INTRODUCTION — Angiomyolipomas (AMLs) are benign neoplasms occurring in the kidney and are composed of varying amounts of tissue resembling blood vessels, smooth muscles, and adipose. The vast majority of AMLs are benign but malignant transformation has been reported [1-4].
Renal AMLs may occur sporadically or in association with either tuberous sclerosis complex (TSC), sporadic lymphangioleiomyomatosis (LAM), or a combination (TSC-LAM). The management of AMLs depends upon factors such as the clinical presentation (eg, whether the patient is symptomatic with bleeding) and the size, number, and pathologic features of the lesions (algorithm 1). Some lesions also require monitoring over time.
This topic will discuss the management and prognosis of renal AMLs. Other related issues are discussed elsewhere:
●Epidemiology, pathogenesis, clinical manifestations, and diagnosis of renal AMLs (see "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis")
●Renal manifestations of TSC (see "Renal manifestations of tuberous sclerosis complex")
●Renal AMLs associated with LAM (see "Sporadic lymphangioleiomyomatosis: Clinical presentation and diagnostic evaluation", section on 'Renal angiomyolipomas')
●A general overview of TSC-LAM (see "Tuberous sclerosis complex associated lymphangioleiomyomatosis in adults")
●An evaluation of incidental lesions of the kidney (see "Evaluation of the incidental kidney lesion")
IDENTIFICATION AND MANAGEMENT OF ACTIVE BLEEDING
Identification of active bleeding — Hemorrhage from a sporadic renal AML is uncommon; in one large study, for example, 0.4 percent of sporadic AMLs bled [5]. Bleeding is more common in patients with tuberous sclerosis complex (TSC), as noted below. (See 'Patients with known TSC or LAM' below.)
Clinical, laboratory, and radiologic features suggestive of active bleeding from the AML include (see "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'):
●Flank pain or tenderness
●Gross hematuria
●Anemia
●Acute deterioration in kidney function
All patients with AML who develop symptoms or signs suggestive of active bleeding should undergo prompt imaging with computed tomography (CT) or magnetic resonance imaging (MRI) to assess for hemorrhage from the AML.
Management of active bleeding — Bleeding from renal AMLs can be mild or catastrophic resulting in hemorrhagic shock, loss of function of the affected kidney, and death [6,7]. Patients with AML who develop active bleeding should receive resuscitative measures (if hemodynamically unstable) and, if feasible, undergo prompt angiography and selective artery embolization (SAE) to stop the bleeding.
Management of hemorrhagic shock from a bleeding AML is the same as for other causes of intraabdominal hemorrhage and is discussed at length elsewhere. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'When to suspect shock' and "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Initial approach' and "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Hemodynamically significant hemorrhage'.)
Patients who cannot have SAE, or who continue to have life-threatening hemorrhage from a renal AML after an attempt at SAE, should undergo a partial or complete nephrectomy.
SAE is typically performed by interventional radiologists. However, depending upon institutional preference and availability of various services, this procedure may also be performed by urologists or general surgeons. At our institution, urologists are typically consulted and involved if the procedure will be performed by interventional radiologists. Such multidisciplinary consultation is beneficial in the event that SAE is unsuccessful and open surgical procedures (eg, partial or total nephrectomy) are needed to contain the bleeding.
SAE is an endovascular procedure by which the arteries supplying blood to a structure (eg, renal AML) are injected with an embolic agent with the goal of permanently occluding the blood supply to and inducing necrosis of the structure [8]. SAE is the preferred initial procedure in patients with acute life-threatening hemorrhage since it rapidly stabilizes the patient's condition and often eliminates the need for additional, more invasive procedures. SAE has resulted in reduction in the need for nephrectomy by 80 to 100 percent among patients with bleeding from renal AMLs [8-10]. Use of SAE is increasing due to its noninvasive nature, improvements in safety (eg, with improved endovascular techniques and embolic materials), and growing procedural expertise.
SAE is generally tolerated well and is associated with fewer complications compared with open surgical procedures [8]. Complications that can occur from SAE include those related to the embolization, endovascular access, or the use of contrast. One of the most common complications occurring in nearly one-half of the patients undergoing SAE is postembolization syndrome (PES). PES is characterized by flank pain, which can be severe after embolization of a large AML, fever, vomiting, and leukocytosis; symptoms typically last one to three days [11-13].
The risk of PES increases with the size of the mass being treated. PES is thought to result from a systemic inflammatory response to infarcted tissue. Although we do not use glucocorticoids to prevent PES, they have been used in some reports with varying degrees of success [14].
Other complications specific to embolization include inadvertent embolization of nearby vessels that can result in extensive renal infarction or infarction of parts of the spine, lower limbs, bowel, adrenal glands, or testicles. However, these complications are rare because of technical improvements over the last few decades. Long-term impact on kidney function is generally minimal but can vary depending upon the size of the infarct caused by embolization [8]. (See 'Prognosis' below.)
Possible complications related to the endovascular access include groin hematoma, arterial dissection, and thrombosis of the accessed arteries. The exposure to iodinated contrast can result in contrast-associated acute kidney injury or allergic reactions to the contrast.
MANAGEMENT OF SPORADIC AML
Pretreatment assessment — In patients diagnosed with sporadic AML, the treatment is guided by the risk of malignant transformation and the risk of future bleeding (algorithm 1).
Assess risk for malignant transformation — The two major histologic variants of AMLs are classic and epithelioid. Among patients with sporadic AML, the epithelioid variant is uncommon. Classic variants, which do not undergo malignant transformation, are "fat-rich" by imaging. By contrast, epithelioid variants, which sometimes undergo malignant transformation, are "fat-poor" or "fat-invisible" by imaging. (See "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Histopathology'.)
Thus, patients with a sporadic AML that is "fat-poor" or "fat-invisible" should generally undergo percutaneous core needle biopsy (algorithm 1). However, if imaging reveals intratumoral necrosis, intratumoral calcifications, presence of lymphadenopathy, or suspected metastasis, then a biopsy is not necessary and the lesion should be surgically excised [15]. (See 'Malignant AML or high risk for malignant transformation' below.)
Biopsy findings that are consistent with a high risk of malignant transformation include: >70 percent epithelioid cells; vascular invasion; ≥2 mitotic figures per 10 high-power fields; atypical mitotic figures; and necrosis [16,17].
Assess risk of bleeding — As noted above, bleeding from renal AMLs can be mild or catastrophic resulting in hemorrhagic shock, loss of function of the affected kidney, and death [6,7]. The risk of bleeding increases with the size of the AML and the growth of the vasculature within it. We evaluate bleeding risk with imaging.
The initial imaging study (CT or MRI) performed for diagnosis of the AML can identify risk factors for bleeding. In addition, among patients who are selected for surveillance (with serial imaging), the rate of AML growth is associated with risk of bleeding.
Imaging and other features that are associated with a higher risk of bleeding include (algorithm 1) [18-31]:
●AML >6 cm in diameter – In general, larger AMLs have a higher risk of bleeding than smaller AMLs [18,20,21]. In a systematic review of six studies including more than 1300 patients with AML, approximately 75 percent of hemorrhages occurred among patients with an AML >6 cm in diameter [20]. Setting a threshold of >4 cm for prophylactic embolization, which was the criteria used in the past, would be associated with a large number of unnecessary procedures.
●Intralesional blood vessel or aneurysm >5 mm in greatest width – Intralesional blood vessels or aneurysms can be difficult to visualize by imaging unless angiography is performed as part of the procedure [22,23] and, therefore, such information may not be available for every patient. We do not routinely obtain a dedicated angiographic study to look for intralesional aneurysms among patients who do not have evidence of active bleeding.
●Pregnancy or hormonal therapy – Estrogen and progesterone promote the growth of renal AMLs among pregnant patients and those treated with hormone replacement therapy [24-30]. In addition, estrogen and progesterone, coupled with cardiovascular adaptations in pregnancy, can increase the risk of hemorrhagic complications. (See "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Additional pathogenetic mechanisms in females'.)
●AML growth rate >2.5 mm per year – A growth rate of this rapidity is associated with failure of active surveillance [20,31-33]. A growth rate <2.5 mm per year is considered low risk and growth >5 mm per year is considered high risk; the risk associated with annual growth of 2.5 to 5 mm is less certain but likely intermediate.
●Other potential risk factors – Other risk factors may include uncontrolled hypertension and anticoagulation or coagulopathy.
Malignant AML or high risk for malignant transformation — Patients who have been diagnosed as having epithelioid AML with malignant transformation require definitive management. Similarly, solitary AMLs deemed high risk for malignant transformation should also be treated.
Surgical management rather than selective artery embolization (SAE) is typically chosen for such patients, although angiographic treatment may be appropriate for patients with multiple comorbidities and/or reduced kidney function. A multidisciplinary approach to management is appropriate including, for example, urologists, nephrologists, oncologists, and pathologists. Surgical and angiographic treatment of such lesions is similar to that in patients with renal cell carcinoma; the details are presented elsewhere. (See "Definitive surgical management of renal cell carcinoma" and "Radiofrequency ablation and cryoablation for renal cell carcinoma".)
Patients with an epithelioid AML that has undergone malignant transformation also require an evaluation for distant metastases and may need systemic therapy [34]. This is presented separately. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma" and "Systemic treatment of metastatic soft tissue sarcoma".)
Patients who have undergone surgical removal of an epithelioid AML with high-risk histologic features should undergo serial imaging with MRI at six months, one year, and yearly for five years to assess for recurrence.
AML with low risk of malignant transformation — In patients with sporadic AML at low risk for malignant transformation, the decision between intervention versus surveillance is based upon the size of the lesion (and other risk factors for bleeding) as well as other considerations (eg, patient's comorbidities, occupation) (algorithm 1).
Sporadic AML ≤6 cm — Most patients with a sporadic AML ≤6 cm in diameter undergo routine surveillance (with imaging, to judge changes in the AML over time), rather than intervention with SAE or surgery. (See 'Other patients (no compelling reason to intervene)' below.)
However, in some patients, there is a compelling reason to intervene. (See 'Compelling reasons to intervene' below.)
The treatment of renal AMLs ≤6 cm in diameter is controversial because high-quality data are lacking.
Compelling reasons to intervene — Most patients with sporadic AML ≤6 cm in diameter do not undergo intervention. However, the following are compelling reasons to treat the AML (with SAE, if feasible, rather than surgery) (algorithm 1):
●AML growth rate greater than 2.5 mm per year. This rate of growth is associated with a higher risk of bleeding. A growth rate <2.5 mm per year is considered low risk and growth >5 mm per year is considered high risk; the risk associated with annual growth of 2.5 to 5 mm is less certain but likely intermediate. (See 'Assess risk of bleeding' above.)
●AML with a large intralesional aneurysm (>5 mm diameter). Such patients are at a higher risk of bleeding from their AML. (See 'Assess risk of bleeding' above.)
●AML in a patient who could become pregnant or who is planning treatment with exogenous estrogen or progesterone. Such patients have a high risk of AML growth and bleeding during such states of hormonal excess and should be treated prior to becoming pregnant or receiving hormonal therapy. (See 'Assess risk of bleeding' above.)
●Intolerable symptoms (eg, chronic pain) from their renal AML. Such patients could benefit with improvement in their symptoms upon treatment of the AML. (See "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Living in a setting with limited access to emergency services (eg, as would be needed for hemorrhage from an AML), or inability to undergo repeated imaging (for surveillance).
●Intervention may be warranted in patients with certain high-risk occupations (eg, airline pilots).
Our approach is largely consistent with urology guidelines regarding management of AMLs from Canada (2020) [21] and Europe (2019) [7]. In addition, our approach is based upon findings of multiple small observational studies that examined outcomes of small to moderate AMLs over time and concluded that most smaller lesions remain stable without need for an intervention [21,32,35,36]. As an example, in a large study of 447 patients with a renal AML (96 percent sporadic), 91 percent of patients were not symptomatic from their AML and the remainder either had pain (6.5 percent) or evidence of bleeding (2.5 percent) [32]. Approximately 6 percent of patients required intervention. At a median follow-up of 3.5 years, 91 percent of AMLs (most not treated) either did not grow or grew slowly (average growth rate 2 mm/year).
Other patients (no compelling reason to intervene) — Patients with sporadic AML ≤6 cm in diameter and no compelling reason for intervention should undergo surveillance to assess for interval changes in the AML (algorithm 1).
There are no high-quality data to guide frequency or total duration of follow-up imaging among such patients. In our practice, we perform follow-up imaging using kidney ultrasound at six months after the initial diagnosis, and then yearly thereafter for up to five years (or longer if there is progressive growth of the AML). We use kidney ultrasound follow-up imaging rather than CT or MRI to minimize cost and exposure to ionizing radiation.
However, if the ultrasound suggests that growth has occurred, we obtain a CT or MRI (the same modality as was used to diagnose the AML originally) to better judge the rate of growth and other characteristics of the AML. The criteria for intervention rather than continued surveillance are the same criteria as noted above. (See 'Compelling reasons to intervene' above.)
Sporadic AML >6 cm — Most patients with large sporadic AML (ie, >6 cm in diameter) should undergo intervention (with SAE, if feasible, rather than surgery).
However, surveillance, rather than intervention, may be appropriate among a subset of such patients who have all of the following factors that are associated with a lower risk of bleeding (algorithm 1):
●Minimal vascularity of the AML, defined by the presence of small, stretched vessels that are few in number [22].
●Patient is not anticoagulated or coagulopathic.
●Patient could not become pregnant and does not intend to take estrogen or progesterone therapy.
●Well-controlled blood pressure.
●Patient resides in a region where emergency services are available (in case of hemorrhage).
●Patients does not have a high-risk occupation (eg, airline pilot).
●Documented stability of the lesion (ie, growth rate <2.5 mm annually) based upon previous serial imaging studies. If the lesion is already >6 cm at the time of initial diagnosis, and the above factors associated with low risk are satisfied, it is reasonable to obtain serial imaging every four to six months over the ensuing year to judge stability. However, even among lesions that are growing slowly, intervention may be appropriate when they become substantially larger (decisions about intervention in such settings are typically made by a multidisciplinary team and after discussions with the patient).
The options for intervention include SAE or surgery (nephron-sparing surgery or total nephrectomy). The choice between the procedures depends upon local expertise, size and location of the lesion, and patient preference.
We prefer SAE as a first-line procedure because it is less invasive. However, SAE may be technically infeasible, in which case surgery is performed. When surgery is planned, we generally prefer nephron-sparing surgery rather than total nephrectomy.
There are no trials comparing SAE and surgery for management of AMLs. SAE can reduce AML size by approximately 25 to 80 percent [8], and thereby reduce or eliminate the likelihood of hemorrhage. However, AMLs can regrow following embolization and sequential embolization procedures may be required to ensure a successful outcome. In one study, for example, 71 patients with sporadic or tuberous sclerosis complex (TSC)-associated AMLs (median size 8.9 cm) were scheduled for SAE; six patients were unable to undergo SAE because of technical challenges [37]. Approximately 40 percent of the cohort needed one or more additional SAE procedures an average of two years after the initial procedure. The mean reduction in AML size was approximately 25 percent. During 10 years of follow-up, 10 patients were hospitalized with pain (three with retroperitoneal hemorrhage and seven with hematuria); only four patients eventually required surgery. Major complications of SAE leading to loss of the treated kidney occurred in two patients (one due to abscess and another due to thrombosis of the ipsilateral renal artery). Other, smaller studies have reported similar outcomes [38-43]. Details regarding the SAE procedure and other complications are discussed above. (See 'Management of active bleeding' above.)
If surgical resection of an AML is needed, several options are available. In general, nephron-sparing surgery, such as enucleation or partial nephrectomy, is preferred and usually effective among patients who have an exophytic or an otherwise well-demarcated tumor that is not located centrally (near the hilum). Recurrence rate is typically low after nephron-sparing surgery (approximately 4 to 15 percent) and additional surgery for these recurrent lesions is typically unnecessary (approximately 1 percent) [7].
Total nephrectomy is rarely used for management of a large renal AML. However, it may be indicated for patients who have a centrally located AML (near the hilum) because removal of such lesions with nephron-sparing surgery may lead to significant damage to the hilar vasculature or the ureter.
PATIENTS WHO ARE PREGNANT OR ON HORMONE THERAPY — Estrogen and progesterone promote the growth of renal AMLs among pregnant patients and those treated with these hormones [24-30]. In addition, estrogen coupled with cardiovascular adaptations in pregnancy increase the risk of hemorrhagic complications during pregnancy. (See "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Additional pathogenetic mechanisms in females'.)
As noted above, treatment with exogenous estrogen or progesterone also may increase the risk for hemorrhage from a renal AML. Thus, patients with renal AML who could become pregnant or who need to be treated with hormonal therapy should generally undergo intervention on their AML. (See 'Assess risk of bleeding' above.)
However, individuals with an untreated renal AML occasionally become pregnant, and some pregnant patients have a renal AML discovered incidentally. Similarly, some patients with a renal AML initiate hormone therapy, and patients taking hormone therapy may be diagnosed with renal AML.
Our approach in these scenarios is as follows:
●Pregnant patients – In patients with a previously diagnosed but untreated renal AML who become pregnant, we perform a kidney ultrasound during the first and third trimesters to assess growth. In an individual who has a renal AML incidentally discovered during pregnancy, we perform a kidney ultrasound six months after the initial diagnosis. In general, we do not intervene on AMLs during pregnancy to avoid complications, for example, from hypotension and ionizing radiation. However, intervention is appropriate and feasible in patients who develop a life-threatening hemorrhage [29,30].
●Patients taking estrogen or progesterone therapy – Patients with a known, untreated AML who initiate therapy with estrogen and/or progesterone, and patients taking such medications who are incidentally discovered to have a renal AML, should generally discontinue hormonal therapy. However, if hormonal therapy is necessary or cannot be avoided, then intervention is typically appropriate, particularly if the AML is larger than 3 to 4 cm in diameter. Repeat imaging may be necessary to reassess the size of the lesion. As in nonpregnant patients, our preferred approach to treat the AML is selective artery embolization (SAE), if feasible, rather than surgery. SAE is discussed in more detail above. (See 'Management of active bleeding' above.)
PATIENTS WITH KNOWN TSC OR LAM — Patients with tuberous sclerosis complex (TSC), sporadic lymphangioleiomyomatosis (LAM), and TSC-LAM generally have multiple AMLs at one time or over their lifetime. The management differs from that of sporadic AML because AMLs in TSC, LAM, and TSC-LAM are typically multicentric, grow more quickly, are more likely to hemorrhage, and are higher risk for malignant transformation [32,44]. In addition, such patients have a higher risk of chronic kidney disease, which may impact the choice of treatment modality. (See "Renal manifestations of tuberous sclerosis complex", section on 'Renal cell carcinoma' and "Renal manifestations of tuberous sclerosis complex", section on 'Chronic kidney disease' and "Renal angiomyolipomas (AMLs): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
Our approach to renal AMLs among patients with TSC or LAM depends upon the number of AMLs, the rate of growth, the presence or absence of lesions with malignant transformation or high risk for malignant transformation, and the presence or absence of impaired kidney function:
●Referral to an expert center – If possible, patients with TSC should be managed by a team of clinicians with expertise in this disorder. Thus, referral to a center of excellence is appropriate.
●Assess risk for malignant transformation – As noted above, AMLs that are fat poor or fat invisible should be assessed for risk of malignant transformation (by core needle biopsy or, if appropriate, surgical excision). (See 'Assess risk for malignant transformation' above.)
Patients with lesions that are malignant or high risk for malignant transformation typically undergo surgical excision as well as further evaluation. Such patients are typically managed by a multidisciplinary team consisting of urologists, nephrologists, oncologists, and pathologists.
●Patients with a solitary AML – Patients with TSC or LAM who have a single renal AML are managed in the same way as patients with sporadic AML. (See 'Management of sporadic AML' above.)
●Patients with multiple renal AMLs – Among patients with TSC or LAM who have multiple AMLs, the treatment depends upon their number, size, rate of growth, presence or absence of impaired kidney function, and whether or not the patient is receiving a mammalian target of rapamycin (mTOR) inhibitor for a different manifestation of TSC.
•AMLs growingly rapidly (>2.5 mm per year)
-Preserved kidney function (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2): In patients with multicentric AMLs, preserved kidney function, and two or more AMLs with a high growth rate, we initiate treatment with an mTOR inhibitor (typically everolimus) rather than performing selective artery embolization (SAE) on multiple lesions, which may hasten kidney function decline [45-49].
In patients treated with everolimus or sirolimus, monitoring includes imaging every six months initially and then annually to judge the effect (or failure) of therapy, and routine laboratory monitoring for complications of the drug (including measurement of serum creatinine, urine albumin-to-creatinine ratio, electrolytes, phosphorous, complete blood count, and lipid profile). Adverse effects of mTOR inhibitors are discussed in detail elsewhere. (See "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors", section on 'Adverse effects'.)
Rapid AML growth despite taking an mTOR inhibitor is rare. In such cases, the approach, which may include intervention (such as SAE) is determined after shared decision-making with the patient and the multidisciplinary team.
If only one of the patient's AMLs is growing rapidly and is larger than 4 cm, then we typically choose SAE rather than treating with an mTOR inhibitor.
-Impaired kidney function (eGFR <60 mL/min/1.73 m2): Treatment with an mTOR inhibitor is also appropriate for patients with impaired kidney function who have multiple, rapidly growing AMLs; such patients are usually initiated on an mTOR inhibitor before developing reduced kidney function. More frequent monitoring of serum creatinine and urine albumin excretion is required because acceleration of functional decline or a marked increase in albuminuria may occur as an adverse effect of the medication. The mTOR inhibitor should be discontinued if toxicity is suspected.
•AMLs that are stable or slow-growing (<2.5 mm per year) – Patients with stable or slow growing AMLs are managed with surveillance (ie, annual imaging with MRI or ultrasound). However, intervention (typically with SAE) is appropriate for lesions that are high risk for bleeding. The criteria are similar to those used in patients with sporadic AML. (See 'Assess risk of bleeding' above and 'AML with low risk of malignant transformation' above.)
Our approach is based upon evidence from several trials that everolimus can reduce AML size and prevent AML growth [45-49]. In one trial, for example, 118 patients with TSC and at least one renal AML measuring >3 cm were randomly assigned to everolimus (10 mg daily) or placebo [45]. At 38 weeks, a 30 percent or greater reduction in the size of all target AMLs occurred more commonly with everolimus (80 versus 3 percent), whereas progression of disease, defined as growth of one or more AMLs, development of new AMLs, or bleeding occurred less commonly (0 versus 23 percent). In those receiving everolimus who did not have a reduction in AML size, AMLs remained stable.
Patients from this trial were followed for approximately four years on open-label everolimus [46]. Progression occurred in 14 percent of patients (most of whom had a dose reduction or dose interruption) and 7 percent had kidney function decline to an eGFR <30 mL/min/1.73 m2; however, the majority of patients had stable kidney function.
PROGNOSIS — The most important factor that impacts the long-term outcome of patients with renal AMLs is whether they have a sporadic AML or AMLs associated with tuberous sclerosis complex (TSC).
Sporadic AMLs are general singular and rarely require treatment. Most are discovered incidentally and typically remain stable without symptomatic bleeding. In general, the rate of bleeding requiring intervention, as well as the rate of elective intervention for high-risk AMLs, are low (eg, 0.1 and 1.4 percent, respectively, in one large series) [32]. Loss of kidney function from a sporadic renal AML is rare [50]. With the exception of patients who present with life-threatening hemorrhage, the impact of sporadic AMLs on mortality appears to be minimal, although this has not been systematically evaluated.
By contrast, TSC is associated with renal AMLs that are typically multicentric, grow more quickly, are more likely to hemorrhage, and are higher risk for malignant transformation [32,44,50]. Thus, they are more likely to require treatment and, consequently, result in treatment-associated nephron loss. In addition, patients with TSC often have chronic kidney disease due to factors unrelated to AMLs, such as chronic interstitial disease and secondary focal segmental glomerulosclerosis. Kidney disease, therefore, is one of the leading causes of death among patients with TSC [51-53]. (See "Renal manifestations of tuberous sclerosis complex", section on 'Chronic kidney disease' and "Renal manifestations of tuberous sclerosis complex", section on 'End-stage kidney disease' and "Tuberous sclerosis complex: Management and prognosis", section on 'Prognosis' and "Tuberous sclerosis complex associated lymphangioleiomyomatosis in adults", section on 'Followup and prognosis'.)
SUMMARY AND RECOMMENDATIONS
●Active bleeding from an AML – Patients with a renal angiomyolipoma (AML) who develop flank pain or tenderness or gross hematuria should undergo prompt imaging with computed tomography (CT) or magnetic resonance imaging (MRI) to assess for hemorrhage. Patients who develop active bleeding should receive resuscitative measures (if hemodynamically unstable) and, if feasible, undergo prompt angiography and selective artery embolization (SAE) to stop the bleeding. Patients who cannot have SAE, or who continue to have life-threatening hemorrhage from a renal AML after an attempt at SAE, should undergo a partial or complete nephrectomy. (See 'Identification and management of active bleeding' above.)
●Pretreatment assessment of sporadic AML – In patients diagnosed with sporadic AML, the treatment is guided by the risk of malignant transformation and the risk of future bleeding (algorithm 1) (see 'Pretreatment assessment' above):
•Assess risk of malignant transformation – AMLs that are (by imaging) "fat rich" do not undergo malignant transformation. By contrast, "fat-poor" or "fat-invisible" AMLs (ie, epithelioid AMLs) should generally undergo percutaneous core needle biopsy to assess risk for malignant transformation.
•Assess risk of bleeding – Imaging and other features that are associated with a higher risk of bleeding include: AML diameter >6 cm; intralesional blood vessel or aneurysm >5 mm at greatest width; AML growth rate >2.5 mm per year; anticoagulation or coagulopathy; and uncontrolled hypertension.
●Management of sporadic AML
•Malignant AML or AML at high risk for malignant transformation – Patients who have been diagnosed as having an epithelioid AML with malignant transformation, and patients with an AML deemed high risk for malignant transformation should also be treated. Surgical management rather than SAE is typically chosen for such patients, although angiographic treatment may be appropriate for patients with multiple comorbidities and/or reduced kidney function. (See 'Malignant AML or high risk for malignant transformation' above.)
•Other sporadic AMLs – In patients with a sporadic AML at low risk for malignant transformation, the decision between intervention versus surveillance is based upon the size of the lesion (and other risk factors for bleeding) as well as other considerations (eg, patient's comorbidities, occupation) (algorithm 1). (See 'AML with low risk of malignant transformation' above.)
Most patients with sporadic AML ≤6 cm in diameter undergo routine surveillance (with imaging, to judge changes in the AML over time). However, in patients with sporadic AML ≤6 cm in diameter and one or more of the following criteria, we suggest intervention (with SAE, if feasible) rather than surveillance (Grade 2C) (see 'Sporadic AML ≤6 cm' above):
-Annual AML growth rate faster than 2.5 mm per year
-AML with a large intralesional aneurysm (>5 mm diameter)
-In someone who could become pregnant (or planning exogenous estrogen or progesterone therapy)
-Intolerable symptoms (eg, chronic pain) from their renal AML
-Residence in a setting with limited access to emergency services
-In someone with a high-risk occupation (eg, airline pilots)
In most patients with a large sporadic AML (ie, >6 cm in diameter), we suggest intervention (with SAE, if feasible), rather than surveillance (Grade 2C). However, surveillance, rather than intervention, may be appropriate among a subset of such patients who have all of the following factors that are associated with a lower risk of bleeding (see 'Sporadic AML >6 cm' above):
-Minimal vascularity of the AML
-Not anticoagulated or coagulopathic
-Could not become pregnant and does not intend to take estrogen or progesterone therapy
-Well-controlled blood pressure
-Residing in a region where emergency services are readily available
-No high-risk occupation (eg, airline pilot)
-Documented stability of the lesion (ie, growth rate <2.5 mm annually)
●Tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis (LAM) – Patients with TSC, LAM, and TSC-LAM generally have multiple AMLs at one time or over their lifetime. If possible, all such patients should be managed by a team of clinicians with expertise at a center of excellence. (See 'Patients with known TSC or LAM' above.)`
•Solitary AML – Patients with TSC or LAM who have a single renal AML are managed in the same way as patients with sporadic AML.
•Multiple AMLs that are stable or slow-growing (<2.5 mm per year) – Patients with stable or slow growing AMLs are managed with surveillance (ie, annual imaging with MRI or ultrasound). However, intervention (typically with SAE) is appropriate for lesions that are high risk for bleeding. The criteria are similar to those used in patients with sporadic AML.
•Multiple AMLs growingly rapidly (>2.5 mm per year) – In patients with two or more AMLs with a high growth rate, we initiate treatment with a mammalian target of rapamycin (mTOR) inhibitor (typically everolimus) rather than no treatment or performing SAE on multiple lesions (Grade 2C).
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge William M Bennett, MD, who contributed to earlier versions of this topic review.
