Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex

Abstract

Renal angiomyolipomas are found in up to 80% of tuberous sclerosis complex (TSC) patients. Although these tumours are usually asymptomatic, lesions >3 cm in diameter are prone to bleeding and up to 10% of TSC patients may experience a massive and potentially fatal retroperitoneal haemorrhage. Diagnosis can be complicated because of the initial lack of symptoms and the fat-poor content of atypical renal angiomyolipomas. After diagnosis, tumour growth and the emergence of new tumours must be monitored. Treatment with mammalian target of rapamycin (mTOR) inhibitors can reduce tumour size and is indicated in patients with TSC-associated renal angiomyolipomas >3 cm in diameter. Imaging-based assessment of kidney disease is essential to the diagnosis and management of patients with TSC. The aims of imaging studies in this context are to detect and characterize tumours, assess and detect the risk of complications and evaluate the response to treatment, especially in patients treated with mTOR inhibitors. A multidisciplinary expert panel developed a series of recommendations based on current evidence and professional experience for imaging studies in adults and children with TSC-associated renal angiomyolipoma. The recommendations cover radiological diagnosis and follow-up of the classic and atypical or fat-poor TSC-associated renal angiomyolipomas, biopsy indications, minimal requirements for radiological requests and reports and recommended technical features and protocols for computed tomography and magnetic resonance imaging.

Renal angiomyolipoma-patient characteristics and treatment with focus on active surveillance

“…All eleven TSC-patients in the present study had, at any time, an intervention compared to 61% in the group with sporadic AML. Other authors have reported on a more aggressive course of the AML-disorder in TSCpatients [4]. The eleven patients in our study had in all 13 retroperitoneal bleeding episodes, two episodes of hematuria and five cases of progress in size, leading to 22 AE and three nephrectomies.…”

“…There are two major varieties of renal AML, one associated with tuberous sclerosis complex (TSC) and one sporadic form. Renal AML associated with TSC are often multiple, bilateral, symptomatic and without male or female predominance [4].…”

Imaging of Kidney Cysts and Cystic Kidney Diseases in Children: An International Working Group Consensus Statement

“…Potential risks, such as prolonged sedation or excessive examination time, must be considered when deciding to perform kidney MRI. In patients with AML 3 cm or larger, yearly repeat MRI has been recommended (74). In patients without AMLs at initial MRI, this group suggests annual US for follow up, with repeat MRI every 2-3 years.…”

Metformin effectively treats Tsc1 deletion-caused kidney pathology by upregulating AMPK phosphorylation

“…In total, 60-80% of TSC patients suffer from renal manifestations of aberrant cell growth and dysregulated cell proliferation, resulting in renal cysts and hamartomatous renal tumors such as angiomyolipomas 1,5,6 . Such renal lesions can cause kidney enlargement and tubulointerstitial fibrosis, leading to impaired renal function and/or angiomyolipomaassociated hemorrhage 7,8 . Although more than half of TSC patients fail to be diagnosed at the early stage of this disease, with innovative detection technologies, more and more TSC patients are diagnosed with kidney pathology 9 .…”

“…Currently, mTORC1 is considered a pharmacological target for the treatment of TSC 7,10 . Unfortunately, mTORC1 inhibitors currently used in the clinic seemed to only have a limited cytostatic effect, as the TSC tumors grew again after mTORC1 inhibitors were discontinued, and long-term mTORC1 inhibition could cause detrimental side effects [11][12][13][14][15] .…”