Adult Renal Hamartomas

Abstract Introduction

Angiomyolipoma Leiomyoma Conclusions

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Angiomyolipoma

Epidemiology and Clinical Features

Angiomyolipoma is seen in two distinct clinical settings: sporadic (isolated) or in association with tuberous sclerosis. Although exact figures are difficult to obtain, the sporadic form accounts for approximately 80%-90% of cases of angiomyolipoma (5,7). The two forms vary to some degree in their imaging features but are histologically indistinguishable (5).

Angiomyolipomas are uncommon lesions with a prevalence of 0.3%-3% (5). They constitute only 1% of surgically confirmed renal tumors (8), although this figure probably underestimates the true prevalence of these slow-growing benign lesions, which often do not require surgery or even biopsy. The sporadic form is typically seen in middle-aged patients (mean age, 43 years) and is more common in women by at least a 4:1 ratio (4,5). In a surgical series of 32 patients in the era before computed tomography (CT), the age range was 26-72 years (8).

Patients with angiomyolipomas may present with acute flank pain caused by spontaneous extrarenal hemorrhage; antecedent trauma, if any, is typically very mild. In 25% of cases, emergency laparotomy is needed because of either severe pain or life-threatening bleeding (9). Combining data from four series published between 1965 and 1971, Wong and colleagues (9) reported that, at presentation, 87% had pain; 47%, a palpable mass; and 40%, hematuria.

Today, the most common presentation for patients with angiomyolipomas is incidental discovery during imaging (including ultrasound [US], CT, and magnetic resonance [MR] imaging) performed for evaluation of suspected disease outside the genitourinary system. In a recent study, 60% of the patients with angiomyolipoma were asymptomatic for the lesion (10). This series reflects current clinical practice, in that many of these lesions were not histologically confirmed, because imaging features were sufficiently characteristic to obviate direct tissue examination (3,11,12,13).

Histologic Characteristics

Angiomyolipomas are composed of varying amounts of blood vessels, smooth muscle, and fat (Figure 1). Although less common, one may occasionally see a lesion with only smooth muscle (leiomyoma) or fat (lipoma). The typical angiomyolipoma most often has a prominent fat component (14), but all three tissue types must be seen to establish the diagnosis. Malignant transformation does not occur except in rare cases.

Although calcification and necrosis are rare, hemorrhage is frequent, despite the fact that the tumor blood vessels have a thicker wall than normal vessels. Apparently, the characteristic lack of a complete elastic layer (Figure 2) predisposes this vascular lesion to aneurysm formation (2,15,16) and hemorrhage (4) after minimal or no trauma. Although less commonly implicated than renal cell carcinoma, angiomyo-lipoma is the cause for bleeding in 16%-20% of patients with spontaneous perinephric hemorrhage (17,18). A true capsule is not seen (Figure 3).

The smooth muscle component of angiomyolipoma can occasionally demonstrate substantial hypercellularity, pleomorphism, and mitotic activity-features that may make it difficult for the pathologist to differentiate this lesion from leiomyosarcoma (4). Fat within angiomyoliipomas is of the adult type but is composed of atypical adipocytes with eccentric nuclei (2,4).

Pathologic Characteristics

The gross appearance of angiomyolipoma is determined by the relative proportions of the various cellular components and the presence or absence of associated hemorrhage. A homogeneous yellowish appearance may be seen if the lesion is composed predominantly of fat (Figure 4), but a heterogeneous pattern will be evident if there is a more even distribution of fat, muscle, and vessels (4).

Although most angiomyolipomas clearly arise from within the renal parenchyma, these tumors are exophytic in 25% of cases (8), with little attachment to the peripheral cortex. The intraparenchymal component of the tumor is often reasonably well-circumscribed and expansile at gross inspection (4).

Radiologic Features

Historically, it has been recognized that plain radiography occasionally shows lucent areas within large angiomyolipomas, allowing one to suggest the diagnosis. More typically, however, excretory urography demonstrates an expansile renal mass that cannot be distinguished from renal cell carcinoma.

At sonography, an angiomyolipoma characteristically is more echogenic than surrounding renal parenchyma (19,20) (Figure 5). However, this sonographic feature is also seen in 32% of small (less than 3 cm in diameter) renal cell carcinomas (20). The similarity of angiomyolipoma and renal cell carcinoma at US is especially important to note in view of the trend toward earlier diagnosis of carcinoma (and thus smaller tumors at the time of diagnosis) (20,21). When compared with carcinomas, angiomyolipomas are more likely to demonstrate acoustic shadowing. Echogenic carcinomas are more likely to show a hypoechoic rim and cystic areas within the lesion (22,23). Although these features are helpful for distinguishing between the two lesions, they do not allow a diagnosis to be made with the degree of confidence achieved with CT. It should be noted that the hyperechogenicity of angiomyolipomas is not necessarily due to the fat component itself; some of these lesions are echogenic despite containing little or no fat (24).

With the development of CT, it was realized that detection of fat within a renal lesion allowed confident preoperative diagnosis and, therefore, the potential for avoiding surgery in most cases (Figure 6, Figure 7). Thin-section (3-5 mm) technique is preferred to avoid volume averaging that might prevent demonstration of low attenuation in the tumor, and use of intravenously administered contrast material is not necessary. The ready availability of CT and its noninvasiveness when performed without contrast material make it the examination of choice in patients in whom angiomyolipoma is suspected on the basis of sonographic appearances.

At CT, angiomyolipoma typically appears as a well-marginated, cortical, predominantly fat-attenuation mass with heterogeneous soft-tissue attenuation interspersed throughout the lesion (Figure 8) (14). The soft-tissue attenuation may be the result of hemorrhage (Figure 9, Figure 10) or fibrosis or a manifestation of the vascular or smooth muscle components of the lesion (Figure 10). Published radiologic reports indicate that most lesions are less than 5 cm in diameter, although measurement is difficult if hemorrhage has occurred (7,10). In a study in which radiologic-pathologic correlation was obtained, more than 50% of the lesions exceeded 10 cm in size and 88% extended through the renal capsule (14). In this same series, nearly one-third of the lesions were poorly marginated, but this finding may be representative of a selection bias toward larger, hemorrhagic lesions (14). Although the vascular and smooth muscle portions of the lesion may variably enhance after intravenous administration of contrast material, this finding is not a dominant feature of most angiomyolipomas because they are largely composed of fat.

Approximately 5% of angiomyolipomas do not show fat attenuation on CT scans and cannot be differentiated from renal cell carcinoma (Figure 11, Figure 12) (3,13). Retroperitoneal hemorrhage, a frequent complicating feature, is also well evaluated with CT (Figure 13), but such bleeding may mask the characteristic fat. As a result, renal adenocarcinoma must still be considered in the differential diagnosis. Surgery would be indicated in such a case to establish the diagnosis after initial conservative management of the hemorrhage (17,18).

At MR imaging, most angiomyolipomas can be clearly characterized because of the depiction of intratumoral fat (25) (especially through the use of fat-suppression techniques) (Figure 14). Because use of contrast material is not required during CT for the diagnosis of angiomyolipoma, MR imaging offers no specific advantage. Imaging in the coronal or sagittal plane may, however, allow delineation of the point of origin of the lesion from the renal cortex rather than the adjacent retroperitoneum. Because liposarcoma may displace the kidney but rarely invades the parenchyma, a fat-containing lesion in contiguity with the subcapsular cortex is, for practical purposes, an angiomyolipoma.

Hypervascularity, small aneurysms, lack of normal vessel tapering, and tortuous vessels are characteristic angiographic findings for angiomyolipoma (9). However, this lesion cannot be differentiated from carcinoma on the basis of angiographic appearances (26). If renal-sparing surgery (ie, tumor resection rather than nephrectomy) is considered as a treatment option, angiography may be useful for preoperative planning.

Angiomyolipomas in Tuberous Sclerosis

Tuberous sclerosis, also called Bourneville disease, is a syndrome inherited in an autosomal dominant manner that includes variable expressions of mental retardation, seizures, adenoma sebaceum, and, in the kidney, cysts and angiomyolipomas. Up to 80% of patients with tuberous sclerosis have angiomyolipomas, and these patients constitute up to 20% of all individuals with angiomyolipoma. In some patients, these renal tumors may be the only clinical manifestation of tuberous sclerosis; in one series, two women had offspring with severe central nervous system disease, yet the patients themselves had renal angiomyolipomas as the only evidence of the disorder (8).

Although histologically indistinguishable, angiomyolipomas of tuberous sclerosis and those that occur sporadically have some notable differences. The most striking difference from a clinical standpoint is that angiomyolipomas of tuberous sclerosis are discovered when the patient is younger (mean age, 17 years) (5). In contrast to the marked female predilection of the sporadic form of the disease, angiomyolipomas of tuberous sclerosis occur with an approximately equal prevalence among male and female patients. In addition, lesions are far more likely to be larger, multiple, and bilateral in patients with tuberous sclerosis (Figure 15) (5,27,28). These factors lead to an increased risk of hemorrhage (10).

The link between tuberous sclerosis and renal hamartomas is evident in patients with lymphangiomyomatosis. The latter is considered by many to represent a forme fruste of tuberous sclerosis and is associated with multiple hamartomas, especially along the lymphatic channels of the abdomen and chest. Atypical hamartomas (ie, lacking fat), both renal and pararenal, have been described in a case of lymphangiomyomatosis (29). Other renal masses associated with tuberous sclerosis include simple cysts, which are occasionally large enough to replace renal parenchyma and lead to renal insufficiency. There is also a possible increased risk of renal adenocarcinoma (27).

Differential Diagnosis

Angiomyolipomas without demonstrable fat require tissue diagnosis for the exclusion of renal cell carcinoma (3,27,30). In a few cases (31,32), macroscopic fat was detected within a renal cell carcinoma at CT. In these cases, extensive calcification was also present and was histologically proved to represent ossification, with coexistent marrow fat. Because calcification is extremely rare in angiomyolipomas, and fat without dense calcification is extremely rare in lesions other than angiomyolipoma (33), fat within a noncalcified renal mass remains, for practical purposes, a diagnostic finding of angiomyolipoma (3).

Treatment

Small lesions discovered incidentally in asymptomatic patients do not usually prompt surgery for diagnosis or cure. Although use of fine-needle aspiration has been evaluated in the diagnosis of suspected angiomyolipoma (34), it is generally not performed in the United States. The reasons for this include the fact that most radiologists and clinicians are comfortable with the diagnosis if fat is demonstrated with CT or MR imaging. Because an echogenic renal cell carcinoma may be confused with angiomyolipoma, CT or MR imaging should be performed to confirm the presence of fat in such lesions initially detected at sonography.

Lesions larger than 3.5-4.0 cm in diameter are thought to have a significant risk of hemorrhage, potentially with hypotension or other associated morbidity, and are generally treated with elective resection. However, depending on the size and location of the lesion, total nephrectomy may not be required (26,35,36). Treatment with selective arterial embolization of the lesion may also be used (35), especially in patients with tuberous sclerosis, who may have limited nephronic reserve due to replacement of the renal parenchyma by multiple cysts and angiomyolipomas (36).

Because the natural history of these lesions is unknown, controversy exists about the follow-up of smaller lesions (10,35). Although it has been generally accepted that these lesions do not grow substantially in adults (35,37,38,39), it has recently been shown that some may increase in size to the point at which they are considered at risk for hemorrhage (10,28,36). This progression may be especially true in those patients with multiple lesions (many of whom have tuberous sclerosis) (7). Generally, asymptomatic patients with an angiomyolipoma approaching 4 cm in diameter are followed up annually with US or CT, although in most of these patients the lesions will show little change over time. Patients with lesions greater than 4 cm can be followed up at more frequent intervals, be treated with selective embolization, or undergo elective resection with renal-sparing surgery (10,35).

Abstract Introduction

Angiomyolipoma Leiomyoma Conclusions

Source Information References