Genitourinary Imaging
Original Research
Renal Epithelioid Angiomyolipoma: Imaging Characteristics in Nine Cases With Radiologic-Pathologic Correlation and Review of the Literature
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OBJECTIVE. The purpose of this study was to describe the imaging features of renal epithelioid angiomyolipoma (EAML), a rare subtype of angiomyolipoma, with clinical and pathologic correlation.
MATERIALS AND METHODS. This study was a retrospective review of nine cases from a single institution in which total resection and preoperative imaging were performed and the diagnosis of EAML was made. Imaging included CT (nine cases), MRI (five cases), and ultrasound (one case), and the images were reviewed in consensus by two radiologists. Patient demographics, disease associations, presentation, and outcomes were determined by chart review.
RESULTS. The patients were nine women and one man (mean age, 42 years). Two patients had tuberous sclerosis complex. The size of the nine EAMLs ranged from 1.4 to 22 cm (mean, 7.8 cm). Six lesions had minor components of fat identifiable at imaging. The contrast enhancement pattern was heterogeneous in eight lesions, five of which contained cysts, necrosis, and hematoma. Four presentations were acute hemorrhage, with ruptured EAML in three of the four. Five tumors extended into the renal sinus. Two tumors were locally invasive. One patient had metastatic disease at presentation with epithelioid tumor identified in a single lymph node. The follow-up periods ranged from 0 to 89 months, and there was one case of suspected but not yet proved recurrence.
CONCLUSION. Renal EAML can have a range of imaging appearances and can be indistinguishable from renal cell carcinoma and angiomyolipoma with minimal fat. EAML can be considered when a mass is found that has small foci of macroscopic fat without calcification or when acute hemorrhage of a renal mass occurs.
Keywords: epithelioid angiomyolipoma, malignant angiomyolipoma, renal mass
Angiomyolipoma is the most common mesenchymal renal neoplasm [1] and has been classified under the group of perivascular epithelioid cell tumors. The prevalence of angiomyolipoma in a healthy adult population without tuberous sclerosis complex (TSC) is 0.13% [2]. Approximately 80% of angiomyolipomas are seen sporadically, the others being seen as part of TSC [3]. The classic form of angiomyolipoma has triphasic histopathologic characteristics, containing variable proportions of dysmorphic blood vessels, smooth muscle, and adipose tissue. It is a benign tumor but can have an acute presentation, most notably from spontaneous hemorrhage [4, 5]. On occasion, conventional angiomyolipoma is locally invasive with venous invasion and fatty infiltration of hilar lymph nodes. The diagnosis can often be made at imaging, principally because of the presence of macroscopic adipose tissue identified with CT or MRI and lack of calcification [6, 7]. However, when CT or MRI shows an angiomyolipoma contains minimal or no fat, differentiation from renal cell carcinoma becomes difficult.
Other histologic variants of angiomyolipoma include an epithelioid subtype of monotypic angiomyolipoma (EAML), described by Aydin et al. [8] in 2009 and by Pea et al. [9] in 1998. It has also been referred to as atypical angiomyolipoma and malignant angiomyolipoma. In 2011 Nese et al. [10] estimated that 120 cases of EAML had been reported in the literature. The triphasic histologic features of classic angiomyolipoma can be scant or obscured in EAML, which instead consists predominately of sheets of epithelioid cells with granular eosinophilic cytoplasm. However, the amount of epithelioid composition sufficient to warrant classification as an EAML has not been uniform, ranging from 5% to 100%. EAMLs can have a high degree of cytologic pleomorphism and atypia and can exhibit necrosis [11]. EAML therefore can easily be misdiagnosed as renal cell carcinoma during histologic and imaging examinations [11]. Repeated review of cases previously diagnosed as renal cell carcinoma has shown that some were actually EAML [9, 12]. There are reports in the world literature of EAML with metastatic and aggressive behavior [10, 11, 13]. However, given the relatively low number of cases thus far in the literature and variability in pathologic criteria for designating a tumor EAML, the natural course remains uncertain but suggests that a significant minority of these tumors act in a malignant manner.
The imaging appearance of EAML has been much less well reported than the histopathologic features. To our knowledge, to date the most extensive report on the imaging characteristics of EAML is a 2009 description by Tsai et al. [14] of five cases in which CT showed no fat or calcification and “good enhancement” was found in an early contrast-enhanced phase. The other EAML cases in the literature in which imaging findings are described have been individual reports. Tsai et al. also performed an analysis of the literature and found that no gross fat component was described in any of the other 15 cases of EAML with reported imaging findings, for a total of 20 cases in the literature that mention this imaging feature.
We report the imaging characteristics of nine cases of renal EAML with radiologicpathologic correlation at a single institution and provide a review of the literature. To our knowledge, this is the largest and most detailed radiologic case series reported to date.
| Materials and Methods |   |
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This HIPAA-compliant retrospective review of cases of gross total resection and diagnosis of EAML was approved by our institutional internal review board. The requirement for informed consent was waived. Our surgical pathology database was searched for diagnoses of “epithelioid angiomyolipoma,” “angiomyolipoma, epithelioid,” and “monotypic PEComa” (perivascular epithelioid cell tumor) in cases of gross total resection. The pathologic findings were reviewed to confirm the diagnosis of EAML; the criterion for this repeated review was 80% or greater epithelioid composition. Although this criterion is not universal, it is consistent with the definition used in a recent multicenter pathologic study of EAML from three large institutions (including ours) [15]. The histologic composition of the tumors was evaluated for cystic change, hemorrhage, necrosis, mitotic activity, atypia, tumor margins, and invasion of adjacent tissues. Available immunohistochemical stains were reviewed. The pathologic review was performed by a pathologist with 15 years of experience in genitourinary pathology and a pathology fellow.
The search yielded 13 cases of EAML confirmed at gross total resection from 1999 to 2011. Nine of the 13 cases were included; four cases were excluded because preoperative images were not available. Ultrasound, unenhanced and enhanced CT, and MR images were reviewed in consensus by two radiologists—one with 21 years of experience in genitourinary imaging and one a fellow. Both radiologists were aware of the pathologic diagnosis and did not review the official pre-operative radiology reports.
Contrast-enhanced CT was performed in all nine cases, and unenhanced CT was performed in six of the nine cases. MRI was performed with and without IV gadolinium-based MRI contrast agents in five cases. Ultrasound with color Doppler technique was performed in one case. Images were assessed for presence of macroscopic fat, involvement of the renal hilum, tumor enhancement, evidence of cystic areas, tumor homogeneity or heterogeneity, and hemorrhage. The presence of macroscopic fat was determined subjectively as either a discrete focus of fat attenuation on CT images or of high T1 signal intensity that nulled on fat-saturated MR images. The quantity of macroscopic fat was subjectively estimated in relation with the tumor. Microscopic fat was identified by loss of signal intensity in the tumor on opposed-phase MR images without macroscopic fat. Hemorrhage was seen as subcapsular or perirenal fluid that had high attenuation on CT images or T1 hyperintense areas on MR images that were not suppressed by fat-saturation techniques. Additional CT-specific features analyzed included calcification and unenhanced CT attenuation. MRI-specific features analyzed included microscopic fat (identifiable on opposed-phase images) and T1 and T2 signal characteristics relative to skeletal muscle. Preoperative ultrasound images were evaluated for tumor echogenicity relative to renal parenchyma.
Review of the patients' charts was performed to determine demographic data (age, sex), disease associations (TSC), clinical presentation, and postsurgical outcome.
| Results | |
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The demographic characteristics of the nine patients (eight women, one man; age range, 29–71 years; mean age, 42 years) are shown in Table 1. In all nine cases, the lesion exhibited exophytic growth. Four patients presented with acute bleeding due to angiomyolipoma, although in case 6 the acute bleeding was due to a conventional angiomyolipoma in the same kidney, not the 3.2-cm EAML also resected at surgery.
Follow-up of the nine cases lasted 0–89 months (median, 19.2 months). Follow-up CT 5.5 months after nephrectomy in case 9 revealed new pulmonary nodules measuring up to 1 cm, suggesting metastasis, but the lesions had not been biopsied. Two patients (cases 2 and 7) were dismissed from care by the urology department without clinical or imaging follow-up and another (case 1) after a single 6-month recheck because the diagnosis at the time was thought to be benign.
The imaging characteristics are summarized in Table 2. All nine patients underwent CT, and unenhanced CT images were available for six of them. Five patients underwent MRI, and one underwent ultrasound. The renal lesions were in the right kidney in six cases and the left in three. The lesions were located in the upper renal pole in two cases, interpolar region in three cases, and lower renal pole in four cases. The size of the lesions ranged from 1.4 to 22 cm (mean, 7.8 cm). All nine lesions exhibited exophytic growth.
Small foci of fat were identifiable with CT or MRI in five cases. The largest quantity of fat was seen in case 3 (Fig. 2) and the second largest focus in case 7 (Fig. 4); both cases still had less than the 20% pathologic cutoff criterion. Fat identifiable on images constituted less than 5% of tumor volume of the other three lesions with identifiable fat. Microscopic fat was identified as loss of signal intensity in the tumor on opposed-phase MR images in an additional case (case 8). A single additional conventional angiomyolipoma containing gross fat was present in three patients, and multiple conventional angiomyolipomas were present in two patients with confirmed TSC.
 View larger version (162K) | Fig. 2A —29-year-old woman with epithelioid angiomyolipoma (case 3). A, Axial unenhanced (A) and nephrographic phase enhanced (B) CT images and fat-saturated T2-weighted MR image (C) show mildly high attenuation of soft-tissue component of heterogeneous tumor arising from upper pole of right kidney; small area of fat along anterior aspect of tumor, which extends to renal sinus (arrow, A); heterogeneous contrast enhancement; and cystic-appearing areas. Enlarged veins (arrows, B) are evident at periphery of lesion. |
 View larger version (186K) | Fig. 2B —29-year-old woman with epithelioid angiomyolipoma (case 3). B, Axial unenhanced (A) and nephrographic phase enhanced (B) CT images and fat-saturated T2-weighted MR image (C) show mildly high attenuation of soft-tissue component of heterogeneous tumor arising from upper pole of right kidney; small area of fat along anterior aspect of tumor, which extends to renal sinus (arrow, A); heterogeneous contrast enhancement; and cystic-appearing areas. Enlarged veins (arrows, B) are evident at periphery of lesion. |
 View larger version (155K) | Fig. 2C —29-year-old woman with epithelioid angiomyolipoma (case 3). C, Axial unenhanced (A) and nephrographic phase enhanced (B) CT images and fat-saturated T2-weighted MR image (C) show mildly high attenuation of soft-tissue component of heterogeneous tumor arising from upper pole of right kidney; small area of fat along anterior aspect of tumor, which extends to renal sinus (arrow, A); heterogeneous contrast enhancement; and cystic-appearing areas. Enlarged veins (arrows, B) are evident at periphery of lesion. |
 View larger version (193K) | Fig. 2D —29-year-old woman with epithelioid angiomyolipoma (case 3). D, Photomicrographs (H and E, ×40 [D]; H and E, ×400 [E]) show areas of hemorrhage and proliferation of round to polygonal epithelioid cells with round nucleoli and abundant granular cytoplasm. Cystic areas in B and C proved to be true endothelial cyst with organizing hematoma (not shown). |
 View larger version (140K) | Fig. 2E —29-year-old woman with epithelioid angiomyolipoma (case 3). E, Photomicrographs (H and E, ×40 [D]; H and E, ×400 [E]) show areas of hemorrhage and proliferation of round to polygonal epithelioid cells with round nucleoli and abundant granular cytoplasm. Cystic areas in B and C proved to be true endothelial cyst with organizing hematoma (not shown). |
 View larger version (219K) | Fig. 4 —35-year-old man with epithelioid angiomyolipoma (case 7). Axial nephrographic phase enhanced CT image shows large exophytic lobulated mass of soft-tissue attenuation with central cystic change or necrosis and tiny focus of macroscopic fat (arrow). Tumor extends to renal sinus in anterior aspect. Mild contrast washout was present on delayed views (not shown). Cystic change proved after surgery to be necrosis with organized hematoma. |
The lesions appeared mildly hyperattenuating with respect to the renal parenchymal attenuation in four of six patients for whom un-enhanced CT scans were available (Fig. 1). One of these four lesions exhibited homogeneous contrast enhancement. Images depicted hemorrhage in four cases. Perinephric hemorrhage was secondary to ruptured EAML in three cases and subcapsular hemorrhage in another. The three ruptured EAMLs measured 2.4 cm (case 4), 6.0 cm (case 8), and 13.3 cm (case 7). The amount of perinephric hematoma was subjectively estimated by consensus to be small (case 7), moderate (case 6), and large (case 8). At MRI, lesions that had presented with hemorrhage were hyperintense on T1-weighted images in two cases (Fig. 3), and the others were isointense. Signal intensity on T2-weighted images was heterogeneous with areas of high intensity in four of five cases and an area of low signal intensity that had previously bled in one case (case 8).
 View larger version (191K) | Fig. 1 —30-year-old woman with tuberous sclerosis complex (case 2). Unenhanced axial CT image shows epithelioid angiomyolipoma (arrow) of homogeneous mildly high attenuation (40 HU) in anterior aspect of midportion of right kidney and several additional bilateral small conventional fat-containing angiomyolipomas (arrowheads). |
 View larger version (165K) | Fig. 3A —29-year-old woman with epithelioid angiomyolipoma (case 5). A, Axial nephrographic phase enhanced CT scan (A) and opposed-phase T1-weighted gradient-echo MR image (B) show heterogeneous enhancement, cystic spaces, areas of hemorrhage (T1 signal hyperintensity without India ink artifact at interfaces) with fluid-fluid levels (arrow, A), and tumor extension to renal sinus. |
 View larger version (176K) | Fig. 3B —29-year-old woman with epithelioid angiomyolipoma (case 5). B, Axial nephrographic phase enhanced CT scan (A) and opposed-phase T1-weighted gradient-echo MR image (B) show heterogeneous enhancement, cystic spaces, areas of hemorrhage (T1 signal hyperintensity without India ink artifact at interfaces) with fluid-fluid levels (arrow, A), and tumor extension to renal sinus. |
Eight of the nine cases were heterogeneous on enhanced CT or MR images. Tumor enhancement ranged from mild (three cases) through moderate (three cases) to moderate to marked (three cases). Solely peripheral enhancement was found in one tumor. Enlarged vessels were present in the lesions in six cases. Case 9 was notable for large, tortuous tumor vessels, which prompted tumor embolization before resection (but after the described CT and MRI).
In the patient who underwent ultrasound imaging, the lesion was heterogeneous and centrally mildly hyperechoic with the periphery of the lesion isoechoic to renal parenchyma (Fig. 5A).
 View larger version (139K) | Fig. 5A —55-year-old woman with epithelioid angiomyolipoma (case 8). A, Longitudinal color Doppler ultrasound image shows 4-cm-diameter heterogeneous mass extending to right renal sinus with no appreciable internal Doppler signal. Lesion is centrally mildly hyperechoic and peripherally isoechoic to renal parenchyma (arrows). Examination was performed 1 year after initial presentation because of acute hemorrhage of tumor (presentation image not shown). |
 View larger version (211K) | Fig. 5B —55-year-old woman with epithelioid angiomyolipoma (case 8). B, Axial enhanced CT image obtained at time of planned cryoablation shows new findings suspicious for local tumor invasion of perinephric fat (arrow), which prompted treatment change from ablation to radical nephrectomy. Homogeneous low attenuation in central aspect of lesion was slightly hyperechoic at ultrasound (A) and corresponded to organized hematoma. Epithelioid angiomyolipoma with perinephric fat invasion was confirmed at surgery. |
Cystic components were found at imaging in four cases (Figs. 2–4 and 6). The lesion in case 9 was notable for having large branching areas of central fluid attenuation with associated surrounding calcification centrally within the mass. This central fluid was progressively found to become denser on excretory phase enhanced CT scans and abutted the normal renal pelvis. These findings suggest that rather than true tumor calcification, this area was actually a distorted and peripherally calcified intrarenal collecting system that had become engulfed by the tumor (Figs. 6A and 6B). None of the other cases had calcification.
 View larger version (163K) | Fig. 6A —33-year-old woman with tuberous sclerosis complex (case 9). A, Coronal nephrographic phase enhanced CT scan shows coarse central calcifications surrounding areas of fluid attenuation and heterogeneous avid enhancement of tumor, which surrounds distorted renal pelvis. Also evident are multiple enlarged lymph nodes with central low-attenuation changes superior to tumor (arrows). |
 View larger version (159K) | Fig. 6B —33-year-old woman with tuberous sclerosis complex (case 9). B, Coronal excretory phase CT image shows new gradient of increased attenuation from renal pelvis (long arrow) to areas of central fluid with peripheral calcification (short arrow) consistent with connection to renal pelvis. |
 View larger version (217K) | Fig. 6C —33-year-old woman with tuberous sclerosis complex (case 9). C, Axial enhanced CT image shows multiple enlarged left suprarenal lymph nodes with internal areas of lower attenuation but not fat attenuation. |
 View larger version (175K) | Fig. 6D —33-year-old woman with tuberous sclerosis complex (case 9). D, Axial fat-saturated T2-weighted MR image shows heterogeneous signal intensity with areas of fluid signal intensity and numerous large vascular flow voids in mass (arrows) with pulsatile artifacts in anteroposterior phase-encoding direction. Numerous conventional fat-containing angiomyolipomas were present in contralateral right kidney on CT and MRI. |
 View larger version (168K) | Fig. 6E —33-year-old woman with tuberous sclerosis complex (case 9). E, Axial CT image (lung windows) shows new 1.0-cm round pulmonary nodule in left lower lobe (arrow) with cystic changes in lungs due to tuberous sclerosis complex. |
Five tumors extended into the renal sinus (Figs. 2–6). In case 8, new local perinephric fat invasion was suggested preoperatively at the time of a planned percutaneous cryo-ablation and prompted a treatment change to radical nephrectomy (Fig. 5B). The lesion in case 9 extensively replaced most of the kidney and perinephric fat. There was no imaging evidence of vascular invasion in any of our cases. The patient in case 9 had multiple enlarged suprarenal lymph nodes, many of which were noted to be cystic at CT and MRI but without identifiable internal fat (Fig. 6).
The pathologic characteristics are summarized in Table 3. All nine lesions had a predominance of epithelioid cells with granular eosinophilic cytoplasm. Variable but small amounts of thick-walled vessels, spindle-shaped smooth-muscle cells, and fat were also present. Nuclear pleomorphism was evident, and some cases exhibited marked nuclear enlargement with macronucleoli. The chromatin pattern varied from vesicular to hyperchromatic. Six lesions had evidence of organizing hematoma. Two lesions had cystic spaces at histologic examination. In case 7, the histologic correlate was necrosis and organizing hematoma. The lesion in case 9 also had histologic evidence of tumor necrosis, but the tumor had been embolized before resection. Mitotic activity was not markedly increased in any case (< 1 mitosis per 10 high power field in all cases). The presence of perinephric fat invasion suggested preoperatively was confirmed pathologically in case 8. In case 9 the lesion invaded and replaced most of the kidney. No case had evidence of vascular invasion.
Case 9 was notable for lymph node involvement. One of seven resected nodes was involved by epithelioid tumor, and three of the other six lymph nodes were involved by conventional angiomyolipoma. In cases 4 and 7, immunohistochemical stains were available for review. Both lesions were homatropinemethylbromide–45–positive. Case 7 also had positive results of Melan-A and smooth-muscle actin immunostains.
| Discussion | |
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The 2004 World Health Organization Classification of Tumors [16] classifies EAML as a potentially malignant neoplasm. However, the degree of epithelioid tumor component that warrants classification as an EAML is unclear. For example, it is stated that epithelioid cellular morphologic features can be seen as a component of conventional angiomyolipoma, but EAML composed partially or entirely of epithelioid cells with malignant potential is also listed as a separate entity [16]. Nese et al. [10] in a clinicopathologic study in 2011 described the most well-defined and homogeneous, to our knowledge, collection of 41 EAML cases to date. They defined the lesions as “pure epithelioid PEComa of the kidney,” which was composed of “purely epithelioid cells,” but they allowed a less than 2% focal adipocytic component. Brimo et al. [13], however, in a clinicopathologic study of 40 cases, suggested that any epithelioid morphologic features define an EAML (their range was a 5–100% epithelioid component). No mention was made of the imaging characteristics in either of those pathologic studies. In the limited available literature describing any imaging characteristics of EAML, the pathologic criteria have not been well defined. Regardless of the pathologic criteria used to diagnose EAML, tumors with pure or near-total epithelioid histo-logic composition can easily be misdiagnosed as another tumor, particularly renal cell carcinoma, at both pathologic and radiologic examinations [8, 9].
Even with our narrow pathologic inclusion definition of EAML, our nine cases had a wide range of presentations and imaging characteristics. Appearances ranged from small, well-defined, and homogeneous tumors to large and markedly heterogeneous masses. In one of the nine cases (case 2), the tumor appeared as a well-defined hyperattenuating renal mass with homogeneous contrast enhancement on CT images. This finding is similar to the CT findings of angiomyolipoma with minimal fat [17].
Epithelioid morphologic features can be one of the monotypic types of fat-poor angiomyolipoma. Therefore, EAML with no identifiable fat on images would be difficult to differentiate from the other subtypes of fat-poor angiomyolipoma, which can be difficult to differentiate from renal cell carcinoma [18]. For example, four of six lesions in our study had slightly high attenuation (≥ 40 HU) compared with renal parenchyma on unenhanced CT images. One lesion had loss of signal intensity on opposed-phase MR images, which can be seen in both fat-poor angiomyolipoma and clear cell renal cell carcinoma. Similarly, the T2-weighted MRI signal intensity and the contrast enhancement characteristics that have been found helpful for differentiating small fat-poor angiomyolipoma from renal cell carcinoma [19] overlapped in our small subset. The imaging findings described herein and in the literature to date are nonspecific, primarily overlapping with renal cell carcinoma without calcification.
Central areas of shell-like calcification were present in one of our cases, associated with a distorted intrarenal collecting system that had become engulfed by the tumor. To our knowledge, this finding has not been previously reported in the literature [10]. The other eight cases had no calcification. There have been rare case reports of classic angiomyolipoma containing calcification [20]. Renal cell carcinoma rarely contains fat and calcification. The fat component in renal cell carcinoma is usually subtle, whereas the calcifications are larger and coarse. Renal cell carcinoma containing fat without calcification is extremely rare [21].
The results in our series newly suggest that EAML should be a consideration (in addition to the other fat-poor subtypes of monotypic angiomyolipoma and rarely renal cell carcinoma with fat and without calcification) when a patient has a mass without calcification but with very small amounts of fat. Five of our nine patients had a small component of fat in or adjacent to the tumors identifiable on CT or MR images. The tiny amount of fat in three of the five lesions (cases 4, 6, and 9) would likely have still remained consistent with the definition of pure epithelioid perivascular epithelioid cell tumor (PEComa) of the kidney by Nese et al. [10], allowing a less than 2% focal adipocytic component. The lesions in cases 3 and 7 had greater than 2% fat content but were within our cutoff criterion of at least 80% epithelioid composition. In addition, in one of our cases (case 8), microscopic fat was identified on opposed-phase gradient-echo MR images. These imaging findings diverge from those described in the limited literature. In a literature review in 2009, Tsai et al. [14] found that none of 20 cases of EAML with described imaging findings had imaging evidence of fat. However, the pathologic criteria and imaging techniques used in their study were not well defined, and the authors did not include a radiologist.
The clinical implications of EAML have been mixed. One of the lesions in our study (case 9) had lymph node involvement and was locally invasive. At the first follow-up examination, the patient also had new pulmonary nodules suspicious for pulmonary metastasis that had not been pathologically proven (Fig. 5E). Nodal involvement at surgery was found to be due to both EAML and conventional angiomyolipoma, which rarely metastasizes. One additional tumor was locally invasive (case 8). None of the lesions in our study had evidence of vascular invasion, although vascular invasion can occur in EAML and conventional angiomyolipoma [22, 23]. In the world literature there have been case reports and series of EAML with metastatic and aggressive behavior. In a review of 40 case reports and series of EAML with a total of 69 cases, Faraji et al. [11] in 2009 found an adverse outcome in 40% of patients (follow-up, 22.5 ± 18 months). In a multicenter clinicopathologic review of 40 cases, Brimo et al. [13] in 2010 found a 26% rate of malignancy. In a multicenter clinicopathologic review of 41 cases (which included 16 previously published cases), Nese et al. [10] in 2011 found a 17% rate of recurrence and 49% rate of metastasis, 33% of patients dying of the disease. However, Aydin et al. [8] described benign clinical outcomes in all 15 of their patients. This variability in outcome among reports could be related to the varying definitions of what constitutes an EAML, small sample sizes, and the source of cases (primary versus referral pathology cases). Our series comprised grossly resected lesions at our institution. Multicenter series composed of referral and pathology consult cases may be biased toward more atypical and aggressive tumors. Given the relatively small number of cases thus far in the literature (estimated at 120 by Nese et al. in 2011) and the variability in pathologic criteria used for designating a tumor EAML, the natural course remains uncertain but is worrisome. Management of EAML is debatable because of the unclear natural history of the tumors, but given the evidence of malignant behavior, it is often managed as renal cell carcinoma is [24].
Imaging can be helpful in the evaluation of ancillary features that have been suggested to have prognostic implications in outcome among EAML patients, including tumor size, presence of other angiomyolipomas or stigmata of TSC, metastasis, lymph-adenopathy, extrarenal extension, renal pelvic involvement, and renal vein involvement [10, 24]. Cui et al. [25] reported a case of large renal EAML with large retroperitoneal metastatic lymphadenopathy. In case 9 of our series, preoperative CT and MRI showed enlarged lymph nodes, one of which proved to be metastatic EAML and some of which were infiltrated by conventional angiomyolipoma. These lesions could not be differentiated with either CT or MRI. Extension into the renal sinus, which can mimic renal cell carcinoma engulfing renal sinus fat, was present in five cases.
The findings in our series newly suggest that EAML, in addition to conventional angiomyolipoma and other malignant tumors, should be a consideration when a patient has acute hemorrhage of a renal mass. Surprisingly, four of our patients presented with acute hemorrhage, although one hemorrhage was due to rupture of an adjacent conventional angiomyolipoma. Literature review revealed only one earlier report of spontaneous hemorrhage due to EAML, by Arrabal-Polo et al. [26] in 2009. However, the composition of the tumor in their report is unclear because they describe features of conventional angiomyolipoma “mixed with mature fatty tissue” and an unquantified component of epithelioid morphologic characteristics. Their CT image of the tumor shows a 4 × 3 × 4.5 cm mass of predominantly fat composition. If a less restrictive pathologic definition is used—such as that of Brimo et al. [13], whereby as little as 5% epithelioid content is allowed to define an EAML—rather than our definition or that of Nese et al. [10], in addition to being a previous case of EAML presenting with hemorrhage, the report by Arrabal-Polo et al. can also be considered an example of EAML with fat identifiable at CT.
Several publications have described an association between EAML and TSC, including evidence that some tumors originally diagnosed as renal cell carcinoma are actually found to be EAML at repeated review [9]. Eleven of 34 cases (32%) described by Nese et al. [10] and 16 of 61 published cases (26%) in their literature review were seen in patients with TSC. Two of our nine cases were associated with TSC, the tumors being identified at surveillance and considered suspicious for renal cell carcinoma. Three of the other seven patients were noted to have a single concomitant conventional angiomyolipoma. Foci of fat in the EAML were identifiable on images of three of the five patients with additional conventional angiomyolipomas. EAML should be included in the differential diagnosis of an atypical enhancing renal mass in a patient with additional fat-containing angiomyolipomas elsewhere. Scrutiny for tiny foci of fat within a lesion is warranted. However, it remains difficult to differentiate EAML with minimal fat from classic angiomyolipoma with minimal fat or rare renal cell carcinoma containing fat without the finding of calcification on CT and MR images.
The primary limitations of our study were the small number of cases, a consequence of the rarity of this recently recognized tumor; the series being grossly resected tumors at a single center; and the limited spectrum of images available for each patient. The imaging appearance of EAML in the literature remains limited.
| Conclusions | |
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EAML is an uncommon but clinically important tumor with potential for aggressive, malignant behavior. EAML can easily be confused with other tumors at imaging and histopathologic examinations but should be considered in the evaluation of a fat-poor noncalcified renal mass, especially in younger women and patients with TSC and additional angiomyolipomas. The findings in our series newly suggest that EAML should be a consideration when a patient has acute hemorrhage of a renal mass. Understanding of the potentially aggressive and malignant nature of these tumors is critical to obtaining and accurately evaluating preoperative and follow-up images in these patients.
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