990.tb07187.x
123. Ou YC, Wu HC, Yang CR, Chang CL, Hwang TI, Chang CH. Renal angiomyolipoma: Experience of 23 patients. Zhonghua Yi Xue Za Zhi Chin Med J Free China Ed. 1991 Sep;48(3):217–23.
124. Jou Y-C, Chen W-P, Huang C-L. Urgent angioembolization with early elective nephron-sparing surgery for spontaneously ruptured renal angiomyolipoma. J Chin Med Assoc JCMA. 2009 Aug;72(8):450–2. http://dx.doi.org/10.1016/S1726-4901(09)70405-8
125. Wang D, Li H-Z, Ji Z-G. Effectiveness and safety of laparoscopic enucleation combined with selective arterial embolization for renal angiomyolipoma. Cancer Biomark Sect Dis Markers. 2017;19(2):177–83. http://dx.doi.org/10.3233/CBM-160501
126. Qin C, Wang Y, Li P, Li P, Tao J, Shao P, et al. Super-selective artery embolization before laparoscopic partial nephrectomy in treating renal angiomyolipoma. Urol Int. 2017 Apr 14. http://dx.doi.org/10.1159/000472261
127. Fazeli-Matin S, Novick AC. Nephron-sparing surgery for renal angiomyolipoma. Urology. 1998 Oct;52(4):577–83. http://dx.doi.org/10.1016/S0090-4295(98)00236-2
128. Siena G, Minervini A, Tuccio A, Vittori G, Salvi M, Sebastianelli A, et al. Nephron-sparing surgery for giant angiomyolipomas of kidney. Arch Ital Urol Androl Organo Uff Soc Ital Ecogr Urol E Nefrol. 2012 Sep;84(3):146–50.
129. Liu W, Qi L, Chen M, Wang L, Liu L, Zhu B, et al. Laparoscopic retroperitoneal enucleation-separation surgery for renal angiomyolipoma: Perioperative and oncologic outcomes based on a randomized controlled trial. J Endourol. 2016 Aug;30(8):901–5. http://dx.doi.org/10.1089/end.2016.0195
130. Murray TE, Doyle F, Lee M. Transarterial embolization of angiomyolipoma: A systematic review. J Urol. 2015 Sep;194(3):635–9. http://dx.doi.org/10.1016/j.juro.2015.04.081
131. Kothary N, Soulen MC, Clark TWI, Wein AJ, Shlansky-Goldberg RD, Crino PB, et al. Renal angiomyolipoma: Long-term results after arterial embolization. J Vasc Interv Radiol JVIR. 2005 Jan;16(1):45–50. http://dx.doi.org/10.1097/01.RVI.0000143769.79774.70
132. Lee S-Y, Hsu H-H, Chen Y-C, Huang C-C, Wong Y-C, Wang L-J, et al. Evaluation of renal function of angiomyolipoma patients after selective transcatheter arterial embolization. Am J Med Sci. 2009 Feb;337(2):103–8. http://dx.doi.org/10.1097/MAJ.0b013e31817f6dd9
133. Baba Y, Hayashi S, Ikeda S, Jinguji M, Nakajo M, Nakajo M. Evaluation of split renal function before and after renal arterial embolization for angiomyolipoma using absolute ethanol. Cardiovasc Intervent Radiol. 2014 Oct;37(5):1220–5. http://dx.doi.org/10.1007/s00270-013-0780-2
134. Hatano T, Chikaraishi K, Inaba H, Endo K, Egawa S. Outcomes of everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex: A single-institution experience in Japan. Int J Urol Off J Jpn Urol Assoc. 2016 Oct;23(10):833–8. http://dx.doi.org/10.1111/iju.13168
135. Robles NR, Peces R, Gomez-Ferrer A, Villacampa F, Alvarez-Ossorio JL, Perez-Segura P, et al. Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: A Spanish expanded access trial. Orphanet J Rare Dis. 2016 Sep 26;11(1):128. http://dx.doi.org/10.1186/s13023-016-0517-9
136. Tsai J-D, Wei C-C, Yang S-H, Fan H-C, Hsu C-C, Tung M-C, et al. The effects of everolimus on tuberous sclerosis complex-associated renal angiomyolipoma: A preliminary report. Nephrol Carlton Vic. 2016 Aug 27. http://dx.doi.org/10.1111/nep.12912
137. Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):140–51. http://dx.doi.org/10.1056/NEJMoa063564
138. Davies M, Saxena A, Kingswood JC. Management of everolimus-associated adverse events in patients with tuberous sclerosis complex: A practical guide. Orphanet J Rare Dis. 2017 Feb 15;12(1):35. http://dx.doi.org/10.1186/s13023-017-0581-9
139. Kingswood JC, Crawford P, Johnson SR, Sampson JR, Shepherd C, Demuth D, et al. The economic burden of tuberous sclerosis complex in the UK: A retrospective cohort study in the clinical practice research datalink. J Med Econ. 2016 Nov;19(11):1087–98. http://dx.doi.org/10.1080/13696998.2016.1199432
140. Kingswood JC, Nasuti P, Patel K, Myland M, Siva V, Gray E. The economic burden of tuberous sclerosis complex in UK patients with renal manifestations: A retrospective cohort study in the clinical practice research datalink (CPRD). J Med Econ. 2016 Dec;19(12):1116–26. http://dx.doi.org/10.1080/13696998.2016.1202254
141. Bissler J, Cappell K, Charles H, Song X, Liu Z, Prestifilippo J, et al. Long-term clinical morbidity in patients with renal angiomyolipoma associated with tuberous sclerosis complex. Urology. 2016 Sep;95:80–7. http://dx.doi.org/10.1016/j.urology.2016.04.027
142. Song X, Liu Z, Cappell K, Gregory C, Said Q, Prestifilippo J, et al. Healthcare utilization and costs in patients with tuberous sclerosis complex-related renal angiomyolipoma. J Med Econ. 2017 Apr;20(4):388–94. http://dx.doi.org/10.1080/13696998.2016.1272461
143. Kingswood JC, d’Augeres GB, Belousova E, Ferreira JC, Carter T, Castellana R, et al. Tuberous sclerosis registry to increase disease Awareness (TOSCA)—Baseline data on 2093 patients. Orphanet J Rare Dis. 2017 Jan 5;12(1):2. http://dx.doi.org/10.1186/s13023-016-0553-5
144. Seibert D, Hong C-H, Takeuchi F, Olsen C, Hathaway O, Moss J, et al. Recognition of tuberous sclerosis in adult women: Delayed presentation with life-threatening consequences. Ann Intern Med. 2011 Jun 21;154(12):806–13, W-294.