Renal angiomyolipoma: left and right, observation and treatment

Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney, consisting of three components: mature adipose tissue, atypical smooth muscle cells, and thick-walled vessels. Classic AML contains macroscopic fat and is usually easily recognizable on CT and MRI. However, "fat-poor" and "fat-invisible" variants exist, as well as epithelioid AML (EAML), which has a potentially malignant behavior, complicating diagnosis and management. [1]

AML can be sporadic (usually solitary and unilateral) or associated with tuberous sclerosis complex (TSC) or lymphangioleiomyomatosis (LAM)—in these cases, tumors are often multifocal, bilateral, and have a higher risk of growth and bleeding. Understanding the clinical and genetic context is important because the approach to monitoring and treatment in TSC/LAM differs markedly from that in sporadic AML. [2]

Historically, a tumor size >4 cm was considered a "bleeding risk" criterion. Current data clarify: an intratumoral aneurysm >5 mm is a much more accurate predictor of rupture, while diameter alone is less specific. This influences decisions about prophylactic embolization and other interventions. [3]

Treatment includes active surveillance for low-risk patients, selective arterial embolization (SAE), nephron-preserving surgery or ablation for complications/growth, and, for TSC/LAM-associated tumors, targeted therapy with mTOR inhibitors (everolimus, sirolimus), which reduce AML volume and the risk of bleeding. The choice of treatment is a balance between the risk of rupture, nephron preservation, and quality of life. [4]

Code according to ICD-10 and ICD-11

In ICD-10, renal angiomyolipoma is coded under the heading D30.0 - Benign renal tumor (with side-specific specifications: D30.01 - right, D30.02 - left, D30.00 - unspecified). This is the most appropriate choice for sporadic and TSC-associated AMLs without indication of malignancy. [5]

ICD-11 uses a cluster approach: a core code for benign neoplasm of the urinary system/kidney (selected in the ICD-11 browser), to which extension codes (e.g., lateralization) are appended. Post-coordination for morphology is permitted (morphology code "angiomyolipoma") when appropriate. Local registry rules may vary, so the official ICD-11 browser should be used for reporting. [6]

If a patient is diagnosed with an epithelioid variant with aggressive features, coding may include a note of potentially malignant behavior according to the morphological classification (PEComa spectrum). Clarifying notes are particularly important for routing and decision-making. [7]

Table 1. Coding (quick reminder)

Situation	ICD-10	ICD-11 (approach)
Classical renal AML	D30.0 (with side clarification)	Stem code of benign renal tumor + postcoordination (morphology "angiomyolipoma") + lateralization
AML in TSC/LAM	D30.0 + associated TSC/LAM codes	As above + accompanying TSC/LAM code
Epithelioid AML (EAML)	D30.0 (with morphological clarification)	Benign/potentially malignant mesenchymal tumor (PEComa spectrum) by morphology

Epidemiology

AML is the most common benign renal tumor; most cases are discovered incidentally during imaging for another reason. Sporadic AML predominates in middle-aged women and is usually solitary. TSC-associated AML occurs in 50-85% of patients with this syndrome and is most often multifocal and bilateral. [8]

The risk of clinically significant bleeding is low in small, asymptomatic sporadic tumors and increases with the proportion of the vascular component and the presence of intratumoral aneurysms. In women of childbearing age and during pregnancy, the risk of rupture is higher, requiring a more proactive approach. [9]

In the era of accessible imaging, the proportion of detected "fat-poor/fat-invisible" AMLs is increasing, leading to a greater number of referrals for further investigation and biopsy/dynamic studies due to their similarity to renal cell carcinoma (RCC). This highlights the value of advanced MRI features and multidisciplinary discussion. [10]

Table 2. Frequency and clinically associated features

Category	Characteristic
Sporadic AML	More often female, single, unilateral
TSC-associated AML	50-85% of patients with TSC; bilateral/multiple, higher risk of growth/bleeding
Risk of bleeding	Higher with an aneurysm >5 mm, during pregnancy, with a large vascular component
"Fat-poor/invisible" AML	An increasing proportion of findings more often require advanced imaging/biopsy

Reasons

AML belongs to the PEComa (perivascular epithelioid cell tumor) family of tumors. Pathogenetically, many AMLs are associated with the inactivation of the TSC1/TSC2 genes (both in TSC/LAM and in some sporadic cases), which leads to hyperactivation of the mTORC1 signaling pathway and excessive cell growth. This explains the effect of mTOR inhibitors (everolimus/sirolimus) – tumors shrink in volume when the pathway is blocked. [11]

Sporadic AML develops without an obvious hereditary predisposition, but some patients exhibit somatic alterations in the TSC genes. Associations with hormonal factors (female gender, pregnancy) are observed clinically; expression of estrogen/progesterone receptors has been described in a number of series, correlating with the risk of bleeding during pregnancy. [12]

Epithelioid AML (EAML) is a rare variant with aggressive potential (local invasion, metastasis). Molecularly, it also belongs to the PEComa family. Correct identification of EAML determines treatment strategy (often surgical) and follow-up. [13]

Risk factors

Risk factors include TSC and LAM (sporadic or TSC-associated), female gender, childbearing age, and pregnancy. In TSC/LAM, tumors are typically more numerous and prone to growth, increasing the likelihood of lifelong interventions. [14]

The risk of bleeding is increased by a large vascular component, intratumoral aneurysms >5 mm (the most reliable predictor), rapid growth, large size (especially >6 cm), and limited access to emergency care. Women of childbearing age require an individualized strategy, especially when planning a pregnancy. [15]

The risk of misdiagnosis (and, consequently, overtreatment) increases with “fat-poor/invisible” AMLs that mimic RCC – here, experienced interpretation of MR signs (including in/opposed-phase sections), dynamic observation, and selective biopsy are important. [16]

Table 3. What really increases the risk of rupture

Predictor	Significance
Intratumoral aneurysm >5 mm	The strongest and most specific predictor
Rapid growth (>2.5 mm/year; >5 mm/year - high risk)	For observation or preventive SAE
Large size (especially >6 cm)*	It is less specific in itself than an aneurysm.
Pregnancy/childbearing age	Hormonal/hemodynamic factors

* In a number of European consensuses, prophylactic embolization is discussed starting from a diameter of ~4 cm, but the criterion is specified based on the anamnesis, growth and presence of aneurysms. [17]

Pathogenesis

The key link is hyperactivation of the mTORC1 pathway due to TSC1/TSC2 inactivation, which leads to uncontrolled growth of smooth muscle/epithelioid cells and the formation of vascular malformations. This causes the tissue triad (fat, vessels, muscle) and explains the bleeding: tumor vessels are thickened, tortuous, and prone to aneurysms. [18]

During pregnancy, circulating blood volume, renal blood flow, and hormonal influences increase, which can accelerate the growth of AML and dilation of vessels/aneurysms, resulting in a higher risk of spontaneous rupture. TSC/LAM is characterized by multifocality due to a systemic genetic defect. [19]

Epithelioid AML is characterized by a predominance of epithelioid cells and can demonstrate an aggressive course with invasion/metastases (PEComa spectrum), requiring a different level of oncological alertness and management. [20]

Symptoms

Most sporadic AMLs are asymptomatic. When symptoms are present, nagging flank/lower back pain and macro- or microscopic hematuria are typical. Large tumors may be palpable. The most serious manifestation is spontaneous retroperitoneal bleeding (Lenks syndrome): sudden pain, a drop in blood pressure, tachycardia, and anemia, which requires emergency care. [21]

In TSC/LAM, symptoms are more often associated with multiple/large lesions and their growth, recurrent pain and anemia are also common. The epithelioid variant may present atypically, including signs of local invasion. [22]

Table 4. When to go to the hospital urgently

Sign	Possible cause
Sudden severe pain in the side/abdomen + drop in blood pressure	AML rupture/bleeding
Progressive anemia, weakness	Chronic blood loss
Fever + pain	Necrosis/infection of hemorrhage
Rapid growth of education	Risk of vascular complications/anomalies

Forms and stages

By composition: fat-rich, fat-poor, and fat-invisible AML - classification is based on the amount of visualized fat and helps choose the visualization method/tactics. Fat-poor variants more often mimic SCC. [23]

In context: sporadic versus TSC/LAM-associated. The latter is multifocal, bilateral, and more often requires drug therapy (mTOR inhibitors) and preventive embolization in the presence of risk factors. [24]

A separate form is epithelioid AML (EAML) with potential malignancy; it is distinguished in modern classifications, since it requires oncovigilance and, as a rule, surgery with careful monitoring. [25]

Complications and consequences

The main complication is bleeding into the tumor/retroperitoneum. Risk is increased by aneurysms >5 mm, rapid growth, large size, and pregnancy. In the case of a massive rupture, hemorrhagic shock and the need for emergency SAE/surgery are possible. [26]

After SAE, post-embolization syndrome (pain, fever), rare recurrent bleeding, or growth of residual nodes are possible—dynamic therapy is required. After partial nephrectomy, risks include urinomas, bleeding, and decreased kidney function, but with a modern nephron-sparing approach, outcomes are favorable. [27]

In patients with TSC/LAM, a rebound effect (AML regrowth) has been reported with mTOR inhibitor discontinuation, so low maintenance doses after induction are being considered. This is taken into account in long-term therapy planning. [28]

Epithelioid AML can cause local invasion and metastases - oncological vigilance, revision of histology in a reference center and personalized tactics are important. [29]

Diagnostics

Ultrasound. Often the first examination: classic AML is usually hyperechoic (brighter than the renal sinus). However, hyperechogenicity is not specific: some RCCs also have this appearance, especially with a small amount of fat. If "suspicious" signs (heterogeneity, shadow, rapid growth) are detected, CT/MRI is performed. [30]

CT. A hallmark of classic AML is negative-density lesions (usually <-10 HU) on native scans, which is virtually pathognomonic. In "fat-poor/invisible" variants, fat may not be visible; in this case, indirect signs are sought, dynamic contrast enhancement, and vascular structures are assessed, but CT may not be specific enough. [31]

MRI. A key tool for "fat-poor" tumors: the in/opposed-phase (chemical shift) method reveals microscopic fat (signal loss in the opposed-phase), helping to differentiate AML from RCC; the T2 signal in "fat-poor" AML is often decreased. If EAML is suspected, multiphase protocols are used. [32]

Angiography/CT angio. These are necessary for the assessment of intratumoral aneurysms and planning of SAE; the presence of aneurysms >5 mm is currently considered the main indicator of the risk of rupture. Biopsy is indicated in cases of diagnostic uncertainty (suspected RCC/EAML), but is not required if there is a clear visual picture of classic AML. [33]

Table 5. What, when and why

Method	Role	Comments
Ultrasound	Screening/incidental finding	Hyperechogenicity is not specific
CT with/without contrast	Fat confirmation	<-10 HU - almost pathognomonic
MRI (in/opposed-phase)	"Fat-poor" nodes	Signal loss → microfat
(CT) angiography	Search for aneurysms	>5 mm - high risk of bleeding
Biopsy	When in doubt with PKR/EAML	Selectively, after consultation

Differential diagnosis

The main "doppelganger" is renal cell carcinoma (RCC), especially in the case of fat-poor/fat-invisible AML. The following are helpful: chemical-shift MRI (signal reduction), absence of calcifications, and type of vascularization; if in doubt, biopsy. Epithelioid AML can even mimic RCC on MRI. [34]

Other options: oncocytoma, chromophobe RCC, rare mesenchymal tumors. In some cases, dynamic observation (growth curve) is useful - RCC often grows uniformly, while AML can grow "suddenly" due to hemorrhages/fat lobules. [35]

A separate block is epithelioid AML (EAML): potentially malignant, falls within the PEComa spectrum; if suspected, resection with verification in reference pathology is preferred. [36]

Table 6. How AML differs from RCC (simplified)

Sign	AML	anti-ship missiles
Native CT	Often <-10 HU (fat)	Density >0 HU, often calcifications
In/opposed-phase MRI	Signal loss (microfat)	There is usually no significant loss
Angio-signs	Tortuous vessels, aneurysms	Feeding vessels without aneurysms
Biopsy	PEComa phenotype	Cancer histotypes (clear cell, etc.)

Treatment

Active surveillance. Suitable for asymptomatic patients with low risk: small (usually <4 cm) nodules without aneurysms, slow growth (<2.5 mm/year). Monitoring: ultrasound/CT/MRI at 6-12 month intervals, then less frequently if stable. The 4 cm threshold is now interpreted flexibly, taking into account growth, aneurysms, and pregnancy plans. [37]

Selective arterial embolization (SAE). The method of choice for bleeding and effective prophylaxis in high-risk settings (aneurysm >5 mm, rapid growth, large node in women of childbearing age/during pregnancy). Advantages: organ-preserving strategy, rapid bleeding control; disadvantages: possible regrowth/recanalization, post-embolization syndrome. [38]

Nephron-sparing surgery/ablation. Partial nephrectomy is indicated in cases of diagnostic uncertainty (suspected RCC/EAML), giant/symptomatic nodules, and when SAE is contraindicated/failed. Cryo- or RF ablation is possible in carefully selected patients with accessible sites. The goal is tumor control while maximally preserving renal function. [39]

MTOR inhibitors (everolimus/sirolimus). The standard for TSC/LAM-associated AML with clinical significance: they reduce tumor volume, reduce the risk of bleeding, and reduce the need for procedures. Data from RCTs/registries (EXIST-1/2, etc.) and guidelines confirm efficacy and acceptable tolerability; low-dose maintenance therapy after induction is possible to prevent rebound. Everolimus is also considered for sporadic AML if pharmacological volume reduction is required (off-label - according to local practice). Management includes monitoring for side effects (stomatitis, dyslipidemia, edema, pneumonitis) and drug interactions. [40]

Table 7. Choice of tactics (clinical scenarios)

Situation	Preferred approach
Small asymptomatic AML without aneurysms	Observation (MR/CT 6-12 months)
AML with aneurysm >5 mm / rapid growth	Preventive SAE
Bleeding/Lenx syndrome	Emergency SAE ± follow-up management
Diagnostic uncertainty (RCR/EAML)	Partial nephrectomy or biopsy
TSC/LAM + clinically significant AML	Everolimus/sirolimus ± SAE as indicated

Table 8. Pros/cons of methods

Method	Pros	Cons
Observation	Maximum nephron, no invasiveness	Requires discipline and access to visualization
SAE	Fast, organ-preserving, effective against bleeding	Post-embolization syndrome, risk of recurrence
Partial nephrectomy	Accurate verification/radicality	Risks of surgery, possible loss of parenchyma
Ablation (cryo/RFA)	Minimally invasive for select patients	Localization/Size Restrictions
Everolimus/sirolimus	Volume reduction, control with TSC/LAM	Side effects, possible rebound upon discontinuation

Prevention

There is no specific prevention for sporadic AML. The key is early detection and risk stratification based on size, growth rate, and the presence of aneurysms. Women of childbearing age with known AML should discuss prophylactic SAE/medication options before planning a pregnancy if they have risk factors. [41]

For patients with TSC/LAM, prevention of complications relies on regular nephrological and radiological monitoring and timely administration of mTOR inhibitors when indicated; discontinuation of therapy should be accompanied by a surveillance plan due to the risk of rebound. [42]

Forecast

Most patients with sporadic AML have a favorable prognosis: the lesion is stable, and complications are rare with appropriate monitoring. With timely detection of aneurysms and performing SAE, the risk of rupture is minimal, and renal function is preserved. [43]

In TSC/LAM-associated tumors, the prognosis is determined by overall disease control. Treatment with mTOR inhibitors can reduce the volume of AML and reduce the frequency of interventions, but recurrence is possible when treatment is discontinued. Long-term follow-up with a multidisciplinary team is essential. Epithelioid AML requires oncologic vigilance and an individualized treatment plan. [44]

FAQ

1) Does AML always require surgery?

No. Small, asymptomatic nodules without risk factors are more commonly observed. Intervention is necessary in the case of bleeding, high risk of rupture (aneurysm >5 mm/rapid growth), diagnostic uncertainty, or severe symptoms. [45]

2) Is it true that >4 cm requires surgery?

The modern approach is more nuanced. Size is important, but an aneurysm >5 mm and dynamic growth are more reliable predictors of bleeding. The decision is made individually, taking into account age, access to emergency care, and pregnancy plans. [46]

3) Is it possible to “reduce swelling with pills”?

Yes, for TSC/LAM-associated AML, mTOR inhibitors (everolimus/sirolimus) are used, which reduce the volume and reduce the risk of bleeding; sometimes low maintenance doses are used. The decision is made by a specialist, taking into account the side effects. [47]

4) How dangerous is AML during pregnancy?

The risk of rapid growth and rupture increases. Women with known AML planning pregnancy are advised to assess their risk (aneurysm, size, growth) and consider prophylactic SAE/other measures. [48]

5) How to distinguish AML from cancer on images?

The presence of macroscopic fat on CT is practically pathognomonic for AML. In "fat-poor" variants, MRI signs (chemical shift), angiography (aneurysms), and dynamics are helpful; if in doubt, biopsy or organ-preserving resection are indicated. [49]