DOI: 10.1148/rg.231025109
(Radiographics. 2003;23:241-246.)
© RSNA, 2003
Best Cases from the AFIP
Angiomyolipomas in Tuberous Sclerosis1
Lloyd G. Logue, DO,
Robin E. Acker, MD and
Anna E. Sienko, MD
1 From the Department of Radiological Sciences, University of Oklahoma Health Sciences Center, College of Medicine, Everett Tower, Rm 1606, 1200 Everett Dr, Oklahoma City, OK 73104. Received June 11, 2002; revision requested July 8 and received August 19; accepted August 20. Address correspondence to L.G.L. (e-mail: radiologue@sbcglobal.net).
Index Terms: Angiomyolipoma, 81.3141 • Kidney neoplasms, 81.3141 • Sclerosis, tuberous, 81.18
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History
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A 28-year-old pregnant woman presented with eclampsia. An emergent cesarean section was performed, and recovery was uneventful. Shortly after discharge from the hospital, she began having right-sided back pain. Empiric treatment with antibiotics was initiated on the basis of a urine sample with leukocyte esterase positivity and pyuria. Because there was no relief as a result of the treatment, she returned for further evaluation. Abdominal palpation revealed a tender mass, approximately 4 cm below the right costal margin in the right upper quadrant. She experienced transient episodes of hypertension. Laboratory analysis showed microcytic anemia and microhematuria.
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Imaging Findings
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Abdominal computed tomography (CT) showed extensive replacement and distortion of the renal parenchyma by multiple tumors that featured predominantly fat attenuation. The midpole of the right kidney contained a well-defined, 7-cm-diameter lesion of soft-tissue attenuation at nonenhanced CT, which homogeneously and intensely enhanced in the arterial phase of contrast material–enhanced CT (Fig 1). Within the inferior pole of the right kidney, there was a large heterogeneous lesion that exhibited a whorled pattern of mixed high attenuation and soft-tissue attenuation at nonenhanced CT (Fig 2). Selective angiography of the right renal artery demonstrated enlargement of the ventral branch artery, where a jet of contrast material was seen filling a large saccular aneurysm. There was filling of tortuous irregular tumor vessels and multiple smaller saccular macro- and microaneurysms scattered within the renal parenchyma (Fig 3). Magnetic resonance (MR) imaging of the brain, performed at the suggestion of the radiologist, revealed ill-defined areas of increased signal intensity on T2-weighted images in the subcortical white matter of both occipital lobes and in the right basitemporal cortex. A nodular area of subependymal enhancement was demonstrated in the inferior aspect of the left lateral ventricle on contrast-enhanced T1-weighted images (Fig 4), thus confirming the radiologist’s suspicion of tuberous sclerosis.
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Figure 1a. (a) Nonenhanced CT scan shows multiple well-defined tumors of fat attenuation (arrows) that replace and displace the renal parenchyma bilaterally. The right kidney contains a large lesion of soft-tissue attenuation that has less defined borders (arrowheads). (b) Contrast-enhanced CT scan obtained at the same level shows intense homogeneous enhancement of the soft-tissue mass of the right kidney, an appearance consistent with a large saccular aneurysm (arrowheads) with surrounding hemorrhage (arrow).
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Figure 1b. (a) Nonenhanced CT scan shows multiple well-defined tumors of fat attenuation (arrows) that replace and displace the renal parenchyma bilaterally. The right kidney contains a large lesion of soft-tissue attenuation that has less defined borders (arrowheads). (b) Contrast-enhanced CT scan obtained at the same level shows intense homogeneous enhancement of the soft-tissue mass of the right kidney, an appearance consistent with a large saccular aneurysm (arrowheads) with surrounding hemorrhage (arrow).
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Figure 2a. (a) Nonenhanced CT scan shows a whorled configuration of hyperattenuating fluid (arrow) within the lower pole of the right kidney, an appearance that suggests recent intratumoral hemorrhage. (b) Contrast-enhanced CT scan obtained at the same level shows multiple saccular aneurysms (arrows) within the hemorrhagic tumor of the right kidney.
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Figure 2b. (a) Nonenhanced CT scan shows a whorled configuration of hyperattenuating fluid (arrow) within the lower pole of the right kidney, an appearance that suggests recent intratumoral hemorrhage. (b) Contrast-enhanced CT scan obtained at the same level shows multiple saccular aneurysms (arrows) within the hemorrhagic tumor of the right kidney.
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Figure 3. Selective renal arteriogram shows mass effect and splaying of the renal arteries. The giant saccular aneurysm contains a jet of contrast material (arrowheads). Multiple smaller saccular aneurysms are also present (arrows).
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Pathologic Evaluation
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On the basis of the imaging findings and the patient’s need for repeated blood transfusions, a right nephrectomy was performed after coil embolization of the giant saccular aneurysm and the main right renal artery. The fresh pathologic specimen showed the thrombosed giant saccular aneurysm at the midpole of the right kidney and the large area of hemorrhage in the lower pole of the right kidney (Fig 5). The description of the gross pathologic sample also included multiple yellow-tan nodules of varying sizes that occupied at least 80% of the right kidney, displacing and compressing small thin areas of normal renal parenchyma. The histologic evaluation confirmed the presence of adipose tissue, smooth muscle, and thick-walled blood vessels (Fig 6). Sections showed a disrupted aneurysm that corresponded to the hemorrhage shown at CT (Fig 7).
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Figure 5. Photograph of the fresh cut specimen shows a tan angiomyolipoma (arrowheads) and two large cystlike areas, which represent the giant saccular aneurysm (black arrow) and a large hemorrhagic angiomyolipoma (white arrow).
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Figure 6. Photomicrograph (original magnification, x10; hematoxylin-eosin stain) of one of the numerous tan nodules that replaced the renal parenchyma shows smooth muscle (left), thick-walled blood vessels (lower left center), and fatty tissue (upper right). A band of recognizable residual renal parenchyma is noted between the vessels and fatty tissue.
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Figure 7a. (a) Photomicrograph (original magnification, x10; hematoxylin-eosin stain) of a blood vessel shows an aneurysm with complete disruption of the right side of the vascular wall (arrowheads). The blood vessel wall is intact on the left side (arrow). (b) Higher-power photomicrograph (original magnification, x20; hematoxylin-eosin stain) of the disrupted vascular wall shows blood (arrowheads) dissecting into and between fibromuscular and elastic fibers (arrows). (c) Photomicrograph (original magnification, x20; elastic stain) shows disrupted and fragmented elastic fibers (arrowheads).
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Figure 7b. (a) Photomicrograph (original magnification, x10; hematoxylin-eosin stain) of a blood vessel shows an aneurysm with complete disruption of the right side of the vascular wall (arrowheads). The blood vessel wall is intact on the left side (arrow). (b) Higher-power photomicrograph (original magnification, x20; hematoxylin-eosin stain) of the disrupted vascular wall shows blood (arrowheads) dissecting into and between fibromuscular and elastic fibers (arrows). (c) Photomicrograph (original magnification, x20; elastic stain) shows disrupted and fragmented elastic fibers (arrowheads).
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Figure 7c. (a) Photomicrograph (original magnification, x10; hematoxylin-eosin stain) of a blood vessel shows an aneurysm with complete disruption of the right side of the vascular wall (arrowheads). The blood vessel wall is intact on the left side (arrow). (b) Higher-power photomicrograph (original magnification, x20; hematoxylin-eosin stain) of the disrupted vascular wall shows blood (arrowheads) dissecting into and between fibromuscular and elastic fibers (arrows). (c) Photomicrograph (original magnification, x20; elastic stain) shows disrupted and fragmented elastic fibers (arrowheads).
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Discussion
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Tuberous sclerosis (Bourneville disease) is a phacomatosis, classically described as the triad of adenoma sebaceum, seizures, and mental retardation. The inheritance is autosomal dominant; however, spontaneous mutation occurs in 56%–80% of individuals with tuberous sclerosis. Features central to the diagnosis of tuberous sclerosis include facial angiofibroma (adenoma sebaceum) or forehead plaque, nontraumatic ungual or periungual fibroma, hypomelanotic macules (three or more), shagreen patch (connective tissue nevus), multiple retinal nodular hamartomas, cortical tuber, subependymal nodule, subependymal giant cell astrocytoma, cardiac rhabdomyoma (single or multiple), lymphangiomyomatosis, and renal angiomyolipoma. Less specific features of tuberous sclerosis include multiple randomly distributed pits in dental enamel, hamartomatous rectal polyps, bone cysts, cerebral white matter radial migrational lines, gingival fibromas, nonrenal hamartoma, retinal achromic patch, "confetti" skin lesions, and multiple renal cysts (1).
The origin of tuberous sclerosis has been traced to at least two loci on chromosomes 9 and 16, referred to as TSC1 and TSC2, respectively (2). The TSC2 gene, positioned adjacent to the polycystic kidney disease 1 locus (PKD1), accounts for the majority of the disease. The occurrence of renal cysts in patients with tuberous sclerosis may be explained by an occasional simultaneous deletion of the adjacent PKD1 and TSC2 genes. A similar set of circumstances may also explain the occurrence of lymphangiomyomatosis with tuberous sclerosis (3).
The first histologic description of an angiomyolipoma appeared in the literature in a 1911 report by Fischer (4). The components of this tumor include mature adipose tissue, smooth muscle, and thick-walled blood vessels, for which the tumor was finally named by Morgan et al in 1951 (5). Historically, angiomyolipomas have been classified as hamartomas or choristomas; however, the most recent literature places these mesenchymal renal tumors into a family of clonal neoplasms due to current evidence supporting the common ancestry of the constituent tissues from the perivascular epithelioid cell (6,7).
Angiomyolipomas occur as isolated, sporadic entities in 80% of cases, most commonly manifesting in middle-aged women. The other 20% of angiomyolipomas develop in association with tuberous sclerosis. The penetrance of such lesions in the tuberous sclerosis complex can be up to 80% (8,9). Although the histologic appearance of angiomyolipomas in these two entities is identical, the disease progression may not be. Angiomyolipomas that occur in association with tuberous sclerosis manifest at a younger age (31.5 years vs 53.6 years, P < .05), are likely to be larger and bilateral, and are prone to grow and need surgical treatment (8). L’Hostis et al (7) observed the presence of both progesterone and estrogen receptors in angiomyolipomas and found that progesterone and estrogen immunoreactive angiomyolipomas were predominantly found in women and in patients with tuberous sclerosis. These findings may further explain the more aggressive nature of the disease process in patients with tuberous sclerosis, the hormonal potentiation of tumor growth and hemorrhage in conditions such as pregnancy, and the overwhelming female predominance in the sporadic form of angiomyolipoma without tuberous sclerosis (7,10–12).
Angiomyolipomas are commonly incidental findings, but they may manifest with symptoms of abdominal and flank pain, nausea, vomiting, and fever. Common findings described include a palpable mass, abdominal tenderness, hematuria, anemia, shock, hypertension, urinary tract infections, and renal failure. These signs and symptoms are usually a result of mass effect and hemorrhage. The propensity to hemorrhage is multifactorial and includes focal deficiencies of elastic tissue in abnormally rigid and thick blood vessels, hypervascularity, and venous invasion (13–15). The defects in the vessel elastic tissue also predispose these lesions to develop aneurysms, as in the case presented.
Many imaging modalities show typical but nonspecific findings. Clusters of saccular micro- and macroaneurysms have been reported to be the most characteristic finding of angiomyolipoma at angiography, with other suggestive features including a dense well-organized early arterial network, a late whorled appearance, sharp margination, and no appreciable arterial-venous shunting (13,16). Most aneurysms associated with angiomyolipomas are small and are not detected at CT, unlike the giant aneurysm seen in our case. Angiomyolipomas are well-defined hyperechoic masses at ultrasonography (US) regardless of the relative fat component (17). As with other fat-containing tumors, these lesions demonstrate high signal intensity on T1-weighted images and marked fat suppression at MR imaging.
Typically, more specific imaging results are obtained during CT examination of angiomyolipomas. Single or multiple well-circumscribed noncalcified renal cortical tumors containing tissue with fat attenuation of less than -20 HU are characteristic findings of angiomyolipoma at nonenhanced CT (9,13,17). Although demonstration of intratumoral fat attenuation is almost pathognomonic for this lesion, there are other rare benign and malignant processes that should be considered: perirenal fat entrapment, lipid necrosis, or osseous metaplasia, all of which may occur in renal cell carcinoma (17). Other rare renal lesions that can contain fat are liposarcoma, myolipoma, lipoma, oncocytoma, and Wilms tumor (9,17). Angiomyolipoma may have varying degrees of soft-tissue attenuation, depending on the relative proportion of vascular or smooth muscle composition and on the presence of intratumoral hemorrhage. Therefore, the absence of intratumoral fat does not preclude the diagnosis of angiomyolipoma. However, even in the presence of other characteristic angiomyolipomas, renal tumors that are devoid of fat should incite suspicion that a more aggressive lesion may coexist, such as malignant epithelioid angiomyolipoma, renal cell carcinoma, and leiomyosarcoma (9,10,17). Although atraumatic renal and perirenal hemorrhage can occur secondary to benign renal tumors, vasculitis, aneurysm, systemic anticoagulation, infection, or nephritis, malignant renal neoplasms are still the most common cause (5,18).
The imaging findings of angiomyolipoma are often classic, but as described earlier, situations can arise where both the radiographic and pathologic diagnosis can be elusive. Absence of fat attenuation, multicentric tumor involvement including other organs and regional lymph nodes, and invasion into structures such as the inferior vena cava and right atrium can result in an erroneous radiographic conclusion suggesting malignancy (19). The diagnosis can be further complicated in these cases by the dramatic hypercellularity, pleomorphism, and mitotic activity occasionally exhibited in the histologic samples of the smooth muscle components, making differentiation from a malignant neoplasm difficult (9). Immunohistochemical analysis with the monoclonal antibody specific for human melanoma (HMB-45) may be helpful in differentiating angiomyolipoma from malignant neoplasm with the exception of the malignant epithelioid variant of angiomyolipoma (7).
Although many angiomyolipomas do not show growth over time, those that occur with the tuberous sclerosis complex are more likely to show progressive evolution and are more likely to need intervention such as selective arterial embolization, renal sparing surgery, or nephrectomy. The need for intervention, including prophylactic embolization, should be predicated on the presence of rapid growth or the development of symptoms related to retroperitoneal hemorrhage and mass effect. Tumor diameter greater than 4 cm has also been used as a criterion for prophylactic treatment, since many studies show a higher frequency of hemorrhagic complications with larger tumors (8,20). However, according to Antonopoulos et al (21), these tumors do not have to be large (>4 cm in diameter) before serious life-threatening hemorrhage can occur, as previous studies have suggested, and at least one study has shown that smaller tumors less than 4 cm in diameter have a more rapid doubling time (22). Conservative observation and follow-up examinations of asymptomatic patients with tuberous sclerosis and angiomyolipoma are recommended with biannual imaging that may include US, CT, or MR imaging. Pregnancy may also be a justification for more aggressive treatment and follow-up given the evidence for significant hormonal influence on tumor growth and hemorrhage. Particular attention to uncharacteristic lesions is recommended due to the rare association between angiomyolipoma and synchronous malignant neoplasms such as renal cell carcinoma and malignant epithelioid angiomyolipoma (2,23).
Our patient had an uncomplicated recovery after selective embolization and nephrectomy but later died of asphyxia in an unwitnessed seizure. Because the hypertension and seizures affected the patient some 4 weeks after delivery, these symptoms were presumably a manifestation of the tuberous sclerosis and angiomyolipoma and not secondary to eclampsia.
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Footnotes
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Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing two beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998; 13:624-628.[Medline]
- Choyke PL. Inherited cystic diseases of the kidney. Radiol Clin North Am 1996; 34:925-946.[Medline]
- Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med 2001; 163:253-258.[Abstract/Free Full Text]
- Fischer W. Die nierentumoren beider tuberosen hirnsklerose. Zeigler Beitr Path Anat Allg Path 1911; 50:235.
- Morgan GS, Straumfjord JV, Hall EJ. Angiomyolipoma of the kidney. J Urol 1951; 65:525.
- Bonetti F, Martignoni G, Colato C, et al. Abdominopelvic sarcoma of perivascular epithelioid cells: report of four cases in young women, one with tuberous sclerosis. Mod Pathol 2001; 14:563-568.[CrossRef][Medline]
- L’Hostis H, Deminiere C, Ferriere JM, Coindre JM. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases. Am J Surg Pathol 1999; 23:1011-1020.[CrossRef][Medline]
- Steiner MS, Goldman SM, Fishman EK, Marshall FF. The natural history of renal angiomyolipoma. J Urol 1993; 150:1782-1786.[Medline]
- Wagner BJ, Wong-You-Cheong JJ, Davis CJ, Jr. Adult renal hamartomas. RadioGraphics 1997; 17:155-169.[Abstract]
- Cibas ES, Goss GA, Kulke MH, Demetri GD, Fletcher CD. Malignant epithelioid angiomyolipoma (‘sarcoma ex angiomyolipoma’) of the kidney: a case report and review of the literature. Am J Surg Pathol 2001; 25:121-126.[Medline]
- Desai S, Hejmadi R, Krishnamurthy S, Chinoy RF. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases. Am J Surg Pathol 2001; 25:972-973.[Medline]
- Eble JN. Angiomyolipoma of kidney. Semin Diagn Pathol 1998; 15:21-40.[Medline]
- Gentry LR, Gould HR, Alter AJ, Wegenke JD, Atwell DT. Hemorrhagic angiomyolipoma: demonstration by computed tomography. J Comput Assist Tomogr 1981; 5:861-865.[Medline]
- Mouded IM, Tolia BM, Bernie JE, Newman HR. Symptomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture. J Urol 1978; 119:684-688.[Medline]
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- Silbiger ML, Peterson CC, Jr. Renal angiomyolipoma: its distinctive angiographic characteristics. J Urol 1971; 106:363-365.[Medline]
- Helenon O, Merran S, Paraf F, et al. Unusual fat-containing tumors of the kidney: a diagnostic dilemma. RadioGraphics 1997; 17:129-144.[Abstract]
- Kendall AR, Senay BA, Coll ME. Spontaneous subcapsular renal hematoma: diagnosis and management. J Urol 1988; 139:246-250.[Medline]
- Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urol 1994; 152(6 pt 1):1988-1991.[Medline]
- Oesterling JE, Fishman EK, Goldman SM, Marshall FF. The management of renal angiomyolipoma. J Urol 1986; 135:1121-1124.[Medline]
- Antonopoulos P, Drossos C, Triantopoulou C, Picramenos D, Dalamarinis C, Costacopoulos A. Complications of renal angiomyolipomas: CT evaluation. Abdom Imaging 1996; 21:357-360.[CrossRef][Medline]
- Yamamoto S, Nakamura K, Kawanami S, Aoki T, Watanabe H, Nakata H. Renal angiomyolipoma: evolutional changes of its internal structure on CT. Abdom Imaging 2000; 25:651-654.[CrossRef][Medline]
- Jimenez RE, Eble JN, Reuter VE, et al. Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases. Mod Pathol 2001; 14:157-163.[CrossRef][Medline]
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History
Imaging Findings
