Vol 16, No 3 (2020)
Review paper
Published online: 2020-07-08

open access

Page views 1973
Article views/downloads 2332
Get Citation

Connect on Social Media

Connect on Social Media

Diagnosis and treatment of angiomyolipoma (AML) tumours

Aleksandra Sobiborowicz12, Anna M. Czarnecka13, Anna Szumera-Ciećkiewicz45, Piotr Rutkowski1, Tomasz Świtaj1
Oncol Clin Pract 2020;16(3):116-132.


Angiomyolipoma (AML) is the most commonly occurring tumour from the PEComa family (PEC tumours; perivascular
epithelioid cell tumours), a rare group of neoplasms of mesenchymal origin. AML may occur sporadically or
in the course of tuberous sclerosis and lymphangioleiomyomatosis. The sporadic type form is the most common
subtype of benign kidney tumours and is four times more frequent in women. Kid ney tumours of the angiomyolipoma
type are most commonly detected by chance during an abdominal cavity ultrasound scan, during which
they are visible as hyperechogenic tumours, and in most cases they are not a diagnostic problem. AML growth
is slow, and complications are rare. The main AML complication can be bleeding to the retroperitoneal space or
to the pelvicalyceal system. The typical method of AML care is active surveillance (AS). Asymptomatic tumours
with a diameter under 4 cm require control by ultrasound examination every 12 months whereas tumours with
a diameter of less than 2 cm are considered not to require control ultrasounds. AML with a diameter of over 4 cm
require more frequent ultrasound scans — every six months. The size of the tumour, the presence of symptoms
(e.g. pain in a tumour projection, haematuria), planned pregnancy, or suspicion of a malignant tumour are critical
in therapeutic decisions. Active treatment options include: embolisation, ablation techniques, nephron-sparing
surgery (NSS), and radical nephrectomy. In adult patients with tuberous sclerosis, who require treatment but do
not require rapid surgical treatment, everolimus is used. In the case of AML, initially doses of 1 × 10 mg per day
should be used (an appropriate dose decrease is required in the case of liver insufficiency), and subsequently
treatment may be individualised after determining the lowest effective dose with acceptable adverse effects. A rare
epithelioid variety of AML (EAML) shows the potential for a malignant course. The basis of EAML treatment is
radical resection, ensuring a high percentage of cures. For non-resectable EAML, chemotherapy, mTOR inhibitors,
and VEGFR inhibitors (pazopanib, apatinib) are used, but objective responses have been described only in
a very small percentage of patients

Article available in PDF format

View PDF Download PDF file


  1. Klimczak A, Pękul M, Wiater K, Rutkowski P. PEComa — grupa rzadkich nowotworów pochodzenia mezenchymalnego. NOWOTWORY Journal of Oncology. 2011; 61(1): 52–56.
  2. Fittschen A, Wendlik I, Oeztuerk S, et al. Prevalence of sporadic renal angiomyolipoma: a retrospective analysis of 61,389 in- and out-patients. Abdom Imaging. 2014; 39(5): 1009–1013.
  3. Słowińska M, Jóźwiak S, Peron A, et al. Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? Orphanet J Rare Dis. 2018; 13(1): 25.
  4. Bissler JJ, Christopher Kingswood J. Renal manifestation of tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018; 178(3): 338–347.
  5. Johnson SR, Cordier JF, Lazor R, et al. Review Panel of the ERS LAM Task Force. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010; 35(1): 14–26.
  6. Aydin H, Magi-Galluzzi C, Lane BR, et al. Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. Am J Surg Pathol. 2009; 33(2): 289–297.
  7. Lee W, Choi SeY, Lee C, et al. Does epithelioid angiomyolipoma have poorer prognosis, compared with classic angiomyolipoma? Investig Clin Urol. 2018; 59(6): 357–362.
  8. Casper KA, Donnelly LF, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002; 225(2): 451–456.
  9. Kingswood JC, Belousova E, Benedik MP, et al. Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness. Nephrol Dial Transplant. 2019; 34(3): 502–508.
  10. Delhorme JB, Fontana A, Levy A, et al. Renal angiomyolipomas: At least two diseases. A series of patients treated at two European institutions. Eur J Surg Oncol. 2017; 43(4): 831–836.
  11. Seyam RM, Alkhudair WK, Kattan SA, et al. The risks of renal angiomyolipoma: reviewing the evidence. J Kidney Cancer VHL. 2017; 4(4): 13–25.
  12. Brimo F, Robinson B, Guo C, et al. Renal epithelioid angiomyolipoma with atypia: a series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy. Am J Surg Pathol. 2010; 34(5): 715–722.
  13. Faraji H, Nguyen BN, Mai KT. Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study. Development of criteria for screening the entity with prognostic significance. Histopathology. 2009; 55(5): 525–534.
  14. Nese N, Martignoni G, Fletcher CD, 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; 35(2): 161–176.
  15. Yang L, Feng XL, Shen S, et al. Clinicopathological analysis of 156 patients with angiomyolipoma originating from different organs. Oncol Lett. 2012; 3(3): 586–590.
  16. He W, Cheville JC, Sadow PM, et al. Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors. Mod Pathol. 2013; 26(10): 1355–1364.
  17. Lei JH, Liu LR, Wei Q, et al. A four-year follow-up study of renal epithelioid angiomyolipoma: a multi-center experience and literature review. Sci Rep. 2015; 5: 10030.
  18. Kutikov A, Fossett LK, Ramchandani P, et al. Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. Urology. 2006; 68(4): 737–740.
  19. Wang SF, Lo WO. Benign Neoplasm of Kidney: Angiomyolipoma. J Med Ultrasound. 2018; 26(3): 119–122.
  20. Stachurski L, Pętlak O, Szyfer W. Obustronny naczyniakomięśniakotłuszczak nerki (angiomolipoma) leczony operacyjnie. Urologia Polska 1985; 38(4).
  21. Nelson C, Sanda M. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002: 1315–1325.
  22. Prasad TV, Singh A, Das CJ, et al. An unusually large renal angiomyolipoma peeping into the right atrium. BMJ Case Rep. 2016; 2016.
  23. Mettler J, Al-Katib S. Aggressive Renal Angiomyolipoma in a Patient With Tuberous Sclerosis Resulting in Pulmonary Tumor Embolus and Pulmonary Infarction. Urology. 2018; 119: e1–e2.
  24. Nonomura A, Enomoto Y, Takeda M, et al. Angiomyolipoma of the liver: a reappraisal of morphological features and delineation of new characteristic histological features from the clinicopathological findings of 55 tumours in 47 patients. Histopathology. 2012; 61(5): 863–880.
  25. Jóźwiak S, Sadowski K, Borkowska J, et al. Liver angiomyolipomas in tuberous sclerosis complex-their incidence and course. Pediatr Neurol. 2018; 78: 20–26.
  26. Ozturk S, Unver M, Onen Z, et al. Giant extrarenal retroperitoneal angiomyolipoma: a rare case of a large size tumor. Clin Genitourin Cancer. 2018; 16(5): e1025–e1027.
  27. Hulbert J, Graf R. Involvement of the spleen by renal angiomyolipoma: metastasis or multicentricity? J Urol. 1983; 130(2): 328–329.
  28. Wang Y, Zhang X, Liu P, et al. Duodenal angiomyolipoma with multiple systemic vascular malformations and aneurysms: A case report and literature review. Oncol Lett. 2017; 14(6): 6659–6663.
  29. Ail D, Paulose R, Kalitha A, et al. Gastric angiomyolipoma masquerading as gastric malignancy. ACG Case Reports Journal. 2018; 5(1): e96.
  30. Peh SC, Sivanesaratnam V. Angiomyolipoma of the vagina--an uncommon tumour. Case report. Br J Obstet Gynaecol. 1988; 95(8): 820–823.
  31. Chen KT. Angiomyolipoma of the vagina. Gynecol Oncol. 1990; 37(2): 302–304.
  32. Garg M, Duhan A, Bindroo S, et al. Isolated angiomyolipoma of vulva: A case report of an uncommon tumor at an uncommon site. J Cancer Res Ther. 2015; 11(3): 645.
  33. Anderson AE, Yang Xu, Young RH. Epithelioid angiomyolipoma of the ovary: a case report and literature review. Int J Gynecol Pathol. 2002; 21(1): 69–73.
  34. Lee SJ, Yoo JY, Yoo SH, et al. Uterine angiomyolipoma with metastasis in a woman with tuberous sclerosis: a case report. Eur J Gynaecol Oncol. 2013; 34(4): 339–342.
  35. Castillenti T, Bertin A. Angiomyolipoma of the spermatic cord: case report and literature review. J Urol. 1989; 142(5): 1308–1309.
  36. Sultan G, Masood B, Qureshi H, et al. Angiomyolipoma of the scrotum: report of a rarely seen case and review of the literature. Turk J Urol. 2017; 43(2): 223–226.
  37. Piattelli A, Fioroni M, Rubini C, et al. Angiomyolipoma of the palate. Report of a case. Oral Oncol. 2001; 37(3): 323–325.
  38. Banerjee SS, Eyden B, Trenholm PW, et al. Monotypic angiomyolipoma of the nasal cavity: a heretofore undescribed occurrence. Int J Surg Pathol. 2001; 9(4): 309–315.
  39. Weindling SM, Menke DM, Bolger WE. Maxillary sinus angiomyolipoma: A case report and overview. Ear Nose Throat J. 2015; 94(7): E1–E4.
  40. Cheah SC, Jaafar R, Jais MH. Huge buccal angiomyolipoma: a rare entity. Braz J Otorhinolaryngol. 2017 [Epub ahead of print].
  41. Tchernev G, Philipov S, Ananiev J, et al. Angiomyolipoma of the helix without signs of systemic involvement: successful surgical approach. Int J Immunopathol Pharmacol. 2014; 27(4): 611–614.
  42. Lu D, Yang H, Liu SXi, et al. A rare benign parotid gland tumor: angiomyolipoma. J Craniofac Surg. 2013; 24(6): e619–e621.
  43. Hayashi K, Yamamoto M, Nishimura H, et al. Angiomyolipoma of the anterior mediastinum — a case report. Nihon Kyobu Geka Gakkai Zasshi. 1994; 42(4): 584–587.
  44. Knight CS, Cerfolio RJ, Winokur TS. Angiomyolipoma of the anterior mediastinum. Ann Diagn Pathol. 2008; 12(4): 293–295.
  45. D'Antonio A, Caleo A, Caleo O, et al. Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a rare extrarenal tumor. Ann Diagn Pathol. 2009; 13(5): 347–350.
  46. Kim HJ, Chung CM, Park JY, et al. Angiomyolipoma of the Glabellar Region. Arch Craniofac Surg. 2017; 18(3): 202–206.
  47. Insabato L, De Rosa G, Terracciano LM, et al. Primary monotypic epithelioid angiomyolipoma of bone. Histopathology. 2002; 40(3): 286–290.
  48. Chen GX, Wang MH, Hu CL, et al. Angiomyolipoma of the rib: A rare case report. Mol Clin Oncol. 2016; 4(1): 126–128.
  49. Garoufalia Z, Machairas N, Kostakis ID, et al. Malignant potential of epithelioid angiomyolipomas of the liver: A case report and comprehensive review of the literature. Mol Clin Oncol. 2018; 9(2): 226–230.
  50. Lau SK, Marchevsky AM, McKenna RJ, et al. Malignant monotypic epithelioid angiomyolipoma of the retroperitoneum. Int J Surg Pathol. 2003; 11(3): 223–228.
  51. Tuma J, Moch H, Stuckmann G, et al. Two in One: Epithelioid angiomyolipoma within a classic kidney angiomyolipoma — a case report. BMC Nephrol. 2018; 19(1): 123.
  52. Książek A, Załuska W, Wysocki MW. Naczyniakomięśniakotłuszczak nerki. 2018.
  53. Park BK. Renal angiomyolipoma: radiologic classification and imaging features according to the amount of fat. AJR Am J Roentgenol. 2017; 209(4): 826–835.
  54. Park SG, Park BK. New radiologic classification of renal angiomyolipoma: frequently asked questions. Clin Imaging. 2019; 55: 156–160.
  55. Park BK. Renal Angiomyolipoma Based on New Classification: How to Differentiate It From Renal Cell Carcinoma. AJR Am J Roentgenol. 2019; 212(3): 582–588.
  56. Bauman TM, Potretzke AM, Wright AJ, et al. Patient and nonradiographic tumor characteristics predicting lipid-poor angiomyolipoma in small renal masses: Introducing the BEARS index. Investig Clin Urol. 2017; 58(4): 235–240.
  57. Williams CH, Hickle K, Bakke K, et al. Hepatic epithelioid angiomyolipoma treated with laparoscopic resection: case report and review of the literature. Case Reports Hepatol. 2019: 2362618.
  58. Liu W, Wang J, Huang Q, et al. Comparison of MRI features of epithelioid hepatic angiomyolipoma and hepatocellular carcinoma: imaging data from two centers. Front Oncol. 2018; 8: 600.
  59. Soma T, Ishioka J, Tanaka H, et al. Potential for computer-aided diagnosis using a convolutional neural network algorithm to diagnose fat-poor angiomyolipoma in enhanced computed tomography and T2-weighted magnetic resonance imaging. Int J Urol. 2018; 25(11): 978–979.
  60. Cui EM, Lin F, Li Q, et al. Differentiation of renal angiomyolipoma without visible fat from renal cell carcinoma by machine learning based on whole-tumor computed tomography texture features. Acta Radiol. 2019; 60(11): 1543–1552.
  61. Malewski W. Diagnostyka i leczenie nerkowych naczyniakomięśniakotłuszczaków nerki. Przegląd Urologiczny 2016; 5(99).
  62. Chen LS, Zhu ZQ, Wang ZT, et al. Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal angiomyolipoma from renal cell carcinoma: a meta-analysis. Eur Radiol. 2018; 28(5): 1854–1861.
  63. Dębska-Ślizień A, Tarasewicz A, Król E, et al. Zasady postępowania z chorym z nerkową manifestacją stwardnienia guzowatego. Stanowisko Grupy Roboczej Stwardnienia Guzowatego Polskiego Towarzystwa Nefrologicznego. Nefrologia i Dializoterapia Polska. 2016; 20: 134–147.
  64. Domańska-Pakieła D, Kotulska K, Jóźwiak S. Stwardnienie guzowate: postępy w diagnostyce i leczeniu. Neurologia Dziecięca. 2008; 17(33): 11–22.
  65. Thway K, Fisher C. PEComa: morphology and genetics of a complex tumor family. Ann Diagn Pathol. 2015; 19(5): 359–368.
  66. Jinzaki M, Silverman SG, Akita H, et al. Diagnosis of renal angiomyolipomas: classic, fat-poor, and epithelioid types. Semin Ultrasound CT MR. 2017; 38(1): 37–46.
  67. Tsai HY, Lee KH, Ng KF, et al. Clinicopathologic analysis of renal epithelioid angiomyolipoma: Consecutively excised 23 cases. Kaohsiung J Med Sci. 2019; 35(1): 33–38.
  68. LeRoy MA, Rao P. Angiomyolipoma with epithelial cysts. Arch Pathol Lab Med. 2016; 140(6): 594–597.
  69. Wood A, Young F, O'Donnell M. Angiomyolipoma with epithelial cysts masquerading as a cystic renal cell carcinoma. Curr Urol. 2017; 9(4): 209–211.
  70. Nell RJ, Wong DD, van Vliet C, et al. Inflammatory angiomyolipoma of the liver: a diagnostic pitfall. Pathology. 2018; 50(3): 352–355.
  71. Guan H, Zhang L, Zhang Q, et al. Primary angiosarcoma arising in an angiomyolipoma of the kidney: case report and literature review. Diagn Pathol. 2018; 13(1): 53.
  72. Wang CN, Wang SY, Lin MJ, et al. Occult renal cell carcinoma of eosinophilic morphology detected within renal angiomyolipoma mass in a patient with tuberous sclerosis complex. Chin Med J (Engl). 2017; 130(12): 1505–1506.
  73. Roma AA, Magi-Galluzzi C, Zhou M. Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. Arch Pathol Lab Med. 2007; 131(1): 122–125.
  74. Makhlouf HR, Remotti HE, Ishak KG. Expression of KIT (CD117) in angiomyolipoma. Am J Surg Pathol. 2002; 26(4): 493–497.
  75. Caliò A, Brunelli M, Segala D, et al. t(6;11) renal cell carcinoma: a study of seven cases including two with aggressive behavior, and utility of CD68 (PG-M1) in the differential diagnosis with pure epithelioid PEComa/epithelioid angiomyolipoma. Mod Pathol. 2018; 31(3): 474–487.
  76. Bi XG, Guo L, Wang XL, et al. Distinct subcellular localization of E-cadherin between epithelioid angiomyolipoma and triphasic angiomyolipoma: A preliminary case-control study. Oncol Lett. 2017; 14(1): 695–704.
  77. Park JH, Lee C, Suh JaH, et al. Renal epithelioid angiomyolipoma: Histopathologic review, immunohistochemical evaluation and prognostic significance. Pathol Int. 2016; 66(10): 571–577.
  78. Mete O, van der Kwast TH. Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms. Arch Pathol Lab Med. 2011; 135(5): 665–670.
  79. Komarowska H, Bednarek-Rajewska K, Kański M, et al. Epithelioid angiomyolipoma mimicking adrenal cortical carcinoma: A diagnostic pitfall. Oncol Lett. 2015; 10(4): 2130–2134.
  80. Yan Z, Grenert JP, Joseph NM, et al. Hepatic angiomyolipoma: mutation analysis and immunohistochemical pitfalls in diagnosis. Histopathology. 2018; 73(1): 101–108.
  81. Randle SC. Tuberous sclerosis complex: a review. Pediatr Ann. 2017; 46(4): e166–e171.
  82. Krymskaya VP. Tumour suppressors hamartin and tuberin: intracellular signalling. Cell Signal. 2003; 15(8): 729–739.
  83. Li S, Zhang Y, Wang Z, et al. Genotype-phenotype correlation of patients with tuberous sclerosis complex-associated renal angiomyolipoma: a descriptive study. Hum Pathol. 2018; 82: 61–67.
  84. Kenerson H, Folpe AL, Takayama TK, et al. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol. 2007; 38(9): 1361–1371.
  85. Pleniceanu O, Omer D, Azaria E, et al. mTORC1 inhibition is an effective treatment for sporadic renal angiomyolipoma. Kidney Int Rep. 2018; 3(1): 155–159.
  86. Cho JH, Patel B, Bonala S, et al. The Codon 72 Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis. Mol Cancer Res. 2019; 17(8): 1639–1651.
  87. Thibodeau MyL, Steinraths M, Brown L, et al. Genomic and cytogenetic characterization of a balanced translocation disrupting NUP98. Cytogenet Genome Res. 2017; 152(3): 117–121.
  88. Małuszek M. Multifunctionality of MDM2 protein and its role in genomic instability of cancer cells. Postepy Biochem. 2015; 61(1): 42–51.
  89. Inoue C, Saito R, Nakanishi W, et al. Renal epithelioid angiomyolipoma undergoing aggressive clinical outcome: the MDM2 expression in tumor cells of two cases. Tohoku J Exp Med. 2019; 247(2): 119–127.
  90. Kidawa A, Kurpiński A, Idzikowski K. Obustronny naczyniakomięśniakotłuszczak angiomyolipoma) nerek. Urologia Polska. 1992; 45(3).
  91. Ruud Bosch JLH, Vekeman F, Duh MS, et al. Factors associated with the number and size of renal angiomyolipomas in sporadic angiomyolipoma (sAML): a study of adult patients with sAML managed in a Dutch tertiary referral center. Int Urol Nephrol. 2018; 50(3): 459–467.
  92. Fernández-Pello S, Hora M, Kuusk T, et al. Management of Sporadic Renal Angiomyolipomas: A Systematic Review of Available Evidence to Guide Recommendations from the European Association of Urology Renal Cell Carcinoma Guidelines Panel. Eur Urol Oncol. 2019 [Epub ahead of print].
  93. Wang C, Li X, Peng L, et al. An update on recent developments in rupture of renal angiomyolipoma. Medicine (Baltimore). 2018; 97(16): e0497.
  94. Arslan B, Gürkan O, Çetin B, et al. Evaluation of ABO blood groups and blood-based biomarkers as a predictor of growth kinetics of renal angiomyolipoma. Int Urol Nephrol. 2018; 50(12): 2131–2137.
  95. Janssens P, Van Hoeve K, De Waele L, et al. Renal progression factors in young patients with tuberous sclerosis complex: a retrospective cohort study. Pediatr Nephrol. 2018; 33(11): 2085–2093.
  96. Rentz AM, Skalicky AM, Liu Z, et al. Burden of renal angiomyolipomas associated with tuberous sclerosis complex: results of a patient and caregiver survey. J Patient Rep Outcomes. 2018; 2: 30.
  97. Ljungberg B, Albiges L, Bensalah K, et al. European Association of Urology Guidelines on Renal Cell Carcinoma 2017. 2017.
  98. Chan KE, Chedgy E, Bent CL, et al. Surveillance imaging for sporadic renal angiomyolipoma less than 40 mm: lessons learnt and recommendations from the experience of a large district general hospital. Ann R Coll Surg Engl . 2018; 100(6): 480–484.
  99. Ouzaid I, Autorino R, Fatica R, et al. Active surveillance for renal angiomyolipoma: outcomes and factors predictive of delayed intervention. BJU Int. 2014; 114(3): 412–417.
  100. Vos N, Oyen R. Renal angiomyolipoma: the good, the bad, and the ugly. J Belg Soc Radiol. 2018; 102(1): 41.
  101. Kuusk T, Biancari F, Lane B, et al. Treatment of renal angiomyolipoma: pooled analysis of individual patient data. BMC Urol. 2015; 15: 123.
  102. Bissler JJ, Kingswood JC, Radzikowska E, et al. Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study. PLoS One. 2017; 12(8): e0180939.
  103. Buj Pradilla MJ, Martí Ballesté T, Torra R, et al. Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex. Clin Kidney J. 2017; 10(6): 728–737.
  104. Ryan JW, Farrelly C, Geoghegan T. What are the indications for prophylactic embolization of renal angiomyolipomas? A review of the current evidence in the literature. Can Assoc Radiol J. 2018; 69(3): 236–239.
  105. Peng Zf, Yang Lu, Wang Tt, et al. Efficacy and safety of sirolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a systematic review. J Urol. 2014; 192(5): 1424–1430.
  106. Canpolat M, Gumus H, Kumandas S, et al. The use of rapamycin in patients with tuberous sclerosis complex: Long-term results. Epilepsy Behav. 2018; 88: 357–364.
  107. Kingswood JC, Jozwiak S, Belousova ED, 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. 2014; 29(6): 1203–1210.
  108. Bissler JJ, Kingswood JC, Radzikowska 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. 2013; 381(9869): 817–824.
  109. Bissler JJ, Budde K, Sauter M, et al. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019; 34(6): 1000–1008.
  110. Bissler JJ, Nonomura N, Budde K, et al. Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. PLoS One. 2018; 13(9): e0201005.
  111. Bissler JJ, Franz DN, Frost MD, et al. The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma. Pediatr Nephrol. 2018; 33(1): 101–109.
  112. Cai Yi, Guo H, Wang W, et al. Assessing the outcomes of everolimus on renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial. Orphanet J Rare Dis. 2018; 13(1): 43.
  113. Zonnenberg BA, Neary MP, Duh MS, et al. Observational study of characteristics and clinical outcomes of Dutch patients with tuberous sclerosis complex and renal angiomyolipoma treated with everolimus. PLoS One. 2018; 13(11): e0204646.
  114. Hatano T, Inaba H, Endo K, et al. Intermittent everolimus administration for renal angiomyolipoma associated with tuberous sclerosis complex. Int J Urol. 2017; 24(11): 780–785.
  115. Wei CC, Tsai JD, Sheu JN, et al. Continuous low-dose everolimus shrinkage tuberous sclerosis complex-associated renal angiomyolipoma: a 48-month follow-up study. J Investig Med. 2019; 67(3): 686–690.
  116. Toriu N, Mizuno H, Sawa N, et al. Everolimus reduces the size of tuberous sclerosis complex-related huge renal angiomyolipomas exceeding 20 cm in the longest diameter. Case Rep Oncol. 2018; 11(2): 258–267.
  117. Hatano T, Matsu-Ura T, Mori KI, et al. Effect of everolimus treatment for regrown renal angiomyolipoma associated with tuberous sclerosis complex after transcatheter arterial embolization. Int J Clin Oncol. 2018; 23(6): 1134–1139.
  118. Hatano T, Atsuta M, Inaba H, et al. Effect of everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex: an evaluation based on tumor density. Int J Clin Oncol. 2018; 23(3): 547–552.
  119. Brakemeier S, Vogt L, Adams L, et al. Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC). PLoS One. 2017; 12(12): e0189132.
  120. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008; 358(2): 140–151.
  121. Dabora SL, Franz DN, Ashwal S, 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.
  122. Davies DM, de Vries PJ, Johnson SR, et al. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011; 17(12): 4071–4081.
  123. Cabrera-López C, Martí T, Catalá V, et al. Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial. Orphanet J Rare Dis. 2012; 7: 87.
  124. De Bree E, Stamatiou D, Chryssou E, et al. Late local, peritoneal and systemic recurrence of renal angiomyolipoma: A case report. Mol Clin Oncol. 2019; 10(1): 43–48.
  125. Klompenhouwer AJ, Verver D, Janki S, et al. Management of hepatic angiomyolipoma: A systematic review. Liver Int. 2017; 37(9): 1272–1280.
  126. Zhan R, Li YQ, Chen CY, et al. Primary kidney malignant epithelioid angiomyolipoma: Two cases report and review of literature. Medicine (Baltimore). 2018; 97(32): e11805.
  127. Damaskos C, garmpis N, garmpi A, et al. Angiomyolipoma of the liver: a rare benign tumor treated with a laparoscopic approach for the first time. In vivo. 2017; 31(6): 1169–1173.
  128. Seker M, Aksoy S, Babacan NA, et al. Renal epithelioid angiomyolipoma: successfully treated with chemotherapy. Acta Medica. 2013; 2: 35–37.
  129. Espinosa M, Roldán-Romero JM, Duran I, et al. Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation. BMC Cancer. 2018; 18(1): 561.
  130. Higa F, Uchihara T, Haranaga S, et al. Malignant epithelioid angiomyolipoma in the kidney and liver of a patient with pulmonary lymphangioleiomyomatosis: lack of response to sirolimus. Internal Medicine. 2009; 48(20): 1821–1825.
  131. Wolff N, Kabbani W, Bradley T, et al. Sirolimus and temsirolimus for epithelioid angiomyolipoma. J Clin Oncol. 2010; 28(5): e65–e68.
  132. Shitara K, Yatabe Y, Mizota A, et al. Dramatic tumor response to everolimus for malignant epithelioid angiomyolipoma. Jpn J Clin Oncol. 2011; 41(6): 814–816.
  133. Kohno J, Matsui Y, Yamasaki T, et al. Role of mammalian target of rapamycin inhibitor in the treatment of metastatic epithelioid angiomyolipoma: a case report. Int J Urol. 2013; 20(9): 938–941.
  134. Faria E, Turturro F, Rao P, et al. Malignant epithelioid angiomyolipoma: tumor and metabolic response to everolimus as evaluated with positron emission tomography. Clin Genitourin Cancer. 2013; 11(4): e1–e5.
  135. Wyluda E, Baquero G, Lamparella N, et al. Fatal malignant metastastic epithelioid angiomyolipoma presenting in a young woman: case report and review of the literature. Rare Tumors. 2013; 5(3): e46.
  136. Hong J, Lee J, Kim K-M, Joo Kim S. Tumor response to temsirolimus for epithelioid angiomyolipoma and novel mutation of SMARCB1/INI1 tumor suppressor gene. Journal of Cancer Therapy. 2014; 05: 1215–1222.
  137. Binyamin K, Mecz Y, Stein A, et al. An aggressive case of malignant renal pecoma non-responsive to motor inhibition: a case report. Journal of Clinical Case Reports. 2016; 6(10): 1–3.
  138. Anwar H, Sachpekidis C, Schwarzbach M, Dimitrakopoulou-Strauss A. Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy. Hell J Nucl Med. 2017; 20(2): 169–171.
  139. Huľová S, Sycova-Mila Z, Macák D, et al. Diagnostic challenges and extraordinary treatment response in rare malignant PEComa tumor of the kidney. Klin Onkol. 2018; 31(6): 448–452.
  140. Lattanzi M, Deng FM, Chiriboga LA, et al. Durable response to anti-PD-1 immunotherapy in epithelioid angiomyolipoma: a report on the successful treatment of a rare malignancy. J Immunother Cancer. 2018; 6(1): 97.
  141. Tayal J, Doval D, Kamboj M, et al. Case report of everolimus-induced sustained partial response in metastatic renal epithelioid angiomyolipoma. Türk Üroloji Dergisi/Turkish Journal of Urology. 2019; 45(-1): 139–142.
  142. Ge X, Xue X, Zhang Ge, et al. Successful treatment of liver and abdomen metastasis of renal epithelioid angiomyolipoma with apatinib: a case report. Translational Cancer Research. 2017; 6(5): 1015–1019.