Angiomyolipoma (AML) is a type of benign renal tumor, with an estimated prevalence of 0.3–3% of all renal tumors and a greater female predilection (1, 2). It is characteristically a solid “triphasic” tumor composed of dysmorphic blood vessels, smooth muscle components, and mature adipose tissue which may be present in varying amounts (3). AML was once considered a hamartoma and, most recently, a choristoma; it is now considered a part of perivascular epithelioid cell tumors (PEComa) (4–6). PEComa are mesenchymal neoplasms formed by nests and sheets of epithelioid and spindle cells that show immunoreactivity for both smooth muscle and melanocytic markers (7). The PEComas now include AML, pulmonary clear cell “sugar” tumor and lymphangioleiomyomatosis (LAM), primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other neoplasms with similar characteristics (8). Renal angiomyolipomatosis is a common manifestation in patients with tuberous sclerosis (TS) and LAM, where AMLs are larger, multiple, almost always bilateral, and have a greater predisposition to bleeding. AML is sporadic and isolated in 80% of cases, while the remaining 20% is associated with tuberous sclerosis complex (TSC) or pulmonary LAM (9, 10). Radiologically, the sporadic AML is predominantly classified into classic (common) and fat-poor AML (uncommon). Fat-poor AML is further classified into three subtypes: hyperattenuating AML (approximately 4.5% of all AMLs), isoattenuating AML (rare), and AML with epithelial cyst (rare). Another type of sporadic AML is epithelioid AML (rare). Syndromic AML is subdivided into AML in TSC and AML in LAM (11).The majority (>80%) of AMLs are detected incidentally during imaging. Most patients are asymptomatic when AML is diagnosed (10). The most common presentation is spontaneous retroperitoneal hemorrhage, although this happens in less than 15% of cases (10). Other clinical presentations are anemia, hematuria, palpable mass, flank pain, urinary tract infection, or renal failure (12, 13). As most classic AMLs do not increase in size and remain asymptomatic, the management is conservative. However, some grow gradually, showing a growth rate of 5% or 0.19 cm per year (14, 15). Oesterling et al. (16) proposed an algorithm for the management of AML based on tumor size and symptoms. For small AML (≤ 4 cm), follow-up with ultrasound (US) imaging is recommended every 12 months; for small AML in symptomatic patients, arterial embolization or partial nephrectomy can be chosen although observation is often favored in clinical practice. Treatment is recommended for symptomatic patients with large tumors, especially if the AML has bled. In asymptomatic patients with large AML, follow-up with computed tomography (CT) or US is recommended (16). Other options introduced for AML treatment are transarterial ethanol and percutaneous ablation using cryoablation or radiofrequency (17–19).

In this article, we describe the radiological features of renal angiomyolipomatosis. A PubMed search was performed by a radiologist for the term “angiomyolipomatosis.” The research showed 20 articles published in a period from 1969 to 2013. A total of 10 articles were excluded: four in German, three in French, one in Russian, and two did not describe the radiological features of renal angiomyolipomatosis. The remaining 10 articles in English, Italian, and Spanish languages describing radiological features of renal angiomyolipomatosis were selected.

Tuberous sclerosis is largely the result of loss-of-function mutations of TSC1 (9q34) or TSC2 (16p13.3) genes. In addition to conditions such as mental retardation and seizures, TSC is associated with AMLs, LAM, pulmonary multifocal micronodular hyperplasia, subependymal giant cell tumors, cutaneous angiofibromas, and cardiac rabdomyomas (20). AMLs occur in 55–75% of patients with TS; AMLs in TS typically develop at a young age and are frequently multiple, almost always bilateral and larger in size, presenting as angiomyolipomatosis (Figure 1) (11, 21). Patients with TSC are more likely to show multiple, bilateral, and larger AMLs than AMLs in sporadic cases (22, 23). Most of the AMLs in TSC manifest as the classic type, while fat-poor AMLs are found in over one-third of these patients. Fat-poor AMLs in TSC tend to be larger than those of the sporadic form (24).

As renal cell carcinoma may occur in patients with TSC, renal masses without visible characteristic adipose tissue may require a percutaneous biopsy or closer follow-up (15). Patients with TSC have also shown the presence of epithelioid AML and AML with epithelial cysts; TSC patients are more likely to show these two variants of AML compared to AMLs found sporadically (25, 26). Epithelioid AML shows variable biological behavior including malignancy; in fact, during adulthood, it can infiltrate adjacent tissue or metastasize to the lungs, liver, peritoneum, or bone (27, 28).

As patients with TSC risk premature loss of nephrons due to increasing numbers and dimensions of cysts and AMLs, selective arterial embolization, percutaneous ablation, or partial nephrectomy are preferred conservative therapies for the treatment of these lesions (29). Moreover, these patients present a high risk of spontaneous hemorrhage; AML >4 cm and AML aneurysms >0.5 cm are risk factors for AML hemorrhage (30, 31). Approximately 43% of patients with TSC may have recurrent AML bleeding, which is not usually seen in sporadic AMLs (32, 33). Indeed, angiomyolipomatosis is often associated with multiple spontaneous bleeding events. The mTOR inhibitor sirolimus allows the prevention of tumor growth and recurrence of bleeding in patients with TSC by inhibiting the activation of the mTOR pathway (34). Transcatheter embolization is an effective treatment for controlling bleeding in the acute context and can be performed in combination with surgery (17).

Renal angiomyolipomatosis can be detected in patients with LAM, a rare disease characterized by destructive cystic changes in the lungs. Sporadic LAM manifests itself in one in 400,000 adult females; it may also happen in TSC, occurring in 30–40% of adult females and rarely in males and children (11, 35). In addition to renal AMLs, LAM presents other disorders including lymphangioleiomyomas, abdominal lymphadenopathy, and chylous ascites, and an increase in the frequency of meningioma (11, 35–38). As well as sporadic AMLs, the guidelines for LAM patients with AMLs recommend US examination per year for small AMLs (<4 cm), while larger AMLs and AMLs with aneurysms of 5 mm or greater diameter should be checked twice a year with US examination. The treatments of choice for a bleeding AML are renal arterial embolization and partial nephrectomy. Furthermore, the mTOR inhibitor sirolimus reduces the volume of AML (34, 35, 39).

Several studies have described the radiological features of angiomyolipomatosis; for this review, we analyzed the radiological features described in several clinical cases. Imaging features of the cases of renal angiomyolipomatosis described in the literature are listed in Table 1 (40–49).

Renal angiomyolipomatosis generally occurs with multiple and diffuse AMLs, bilaterally localized. Often the masses extend almost entirely covering the abdomen, displacing the intestine. Signs of previous bleeding may be present. Renal cysts could also be detected. In AMLs with a predominantly fatty component, the adipose tissue localized within these lesions assumes fundamental importance in the diagnosis. On US examination, it appears hyperechoic compared to renal cortex. In CT examination, it appears as hypodense area of adipose tissue density, mixed, or with soft-tissue attenuation due to vascular or smooth muscle components, hemorrhage or fibrosis (2).

Bosniak described the angiographic features of AML. The author observed three patterns in particular: aneurysmal and tortuous vessels, berry-like aneurysms, and slow-flowing vessels with contrast medium retention (50).

On magnetic resonance imaging (MRI), it appears isointense compared with fat on T1-weighted images; moreover, with the use of in-phase and opposed-phase imaging, AMLs with predominant adipose component show the characteristic India ink artifact that appears at the interface between the lesion and the normal renal parenchyma on opposed-phase T1-weighted images. In T2-weighted images, however, the intensity can be variable, depending on the amount of adipose tissue present in the lesion, resulting homogeneously high in AMLs with a higher adipose component (Figure 2) (51–54).

The diagnosis is more difficult if there is the presence of fat-poor AML, epithelial AML, and AML with epithelial cysts, as we must discriminate these lesions from malignant lesions, such as renal cell carcinoma or the same epithelioid AML with malignant biological behavior, being able to be present in renal angiomyolipomatosis. For example, it is difficult to differentiate fat-poor AML from other solid tumors, especially renal cell carcinoma. In this case, double-echo gradient-echo chemical-shift MRI could be used in which the values of the signal intensity are measured on the renal lesion and on the spleen in on-phase and opposed-phase T1-weighted gradient-echo MRI (54). The presence of small calcifications within the lesion, which can be easily detected with CT, is considered to be suggestive of renal cell carcinoma (55). Furthermore, central necrosis is indicative of renal cell carcinoma, this being frequently present in medium-to-large clear cell renal cell carcinoma and very rare in AML. In fat-poor AML, the low amounts of adipose tissue can be detected on opposed-phase and in-phase imaging. It also appears homogeneously hypointense on T2-weighted images (53).

Finally, even contrast enhancement US can be used in the differential diagnosis between malignant and benign renal lesions (56). In a retrospective study, Lu et al. found a slow centripetal enhancement in the cortical phase and a homogeneous enhancement in the peak phase in fat-poor renal AML (57).

Jinzaki et al. proposed an AML classification in which clinical features, radiologic features, and pathologic features coexist. This section focuses on the radiologic characteristics indicated in the AML classification of Jinzaki et al. (11).

Song et al. classified renal AML into fat-rich, fat-poor, and fat-invisible AML based on the amount of fat detected by CT or MRI (86). Fat-rich AML was identified by attenuation value less than or equal to −10 HU obtained by placing a ROI in the most hypodense area of the lesion (61). When the most hypodense area showed attenuation value greater than −10 HU, the chemical shift imaging was evaluated. Tumor-to-spleen ratio and signal intensity index were calculated using the values obtained by placing the ROI in the most hypointense area on opposed-phase images. Fat-poor AML was detected when the tumor-to-spleen ratio was <0.71 or when the signal intensity index value was >16.5%. Fat-invisible AML was detected when the tumor-to-spleen ratio was ≥0.71 and when the signal intensity index value was ≤16.5% (86). Both fat-poor AML and fat-invisible AML exhibit attenuation values greater than –10 HU on unenhanced CT. Song et al. showed that the attenuation value of fat-invisible AML detected in the ROI located in the most hypodense area of the lesion was greater than that of the fat-poor AML (86).

Renal angiomyolipomatosis is a common manifestation in patients with TS and LAM. AMLs are larger, multiple, almost always bilateral, and have a greater predisposition to bleeding, which is the reason why follow-up must be performed in these patients. Furthermore, specific subtypes of AML, such as poor-fat AML, are difficult to distinguish from malignant lesions. For this reason, further imaging examinations must be performed to obtain further information on the nature of the lesions.

The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article.