Angiomyolipoma (AML) is a benign renal tumor composed of adipose tissue, smooth muscle cells, and blood vessels. The increasing use of imaging studies has allowed this neoplasm to be detected earlier. AMLs occasionally can become quite enlarged and present with features similar to retroperitoneal liposarcoma. Diagnosis and treatment depend on whether symptoms are present and confirmatory imaging studies. The authors report the case of a giant AML involving the renal hilum. They also provide a review of the literature and discuss the presentation, diagnosis, and treatment of these tumors.

Angiomyolipoma (AML) is a benign neoplasm composed of varying admixtures of blood vessels, smooth muscle cells, and adipose tissue.^1-3 Although previously considered to be a hamartoma or choristoma, recent evidence demonstrates monoclonality and cytogenetic abnormalities that support neoplastic derivation. AMLs are more common in women and rarely occur before puberty. Twenty percent of these tumors are seen in patients with tuberous sclerosis (TS), which is an autosomal-dominant disorder characterized by mental retardation, epilepsy, and characteristic skin lesions.⁴ A majority of patients with TS (80%) develop AMLs.⁵ The average size of these tumors is 2 to 8 cm, with cases involving tumors of up to 20 cm reported in the literature.^1-3,6 The increased use of imaging studies has allowed earlier detection of these lesions, and now they are frequently identified in the asymptomatic stages.

Although most AMLs are small and require no intervention, they can become quite large and result in significant discomfort secondary to compression of intra-abdominal organs. There is also a significant risk of bleeding when these lesions enlarge to greater than 4 cm in diameter. Although benign, AMLs are similar in appearance to both benign and malignant tumors and must be differentiated from these lesions, especially when observation is the chosen course of treatment (Table).

Case report
A 44-year-old previously healthy woman noted abdominal fullness, nocturia, right upper quadrant pain, and constipation. On physical examination, a right upper quadrant mass measuring approximately 15 cm was visible. The mass was minimally mobile on palpation. The patient’s initial computed tomography (CT) scan showed a large, mixed-composition, right retroperitoneal mass that was inseparable from the right kidney and located near the right lobe of the liver (Figure 1). It was unclear whether the mass was invading any adjacent organs. Magnetic resonance imaging (MRI) of the abdomen revealed a well-encapsulated, large, heterogeneous retroperitoneal mass measuring 14.2 x 10 x 17.5 cm (Figure 2). The mass appeared to arise from the right kidney, consisted predominantly of fatty tissue, and demonstrated significant vascularity. No hepatic invasion was noted, and the inferior vena cava was deviated to the left by the mass, resulting in a plane between the mass and the vessel. Magnetic resonance angiography showed vascularity of the mass originating from the right kidney. Venous drainage occurred through the right renal venous structures.

Although a diagnosis of AML was suspected, preparations were made to treat this as a retroperitoneal sarcoma with multiorgan resection as needed. Intraoperatively, the mass arose and was inseparable only from the right kidney. Clear uninvolved planes were found between the mass and the duodenum, right colon, gallbladder, and liver. The patient underwent resection of the mass in continuity with the right kidney (Figure 3).

Frozen-section evaluation was consistent with AML. Histopathology showed an encapsulated soft tissue mass extending from the renal hilum, which measured 17.5 cm at its greatest dimension and weighed 1,580 g (Figure 4). The lesion was characterized microscopically by a proliferation of cells, including those demonstrating adipose and smooth muscle differentiation, with the formation of thick-walled vascular structures (Figure 5). The patient’s postoperative course was uneventful, and she was discharged home on postoperative day 4.

Discussion
AML is a benign mesenchymal tumor with a prevalence of 0.3% to 3% of all surgically resected renal tumors.¹ It is characterized by varying amounts of adipose tissue, smooth muscle cells, and thick-walled vessels, and most likely arises from the perivascular epithelioid cells. It is more common in women and rarely encountered before puberty. Approximately 20% of AMLs are seen in patients with TS.⁴ Penetrance for each of these traits is far from complete, and approximately 80% of patients with TS will develop AMLs. Among this patient population, the mean age at presentation is 30 years, and the female-to-male ratio is 2:1. Most patients with AMLs, however, do not have TS, and the tumor is a sporadic occurrence. While there is a higher female predominance in non-TS patients, most of these patients present later in life, during the fifth or sixth decades.^2,3

In patients with TS, AMLs are more likely to be symptomatic, bilateral, and multicentric, and have accelerated growth rates.³ Previously, most of these tumors were diagnosed only after symptoms manifested. Massive retroperitoneal hemorrhage from the aneurysmal vessels contained in these neoplasms is known as Wunderlich’s syndrome, a condition that has been found in up to 10% of patients and represents the most significant and feared complication of AML.⁶

Common signs and symptoms of AMLs include flank pain, hematuria, and a palpable mass. Hypovolemic shock secondary to bleeding can be fatal if not promptly identified and treated.⁷ Pregnancy increases the risk of hemorrhage from these tumors. More subtle presentations include anemia and hypertension. In more than 50% of cases, AMLs are incidental findings on abdominal imaging studies.

Radiographic findings of AML allow a definitive, preoperative diagnosis to be made in most cases. CT scanning usually shows a fatty mass intermixed with areas of increased tissue density, although the amount of fat present is variable and can even be absent. Angiography shows aneurysmal dilation in 50% of cases, which suggests the diagnosis. However, CT scanning is the most useful and reliable diagnostic imaging modality for identifying these tumors (Figure 1). The presence of even a small amount of fat within a renal lesion on CT scanning (confirmed by Hounsfield unit ≤10) suggests a diagnosis of AML instead of renal cell carcinoma. In 14% of cases, however, fat cannot be identified on CT scanning because there is a reduced proportion of mature adipose tissue, preventing a definitive diagnosis from being made. Patients with tumors that have calcifications or indeterminate features on CT scanning should be treated aggressively, because the likely diagnosis in most of these cases is renal cell carcinoma.

Although AMLs are considered benign tumors, extrarenal occurrences have been reported in the hilar lymph nodes, retroperitoneum, and liver, and direct extension into the venous system has been observed.² A uniformly benign clinical course in these rare cases favors a multicentric origin rather than metastasis. AMLs can exhibit regions of hypercellularity with cellular atypia. In such cases, the differential diagnosis can include various types of sarcoma, including fibrosarcoma, leiomyosarcoma, liposarcoma, and sarcomatoid renal cell carcinoma, depending on the relative amounts of adipose, vascular, or smooth muscle tissue present. Positive immunoreactivity for HMB-45, a monoclonal antibody against a melanoma- associated antigen, is characteristic for AMLs and positive in 100% of tumors. This marker can be useful to differentiate AML from other tumor types.⁸ Malignant transformation of AML, if it does occur, is extremely rare. Most symptomatic patients have AMLs that are 4 cm or larger. In Oesterling and colleagues’ study, 82% of patients with symptoms had AMLs measuring 4 cm or greater in diameter, and 9% were in hemorrhagic shock at the time of presentation.⁶ In a report by Dickinson and associates, only 23% of patients with tumors smaller than 4 cm were symptomatic.⁹ Steiner and associates reported that 52% of patients with AMLs of 4 cm or greater were symptomatic, with 30% requiring surgical intervention, whereas tumors smaller than 4 cm did not require surgery and were asymptomatic 76% of the time.⁷ Tumors smaller than 4 cm have slower growth rates and rarely cause hemorrhage. Multicentric AMLs and those observed in patients with TS have increased growth rates, expanding approximately 20% per year versus a mean growth rate of 5% per year for solitary AMLs.¹⁰

Guidelines for management
In general, asymptomatic AMLs with a diameter of 4 cm or smaller can be followed expectantly, and patients should undergo imaging studies at 6- to 12-month intervals to evaluate the growth rate and clinical course. For larger tumors, particularly if the patient is symptomatic, surgical intervention should be considered. A nephron-sparing approach, via partial nephrectomy or selective embolization, is preferred in patients with small AMLs requiring intervention because of symptoms, in patients with TS or multicentric AMLs, and in patients for whom preservation of renal function is important. Nephron-sparing surgery can be performed with safety and maximum preservation of renal function.^11,12 Selective embolization is an option that should be considered. Data on 17 patients in two series have documented long-term success in most cases, although some patients required repeat embolization due to regrowth or development of new lesions.^13,14

Acute or potentially life-threatening hemorrhage requires exploration and total nephrectomy. If a patient has TS, bilateral disease, preexisting renal insufficiency, or other medical or urologic disease that could affect future renal function, selective embolization should be considered if the patient is stable enough. In such circumstances, selective embolization can temporize the disease, and may provide definitive treatment in many cases. Selective embolization decreases tumor size, prevents hemorrhage, and preserves kidney function in patients with TS and renal AML.¹¹ Long-term follow-up, however, reveals a high recurrence rate in AML patients with TS who undergo selective embolization; thus, lifelong surveillance for recurrence is essential after AML embolization in this patient population.¹⁵

Conclusion
Although benign, renal AMLs may require surgical intervention, particularly if the tumor is enlarging or the patient is at risk for hemorrhage. Certainty of diagnosis can be difficult without definitive tissue examination. Nephron-sparing surgery and embolization are acceptable treatment options in selected cases, while radical nephrectomy is more likely required for large lesions and those involving the renal hilum.

References
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