Renal Angiomyolipoma
Emir S. SandhuHarvard Medical School, Year
IIIGillian Lieberman, MD
Emir Sandhu, HMS IIIGillian Lieberman, MD
Nov-Dec 2011
A Comparison of Sporadic and Genetic Cases
Mini-Seminar Outline1.
Renal Angiomyolipoma
(AML): Facts
2.
Angiomyolipoma: Associated Syndromes3.
Clinical presentation of AMLs
4.
Epidemiology 5.
Overview of Renal Anatomy
6.
Meet Our Patient: Clinical Presentation7.
Our Patient: Diagnostic Workup
8.
AMLs: Role of Angiography9.
Our Patient: Therapeutic Management of AMLs
10.
Companion Patient: Tuberous Sclerosis11.
Tuberous Sclerosis: Facts and Role of Imaging
Emir Sandhu, HMS IIIGillian Lieberman, MD
2
Renal Angiomyolipoma: Facts• Benign renal tumor• 3 major histologic
components, consisting of
mature fat cells, smooth muscle, blood vessels. • Characteristic features including adipose
tissue shown below:
Image: http://path.upmc.edu/cases/case165.html
Emir Sandhu, HMS IIIGillian Lieberman, MD
3
Associated Syndromes: Tuberous Sclerosis
• Neurocutaneous
syndrome• 10% of angiomyolipomas
are associated with
Tuberous Sclerosis • Rare multi-system genetic disease that causes non-
malignant tumor formation, typically manifesting in brain, skin, kidney, heart, eyes, lungs.
• Associated symptoms include seizures, developmental delay, lung and kidney disease.
More to come on Tuberous Sclerosis.
Emir Sandhu, HMS IIIGillian Lieberman, MD
4
Associated Syndromes: Sporadic Lymphangioleiomyomatosis
• Smooth muscle infiltration into alveoli.
• Female predominance.• Often occurs
concurrently with TS. • Rarely can occur
sporadically. 60% of sporadic cases also develop AMLs.
• AMLs
histo- pathologically identical
to those seen in TS.
Emir Sandhu, HMS IIIGillian Lieberman, MD
Images: (Left) High-resolution axial CT revealing cystic parenchymal
changes of LAM. (Right) Renal CT showing multiple lesions (-15 to -100 HU) characteristic of fat.
Images: Bissler
and Kingswood, (2004).
5
Angiomyolipoma:
Clinical Presentation• Most common symptoms are the following:
– Flank pain– Hematuria: may lead to hypotension (parenchymal,
subcapsular, and/or perirenal
hemorrhage)• Underlying Pathology:
– Arteries within AMLs
lack an internal elastic membrane.
– AMLs
have disorganized adventitial smooth muscle. – Progresses to bleeding and aneurysms.
Emir Sandhu, HMS IIIGillian Lieberman, MD
6
AML:
Internal Elastic Membrane
Emir Sandhu, HMS IIIGillian Lieberman, MD
Shown above is an artery in AML (left) compared with a normal artery (right). The AML artery characteristically lacks an internal elastic membrane, surrounded by a collar of myomatous
cells.
Image: Meilstrup
et al, 1995 7
Angiomyolipoma: EpidemiologyBased on a study performed by Fujii
et al in 1995:
• Renal ultrasonography
performed on 17,900 healthy adult patients in Japan.
• Patients had no signs of urinary tract malignancies.• Hyperechoic
renal masses suggestive of angiomyolipoma
found in 41 (0.23%).• Upon further diagnostic confirmation, renal
angiomyolipoma
identified in 24 patients (0.13%)• Stratification by gender reveals approximately 0.1% in
males and 0.22% in females• Separate study of 8501 autopsies demonstrated similar
incidence.
Emir Sandhu, HMS IIIGillian Lieberman, MD
8
Mini-Seminar Outline1.
Renal Angiomyolipoma: Facts
2.
Angiomyolipoma: Associated Syndromes3.
Clinical presentation of AMLs
4.
Epidemiology 5.
Overview of Renal Anatomy
6.
Meet Our Patient: Clinical Presentation7.
Our Patient: Diagnostic Workup
8.
AMLs: Role of Angiography9.
Our Patient: Therapeutic Management of AMLs
10.
Companion Patient: Tuberous Sclerosis11.
Tuberous Sclerosis: Facts and Role of Imaging
Emir Sandhu, HMS IIIGillian Lieberman, MD
9
Renal Anatomy: An Overview
Emir Sandhu, HMS IIIGillian Lieberman, MD
Images: Renal Anatomy at http://biomed.brown.edu. Accessed 12/11/11. 10
Meet Our Patient: Clinical Presentation• 38 year-old female who recently emigrated from
China, initially presents to nephrology clinic.• When in China, patient had an MRI suggesting she
had a benign tumor on her right kidney.• She was referred following renal ultrasound ordered
by her primary care physician, which revealed a cortical-based echogenic
mass in the right kidney,
measuring approximately 3.9 x 3.5 cm, that was causing moderate hydronephrosis.
• On later visit, Urology felt the mass had been stable for the past year, and wanted to repeat MRI in 6 months.
Emir Sandhu, HMS IIIGillian Lieberman, MD
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Our Patient: Past Diagnostic Workup• 10/2008 MRI: 4.8 x 4.2 cm • 10/2010 MRI: 6.8 x 4.4 cm• 1/2011 Presented to the BIDMC ED with
dull right flank pain. No hematuria, dysuria, or urinary frequency.
• 5/2011: Seen by Urology, no plan for procedure. Follow up in 6 months.
• 10/2011: MRI: 8.9 x 5.7 cm• 11/2011: Decides on intervention.
Emir Sandhu, HMS IIIGillian Lieberman, MD
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Our Patient: Echogenic
Mass on US
Emir Sandhu, HMS IIIGillian Lieberman, MD
Shown on sagittal
ultrasound of the right kidney is a cortical- based, echogenic
mass measuring 3.9 x 3.5 cm. There is
moderate hydronephrosis
with no evidence of stones.Image: BIDMC PACS
13
Our Patient: Right Kidney Doppler
Emir Sandhu, HMS IIIGillian Lieberman, MD
Shown is a sagittal
ultrasound of the right kidney. Note the poor Doppler flow evident within the renal mass.
Image: BIDMC PACS14
Companion Patient:
AML on CT• Presence of fat in
kidney highly suggestive of AML.
• Fat is -20 to -80 Hounsfield Units (prior to contrast)
• Contrast may be given to reveal aneurysms
Emir Sandhu, HMS IIIGillian Lieberman, MD
Image above: Small AML shown in upper pole of right kidney (arrow), measuring -46
HU on axial CT scan.
Image: Meilstrup
et al. (1995)15
Our Patient: AML on Axial Vibe MRI
Emir Sandhu, HMS IIIGillian Lieberman, MD
On axial MRI: Large 8.9 x 5.7 cm mass centered in lower pole of the R kidney, extending into the R hilum
inferiorly. Diffuse low- grade enhancement seen, consistent with AML. There is also a 4-
mm lesion in the lower pole of the R kidney, also an AML.Image: BIDMC PACS
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Our Patient: T1 Axial In-Phase MRI
Emir Sandhu, HMS IIIGillian Lieberman, MD
Shown on the left is our patient’s T1 axial, in phase MRI. Note the effect of fat suppression compared with the axial
vibe image shown on the right.
Image: BIDMC PACS 17
Our Patient: T1 Out-of-Phase MRI
Emir Sandhu, HMS IIIGillian Lieberman, MD
On axial out-of-phase MRI, the India Ink Artifact is shown, which represents signal drop-out in voxels
that contain both fat and non-fat components. It is seen surrounding interfaces, as if someone had
outlined the interfaces with ink. A renal AML is also shown.Image: BIDMC PACS
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Mini-Seminar Outline1.
Renal Angiomyolipoma: Facts
2.
Angiomyolipoma: Associated Syndromes3.
Clinical presentation of AMLs
4.
Epidemiology 5.
Overview of Renal Anatomy
6.
Meet Our Patient: Clinical Presentation7.
Our Patient: Diagnostic Workup
8.
AMLs: Role of Angiography9.
Our Patient: Therapeutic Management of AMLs
10.
Companion Patient: Tuberous Sclerosis11.
Tuberous Sclerosis: Facts and Role of Imaging
Emir Sandhu, HMS IIIGillian Lieberman, MD
19
AML: Role of Renal Angiography• Not often used to diagnosis
AML• Often used for management
of bleeding• AMLs
have circumferential
peripheral vessels with whorled appearance during nephrographic
phase
• Multiple aneurysms are also characteristic.
• In study by Becker, et al: aneurysms found on 16 of 34 AML cases
Emir Sandhu, HMS IIIGillian Lieberman, MD
Image above: Angiography of R kidney revealing AML of the upper pole with
aneurysms. Image: Meilstrup
et al. (1995) 20
AML: Treatment RecommendationsSteiner Study: 35 patients with AML evaluated.
Recommendations:• Lesions <4cm should be followed with yearly CT/US.• Asymptomatic patient with lesion >4cm should have
semi-annual US.• Symptomatic patient with lesion >4cm should
undergo renal-sparing surgery or arterial embolization.
• Prophylactic intervention for patient with Tuberous Sclerosis and lesion >4cm, irrespective of symptoms.
• Two established treatment options include renal- sparing surgery or embolization.
From: Steiner MS, et al. (1993).
Emir Sandhu, HMS IIIGillian Lieberman, MD
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Our Patient: AML EmbolizationEmir Sandhu, HMS IIIGillian Lieberman, MD
Based on these treatment recommendations, our patient underwent embolization
of her AML.
-
Particle embolization
was performed to reduce flow rate through AML, closely monitored under fluoroscopic visualization. -Post-emblotherapy
R renal arteriogram demonstrated an avascular
tumor with no detectable venous or arterial flow from an inferior polar branch of the R renal artery.
Images: BIDMC PACS 22
Companion Patient #2: Tuberous Sclerosis
Image: T1-weighted coronal MRI.
Shown to the left in our companion patient are two lesions with increasing signal intensity (arrows) similar to subcutaneous fat (asterisk).
These are compatible with large angiomyolipoma.
Emir Sandhu, HMS IIIGillian Lieberman, MD
Image: Bissler
and Kingswood, (2004).23
Mini-Seminar Outline1.
Renal Angiomyolipoma: Facts
2.
Angiomyolipoma: Associated Syndromes3.
Clinical presentation of AMLs
4.
Epidemiology 5.
Overview of Renal Anatomy
6.
Meet Our Patient: Clinical Presentation7.
Our Patient: Diagnostic Workup
8.
AMLs: Role of Angiography9.
Our Patient: Therapeutic Management of AMLs
10.Companion Patient: Tuberous Sclerosis
11.
Tuberous Sclerosis: Facts and Role of Imaging
Emir Sandhu, HMS IIIGillian Lieberman, MD
24
Tuberous Sclerosis: Facts• Bilateral renal involvement typical. • 1/3 of cases are familial, remaining sporadic.• Transmitted in an autosomal
dominant trait.
• Characteristic formation of tubers in the skin, brain, kidneys, and other organs.
• Incidence is estimated to be approximately 1 in 6,000 live births.
• Two genes identified, TSC1 and TSC2, located on chromosomes 9 and 16 respectively.
Emir Sandhu, HMS IIIGillian Lieberman, MD
25From: Kumar V, et al. Robbins & Cotran
Pathologic Basis of Disease.(2009).
Tuberous Sclerosis: Diagnostic Criteria
Major Features Minor featuresFacial anglofibromas/forehead plaque Multiple pits in dental enamelNon-traumatic ungual
fibroma Hamartomatous
rectal polypsHypomelanotic
macules Bone cystsShagreen
patch (connective tissue nevus) Cerebral white matter radial migration lines
Multiple retinal nodular hamartomas Gingival fibromasCortical tuber Nonrenal
hamartomasSubependymal
nodule Retinal achromic
patchSubependymal
giant cell astrocytoma “Confetti”
skin lesionsCardiac rhabdomyoma Multiple renal cystsLymphangiomyomatosisRenal angiomyolipoma
Definitive diagnosis: 2 major features OR 1 major + 2 minor features required.
Emir Sandhu, HMS IIIGillian Lieberman, MD
26From: Roach ES, et al. (1999).
Tuberous Sclerosis: Renal Manifestation
• Most common TS manifestation is the formation of angiomyolipomas.
• Benign cysts and (less often) lymphangiomas
can also occur in patients with TS.
• Both cysts and angiomyolipomas
tend to present bilaterally.
• Many patients, however, have no symptoms referable to the kidney.
Emir Sandhu, HMS IIIGillian Lieberman, MD
27From: Casper KA, et al. (2002).
Tuberous Sclerosis: Role of Imaging• Renal US should be performed at time of diagnosis to define
extent of angiomyolipomas
and/or presence of polycystic disease.
• US recommended every 1-3 years to monitor growth of lesions and possible signs of malignancy. – Ex: of concern would be a non-cystic mass lacking low
density (-10 to -100 HU) to suggest benign AML.
• If malignant transformation suspected or large angiomyolipoma(s) present: – CT or MR recommended to evaluate abnormality.– Avoid gadolinium based imaging in those with GFR < 30
mL/min given risk of nephrogenic
systemic fibrosis.
Emir Sandhu, HMS IIIGillian Lieberman, MD
28From: Roach ES, et al. (1999).
Tuberous Sclerosis: Renal Complications• Angiomyolipomas
can become quite large, leading to
abdominal or flank pain, bleeding into lesion (typically when > 4 cm diameter)
• Renin-dependent hypertension, due to focal areas of ischemia around lesions. Chronic renal failure also can occur.
• RCC also is a known complication. Occurs in 1-2% of patients, substantially lower than VHL syndrome. – Histology is usually consistent with clear cell carcinoma.
Emir Sandhu, HMS IIIGillian Lieberman, MD
29
From: Steiner MS, et al. (1993).Rakowski
SK, et al. (2006).
Summary of Learning ObjectivesIn this mini-seminar, we have covered the following
topics:– Renal Angiomyolipoma:
• Clinical presentation• Associated genetic syndromes• Diagnostic evaluation• Relevant imaging findings• Therapeutic management
– Tuberous Sclerosis: • Clinical presentation• Renal manifestations and complications• Role of imaging and diagnostic criteria
Emir Sandhu, HMS IIIGillian Lieberman, MD
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References1.
Bissler
JJ, Kingswood, JC. Renal angiomyolipomata. Kidney Int. 2004 Sep;66(3):924-
34.
2.
Becker JA, et al. Angiomyolipoma
(hamartoma) of the kidney: An angiographic review. Acta Radiol Diagn. 1973 Sep;14(5):561-568.
3.
Brown University. Brown L, et al. The Past, The Present and The Future of Dialysis: Renal Anatomy. Accessed December 11, 2011. http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/WAK/renalphys/renalana
tomy.html.
4.
Casper KA, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002 Nov;225(2):451-6.
5.
Kumar V, et al. Robbins & Cotran
Pathologic Basis of Disease. 8th ed. Philadelphia, PA: Saunders Elsevier; 2009.
6.
Lemaitre L, et al. Imaging of angiomyolipomas. Semin Ultrasound CT MR. 1997 Apr;18(2):100-14.
7.
Meilstrup
JW, et al. Other renal tumors. Semin Roentgenol. 1995 Apr;30(2):168-84.8.
O’Callaghan FJ, et al. An epidemiological study of renal pathology
in tuberous sclerosis complex. BJU Int. 2004;94(6):853.
9.
Rakowski
SK, et al. Renal manifestations of tuberous sclerosis complex: Incidence, prognosis and predictive factors. Kidney Int. 2006;70(10):1777.
10.
Roach ES, et al. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. 1999 Jun;14(6):401-7.
11.
Steiner MS et al: The natural history of renal angiomyolipoma. J Urol. 1993;150:1782. 31
AcknowledgementsI would like to extend a warm thank you to the
following people for their help with my presentation:
Dr. Gillian LiebermanDr. Samir
Shah
Claire OdomMy fellow medical students
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